One size does not fit all: notable individual variation in brain activity correlates of antidepressant treatment response

IntroductionTo date, no robust electroencephalography (EEG) markers of antidepressant treatment response have been identified. Variable findings may arise from the use of group analyses, which neglect individual variation. Using a combination of group and single-participant analyses, we explored individual variability in EEG characteristics of treatment response.MethodsResting-state EEG data and Montgomery-Åsberg Depression Rating Scale (MADRS) symptom scores were collected from 43 patients with depression before, at 1 and 12 weeks of pharmacotherapy. Partial least squares (PLS) was used to: 1) identify group differences in EEG connectivity (weighted phase lag index) and complexity (multiscale entropy) between eventual medication responders and non-responders, and 2) determine whether group patterns could be identified in individual patients.ResultsResponders showed decreased alpha and increased beta connectivity, and early, widespread decreases in complexity over treatment. Non-responders showed an opposite connectivity pattern, and later, spatially confined decreases in complexity. Thus, as in previous studies, our group analyses identified significant differences between groups of patients with different treatment outcomes. These group-level EEG characteristics were only identified in ~40-60% of individual patients, as assessed quantitatively by correlating the spatiotemporal brain patterns between groups and individual results, and by independent raters through visualization.DiscussionOur single-participant analyses suggest that substantial individual variation exists, and needs to be considered when investigating characteristics of antidepressant treatment response for potential clinical applicability.Clinical trial registrationhttps://clinicaltrials.gov, identifier NCT00519428

Context matters: How do task demands modulate the recruitment of sensorimotor information during language processing?

Many theories of semantic representation propose that simulations of sensorimotor experience contribute to language processing. This can be seen in the body-object interaction effect (BOI; how easily the human body can interact with a word’s referent). Words with high BOI ratings (e.g., ball) are processed more quickly than words with low BOI ratings (e.g., cloud) in various language tasks. This effect can be modulated by task demands. Previous research established that when asked to decide if a word is an object (entity condition), a BOI effect is observed, but when asked to decide if a word is an action (action condition), there is no BOI effect. It is unclear whether the null behavioral effect in the action condition reflects top-down modulation of task-relevant sensorimotor information or the absence of bottom-up activation of sensorimotor simulations. We investigated this question using EEG. In Experiment 1 we replicated the previous behavioral findings. In Experiment 2, 50 participants were assigned to either the entity or action conditions and responded to the same word stimuli. In both conditions we observed differences in ERP components related to the BOI effect. In the entity condition the P2 mean amplitude was significantly more positive for high compared to low BOI words. In the action condition the N400 peak latency was significantly later for high compared to low BOI words. Our findings suggest that BOI information is generated bottom-up regardless of task demands and modulated by top-down processes that recruit sensorimotor information relevant to the task decision

Distinct patterns of functional and effective connectivity between perirhinal cortex and other cortical regions in recognition memory and perceptual discrimination.

Traditionally, the medial temporal lobe (MTL) is thought to be dedicated to declarative memory. Recent evidence challenges this view, suggesting that perirhinal cortex (PrC), which interfaces the MTL with the ventral visual pathway, supports highly integrated object representations in recognition memory and perceptual discrimination. Even with comparable representational demands, perceptual and memory tasks differ in numerous task demands and the subjective experience they evoke. Here, we tested whether such differences are reflected in distinct patterns of connectivity between PrC and other cortical regions, including differential involvement of prefrontal control processes. We examined functional magnetic resonance imaging data for closely matched perceptual and recognition memory tasks for faces that engaged right PrC equivalently. Multivariate seed analyses revealed distinct patterns of interactions: Right ventrolateral prefrontal and posterior cingulate cortices exhibited stronger functional connectivity with PrC in recognition memory; fusiform regions were part of the pattern that displayed stronger functional connectivity with PrC in perceptual discrimination. Structural equation modeling revealed distinct patterns of effective connectivity that allowed us to constrain interpretation of these findings. Overall, they demonstrate that, even when MTL structures show similar involvement in recognition memory and perceptual discrimination, differential neural mechanisms are reflected in the interplay between the MTL and other cortical regions

The modulatory effect of adaptive task-switching training on resting-state neural network dynamics in younger and older adults

With increasing life expectancy and active aging, it becomes crucial to investigate methods which could compensate for generally detected cognitive aging processes. A promising candidate is adaptive cognitive training, during which task difficulty is adjusted to the participants’ performance level to enhance the training and potential transfer effects. Measuring intrinsic brain activity is suitable for detecting possible distributed training-effects since resting-state dynamics are linked to the brain’s functional flexibility and the effectiveness of different cognitive processes. Therefore, we investigated if adaptive task-switching training could modulate resting-state neural dynamics in younger (18–25 years) and older (60–75 years) adults (79 people altogether). We examined spectral power density on resting-state EEG data for measuring oscillatory activity, and multiscale entropy for detecting intrinsic neural complexity. Decreased coarse timescale entropy and lower frequency band power as well as increased fine timescale entropy and higher frequency band power revealed a shift from more global to local information processing with aging before training. However, cognitive training modulated these age-group differences, as coarse timescale entropy and lower frequency band power increased from pre- to post-training in the old-training group. Overall, our results suggest that cognitive training can modulate neural dynamics even when measured outside of the trained task

