Effect
Note—IS, item-specific; LW, list-wide; PC, proportion congruence, with the number referring to the proportion of congruent trials. Stroop effect = RT(incongruent) - RT(congruent).
Given that list-wide proportion congruence had no significant effect on the magnitude of Stroop interference, we then analyzed the item-specific PC-25 and item-specific PC-75 trials to determine whether performance was affected by item-specific proportion congruence. A 2 × 2 × 2 mixed ANOVA was conducted with trial type (congruent vs. incongruent) as a within-subjects factor and item-specific proportion congruence (item-specific PC-25 vs. item-specific PC-75) and age (young vs. old) as between-subjects factors. RTs were slower for incongruent than for congruent trials [ F (1,68) = 262.70, MS e = 2,689.53], older adults were slower than younger adults [ F (1,68) = 39.12, MS e = 26,844.40], and the magnitude of slowing on the incongruent trials relative to the congruent trials was larger for older adults [ F (1,68) = 20.29, MS e = 2,689.53]. Most critically, there was strong evidence of an item-specific proportion congruence effect. The Stroop effect increased reliably from the item-specific PC-25 condition ( M = 89 msec) to the item-specific PC-75 condition ( M = 190 msec) [ F (1,68) = 33.66, MS e = 2,689.53]. Although the increase was larger for older adults (120 to 238 msec) than for younger adults (60 to 142 msec), the three-way interaction was not significant [ F (1,68) = 1.12, p = .29]. As with the list-wide proportion congruence manipulation, the effects of the item-specific manipulation and all interactions involving this factor did not change as a function of experience (first half vs. second half) with the task.
To verify that this pattern of findings did not change when log-transformed RTs were used to account for differences in baseline response latency, we repeated the analyses above. The pattern of results was identical. 2
Mean error rates for item-specific PC-50, PC-25, and PC-75 trials are presented in Table 3 . The analyses of error rate mirror those reported above for RT, focusing first on the effects of list-wide proportion congruence. The 2 × 2 × 2 mixed ANOVA indicated that error rates were higher for incongruent ( M = .03) than for congruent ( M = .004) trials [ F (1,68) = 32.65, MS e = .001] and higher for younger adults ( M = .03) than for older adults ( M = .01) [ F (1,68) = 5.05, MS e = .001]. Most importantly, the list-wide proportion congruence manipulation and all interactions involving this factor were not significant ( F s < 1), suggesting that list-wide proportion congruence did not affect error rate. Consistent with the RT analysis, the nonsignificant interaction between list-wide proportion congruence (33% vs. 67%) and trial type (congruent vs. incongruent) indicated that the Stroop effect in error rate was almost identical for item-specific PC-50 items in the list-wide PC-33 and list-wide PC-67 conditions. This was the case for younger and older adults.
Mean Error Rates for Item-Specific PC-50, PC-25, and PC-75 Trials in Experiment 1
Congruent | Incongruent | Stroop Effect | ||||
---|---|---|---|---|---|---|
M | SE | M | SE | M | SE | |
Young | ||||||
IS PC-25 & LW PC-33 | .009 | .003 | .023 | .004 | .013 | .006 |
IS PC-50 & LW PC-33 | .004 | .002 | .045 | .010 | .041 | .010 |
IS PC-50 & LW PC-67 | .009 | .004 | .044 | .011 | .035 | .010 |
IS PC-75 & LW PC-67 | .002 | .001 | .065 | .016 | .063 | .016 |
Old | ||||||
IS PC-25 & LW PC-33 | .000 | .000 | .013 | .003 | .013 | .003 |
IS PC-50 & LW PC-33 | .002 | .002 | .024 | .008 | .022 | .008 |
IS PC-50 & LW PC-67 | .002 | .002 | .024 | .013 | .022 | .013 |
IS PC-75 & LW PC-67 | .001 | .001 | .023 | .005 | .022 | .005 |
Note. IS, item-specific; LW, list-wide; PC, proportion congruence, with the number referring to the proportion of congruent trials. Stroop effect = error rate(incongruent) - error rate(congruent).
The effects of the list-wide proportion congruence manipulation were then examined separately for the first and second halves of the task. The entire pattern of findings was consistent with the combined block analysis reported above, except that the main effect of age was not significant [ F (1,68) = 1.61, p = .21] during the first half of the task.
To examine whether item-specific proportion congruence had an effect on error rate, a 2 × 2 × 2 mixed ANOVA was again conducted, this time focusing on the item-specific PC-25 and item-specific PC-75 trials. Error rates were higher for incongruent trials ( M = .03) than for congruent trials ( M = .003) [ F (1,68) = 38.11, MS e = .001], younger adults ( M = .03) made more errors than did older adults ( M = .01) [ F (1,68) = 11.87, MS e = .001], and the relatively larger error rate on incongruent relative to congruent trials was larger for younger adults [ F (1,68) = 5.22, MS e = .001, p = .03]. These main effects were qualified by several interactions. Critically, there was strong evidence of an item-specific proportion congruence effect in error rate. The significant two-way interaction between item-specific proportion congruence and trial type indicated that the Stroop effect in error rate was smaller for the item-specific PC-25 condition ( M = .01) than for the item-specific PC-75 condition ( M = .04) [ F (1,68) = 10.83, MS e = .001]. Furthermore, the three-way interaction was also significant [ F (1,68) = 5.00, MS e = .001, p = .03], indicating that the difference in the magnitude of the Stroop effect between the item-specific PC-25 and PC-75 conditions was greater for younger ( M s = .01 vs. .06) than for older ( M s = .01 vs. .02) adults. Examining the age groups separately, 2 × 2 mixed ANOVAs indicated that the item-specific proportion congruence × trial type interaction was significant for younger [ F (1,34) = 8.59, MS e = .00] but not for older [ F (1,34) = 2.52, p = .12] adults.
When the effects of the item-specific manipulation were examined separately for the first and second halves of the task, the pattern of findings was identical to that reported above for the combined block analysis, with a few exceptions. The main effect of group ( p = .06), age × trial type interaction [ F (1,68) = 1.23, p = .27], and age × trial type × item-specific proportion congruence interaction [ F (1,68) = 2.04, p = .16] were not significant during the first half.
The results of Experiment 1 suggest that an item-level control mechanism influenced the magnitude of Stroop interference such that interference was smaller for the mostly incongruent items. A critical question is whether a list-level control mechanism was also operative. The results strongly suggest that it was not, because list-wide proportion congruence had no effect on the magnitude of Stroop interference. This novel finding is contrary to several past reports (e.g., Logan et al., 1984 ; Lowe & Mitterer, 1982 ). The primary difference between the present study and studies such as these that demonstrated a list-wide proportion congruence effect is the design. Past studies perfectly confounded the list-wide manipulation with an item-specific manipulation. Here, we manipulated list-wide proportion congruence while holding item-specific proportion congruence constant. This approach allowed us to evaluate the distinct contributions of list-level and item-level control. The finding that item-level control exerted a significant influence on Stroop performance, but that list-level control did not, calls into question the locus of list-wide proportion congruence effects in previous studies. What formerly has been described as a list-wide control mechanism may actually be control that is operating on an item-by-item basis.
The analyses of age effects were also informative. Like the younger adults, older adults’ Stroop performance (RT and error rate) was not affected by the list-wide proportion congruence manipulation. In contrast, for RT, older adults’ Stroop performance was significantly modulated by item-specific proportion congruence in a manner that was comparable to the modulation observed for younger adults. That is, older adults’ Stroop interference, like that of younger adults, was smaller for the mostly incongruent as compared with the mostly congruent items. This novel observation suggests that older adults are sensitive to proportion congruence manipulations when they are implemented at the level of particular items.
The item-specific proportion congruence effect was age invariant for RT, but not for error rate. For younger adults, the item-specific proportion congruence effect was large and reliable. However, for older adults, the smaller Stroop effect in error rate in the mostly incongruent (item-specific PC-25) relative to the mostly congruent (item-specific PC-75) condition was not statistically reliable. A survey of the means from the critical cells indicates that younger and older adults had similar error rates in the mostly incongruent condition (1%), but younger adults’ error rates in the mostly congruent condition (6%) were inflated relative to older adults’ error rates (2%). Thus, although both groups appear to exploit item-specific proportion congruence similarly in reducing Stroop interference in RT, there does appear to be an age difference in the degree to which item-specific proportion congruence affects error rate. Focusing solely on younger adults’ performance, what differs between the mostly congruent and mostly incongruent conditions are error rates on the incongruent trials, not error rates on the congruent trials. Inflated error rates on the incongruent trials in the mostly congruent condition most likely reflect prediction errors, whereby participants emit the most frequent (but incorrect) response for a particular word. It is reasonable to assume that such prediction errors are correlated positively with the strength of the association between stimuli (words) and responses, and that younger adults would have stronger representations of this association relative to older adults. By this account, the observed age difference is precisely as expected. Additionally, the observed trend ( p = .10) for younger adults’ Stroop effect in error rate to be magnified in the mostly congruent condition in the second relative to the first block, as associations are presumably strengthened, is consistent with this account. We further consider the contribution of stimulus—response learning and other mechanisms to the item-specific proportion congruence effect in the experiments that follow.
The findings of Experiment 1 have important theoretical implications. Typically, the list-wide proportion congruence effect has been attributed to a single color-naming or word-reading policy that is applied uniformly and strategically to all stimuli within a particular condition (list). For instance, computational modeling traditionally has focused on stronger weighting of the color-naming (goal) pathway in the mostly incongruent condition as the primary locus of the list-wide proportion congruence effect (e.g., Botvinick et al., 2001 ; Cohen, Dunbar, & McClelland, 1990 ). The findings of Experiment 1 provide potential difficulties for this view. Our findings instead suggest that a model with a control mechanism that operates at a single level is sufficient as long as that level is item specific and not list wide. Accordingly, Blais et al. (2007) demonstrated that a model that varies control at an item-specific level, by strengthening the connection between the color-naming pathway and a trial-specific response, can accommodate both item-specific and list-wide proportion congruence effects.
The findings of Experiment 1 also converge with prior research using the process-dissociation procedure ( Jacoby, 1991 ). This procedure yielded stronger estimates of the word-reading process for mostly congruent than for mostly incongruent lists ( Lindsay & Jacoby, 1994 ) and for mostly congruent than for mostly incongruent items ( Jacoby et al., 2003 ). In both cases, variations in the word-reading process occurred independently of color naming, and color naming did not vary as a function of list-wide or item-specific proportion congruence. These studies, like the present experiment, imply that a similar control mechanism acts on the word-reading process to produce list-wide and item-specific proportion congruence effects.
Although a theoretical account of Stroop performance that entails a single item-level control mechanism is intriguing, the possibility remains that there are additional, yet undiscovered levels at which control is implemented. In Experiment 2, we pursued the general question of whether participants exploit several features that are available to control word reading in the Stroop task (i.e., use multiple levels of control) or tend to rely on a single level of control that leads to efficient performance.
In Experiment 1, and in prior studies examining item-level control (e.g., Jacoby et al., 2003 ), item-specific proportion congruence was manipulated at the level of word. That is, particular words were grouped together in sets (pairs or triplets), and particular word sets were composed of mostly congruent or incongruent items. As such, particular words were predictive of the likelihood that an item was congruent or incongruent. This item-specific manipulation may encourage use of the word as a “feature” that directs control of the word-reading process on an item-by-item basis.
Similarly, word reading might be controlled on the basis of other features if they too were predictive of proportion congruence. For instance, participants may be capable of extracting low-level, perceptual features of Stroop stimuli (e.g., shapes of particular letters, certain letter combinations, or distinctive font types) that are predictive of (correlated with) proportion congruence. These features then might be used to exert rapid control over the word reading process, such that word reading is permitted to influence performance to varying degrees depending on the specific features of the present item.
In the following experiment, we investigated whether control can operate via multiple levels in the Stroop task. We did this by combining the item-specific manipulation, whereby proportion congruence was manipulated at the level of particular color-word pairs (e.g., BLUE and YELLOW are mostly congruent items and GREEN and WHITE are mostly incongruent items) with a proportion congruence manipulation based on a specific perceptual feature, font type. In one condition, the mostly congruent words appeared in one font type (e.g., Arial), and the mostly incongruent words appeared in a second font type (e.g., Bookman Old Style). We refer to this condition as the multiple-features condition, because particular words and particular features (e.g., BLUE and YELLOW in Arial font) were correlated simultaneously with a proportion congruence level (e.g., mostly congruent). In contrast, in a single-feature condition, proportion congruence was manipulated only at the level of particular color-word pairs. In this condition, the mostly congruent and mostly incongruent words occurred equally often in both font types, and therefore only a single feature, color word, was predictive of proportion congruence.
As demonstrated previously (Experiment 1; Jacoby et al., 2003 ), the manipulation of item-specific proportion congruence at the level of word pairs is expected to produce an item-specific proportion congruence effect, such that interference is greater for mostly congruent than for mostly incongruent word pairs. This effect should occur in the multiple- and single-feature conditions, because both include the item-specific proportion congruence manipulation. The critical question is whether multiple features that are related to proportion congruence can be used simultaneously to control word reading. If participants in the multiple-features condition exploit both the word itself and the font type in service of control over Stroop interference, then the item-specific proportion congruence effect should be magnified in the multiple- relative to the single-feature condition. More precisely, the magnitude of interference should be smaller for mostly incongruent items and larger for mostly congruent items in the multiple-features condition.
Forty Washington University students participated in partial fulfillment of course credit or in exchange for monetary compensation. All participants were native English speakers between the ages of 18 and 25. Older adults did not participate in this or the subsequent experiment.
Four color words and their corresponding colors were divided into two pairs (BLUE and YELLOW, GREEN and WHITE). Words from one pair (e.g., BLUE and YELLOW) were designated mostly congruent (80%), and words from the other pair (e.g., GREEN and WHITE) were mostly incongruent (80%). The two word pairs combined to produce 50% congruent and 50% incongruent trials at the list level.
In the multiple-features condition, the mostly congruent items appeared in one font type (e.g., Arial) and the mostly incongruent items appeared in the second font type (e.g., Bookman Old Style). As a consequence, two features (color word and font type) were correlated with proportion congruence. These features were counterbalanced across participants ( n = 20), such that all possible combinations of font type and color-word pair occurred equally often at each level of proportion congruence. The single-feature condition was identical to the multiple-features condition, with the exception that font type was not correlated with proportion congruence. Rather, items from a particular color-word pair (e.g., BLUE and YELLOW) occurred equally often in both font types. The assignment of word pair to proportion congruence was counterbalanced across participants ( n = 20). The single- versus multiple-features manipulation was carried out between subjects. Participants were assigned randomly to each condition.
The procedure was identical to that of Experiment 1, except as noted below. There were 16 practice trials and two blocks of 108 test trials. The practice trials preserved the proportion congruence manipulation that was implemented in the test trials.
For each participant, RTs less than 200 msec and greater than 3,000 msec were removed. This resulted in the elimination of fewer than 1% of the trials from both the multiple- and single-feature conditions. Overall, errors were low (<1.3%). There were no significant effects in the analysis of error rates other than the finding that more errors were made on incongruent ( M = 2.1%) than on congruent ( M = 0.4%) trials [ F (1,38) = 15.14, MS e = .00, p < .01]. Therefore, to conserve space, we report only the analysis of correct RTs.
A 2 × 2 × 2 mixed-subjects ANOVA was conducted, with condition (multiple features vs. single features) as a between-subjects factor and proportion congruence (mostly congruent vs. mostly incongruent) and trial type (congruent vs. incongruent) as within-subjects factors. Incongruent trials ( M = 700) were responded to more slowly than congruent trials ( M = 612) [ F (1,38) = 214.26, MS e = 1,439]. The proportion congruence × trial type interaction indicated a significant item-specific proportion congruence effect [ F (1,38) = 74.29, MS e = 1,195]. As expected, the magnitude of Stroop interference was smaller for the mostly incongruent condition ( M = 41) than for the mostly congruent condition ( M = 135). As can be seen in Figure 1 , the item-specific proportion congruence effect was observed in both the multiple- and single-feature conditions. Importantly, the absence of a significant three-way interaction indicated that the magnitude of the item-specific proportion congruence effect did not vary as a function of whether multiple features or a single feature was correlated with proportion congruence ( F < 1).
Mean reaction time (RT, in milliseconds) as a function of trial type (C = congruent, I = incongruent) and proportion congruence (MC = mostly congruent, MI = mostly incongruent) for the multiple- and single-feature conditions in Experiment 2.
The findings of Experiment 2 provide some hints regarding the particular features that guide control in the Stroop task. The item-specific proportion congruence effect was observed in the multiple- and single-feature conditions. Both included an item-specific proportion congruence manipulation that varied proportion congruence for particular color-word pairs. This suggests that participants used word information to guide responses. Given the equivalence in the magnitude of the item-specific proportion congruence effect between conditions, it appears that participants in the multiple-features condition did not take advantage of the additional feature, font type, which was also correlated with proportion congruence. This may be because words themselves are highly salient and receive greater attention than do particular perceptual features, such as font type. In this sense, the relationship between particular words and proportion congruence levels may have overshadowed the relationship between particular font types and proportion congruence levels.
Alternatively, this pattern of findings may be related to the underlying mechanisms that reduce susceptibility to Stroop interference when participants respond on the basis of particular words (item-specific manipulation) versus particular word features (font-type manipulation). That is, the words themselves are predictive of the likelihood of congruency (as previously described), and this may lead participants to adopt different word-reading policies for mostly congruent as compared with mostly incongruent words. The words also are associated with particular color responses. For example, when BLUE and YELLOW are mostly congruent, 80% of the time BLUE appears in blue ink and YELLOW appears in yellow. In contrast, BLUE appears rarely in yellow and YELLOW appears rarely in blue. The opposite is true for mostly incongruent items. As suggested by Jacoby et al. (2003) , attending to and responding on the basis of the word can lead to fast and accurate production of the correct response on 80% of the trials (for similar accounts, see Melara & Algom, 2003 ; Musen & Squire, 1993 ; Schmidt & Besner, 2008 ; Schmidt, Crump, Cheesman, & Besner, 2007 ).
Font type, too, predicts the congruency of particular word pairs; therefore, participants may respond differentially to words printed in a mostly congruent relative to a mostly incongruent font type, on the basis of unique word-reading policies that have been established for each font type. In this sense, responding on the basis of item- or font-specific control may represent the action of a similar control mechanism. Unlike the word information that signals item-specific proportion congruence, however, font type does not predict specific responses and therefore does not permit responding on the basis of simple associations. In the present experiment, then, reliance on the word and on the information it carried regarding both the likelihood of congruency and the specific response to produce may have been a sufficiently efficient means of buffering Stroop interference such that other available features (e.g., font type) were not exploited in an effort to implement control over word reading. That is, font type, and the information it carried regarding the likelihood of congruence, may not have offered any additional advantages to performance that the word information alone did not offer already.
This result raises the question of whether font type, if it were the only feature correlated with proportion congruence, would produce a proportion congruence effect. That is, is there a control mechanism that can modulate word reading differentially for mostly congruent and incongruent items when proportion congruence is manipulated at the level of font type rather than at the level of the word itself ? Experiment 3 addressed this question.
Incongruent and congruent stimuli were presented equally often in two distinguishable font types. For one font type, items were mostly congruent; for the other, items were mostly incongruent. Stimuli appearing in each font type were presented equally often in the four colors used in the present experiment. As such, font type could not be used to predict specific responses. If font type, due to its ability to predict congruency, is used to control word reading, then Stroop interference should be smaller for items appearing in the mostly incongruent relative to the mostly congruent font type.
Twenty-two Washington University students participated in partial fulfillment of course credit or in exchange for monetary compensation. All participants were native English speakers, with normal color vision and with normal or corrected-to-normal visual acuity.
At the list level, an equal number of congruent and incongruent stimuli were randomly presented along with eight neutral (%%%%%) items. Each of the four stimulus words (BLUE, GREEN, WHITE, and YELLOW) was presented 50% of the time in the congruent color and 50% of the time in an incongruent color (∼33% of the time in each of the three incongruent colors). Bookman Old Style font was used to compose half of the trials; Arial was used in the other. Items presented in one of the two font types were mostly congruent (∼80%), and items presented in the other font type were mostly incongruent (∼80%). The assignment of font type to proportion congruence was counterbalanced across participants. All four stimulus words and colors appeared equally often in the mostly congruent and mostly incongruent font types.
The procedure was identical to that in Experiment 1, with a few exceptions. Participants completed 20 practice trials (8 in Arial font type and 8 in Bookman Old Style that each included all possible word/color combinations and preserved the font-specific proportion congruence of the test blocks, and 4 neutral trials) prior to completing two blocks of 120 test trials.
For each participant, RTs less than 200 msec and greater than 3,000 msec were removed, which eliminated fewer than 1% of the trials. Overall, errors were low (1.4%). There were no significant effects in the analysis of error rates other than the finding that more errors were made on incongruent ( M = 2.4%) versus congruent ( M = 0.4%) trials [ F (1,21) = 18.69, MS e = .00, p < .01]. Therefore, to conserve space, we report only the analysis of correct RTs.
A 2 × 2 within-subjects ANOVA was conducted with proportion congruence (mostly congruent vs. mostly incongruent) and trial type (congruent vs. incongruent) as factors. Incongruent trials ( M = 738) were responded to more slowly than congruent trials ( M = 632) [ F (1,21) = 103.34, MS e = 2,398]. As indicated by the proportion congruence × trial type interaction, the magnitude of Stroop interference was smaller for the mostly incongruent ( M = 96) than for the mostly congruent ( M = 116) font type [ F (1,21) = 4.78, MS e = 4.78, p < .05]. Given that this is the first report in the literature of a font-specific proportion congruence effect of which we are aware, we subsequently analyzed the proportion congruence × trial type interaction for each block of the task to characterize the time course of the effect. Our reasoning was that the association between font type and proportion congruence might develop slowly, such that the reliability of this interaction may be limited to performance in the second block. The analyses confirmed that this was the case. In Block 2, Stroop interference was smaller for items that appeared in the mostly incongruent font type ( M = 94) than for those that appeared in the mostly congruent font type ( M = 121) [ F (1,21) = 4.60, MS e = 886, p < .05]. Although a similar pattern was observed in Block 1, with interference being smaller for items appearing in the mostly incongruent ( M = 99) relative to the mostly congruent ( M = 110) font type, the interaction was less marked and not statistically reliable ( F < 1).
The observation of a font-specific proportion congruence effect implies that word reading can be modulated differentially for mostly congruent and incongruent items when congruency is signaled by a particular font type. Broadly speaking, this finding suggests that control over word reading in the Stroop task can be exerted at the font level in addition to the item level and list level. 3
Font-level control over Stroop interference may be accomplished by a mechanism that, upon onset of the Stroop stimulus, rapidly extracts predictive perceptual features, such as the font type itself or the shape of the word as written in a particular font type, and uses such features to differentially modulate word reading. A more refined hypothesis is that font type is used as an early signal for controlling a word-reading filter ( Jacoby et al., 2003 ; Jacoby, McElree, & Trainham, 1999 ). The idea here is that the word itself would be filtered more quickly for words appearing in the mostly incongruent relative to the mostly congruent font, such that further processing of the word beyond its low-level perceptual features may be inhibited. Importantly, a similar control mechanism might also underlie the item-specific proportion congruence effect observed previously ( Jacoby et al., 2003 ), although the action of this mechanism may be driven by features of the stimulus different from those that produce the font-specific proportion congruence effect. For instance, one might learn that particular words that are longer or shorter tend to come from a mostly incongruent word pair and use this information to filter word reading. This remains to be tested.