Getting a grip on sensorimotor effects in lexical-semantic processing

One of the strategies that researchers have used to investigate the role of sensorimotor information in lexical-semantic processing is to examine effects of words’ rated body-object interaction (BOI; the ease with which the human body can interact with a word’s referent). Processing tends to be facilitated for words with high BOI compared to words with low BOI, across a wide variety of tasks. Such effects have been referenced in debates over the nature of semantic representations, but their theoretical import has been limited by the fact that BOI is a fairly coarse measure of sensorimotor experience with words’ referents. In the present study we collected ratings for 621 words on seven semantic dimensions (graspability, ease of pantomime, number of actions, animacy, size, danger, and usefulness) in order to investigate which attributes are most strongly related to BOI ratings, and to lexical-semantic processing. BOI ratings were obtained from previous norming studies (Bennett, Burnett, Siakaluk, & Pexman, 2011; Tillotson, Siakaluk, & Pexman, 2008) and measures of lexical-semantic processing were obtained from previous behavioural megastudies involving the semantic categorization task (concrete/abstract decision; Pexman, Heard, Lloyd, & Yap, 2017) and the lexical decision task (Balota et al., 2007). Results showed that the motor dimension of graspability, ease of pantomime, and number of actions were all related to BOI and that these dimensions together explained more variance in semantic processing than did BOI ratings alone. These ratings will be useful for researchers who wish to study how different kinds of bodily interactions influence lexical-semantic processing and cognition

The effects of irrelevant information and stimulus uncertainty on the aging visual memory system

grantor: University of TorontoPrevious research has shown that old observers' behavioral performance on basic spatial frequency memory tasks is comparable to that of young observers. PET research suggests that old observers' preserved behavioral performance may depend on the operation of neural compensatory mechanisms. Presumably, when task difficulty increases, there exists a limit beyond which the elderly brain can no longer compensate. The current study examined whether or not adding irrelevant information and stimulus uncertainty would exceed the capacity of the elderly brain's compensatory mechanisms. We found no age effects for observers aged 60 to 69, and significant age effects for observers aged 70 and above. We conclude if neural compensatory mechanisms subserve the ability to perform like young observers, then these mechanisms continue to work even when irrelevant information and stimulus uncertainty is added to the task for observers aged 60-69, but not for observers aged 70 and above.M.A

The effects of irrelevant information and stimulus uncertainty on the aging visual memory system

grantor: University of TorontoPrevious research has shown that old observers' behavioral performance on basic spatial frequency memory tasks is comparable to that of young observers. PET research suggests that old observers' preserved behavioral performance may depend on the operation of neural compensatory mechanisms. Presumably, when task difficulty increases, there exists a limit beyond which the elderly brain can no longer compensate. The current study examined whether or not adding irrelevant information and stimulus uncertainty would exceed the capacity of the elderly brain's compensatory mechanisms. We found no age effects for observers aged 60 to 69, and significant age effects for observers aged 70 and above. We conclude if neural compensatory mechanisms subserve the ability to perform like young observers, then these mechanisms continue to work even when irrelevant information and stimulus uncertainty is added to the task for observers aged 60-69, but not for observers aged 70 and above.M.A

Sensory modality dependence of neural networks supporting simple working memory

We used functional magnetic resonance imaging (fMRI) and evoked response potentials (ERPs) to examine how the brain subserves cognitive processes when the same tasks and stimuli are presented through different modalities. The stimuli were auditory or visual bandpass-filtered white noise. On a given trial, three stimuli, each with differing center frequencies, were presented in succession. For temporal sequencing tasks, participants indicated when the stimulus with the highest frequency content appeared. For comparison tasks, participants indicated whether the last stimulus' frequency content was lower, intermediate, or higher than the first two stimuli. Task difficulty was equated by establishing 80% accuracy thresholds across subjects and tasks. For the fMRI data, we used task partial least squares (PLS) to identify activation patterns that independently map onto stimulus modality and task demands. Next, we examined PFC functional connections using seed PLS. We found that for each modality, the correlations between the right PFC and the rest of the brain were different in terms of the number of dimensions needed to capture task dependent PFC-brain correlations, and in terms of the voxels that functionally connect with the PFC, suggesting that brain activation patterns associated with modality and task demands interact. We used behavioural PLS to identify neural patterns capturing the optimal association between brain images and reaction time. This analysis also identified a significant interaction between modality and task demands, indicating that task dependent brain-behavior correlations changed with stimulus modality. For the ERP data, we used task PLS to identify the temporal interaction of neural networks that subserve modality and task demands. Source models for the task demand effect in each modality suggest that the spatial distribution of current sources are very similar outside the sensory cortices, but different in terms of time course. Specifically, information for visual processing appears to be updated and held online in a manner that is different from auditory processing, which is done mostly after the offset of the final stimulus. Overall, these results suggest that the neural substrates that support our auditory and visual working memory tasks differ outside the sensory cortices both in terms of activity and interactivity.Ph.D