The font-specific proportion congruence effect is perhaps part of a larger class of context-specific proportion congruence effects. The term context-specific proportion congruence effect was coined by Crump, Gong, and Milliken (2006) , who showed that the magnitude of Stroop interference was significantly smaller when stimuli appeared in a mostly incongruent relative to a mostly congruent location. As with the font-specific proportion congruence effect, the context-specific proportion congruence effect cannot be accounted for by a simple contingency (e.g., stimulus—response learning) account, because the contextual cue (i.e., location) was associated equally often with all possible responses, just as font type was in the present experiment. Admittedly, a more complex contingency account based on compound font type—word—response associations might at least partially account for the font-specific proportion congruence effect and, similarly, the context-specific proportion congruence effect.
An important difference between the font-specific proportion congruence effect and the context-specific proportion congruence effect relates to the different Stroop paradigms that were used to evaluate these effects. Crump et al. (2006 , Experiment 2A) used a priming procedure whereby a color-word prime was presented briefly in black ink and was followed by a display featuring a colored rectangle that appeared above or below fixation in either the mostly congruent or the mostly incongruent location. The participants’ task was to name the color of the rectangle. Crump et al. speculated that the relevant contextual cue (i.e., location) might be modulating the degree to which the prime word is integrated with the color of the rectangle in the probe display, thus impacting Stroop interference. This control mechanism is very different from the notion of a word-reading filter that may be modulating word reading and producing the font-specific proportion congruence effect in our paradigm. A strong appeal of the latter mechanism is that a word-reading filter might explain Stroop interference effects more broadly, as in other common paradigms involving integrated color/word stimuli.
Human behavior is incredibly flexible. In some contexts, stimulus—response associations that are acquired via repeated experience are used to guide responding. Novel or unpredictable contexts, however, often necessitate a shift toward responding on the basis of higher level goals or expectations that may change on a moment-to-moment basis. The present analysis suggests that there are multiple approaches to controlling behavior and that such approaches are bound by contextual features. Similarly, the experiments presented here suggest that there are multiple levels at which one can exert control over Stroop interference and that engagement of these levels is triggered differentially for differing contexts.
In the present study, both younger and older adults demonstrated use of item-specific control, which involves the use of word information rapidly upon stimulus onset to modulate the influence of the word-reading process on Stroop performance ( Jacoby et al., 2003 ). When pairs of words (i.e., items) are mostly incongruent, Stroop effects are significantly smaller than when pairs of words are mostly congruent. As first outlined by Jacoby et al. (2003) , at least two mechanisms may underlie item-level control: a cognitive-control mechanism and an associative-learning mechanism. The cognitive control mechanism purportedly involves stronger dampening of the word-reading process upon stimulus onset particularly in the case of items from a mostly incongruent word pair (see also Jacoby, McElree, & Trainham, 1999 ). In contrast, the associative-learning mechanism involves the production of the color response that is associated most frequently with a particular word. For example, for a mostly incongruent word pair (e.g., BLUE and YELLOW), a participant would quickly produce the response “yellow” when presented with the word BLUE because most of the time this is the correct response. However, when the most frequent response is the incorrect response, as in the case of incongruent trials in a mostly congruent condition, reliance on this associative mechanism can create inflated error rates due to response prediction error, which was observed for younger adults in the mostly congruent condition in Experiment 1. Although the present results do not allow us to adjudicate fully between a control account and an associative learning account, it is important to acknowledge that item-level control can be achieved through either or both of these mechanisms.
In the present study, we also observed font-level control, which to our knowledge is a level of control not previously explored. The initial observation of a font-specific proportion congruence effect occurred in Experiment 3. In this experiment, items that were printed in a particular font type were mostly congruent, whereas items printed in a second font type were mostly incongruent. Stroop effects were significantly smaller for items printed in the mostly incongruent font type. The font-specific proportion congruence effect, like the item-specific proportion congruence effect, must reflect a mechanism that acts after stimulus onset, because 50% of the stimuli within a block of trials appear in the mostly congruent font and 50% appear in the mostly incongruent font. These proportions prohibit participants from anticipating the type of font that will occur on the upcoming trial and adjusting control settings prior to stimulus onset.
In the case of item-specific or font-level control, the particular operations that are engaged immediately after stimulus onset remain to be fully explicated. One possibility is that the two levels of control, at least in part, reflect the action of a single control mechanism that is “turned on” by different features of the stimulus. Participants may detect features (e.g., entire words, in the case of item-specific control, or distinctive font types or shapes, in the case of font-specific control) that are predictive of proportion congruence levels and use control mechanisms to gate word-reading processes accordingly. For example, item-specific and/or font-level control may involve processes that modulate word reading on the basis of the degree of interference (i.e., response conflict) each stimulus produces post-stimulus onset. Particular stimuli (or features of stimuli) that are associated with a high probability of incongruence may lead to greater conflict at onset and relatively stronger gating of word reading. Indeed, if item-specific or font-level control act after the detection of conflict, one might anticipate sequential adjustments in the form of conflict adaptation (see, e.g., Botvinick et al., 2001 ) in paradigms where these control processes are operating. Although the present findings and those using process dissociation (e.g., Jacoby et al., 2003 ; Lindsay & Jacoby, 1994 ) anticipate such adjustments to follow the form of weight changes in the reading pathway, changes might take place in the color pathway instead, as evidenced in the item-specific conflict-monitoring model ( Blais et al., 2007 ).
Alternatively, item-specific and/or font-level control may be acting post-stimulus onset, but prior to the occurrence of interference or conflict. For instance, detection of critical features such as font type may be accompanied by rapid gating of word-reading processes before response conflict arises, particularly in the case of incongruent trials from a mostly incongruent condition. Similarly, in the case of item-specific responding on the basis of learned associations, presentation of the stimulus (word) may lead to rapid retrieval of the associated response prior to the occurrence of conflict. According to this view, item-specific and/or font-level control may involve “early selection” processes ( Jacoby, Kelley, & McElree, 1999 ). These processes should not, however, be equated with the proactive control processes described in the context of the dual mechanisms of control account ( Braver et al., 2007 ). This account conceptualizes proactive control processes as acting prior to stimulus onset, whereas the proposed mechanisms just described may be acting post-stimulus onset.
A third level of control, which operates at the list level, is the most pervasive control mechanism identified in the extant literature regarding proportion congruence effects in Stroop paradigms (e.g., Logan & Zbrodoff, 1979 ; Logan et al., 1984 ). Unlike the item-specific and font levels of control, list-level control is purported to involve proactive global strategies, operating prior to stimulus onset. List-level strategies largely reflect expectations. For example, in mostly incongruent lists, incongruent items are expected. To reduce Stroop interference in such a context, participants are believed to use a consistent trial-to-trial strategy that involves adjusting cognitive control settings away from word reading and toward color naming. In the present study, we did not, however, find evidence of list-level control. In fact, the results of Experiment 1 raise the question of whether prior observations of list-wide proportion congruence effects may reflect item-level control, at least partially and perhaps fully.
Across three experiments, then, we have uncovered two levels of control (item level and font level) that were implemented in service of reducing Stroop interference. The second key question we addressed is whether participants would simultaneously exploit more than one level of control. Experiments 1 and 2 were informative on this issue. Neither showed clear evidence of the simultaneous implementation of two control levels. There are several potential reasons for this finding.
Above, we described both the item-level and font-level mechanisms as being more flexible in nature, rapidly adjusting control settings after stimulus onset on a word-by-word or trial-by-trial basis. If this is the case, one reason that item- and font-level control may not operate simultaneously in contexts that allow for control to be implemented at both levels, as in Experiment 2, is that the two levels of control may be redundant. That is, using both levels simultaneously may not produce reductions in interference proportional to the additional effort that may be required to do so. Alternatively, item- and font-level control may interfere with one another. For instance, if participants divide attention between the two dimensions (word and font type), performance may suffer as compared with when they choose a single dimension and respond accordingly. Of course, both of these explanations assume that the font type manipulation in Experiment 2 was sufficiently salient for participants to have the option of using item- and font-level control simultaneously.
Although a redundancy, interference, or saliency explanation may suffice in explaining why multiple levels of control were not operative when the available levels were item level and font level, these explanations do not fare well in explaining the results of Experiment 1, wherein only an item-level effect was observed even though a list-wide proportion-congruence manipulation was also implemented. An account based on the mechanisms that underlie each level of control is elaborated next in an attempt to explain the patterns observed across Experiments 1 and 2. In these experiments, participants may have elected to attend to the item-specific proportion congruence manipulation that occurred at the level of words, rather than the list-wide or font-type proportion congruence manipulation, because item-level control afforded participants the opportunity to respond to each word on the basis of stimulus—response associations. This type of responding may eliminate the need for engagement in effortful modification of control settings, because stimulus—response associations may be retrieved prior to the occurrence of interference or conflict on incongruent trials. Other levels of control may have little value in such a context. Two predictions follow from this account. The first is that increased use of list-wide or font-specific levels of control should occur to the extent that one reduces the efficiency of item-level control. Second, if two levels of control (e.g., list level and font level) were available in a single task context and neither level permitted responding on the basis of simple stimulus—response learning, one might observe the simultaneous implementation of both levels of control. These predictions remain to be tested.
The present set of experiments indicates that multiple levels of control are used in service of control over Stroop interference. An item level of control surfaced in task contexts in which other levels of control were available but were not used. A second level of control, the font level, was revealed for the first time in the present study. Although a third level of control, list-wide, has been observed in prior reports, we did not observe it here when any item-specific influence that could contribute to its observation was controlled. This finding suggests caution in interpreting list-wide proportion congruence effects in Stroop tasks as reflecting solely strategic or global forms of control. Rather, our findings indicate that an account of proportion congruence effects in Stroop experiments must consider multiple levels of control that are used to modulate Stroop interference and that these levels can operate differentially from trial to trial.
This research was supported partially by National Institute on Aging Grants 5T32AG00030 and AG13845. We are grateful to Swati Chanani, Rachel Edelman, Carlee Beth Hawkins, and Danielle Hirschfield for assistance with data collection.
1 This explanation was elaborated and tested initially in a poster presented by Toth and Jacoby (2003) at the 44th Annual Meeting of the Psychonomic Society in Vancouver, BC.
2 Analysis of the log-transformed RTs indicated that older adults showed larger Stroop interference effects than did younger adults on both the item-specific PC-50 trials [ F (1,68) = 8.11, MS e = .001] and the item-specific PC-25 and PC-75 trials [ F (1,68) = 10.92, MS e = .001]. List-wide proportion congruence had no influence on the magnitude of the Stroop effect ( F < 1), whereas item-specific proportion congruence had large effects on this measure [ F (1,68) = 38.84, MS e = .001]. Most critically, the age × proportion congruence × trial type interactions were nonsignificant for the list-wide and item-specific analyses ( F s < 1), indicating that the list-wide and item-specific manipulations had a similar effect on the magnitude of Stroop interference for younger and older adults. In fact, the increase in Stroop interference from the item-specific PC-25 to the item-specific PC-75 condition was almost identical for older ( M = .06) and younger ( M = .05) adults.
3 List-level control was not observed in Experiment 1 in the present study; however, this is not to say that list-wide control will never emerge in Stroop paradigms. List-wide control may be used, for instance, in task contexts that do not afford item-specific control.
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Communications Biology volume 7 , Article number: 1037 ( 2024 ) Cite this article
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Alterations in functional connectivity (FC) have been observed in individuals with Alzheimer’s disease (AD) with elevated amyloid ( A β ) and tau. However, it is not yet known whether directed FC is already influenced by A β and tau load in cognitively healthy (CH) individuals. A 21-channel electroencephalogram (EEG) was used from 46 CHs classified based on cerebrospinal fluid (CSF) A β tau ratio: pathological (CH-PAT) or normal (CH-NAT). Directed FC was estimated with Partial Directed Coherence in frontal, temporal, parietal, central, and occipital regions. We also examined the correlations between directed FC and various functional metrics, including neuropsychology, cognitive reserve, MRI volumetrics, and heart rate variability between both groups. Compared to CH-NATs, the CH-PATs showed decreased FC from the temporal regions, indicating a loss of relative functional importance of the temporal regions. In addition, frontal regions showed enhanced FC in the CH-PATs compared to CH-NATs, suggesting neural compensation for the damage caused by the pathology. Moreover, CH-PATs showed greater FC in the frontal and occipital regions than CH-NATs. Our findings provide a useful and non-invasive method for EEG-based analysis to identify alterations in brain connectivity in CHs with a pathological versus normal CSF A β /tau.
Alzheimer’s disease (AD) is a neurological disorder in which progressive neurodegeneration and synaptic dysfunction result in impairments in a range of cognitive domains. With the continual rise of the global population and life expectancy, it is anticipated that the prevalence of neurocognitive disorders or dementia will experience a substantial surge, reaching an estimated 74.7 million individuals by 2030 and more than 131.5 million by 2050 worldwide 1 , 2 . Recent research reported early impairments in executive functions and memory among individuals afflicted with A β and/or tau pathologies 3 , 4 , 5 . These findings provide validation for the notion that executive functions and episodic memory 6 , 7 , 8 are indeed affected during the initial stages of AD, primarily due to the alteration or pathology of the frontal and temporal cortices 9 , 10 . More specifically, inhibitory abilities 11 , attentional processes 12 , 13 , and visuospatial functions 14 appear to be particularly compromised. A defining feature of the progression of AD is the reduction in A β protein (resulting in low levels of CSF amyloid- β ( A β ) and the rise in neuronal degeneration biomarkers (such as increased levels of CSF total tau and phosphorylated tau) in individuals with AD. The reduction in CSF A β levels seems to occur in the early progression of AD, becoming apparent more than twenty years before the onset of any clinical symptoms 15 . In individuals with AD or those who are at risk of developing AD, the amyloid- β -to-tau ratio is often low, indicating an accumulation of A β plaques and/or tau tangles in the brain 6 , 16 , 17 . Lei Wang et al, found that lower CSF A β 42 levels and higher tau/ A β 42 ratios were strongly correlated with a reduction in hippocampal volume and indicators of progressive atrophy of the cornu ammonis subfield in pre-clinical AD individuals, but not cognitively healthy (CH) individuals 18 . Compared to the A β 42 and/or tau, the A β 42/tau ratio demonstrated greater sensitivity in detecting pre-symptomatic AD and distinguishing it from frontotemporal dementia 19 . Consequently, it is plausible that A β 42/tau ratio may serve as a sensitive biomarker in detecting the earliest stages of preclinical AD compared to individual biomarkers. Preclinical investigations offer robust evidence supporting functional connectivity as a probable intermediary mechanism linking A β to tau secretion and accumulation 20 . Despite the significant research dedicated to unraveling AD pathogenesis, there is currently a lack of sensitive, specific, reliable, objective, and easily scalable biomarkers or endpoints to guide clinical trials and facilitate early risk detection in clinical settings.
Several large prospective studies attempt to characterize the early diagnostic criteria in people at risk of developing AD. These assessments include pathological markers (both Beta Amyloid ( A β ) and tau pathologies) 21 , neuropsychological scores (Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE)) 22 , neuroimaging (Magnetic resonance imaging (MRI), Magnetoencephalography (MEG), and electroencephalogram (EEG) 23 , and heart rate variability (HRV) 24 . EEG Brain connectivity, MRI brain structures, neuropsychological assessments, and HRV are intricately correlated measures that can predict early AD pathology. For example, a recent examination of HRV from the Multi-Ethnic study of atherosclerosis revealed a correlation between higher HRV and superior cognitive function across various cognitive domains 25 . We previously reported a significant association between high resting HR and less negative alpha event related resynchronization (ERD) during Stroop testing in individuals with pathological A β /tau, compared with those with normal A β /tau 26 . These findings prompt further investigation into brain connectivity involved with pathological A β /tau presence during task-switching tasks. Therefore, we aim to integrate brain activity, neuropsychology, and HRV assessments in this study to facilitate early detection of AD risks, understand disease mechanisms, and ultimately help improving outcomes for individuals affected by AD by addressing the multifaceted nature of the disease.
The abnormality of brain connectivity measured by MRI in regions with early A β -burden (e.g., default mode network (DMN) has been shown when A β fibrils just start to accumulate 27 . However, this abnormality has not been reported or tested in EEG investigations to our knowledge. Both A β and tau pathologies have been shown to impact brain network’s structural and FC 28 . Abnormal FC has been consistently identified in the early stages of AD before the appearance of clinical symptoms or brain structural changes 29 . For instance, a recent study has achieved 90% accuracy in classifying brain A β and tau pathology in subjective cognitive decline from mild cognitive impairment (MCI) individuals using EEG coherence 30 . FC studies have found that abnormal cerebrospinal fluid (CSF) levels of phosphorylated-tau and A β in early AD are linked with disrupted cortical networks involving the anterior and posterior cingulate cortex, and temporal and frontal cortices 31 . We previously reported that ERD increased in CH with pathological A β tau ratio (CH-PATs) 32 , compared to CH with normal A β tau ratio (CH-NATs) in alpha band. Using regional interconnectivity methods, a previous study found that the temporal and frontal regions’ connection is a characteristic pattern for the pathological transition of normal to MCI and the density of edges in these networks is a differential pattern between HC and MCI 33 . The decreased patterns of regional hemispheric interconnectivity in the metabolic network rely on the pathology severity 33 . Therefore, EEG can be a promising, diagnostic, noninvasive, high temporal resolution method, which is a cost-effective biomarker and easily accessible to track and predict the severity of cognitive dysfunction in degenerative diseases. As memory (predominantly localized in the temporal region) and executive functions (mainly associated with the frontal region) are the two sensitive cognitive activities that were abnormal in early AD 9 , 10 , it will be compelling to study frontal and temporal FC in the early stage of AD spectrum.
In the present study, we aimed to: (1) compare effective connectivity (EC) between CH-NATs and CH-PATs during task switching, and explore the potential contribution of task difficulty levels; (2) study the links between EC and Neuropsychological measures, structural MRI brain volumes, and HRV.
The demographic and clinical characteristics of our subjects have been reported in our previous work 32 ). The participants’ age in CH-PATs and CH-NATs were comparable and both groups also had similar educational levels, with mean years of education. There were no differences in cognitive reserve (CR) and intelligence quotient (IQ) scores between CH-NATs and CH-PATs.
The difference between the accuracy (ACC) and reaction time (RT) scored under the effect of trial types (repeat or switch) was notable with a significantly improved RT ( p < 0.0001) and ACC ( p = 0.048) during repeat trials than during switch trials. In addition, the results of this study showed no significant differences in group × trial type interaction in RT, F(1, 108) = 0.0001, p = 0.991 and ACC, F(1, 108) = 0.003, p = 0.960 between the two groups of all CH-PAT and CH-NAT participants. A comparison of the main effect of trial types and group × trial between CH-NATs and CH-PATs was reported previously in our work 32 .
The comparison of the normalized alpha power in resting-state and task-switching at the five regions in the CH-PATs and CH-NATs is shown in Fig. 1 . The CH-NATs showed significantly stronger spectral power of task-switching alpha at temporal, parietal, and occipital electrodes when compared to CH-PATs ( p < 0.0001), ( p = 0.0005 and p < 0.0001), respectively as shown in (Fig. 1 a, b). On the contrary, there were no significant differences between CH-PATS and CH-NATs in frontal or central power. In the resting state, there were no significant differences in alpha power changes between all brain regions (Fig. 1 b, d).
a , b A group comparison between CH-PATs and CH-NATs using t -test in different brain regions (Frontal, temporal, parietal, central, occipital) within the range (200–550 ms), where 0 ms is the onset of the stimulus during task switching and resting-state, respectively. c , d Shows the avereged topographical distribution of alpha power in CH-PATs and CH-NATs during task switching and resting-state, respectively. e , f Shows the mean normalized absolute PSD for all electrodes in the frequency domain (0–50Hz) for CH-NATs and CH-PATs during the switching task and resting state. Frequency bands are decomposed into the following: delta (0.4–4 Hz), theta (4.1–8 Hz), alpha (8.1–12 Hz), and beta (12.1–30 Hz). * P < 0.05, ** P < 0.01, *** P < 0.001.
The mean partial directed coherence (PDC) FC pattern of CH-PATs and CH-NATs were shown in Fig. 2 a, b, respectively, and we qualitatively observed that the main difference between the two groups was that CH-PATs patients exhibited much more and much weaker long-range connections from left and right temporal cortices than CH-NATs. Specifically, compared with the CH-NATs group (0.135 ± 0.017), the averaged information flow in the alpha frequency of CH-PATs was enhanced in the frontal regions during task switching processing (0.223 ± 0.014); t (44) = 18.06, p < 0.0001. On the contrary, CH-NATs showed increased information flow from temporal region (0.187 ± 0.016) compared to CH-PATs (0.09 ± 0.015), t (44) = 21.06, p < 0.001. On the contrary, central, parietal, and occipital regions did not show any significant differences between CH-NATs and CH-PATs. It is also interesting to note that resting-state EC showed a significant difference between CH-NATs and CH-PATs only in the occipital cortex (0.082 ± 0.03), (0.105 ± 0.036), t (44) = 2.36, p = 0.023 as shown in Fig. 2 c, d. Differences in brain connectivity (Switching task connectivity values - Resting state connectivity values) were calculated across five distinct brain regions (Fig. 2 e, f). Results revealed differences between CH-NATs and CH-PATs in frontal ((0.036 ± 0.041), (0.084 ± 0.037), t (44) = 6.985, p < 0.0001) and temporal ((0.072 ± 0.039),(−0.028 ± 0.027), t (44) = 10.21, p < 0.0001)), while no differences were observed in the parietal, occipital, or central regions.
Representation of the functional networks as graphs in the Alpha frequency band at stimuli time (200–550 ms) after the onset of the stimulus. PDC from an area i to j is represented by an arrow. a , c , e Group connectivity comparison between CH-PATs and CH-NATs during task switching, resting state, and the differences between task switching and resting (Task-rest), respectively in the alpha band. b , d , f The directed connectivity of the CH-PATs (left) and CH-NATs (right) during task switching, resting state, and the differences between task switching and resting (Task-rest), respectively in the alpha band. The brain regions are graphically represented with connections depicting causal influence at (200–550 ms). The brain surface templates we used to visualize these connections in Fig. 2 are primarily generated from a commonly used template known as MNI/Talaraich (ICBM152).
To validate the outcomes concerning directed connectivity as measured by PDC, we employed multiple functional phase connectivity methodologies, including Weighted Phase Lag Index (wPLI) and Phase locking value (PLV). Although FC and EC can be associated, they estimate distinct characteristics of brain interactions, and the presence of one does not inherently imply the presence of the other. During task-switching, wPLI results showed that CH-PATs demonstrated significantly higher phase connectivity in frontal and central regions (Supplementary Fig. 1 ). In addition, PLV analysis showed decreased phase coherence in frontal and occipital regions (Supplementary Fig. 2 ). Detailed results, including additional analyses and comparisons utilizing wPLI and PLV algorithms, are presented in this manuscript’s supplementary file.
To examine the potential contribution of task difficulty level to the EC differences, we selectively compared connectivity between “good performers” in CH-PATs and “bad performers” from CH-NATs to bring down the potential differences and check if the frontal and temporal EC differences remained. Task difficulty was determined through the calculation of performance indicators, namely ACC or RT, and brain connectivity. In this context, the ACC results demonstrated a significant difference between CH-NATs (0.79 ± 0.13) and CH-PATs (0.96 ± 0.03) with p < 0.0001. Similarly, the results indicated that CH-NATs showed a significant increase in RT (1743.63 ± 265.6) compared to CH-PATs (1218.47 ± 167.66) with p < 0.0001. For this condition, we sorted the EC based on the ACC and RT data (i.e., low-vs-high-connectivity) and constructed a statistical analysis between CH-PATs and CH-NATs. For instance, using EC based on the ACC classification, the CH-PATs showed increased frontal connectivity (0.22 ± 0.02) compared to CH-NATs (0.131 ± 0.02) with p = 0.0009. Additionally, the CH-PATs showed decreased temporal connectivity (0.09 ± 0.02) compared to CH-NATs (0.187 ± 0.006) with p < 0.0001. Furthermore, using EC based on the RT classification, the CH-PATs showed increased frontal connectivity (0.22 ± 0.01) compared to CH-NATs (0.13 ± 0.02) with p = 0.0008. The CH-PATs showed decreased temporal connectivity (0.09 ± 0.02) compared to CH-NATs (0.188 ± 0.012) with p < 0.0001. This rigorous comparative analysis supported that the EC differences are independent of task difficulty levels. Figure 3 illustrates mean scores for task difficulty based on ACC and RT classifications for the color-Word (cW) test.
a The Reaction Time (RT) was different between CH-NATs and CH-PATs. The values represent the best 50% performance of RT (lowest RT values) in CH-PAT participants and the worst 50% performance (Highest RT values) in CH-NATs during high-load color-word switch trials. The comparison was performed between the two groups for frontal ( b ) and temporal ( c ) connectivity for the same participants. d The ACC was significantly different between CH-NATs and CH-PATs. The values represent the good 50% performance of ACC scores (highest ACC values) in CH-PATs and the worst 50% performance (lowest ACC values) in CH-NATs during high-load color-word switch trials. The comparison was performed between the two groups for frontal ( e ) and temporal ( f ) connectivity for the same participants using a parametric t -test. * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001.
Supplementary Table 1 presents several correlations between task-switching brain connectivity in temporal and frontal brain regions and different neuropsychological tests (i.e., processing speed, working memory, and executive functions) between CH-NATs and CH-PATs. Processing speed tests were used to assess the ability to process information rapidly. The higher the score, the more time it has taken, and the worse the performance. Executive function and working memory tests can provide an estimation of a wide range of skills (i.e., working memory and organization). The higher the score, the more time it has taken, and the better the performance. While CH-PATs showed greater scores in performance in speed processing tests, CH-NATS showed a better performance in executive function and working memory tests. Also, the present study aimed to investigate the relationship between cognitive reserve (CR) and parietal connectivity in two groups, CH-NATs and CH-PATs. Our findings revealed a significant negative correlation between CR and parietal connectivity in the CH-NATs group (r = −0.61, p = 0.030), as shown in Fig. 4 . This suggests that individuals with higher CR tend to exhibit lower parietal connectivity in this group. However, in contrast, the CH-PATs group did not show any differences in CR and parietal EC.
A linear regression model was used to estimate the coefficients of linear correlations (Confidence Intervals = 0.95) that relate a set of predictor variables to a response variable.
In the CH-PATs group, significant negative correlations were observed during task switching between temporal EC and several brain volumetrics: Fusiform Right Side Volume ( r = −0.42, p = 0.043), Hippocampal Occupancy Score (HOC) Norm Percentile ( r = −0.46, p = 0.023), and Fusiform Asymmetry Norm Percentile ( r = −0.41, p = 0.049) as shown in Fig. 5 . However, CH-NATs did not show significant correlations between temporal EC and the same regions. Moreover, CH-NATs showed significant correlations between temporal EC and Entorhinal Cortex Asymmetry Norm Percentile ( r = −0.67, p = 0.013), Fusiform Left Percent Of intracranial volume (ICV) ( r = −0.58, p = 0.041), and Fusiform Asymmetry Norm Percentile ( r = −0.67, p = 0.015). Additional correlations between frontal and temporal connectivity with brain volumetrics in CH-NATs and CH-PATs are reported in Supplementary Table 2 .
a A Correlation analysis between Hippocampal Occupancy Score (HOC) Norm Percentile and temporal EC in two groups;in two groups CH-NATs (blue scatter plots) and CH-PATs (red scatter plots). b Correlation between Fusiform Right Side Volume and temporal EC between two groups; CH-NATs and CH-PATs. A correlation analysis reveals the strength and direction of the association between brain volumetrics and brain connectivity. Spearman correlation was applied and the p < 0.05 and r (association directionality values) are shown.
Spearman’s correlation analysis was also conducted in both groups to explore the relationship between HRV metrics and EC during task-switching paradigms. In the task-switching condition, CH-PATs exhibited noteworthy findings, revealing significant negative correlations between frontal EC with Root mean square of the successive differences (RMSSD) ( r = −0.52, p = 0.020). Conversely, CH-NATs demonstrated significant negative correlations between frontal connectivity and mean RR ( r = −0.87, p = 0.002), as shown in Fig. 6 . On the contrary, CH-NATs did not reveal significant correlations in RMSSD measures and brain connectivity as shown in Fig. 6 .
a A correlation between mean RR and frontal EC during task switching for two groups CH-NATs and CH-PATs. b A correlation between resting RMSSD and frontal connectivity for the two groups. Spearman correlation was applied and p values were set to < 0.05 and r (association directionality values) are shown.
The main objective of the present biomarker study was to characterize the effects of the accumulation of A β pathologies and tau concentrations on the directed brain networks in CH individuals. Participants categorized into our CH-NAT and CH-PAT groups were asymptomatic, with normal neurocognitive tests, and were diagnosed based on CSF A β 42 and Tau measures that were within the published ranges 6 . The CSF A β 42/Tau ratio outperforms the CSF A β 42 or tau levels individually to identify dementia and preclinical phases of AD. Abnormal amyloid levels and tau accumulation can disrupt synaptic function by interfering with neurotransmitter release and synaptic plasticity. This disruption can lead to neurotoxicity, microtubule destabilization, neuroinflammation, and alterations in the strength and efficiency of synaptic connections between neurons, ultimately affecting overall brain connectivity. In this exploratory study, we report on several important findings: (1) CH-PATs compared to CH-NATs, presented higher frontal EC, and lower temporal EC, independent from task difficulties. (2) CH-PATs presented significant correlations between temporal or frontal EC and other measures, including neuropsychological measurements (i.e., processing speed, executive functions, and working memory tests), MRI regional volumetrics, and HRV, supporting compensatory mechanisms. These changes are potentially linked to a less strategic approach while performing the task in CH-PATs, or no improvement in efficiency. These results may indicate that CH-PATs may present compensating mechanisms and may lack learning and self-improvement with functions that as seen in advanced intelligence for self-improving mode. Another similar example is during coding, using functions (temporal lobe in CH-NATs) can improve efficiency, while always using whole codes (frontal lobe) but limited functions (temporal lobe) can be exhaustive for CH-PATs.
The identification of effective EEG biomarkers associated with AD pathology holds substantial promise in unraveling the neural mechanisms underlying this neurodegenerative disorder and facilitating its early diagnosis. Growing evidence suggests that EEG measurements reflect the capacity of AD neuropathology on brain neural signal transmission underlying cognitive processes 34 , 35 , 36 . However, the accuracy and reliability of different types of EEG biomarkers, i.e., power and entropy in facilitating the early detection and prediction of AD progression remain largely unknown. To our knowledge, this is the first study to evaluate the impact of promising EEG connectivity on detecting early AD pathology in CH individuals. We provide strong evidence supporting that the inclusion of multidimensional information (i.e., EEG biomarkers, CSF measures, brain volumetrics, and HRV) is highly effective in assessing patients’ pre-symptomatic clinical status. Taken together, our findings suggest that brain connectivity has the potential for the early detection of risk for cognitive decline in CH individuals independently or in association with other measures. Notably, our study corroborates these findings and highlights the significance of EEG metrics and connectivity as pivotal biomarkers for revealing CH-PATs.
The Behavioral results of this study showed no significant differences between all CH-PATs and CH-NATs groups (results were reported previously in ref. 32 ). Additionally, the after-test survey suggested no subjective difficulty levels between the two groups. This indicates that, at the behavioral level, there is no evidence of cognitive decline in CH-PATs at this early stage of the disease. One possible explanation is that the cognitive deficits associated with CH-PATs are not yet severe enough to manifest at the behavioral level 37 . It is also possible that compensatory mechanisms and/or CR may contribute to similar behavioral performance in both groups 38 . When the brain switches attention between tasks, it successfully alternates, but consistent mental replacement of one task with another requires additional effort in terms of time and cognitive resources. This leads to switching costs, which we also observed in our study. Both CH-PATs and CH-NATs exhibited longer RTs during switch trials compared to repeat trials, indicating the presence of a successful switching cost effect 32 , 39 , 40 . Moreover, to investigate the possible contribution of task difficulty level to the EC differences, we selectively compared connectivity values between the best 50% performance of CH-PATs (Highest accuracy scores and lowest RT scores) and the lowest 50% performance from CH-NATs (lowest accuracy scores and highest RT scores) to bring down the potential differences and check if the frontal and temporal EC differences remained. Presumably, these subsets will bring CH-PATs and CH-NATs data closer in subjective difficulty/concentration. If connectivity analysis continues to exhibit consistent differences, it suggests that the connectivity patterns are fundamental, rather than solely results of task difficulty. Conversely, if the connectivity differences diminish, it indicates that they may indeed be influenced by subjective task difficulty. This approach was motivated by the desire to control for the influence of task difficulty on EC alterations and isolate the effects of intrinsic brain connectivity differences. By focusing on individuals with comparable task performance levels, we were able to minimize the confounding effects of task difficulty, ensuring that any observed EC differences were more likely attributable to inherent neurobiological factors rather than variations in task performance 41 . The good performance (increased ACC values and decreased RT values) in Fig. 3 may suggest that this group of CH-PATs did benefit from cognitive reserve, at least on neural activity during task switching. This also could be due to a compensatory increase in the number of neurons and/or synapses in CH-PATs.
During task switching processing compared to CH-NATs, CH-PATs exhibited higher alpha power values in the frontal region, while lower values were observed in temporal and parietal areas as shown in Fig. 1 . These aberrations may signify two distinct pathophysiological alterations: the reduction in alpha power in AD pathology could be attributed to alterations in cortico-cortical connections 42 . We previously reported increased event-related resynchronization (ERD) in CH-PATs, compared to CH-NATs in the alpha band 32 . In contrast to ERD (Negative values calculated by wavelet transform and corrected with baseline), absolute alpha power (Positive values calculated by welch power) is a measure of the overall power that may detect changes in excitability alterations in the brain and does not provide specific information about task-related processing. ERD and absolute alpha power are both measures used in EEG analysis, but they capture different aspects of brain activity. Furthermore, evidentiary results have found higher resting-state alpha power manifestations in the frontal regions among MCI individuals compared to CH individuals 43 . This increase may suggest the recruitment of compensatory mechanisms. Individuals with a cognitive decline may show less vigilance to external stimuli in the resting state and may exhibit diminished capacity to recruit relevant brain regions when performing a task. Previous investigations have consistently reported slowing EEG activity among individuals with MCI and AD. For instance, a recent work substantiates the presence of distinct power resting state EEG rhythms in older individuals with subjective memory complaints (awareness of memory loss), notably showing greater theta power and a subtle reduction in EEG reactivity 44 . In addition, a decreased alpha/beta power and increased theta/delta power across various brain regions, including the frontal, temporal, parietal, and occipital areas 45 were reported. The degeneration of cholinergic neurons in the basal forebrain projecting to the hippocampus and neocortex is believed to play a pivotal role in this process 46 . The present study also examined the resting-state EEG power analysis in CH-PATs and CH-NATs. Our findings revealed no significant differences in EEG power between the two groups during the resting state. This lack of significant differences suggests that the EEG resting-state brain activity may not be significantly affected by the pathological amyloid/tau. Such results may indicate compensatory mechanisms or variability within the groups, which might contribute to the absence of significant differences. The absence of significance also may indicate that cognitive challenge can help in revealing subtle changes in brain activities 47 , 48 .
In our investigation, we employed directed EC measures in the alpha frequency band, which are reliable, valid, and less influenced by confounding factors such as volume conduction 49 . Unlike undirected functional connectivity (i.e., coherence, phase lag index (PLI), and Phase Locked Value (PLV)) or Structural connectivity (anatomical links between neuronal populations), Effective connectivity (EC) (i.e., partial directed coherence (PDC)) among different EEG features examines the causal and directional influences between distant brain networks. Our study provides evidence of EEG changes associated with pre-clinical AD neuropathologies ( A β and tau). Specifically, we found a significant association between the A β /tau in CSF and an increase in CH-PATs frontal alpha connectivity. Reduced levels of A β peptides in the CSF indicate heightened A β deposition in the brain, while elevated levels of CSF tau protein, derived from damaged neuronal microtubules, serve as reliable biological indicators of AD and predictors of MCI conversion 50 . It has been found that synaptic dysfunction is a fundamental deficit in AD, preceding the emergence of hallmark pathological changes 51 . Soluble A β oligomers and tau fibrillar lesions disrupt synaptic plasticity and contribute to synaptic loss, resulting in the impairment of neural networks. Consequently, MCI and pre-symptomatic AD are better characterized as disruptions in functional and structural integration of neural systems rather than localized abnormalities. Our study observed increased frontal connectivity in CH-PATs. This finding suggests possible compensatory responses within executive networks and the presence of synaptotoxicity and neuronal dysfunction associated with presymptomatic AD-related pathology 52 . Furthermore, preclinical studies have suggested that increased synchrony in cortical circuits among individuals with pathological A β /tau may be attributed to reduced inhibitory neurotransmission mediated by GABAergic mechanisms rather than increased excitatory transmission 53 . Furthermore, tau was hypothesized to be associated with a breakdown in predictive neural coding 54 .
We speculate that CH-NATs exhibited pronounced temporal lobe connectivity in terms of causal interactions, surpassing those observed in CH-PATs. These results align with existing evidence indicating that the preclinical stages and MCI are characterized by significant atrophy and hypometabolism primarily in the posterior hippocampal, cingulate, temporal, and parietal regions. Particularly, these affected regions collectively resemble the memory network and default mode network as delineated in healthy individuals using task-free fMRI paradigms 55 . In summary, decreased brain connectivity is believed to be associated with memory decline 56 .
Furthermore, our analysis of EEG data using three distinct connectivity measures (that is, PDC, PLV, and wPLI) revealed complementary insights into neural connectivity patterns 57 . PDC analysis showed significant EC between the frontal and temporal cortices, pointing to greater information flow from these regions. In contrast, PLV identified significant phase synchronization between the frontal and occipital cortices, suggesting coupled activity potentially related to top-down visual attention processes 58 . WPLI results found significant phase synchronization in the frontal, parietal, and central cortices, indicating inhibitory effects of visuospatial attention, inhibition of return, and inhibitory control 59 . Different brain regions might be more involved in either directional influence or synchronization depending on the cognitive task. The synchronization (Measured by PLV and wPLI) between two regions could be due to a third region influencing both, or other indirect interactions. Conversely, PDC can be established without strong functional synchronization if the causal influence is strong enough to create a statistically significant correlation in their activities. The differences in how these methods handle noise, artifact, spatial, temporal resolutions, and the assumptions they create about neural dynamics can lead to variations in results. Notably, these three methods consistently identified the frontal cortex as a key hub of connectivity. These findings underscore the importance of the frontal cortex in the neural network and illustrate how different connectivity measures can provide a multifaceted understanding of brain activity 60 .
Our results revealed significant associations between brain connectivity and performance on these neuropsychological measures. Regarding memory tasks (e.g., REY-O 3-MINUTE DELAY), CH-PATs show a strong positive correlation between frontal connectivity and performance on episodic memory tasks. This finding suggests that greater connectivity within the working memory brain networks is associated with greater efficiency 61 . Furthermore, we observed a significant negative correlation between frontal connectivity and executive functions tasks (that is, language animals tasks), indicating that decreased connectivity in the temporal or frontal regions is associated with poorer executive functions tasks and may indicate a neural compensatory mechanism. CH-PATs showed a positive correlation between frontal connectivity and Stroop color-naming task as compared to CH-NATs. This suggests that CH-PATs compensate for their processing speed decline by increasing their frontal cortex connectivity (specifically in regions linked with executive functions) to perform better on the Stroop color naming task. Moreover, we found many negative correlations between brain connectivity and attention tasks, indicating that greater connectivity in these regions is associated with decreased attentional performance 62 . These results underscore the importance of brain connectivity with memory and cognitive functioning 63 . The strong correlations observed between specific brain regions and performance on memory and cognitive tasks provide evidence for the role of neural networks in cognitive processes.
Furthermore, results suggest that the relationship between CR and parietal connectivity may vary across different patient populations, with the CH-NATs group showing a distinct pattern of negative correlation. Adults with higher levels of cognitive reserve (CR) are more likely to use other cognitive resources, such as memory strategies, to compensate for their memory impairments. Previous studies showed that individuals with a higher CR use additional brain regions associated with better memory task performance 64 . CR is assumed to reduce the risk of cognitive decline associated with brain changes related to aging by promoting the use of compensatory cognitive processes 65 . CR indicates the efficiency, capacity, and flexibility of cognitive processes in the presence of a challenge, which helps to explain the individual’s ability to cope better with brain pathology (e.g., brain aging, delay of dementia symptoms, stroke) via more adaptable functional brain processes. Although actual biomarkers of CR are still questioned, a possible mechanism for CR has been hypothesized 66 . Neural reserve theory postulates that there exists an inter-individual variability in brain networks that function as a basis of any task. In CH-NATs, a higher CR was correlated with a lower parietal EC (more efficient), which was not observed in CH-PATs. This result may suggest that CR may be exhausted in CH-PATs during this task switching processing.
The association of MRI structural volumes and EEG brain connectivity in alpha may explain how neural structures and brain functions are coupled. The negative correlations in CH-PATs between temporal EC and these brain volumes suggest that a decrease in the volume of these brain regions may be associated with an increase in EC 67 . This could be due to a compensatory increase in the number of neurons and/or synapses in these brain regions. Previous studies have found that people with AD typically have smaller hippocampus than in HCs 68 . This suggests that the reduction of neurons in the hippocampus may constitute one of the initial alterations observed in AD 69 . Other brain regions that are often affected in AD include the temporal, the parietal, and the frontal lobes 69 , 70 . In late-onset AD, cortical atrophy initiates in the temporal cortex and subsequently extends to the parietal cortex via the cingulum bundle. In contrast, in early-onset AD, cortical atrophy originates in the parietal cortex and then spreads to the temporal cortex 71 , 72 . These regions are involved in a variety of cognitive functions, including language, memory, and executive function. Furthermore, recent research observed that both AD and MCI patients showed altered FC of the fusiform gyrus in a resting state compared to normal controls 73 , 74 , which can help explain our findings in supplementary Table 2 . As the disease progresses, the brain tissue in these regions may shrink, leading to further cognitive decline. Our findings uphold the notion that greater connectivity within the frontal regions is associated with brain compensation in pre-symptomatic AD 75 . This relationship aligns with previous studies highlighting the involvement of the frontal cortex in early AD pathology 10 . The results could provide evidence that enlarged regional volumes in CH-PATs may link with greater frontal EC and play a role in compensating for behavioral performance in the presence of AD pathologies.
Despite the probable clinical relevance of autonomic dysfunction in CH individuals with pathological A β /tau, only a few studies have evaluated HRV in presymptomatic AD. Our study observed a significant negative correlation between frontal connectivity and RMSSD in CH-PATs but not in CH-NATs. The level of brain connectivity may serve as a predictor of cognitive flexibility during a cognitive task, whereas HRV may specifically predict cognitive flexibility when influenced by neuronal oscillations 76 . The association of HRV, which measures autonomic function, and cardiovascular disease as well as cognitive dysfunction has been evidenced. There is a strong relationship between cardiovascular risk and an elevated likelihood of developing neurodegenerative diseases 77 . During the initial phases of AD, perturbations in the autonomic nervous system play a role in sustaining chronic hypoperfusion, thereby impacting the self-regulation of the brain and the functioning of the neurovascular unit. Conversely, neurodegenerative alterations characteristic of AD can exert an influence on autonomic functions and HRV by disrupting the vegetative networks situated in the insular cortex and brainstem 78 . This is in line with the previous findings that the preclinical dementia patients demonstrated parasympathetic regulation of slow waves is strongly associated with disrupted FC in the central nervous system 79 . Our data suggested that higher HRV (mean RR or RMSSD) is related to lower temporal and frontal connectivity in CH-NATs. CH-PATs also suggest that higher RMSSD is associated with decreased brain connectivity. Our study supports that memory and executive function networks are related to autonomic regulation and are affected by AD pathology.
The current study has several limitations. Firstly, the study’s sample size was relatively modest, potentially limiting the generalizability of our findings to broader populations or distinct groups. Second, we used the 21-electrode EEG system to study brain connectivity (scalp potentials) in the brain cortex. Future research should focus on a high-density EEG system (i.e., 64, 128, or 256 electrodes) and compare the results with our findings. Third, a notable limitation of this study is the time difference in data collection, with MRI and EEG data being acquired at different time points. This misalignment could potentially introduce confounding variables related to alterations in the participants’ electrophysiological states or external environmental factors over time. Fourth, our analysis was performed at the sensor-space level rather than at the source-space level. While sensor-level analysis offers valuable insights into neural activity patterns, it lacks the precision and specificity that source-level analysis can provide in localizing the origins of these signals within the brain. Fifth, we considered CSF A β and tau in classifying our cohorts. Future research endeavors may explore brain connectivity using PET or plasma A β and tau to study pre-clinical AD progression. Lastly, a significant limitation in estimating causal information flow among brain regions, such as with PDC, particularly with multichannel non-invasive recordings, is the influence of volume conduction arising from surrounding active neuronal sources. Future investigations should explore alternative connectivity algorithms less sensitive to volume conduction and validate findings using high-temporal-resolution methodologies such as MRI or DTI.
To conclude, AD pathology manifests several years before clinical symptoms are recognized, termed the preclinical stage. We investigated this stage to assess whether brain connectivity could detect this early pathophysiology. The results of this study showed the potential of EC as a noninvasive tool in isolating the asymptomatic participants with normal CSF biomarker (CH-NATs)levels from asymptomatic participants with AD (CH-PATs) during task switching. Reduced temporal EC and increased frontal EC were reported in CH-PATs compared to CH-NATs, independent of task difficulties. The increased frontal EC and/or decreased temporal EC in CH-PATs are linked with disrupted brain volumes, neuropsychological, HRV, and CR, suggesting a compensatory mechanism in the presence of AD pathology to retain the same behavioral performance. Our findings indicate that A β /tau pathology may affect specific EEG networks with systemic structural/functional compensations. Overall, EC is a useful, non-invasive tool for assessing EEG-functional-network activities and provides a better understanding of the neurophysiological mechanisms underlying Alzheimer’s disease.
Forty-six cognitively healthy elderly participants were recruited locally through local newspapers and newsletters, the Pasadena Huntington Hospital Senior Health Network, and visits to the senior centers. All participants consented via an Institutional Review Board (IRB) approved protocol (HMRI # 33797). Assessments included collecting demographic data, physical exams, fasting blood studies, disease severity and disability scales, and CSF A β /tau measurements 6 . Inclusion criteria: over 60 years, classified as CH after a comprehensive neuropsychological battery, as referenced in detail 6 . Exclusion criteria: other active, untreated disease, use of anticoagulants, or other contraindications to lumbar puncture.
We reported a cutoff ratio of A β 42/total tau (2.7132) provided at least 85% sensitivity in discriminating AD from non-AD participants; we then used this regression to assign CH participants (CH) into 2 groups, one with normal CSF A β /total tau (CH-NATs) and the other with pathological A β /total tau (CH-PATs). As provisional evidence for the capacity of this CSF A β /total tau to predict clinical decline, a longitudinal study found that 40% of CH-PATs declined cognitively over 4 years to MCI, or AD, while none of the CH-NATs declined 39 , 40 . A detailed description of the data collection, methodological aspects of the entire process, and CSF data analysis procedures have been documented in our prior studies 6 , 32 , 39 .
During the resting state baseline, participants were instructed to remain still and relax for 5 min with their eyes open, followed by another 5 min with their eyes closed. For the task-switching testing each trial consisted of two sequential stimuli, both presenting incongruent colored words (e.g., the word ‘Red’ in green color or the word ‘Green’ in red color), with or without an underline (see Fig. 7 ). Participants were instructed to press a button labeled ‘1’ for red and ‘2’ for green, indicating either the color (c) when underlined or the word (w) when not underlined. The trials were categorized into low-load repeat (color-color (cC) or word-word (wW)) or high-load switching (cW or wC) trials, with the second stimulus denoted using superscript to indicate the study target. The task-switching phase was comprised of three mixed blocks, each containing 64 trials. The blocks included all four conditions (cC, wW, cW, wC) in a random sequence with equal weightage. Our analysis focused on the cW task due to the presence of the persisting task-set inhibition 80 .
Each trial includes two sequential stimuli. Each stimulus is incongruent colored word. Participants were requested to respond to the word itself (no-underline), or to the color of the ink (underlined), by pressing a button (“1” for red, “2” for green). Tasks include a random mixture of low-load repeat trials ( a ) or high-load switch trials ( b ). The paradigm is described from our previous work 32 .
All EEG data were collected during the resting state (eyes closed) or during the switching-task challenge 32 . A 21-head-sensor, dry electrode system (Quasar Wearable Sensing, DSI-24, San Diego, CA, USA) was used to collect EEG signals. Sensor configuration followed the international 10–20 system. EEG signals were sampled at 300 Hz, and bandpass filtered between 0.4 and 45 Hz. For artifact rejection, we applied a − 100 to 100 μV voltage threshold to detect bad epochs. In short, the visual inspection of epochs was performed based on a minimum of artifacts (e.g., excessive muscle activity, eye blinks) and drowsiness. In our study, drowsiness was inspected in EEG signals through careful visual inspection. Specifically, trained individuals examined EEG recordings for characteristic patterns associated with drowsiness, such as slowing of brainwave frequencies, increased theta activity, or intermittent bursts of alpha waves. Inspecting drowsiness is crucial to keep participants awake and alert (verbal notification) to ensure data quality, participant safety, and the validity of our experimental findings in our recordings. When an adequate level of quality was not obtained, we either substituted the epochs with alternative ones or eliminated the EEG data from further analysis if there were no sufficient epochs from the same subject available for analysis. Data quality refers to the standard of quality considered acceptable for the EEG data to be considered reliable for further analysis. This standard encompasses different factors including signal clarity, absence of artifacts, and adherence to predefined criteria for data integrity. For better signal processing, electrooculographic, electrocardiographic, and electromyography were recorded by 3 auxiliary sensors. A trigger channel encoded the time of color-word stimuli onset, the participants’ responses, and the type of test (C or W) for further analysis.
The continuous baseline EEG data were initially converted from the DSI-24 format to MATLAB format (R2022a) 38 . To ensure data quality and remove artifacts, a preprocessing pipeline designed explicitly for developmental EEG data, known as the Harvard Automated Processing Pipeline for EEG (HAPPE), was employed 38 . This subset consisted of 21 channels; Frontal (Fp1, Fp2, F7, F3, Fz, F4, F8), Temporal (T3, T4, T5, T6), Parietal (P3, PZ, P4), Occipital (O1, O2), Central (C3, CZ, C4), and mastoidal (A1, A2), as shown in Fig. 8 . The EEG signals were then referenced to the two mastoids/earlobes electrodes A1 and A2. Before independent component analysis (ICA), a 0.4 Hz digital high-pass filter, and a 45 Hz low-pass filter were applied to the EEG data to remove non-stationary signal drifts across the recording. HAPPE’s artifact removal steps encompassed the elimination of 60 Hz electrical noise using CleanLine’s multi-taper approach, rejection of bad channels, and removal of participant-related artifacts (e.g., eye blinks, movement, muscle activity) through ICA with automated component rejection via EEGLAB and the Multiple Artifact Rejection Algorithm (MARA) 81 . After artifact rejection, any channels removed during bad channel rejection were reconstructed using spherical interpolation to mitigate spatial bias in re-referencing. The resting-state EEG data were segmented into contiguous 2-s windows, and segments containing retained artifacts were rejected based on HAPPE’s amplitude and joint probability criteria, consistent with prior research on developmental EEG 82 . Importantly, there were no significant differences between outcome groups in terms of the mean lengths of the processed EEG data or any of the HAPPE data quality measures. Significant features were determined ( p < 0.05), and assessed for the between groups using Student’s t -test) 82 .
From raw EEG signals, cortical activity is achieved by means of high-resolution EEG techniques. It shows the HAPPE pipeline’s pre-processing steps including ICA, the estimation of directed FC from the cortical time series, threshold application, and eventually the statistical analysis. The Schematic figure also shows the proportional threshold on the PDC metrics by maintaining a proportion p (0 < p < 1) of the high dense connections and setting these connections to the same connectivity value, with all other connections set to 0 86 . The selection of the optimum thresholding value was based on global cost efficiency 96 . The brain network statistics are performed by t -test and Spearman’s rank correlation coefficient or Pearson correlation coefficients where appropriate.
A Fast Fourier Transform (FFT) with multitaper windowing was used to decompose the EEG signal into power for each 2-s segment for each of the channels of interest. For each of the four frequency bands, the summed power across all frequencies within the band was calculated as the measure of total power in that frequency band. All segmentation parameters and analysis windows are consistent with connectivity metrics and FFT was conducted using a Hanning window. Each participant’s data was averaged across the epochs for each electrode and the mean alpha power was computed for each of the following frequency bands: delta (0.4–4 Hz), theta (4–8 Hz), alpha (8–12 Hz), and beta (12–30 Hz). We selected a time window from 200 ms to 550 ms after stimulus onset as it detects brain responses associated with diverse cognitive functions, such as attention, working memory, decision-making, integration of incoming words, and emotion processing 83 . The data analysis process is illustrated in the block diagram in Fig. 8 .
Partial directed coherence (PDC) is one measure of the Granger causality which provides insights about the directionality of information between the brain nodes. PDC is based on the consideration that knowledge of the “driver’s” past increases the prediction of the “receiver’s” present state, compared to only using the receiver’s past. In the presence of volume conduction, however, all EEG channels mutually “drive” each other in this respect. PDC is derived from coefficients of a multivariate autoregressive (MVAR) model, which additionally depends on the scaling of the data. Interestingly, this scaling dependency is sufficient to yield significant spurious information flow from low-variance to high-variance temporally and spatially white noise channels. The MVAR uses Akaike information criterion (AIC) and Schwarz information to select the model order of MVAR 84 , 85 . In this study, the average MVAR model order p for all subjects was 7. Models with lower AIC are principally preferred. PDC is a frequency-domain approach to denote the direct linear relationship between two different signals y i ( t ) and y j ( t ) (equation 1 ) once remarked jointly with a set of other signals. Considering Y ( t ) the set of all observed time series, it can be depicted as an autoregressive model as follows: where p represents the model order, ε (t) is the prediction error matrix and A k are the coefficients matrix with a i j elements in which denotes the relation between signals at lag k . ε (t) has a covariance matrix ξ and their coefficients are usually a white noise with zero mean. This results in PDC factor ( π i j ) and partial coherence function ( ∣ k i j [ f ] ∣ 2 ) that indicates the strength and the direction of communication at frequency f .
Therefore, the PDC value from channel j to channel i can be expressed as follows:
where, \(({\bar{a}}_{i})(\, f)(i = 1,2,\ldots M)\) represents the i t h column of the matrix \(\bar{A(f)}\) and π i j represents the strength of causal interaction of the information flow from channel j to channel i at a frequency of f .
H [ f ] is the Hermitian matrix which is equal to \({\bar{A}}^{-1}[ \, f]\) . \({\bar{A}}_{ij}(f)\) is the complement of A i j ( f ) and represents the transfer function from y j [ t ] to y i [ t ] being also an element of A [ f ] matrix. Finally, a j [ f ] is the j t h column of A [ f ] and π i is the i t h row of π i j .
We applied the proportional threshold on the PDC metrics by maintaining a proportion p (0 < p < 1) of the highly dense connections and setting these connections to the same connectivity value, with all other connections set to 0 86 . The selection of the optimum threshold value was based on global cost efficiency. Proportional thresholding is a commonly used analysis step in reconstructing functional brain networks to ensure equal density across patient and control samples. The proportional threshold method is employed to highlight the most robust and significant connections while reducing visual clutter caused by weaker or less relevant connections. The MVAR model is a mathematical model commonly used in time series analysis to describe the relationship between an observation and a linear combination of its past observations. This MVAR model is generated using the two-time series for a specific frequency f , A k is the MVAR model in the discrete domain, is the covariance of the cross-spectral density matrix, k is the number of EEG channels, and I is the identity matrix. Calculation of the PDC values leads to a large matrix that describes the connectivity between the EEG channels, as shown in equation ( 1 ), where i j ( f ) is the individual PDC value calculated from the time series i to j at frequency f . The PDC values range between 0 and 1 depending on how well one time series predicts the other. The strength of a measure such as PDC is apparent in its formulation because it is normalized according to the destination. When analyzing time series, this operation is taken in a short time Fourier transform approach. A 50 percent overlap between windows, with a window length of 400 Ms, is chosen to capture events that may fall on the border between windows. To reduce memory requirements, frequencies are divided into evenly spaced bins, typically a power of 2; here we chose 30. For k channels, there will be a k x k x 30 x t matrix of PDC values. The first dimension is the source channel and the second corresponds to the destination.
Phase synchronization analysis is crucial in understanding undirected functional connectivity in brain networks derived from EEG data. The Phase Lag Index (PLI) is a widely used measure in neuroscience that quantifies the consistency of phase differences between neural oscillations across different brain regions. Nonetheless, the Weighted Phase Lag Index (wPLI) extends the PLI by considering the magnitudes of the phase differences. This enhancement accounts for the strength of phase coupling between neural oscillations in addition to their consistency. The wPLI is a robust functional connectivity approach used in EEG connectivity analysis, because of its high insensitivity to common sources and volume conduction effects. The formula for wPLI is given by:
Where, ∣ Δ ϕ ( t ) ∣ represents the magnitude of the phase difference. wPLI provides a more refined measure of functional connectivity, capturing both the consistency and strength of phase coupling between brain regions. In contrast to PLI, the wPLI adjusts the weighting of the cross-spectrum based on the magnitude of its imaginary component. It eliminates the influence of cross-spectrum elements (phase lacking) near the real axis (0, π , or 2 π ), which are susceptible to small noise perturbations that might alter their true sign due to the volume conduction effects.
Moreover, the phase locking value (PLV) method is commonly used for calculating the correlation between two electrodes. The PLV is a statistic that can be used to investigate EEG data for task-induced changes in the long-range synchronization of neural activity. To calculate the PLV, two time series are first spectrally decomposed at a given frequency, f 0 , to obtain an instantaneous phase estimate at each time point. Phase synchronization between two narrow-band signals is frequently characterized by the PLV. Consider a pair of real signals s 1 ( t ) and s 2 ( t ), that have been band-pass filtered to a frequency range of interest. Analytic signals \({z}_{i}(t)={A}_{i}(t){e}^{j{\phi }_{i}(t)}\) for i = {1, 2} and \(j=\sqrt{-1}\) are obtained from s i ( t ) using the Hilbert transform:
where H T ( s i ( t )) is the Hilbert transform of s i ( t ) defined as:
and P . V . denotes the Cauchy principal value. Once the analytic signals are defined, the relative phase can be computed as:
The instantaneous PLV is then defined as 87 :
where E [. ] denotes the expected value. The PLV takes values on [0, 1] with 0 reflecting the case where there is no phase synchrony and 1 where the relative phase between the two signals is identical in all trials. PLV can therefore be viewed as a measure of trial-to-trial variability in the relative phases of two signals. In this work, we use the Hilbert transform, but the continuous Morlet wavelet transform can also be used to compute complex signals, producing separate band-pass signals for each scaling of the wavelet 88 . The connectivity results associated with wPLI and PLV are presented in the supplemental section (Figs. S1 and S2 ).
Several tests of working memory, language, executive function, and processing speed were considered in our analysis. A full description of these tests and their references were reported in these studies 6 , 89 .
One crucial factor that has not been taken into account in the previously described studies on strategy use is the potential role of Cognitive reserve (CR) (brain’s ability to withstand aging or pathology by employing compensatory mechanisms) 90 . CR indicates the effectiveness, capability, and adaptability of cognitive processes during cognitive challenges or pathology. This phenomenon elucidates an individual’s capacity to manage brain-related issues such as aging, and delayed onset of dementia symptoms. Various proxies are used to measure CR, including educational level, verbal intelligence quotient (IQ), engagement in work, social interactions, and/or participation in leisure activities 91 . Presently, composite measures offer the most comprehensive assessment of CR, such as education, occupational complexity, and leisure activities. In our study, both IQ estimation and education level were used as proxies for CR. First, scores were transformed into Z-scores. Subsequently, the education and IQ Z-scores were averaged into a single cognitive reserve (CR) score 64 , 66 , 92 .
All MRI images were acquired at the Advanced Imaging and Spectroscopy Center of the Huntington Medical Research Institutes (Pasadena, CA) using a 1.5 Tesla General Electric (GE) clinical scanner with an 8-channel high-resolution head coil. A brief description of MRI and NeuroQuant (Cortechs Labs.ai Inc, San Diego, CA, USA) analyses was reported in our published work 93 . Several brain regions were selected to examine the correlation between brain connectivity and brain atrophy in CH-NATs and CH-PATs. These regions include the fusiform cortex, frontal cortex, hippocampus, entorhinal Cortex, and Amygdala. The normalization factors are often based on automated intracranial volume (ICV) measurements or scaling factors from skull-based or whole-head-based registration to a standard template 94 , 95 .
We examined the correlation between EC and HRV measures. Raw electrocardiogram (ECG) data were collected during the task-switching using AcqKnowledge software (BIOPAC Systems, Inc., Goleta, CA). ECG and HRV recording and analysis details were reported in our previous work 32 . A correlation between CH-PATS and CH-NATs was conducted between brain connectivity and HRV time domain measures (i.e., NN intervals (RR), heart rate (HR), standard deviation of NN (SDNN), and root mean squared successive differences (RMSSD)) and frequency domain (i.e., low frequency (LF) and high-frequency (HF)).
We employed a parametric two-sample t-test, using Bonferroni–Holm correction method, to assess the connection metrics between CH-NATs and CH-PATs. Before conducting the statistical analysis, we used the Kolmogorov-Smirnov method to test the normal distribution of the data. A p -value ( p < 0.05) was used to identify the significant differences between CH-NATs and CH-PATs at the group level. All data are presented as (mean ± SD). Finally, Spearman’s or Pearson correlation was applied to study the association between brain connectivity and neuropsychological, CR scores, brain volumetric, and HRV scores. The p < 0.05 and r (association directionality values) are shown.
All statistical analyses were performed using GraphPad prism statistics software (version 9.5.0) and R programming language (version 2023.06.0), and Matlab (version 2022A, The Mathworks, Inc).
Further information on research design is available in the Nature Portfolio Reporting Summary linked to this article.
Raw data were generated at Huntington Medical Research Institutes (HMRI). All data generated or analyzed during this study are included in this published article and its supplementary information files, specifically in Supplementary Data 1 . Derived data and Matlab codes supporting the findings of this study are available from the corresponding author AA on valid request.
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The authors thank the study participants for their altruistic participation in this research. They also thank Dr. Astrid Suchy-Dicey for her support in submitting this manuscript, as well as Cathleen Molloy for revising the manuscript and handling some data, Shant Rising, and Rachel Woo for taking part in handling some data. Some data relied on in this study were derived from research performed at HMRI by Dr. Michael G. Harrington. This work was supported by the National Institute on Aging, National Institutes of Health (NIH) (grant numbers R56AG063857 and R01AG063857).
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Abdulhakim Al-Ezzi, Ryan Butler, Alfred N. Fonteh, Robert A. Kloner & Xianghong Arakaki
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Conceived and designed the experiments: X.A.; performed the experiments: X.A.; neuropsychological data: A.N.; MRI data: HMRI Brain Imaging Center; Analyzed data: A.A.; Wrote the paper: A.A.; Behavioral analysis: D.W.; Heart rate variability analysis: M.K. and R.A.; Edited the paper: R.A., R.B., A.N., J.J.K., S.S., D.W., A.F., M.K., R.K., and X.A.; All authors contributed to the final manuscript.
Correspondence to Abdulhakim Al-Ezzi or Xianghong Arakaki .
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Al-Ezzi, A., Arechavala, R.J., Butler, R. et al. Disrupted brain functional connectivity as early signature in cognitively healthy individuals with pathological CSF amyloid/tau. Commun Biol 7 , 1037 (2024). https://doi.org/10.1038/s42003-024-06673-w
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IMAGES
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The Stroop effect refers to a delay in reaction times between congruent and incongruent stimuli (MacLeod, 1991). Congruency, or agreement, occurs when a word's meaning and font color are the same. For example, if the word "green" is printed in green. Incongruent stimuli are just the opposite. That is the word's meaning and the color in ...
2) When the computer runs the experiment, it starts really with the first "block" section there is. So in order to understand how the experiment is carried out, you should scroll down a bit and look for a line starting with "block". 3) The "task" section describes one trial. The computer executes this line for line.
The Stroop effect is a simple phenomenon that reveals a lot about how the how the brain processes information. First described in the 1930s by psychologist John Ridley Stroop, the Stroop effect is our tendency to experience difficulty naming a physical color when it is used to spell the name of a different color. This simple finding plays a huge role in psychological research and clinical ...
The Stroop Task is one of the best known psychological experiments named after John Ridley Stroop. The Stroop phenomenon demonstrates that it is difficult to name the ink color of a color word if there is a mismatch between ink color and word. For example, the word GREEN printed in red ink. The wikipedia web site gives a good description of the ...
Introduction. The Stroop Color and Word Test (SCWT) is a neuropsychological test extensively used for both experimental and clinical purposes. It assesses the ability to inhibit cognitive interference, which occurs when the processing of a stimulus feature affects the simultaneous processing of another attribute of the same stimulus (Stroop, 1935).In the most common version of the SCWT, which ...
Control group: In an experiment, the control group doesn't receive the experimental treatment. This group is extremely important when comparing it to the experimental group to see how or if they differ. Independent variable: This is the part of an experiment that's changed. In a Stroop effect experiment, this would be the colors of the words.
Stroop conducted experiments with participants, including the Stroop Test I mentioned earlier, and shared his findings in 1935. After his experiments showed that participants spent a longer time recognizing color names when they didn't match up with the words on the screen, psychologists created different versions of the experiment and ...
Stimuli in Stroop paradigms can be divided into three groups: neutral, congruent and incongruent. Neutral stimuli are those stimuli in which only the text (similarly to stimuli 1 of Stroop's experiment), or color (similarly to stimuli 3 of Stroop's experiment) are displayed. [7] Congruent stimuli are those in which the ink color and the word refer to the same color (for example the word "pink ...
The Victoria version uses, differently from the original Stroop experiments (Stroop, 1935), four colors. Other versions used fewer colors, three as in the most common Golden version ... a comparison now easier to perform without any fluctuation due to different stimuli, different procedures, or different response types. Finally, we believe that ...
Introduction. The Stroop effect is one of the best known phenomena in cognitive psychology. The Stroop effect occurs when people do the Stroop task, which is explained and demonstrated in detail in this lesson. The Stroop effect is related to selective attention, which is the ability to respond to certain environmental stimuli while ignoring ...
unlike words. His experiments derived from this model also reproduced many of the major results in the Stroop literature. The Big Picture Anyone who has tried doing the Stroop experiment themselves knows that the interference caused by an incongruent word in naming its print color is powerful. As soon as we can read, we start to show this
Stroop, in the third experiment, tested his participants at different stages of practice at the tasks and stimuli used in the first and second experiments, examining learning effects. Unlike researchers now using the test for psychological evaluation, Stroop used only the three basic scores, rather than more complex derivative scoring procedures.
Introduction. The Stroop Color and Word Test (SCWT) is a neuropsychological test extensively used for both experimental and clinical purposes. It assesses the ability to inhibit cognitive interference, which occurs when the processing of a stimulus feature affects the simultaneous processing of another attribute of the same stimulus (Stroop, 1935).In the most common version of the SCWT, which ...
The Stroop test. Here is a classic experiment which you can try for yourself. It was first carried out by Stroop in 1935 and shows us that reading words is something we do automatically and can't stop from doing even if we want to. Instructions. Time yourself reading this list of words: list 1. Now time yourself reading this different list of ...
The foundational experiment that Stroop conducted involved presenting subjects with lists of words. These words were colors printed in an ink that either matched or conflicted with the color name (e.g., the word "red" printed in red versus the word "red" printed in blue). Stroop observed that participants took longer to name the color ...
Stroop conducted two main experiments. The first was to have people read the neutral stimulus - the words printed in black ink - and then read the words printed in colored ink. The challenge was that they were asked to say aloud the words they saw and not state the color they were printed in. The second experiment was similar.
The Stroop task is a classic task. In the basic task, you name the color of the stimulus that is presented. In some conditions, the stimulus could be neutral, like a string of x's in this version or the word that is the same color. In these cases, naming the colors are not very difficult. However, in the critical condition, the words are ...
The Stroop Effect refers to the Cognitive and Experimental Psychology finding that more time is needed to name the color of a word when the font color and color name do not match than when the ...
In a Stroop task the written word can either represent the same color, or a different color to the ink it is written in. Here we have made 2 basic "congruent" and 2 "incongruent" trials. We have also added a column to code the correct answer, in this case we want participants to press the left key if the word says red, and press the ...
The Stroop experiment screen will then be presented. Press the button at the top of the page or the space bar to begin the experiment. First a fixation mark in the middle of the screen will be presented. It will be removed if the words are presented in the center. When the word or string of X'x is presented, indicate the color of the stimulus. ...
2.3 Activity 1: The Stroop Effect. In this chapter and the next chapter, we're going to develop your data skills by using data from one of the most famous experiments in psychology: The Stroop Effect. First, take part in this online version of the Stroop test. It only takes a few minutes to complete. You need to be on a device with a keyboard.
The procedure was identical to that in Experiment 1, with a few exceptions. Participants completed 20 practice trials (8 in Arial font type and 8 in Bookman Old Style that each included all possible word/color combinations and preserved the font-specific proportion congruence of the test blocks, and 4 neutral trials) prior to completing two ...
In the second experiment, Stroop found that the interference which was caused by the incongruence of the font colour and the colour word resulted in significantly slower reaction times. The results showed the reaction times were higher by an average of 47 seconds in the colour incongruent condition compared to the colour congruent condition.
This study reveals disrupted brain functional connectivity as an early biomarker in cognitively healthy individuals with pathological CSF amyloid/tau, aiding early Alzheimer's detection.