Effects of endogenous testosterone on oscillatory activity during verbal working memory in youth.

Testosterone levels sharply rise during the transition from childhood to adolescence and these changes are known to be associated with changes in human brain structure. During this same developmental window, there are also robust changes in the neural oscillatory dynamics serving verbal working memory processing. Surprisingly, whereas many studies have investigated the effects of chronological age on the neural oscillations supporting verbal working memory, none have probed the impact of endogenous testosterone levels during this developmental period. Using a sample of 89 youth aged 6-14 years-old, we collected salivary testosterone samples and recorded magnetoencephalography during a modified Sternberg verbal working memory task. Significant oscillatory responses were identified and imaged using a beamforming approach and the resulting maps were subjected to whole-brain ANCOVAs examining the effects of testosterone and sex, controlling for age, during verbal working memory encoding and maintenance. Our primary results indicated robust testosterone-related effects in theta (4-7 Hz) and alpha (8-14 Hz) oscillatory activity, controlling for age. During encoding, females exhibited weaker theta oscillations than males in right cerebellar cortices and stronger alpha oscillations in left temporal cortices. During maintenance, youth with greater testosterone exhibited weaker alpha oscillations in right parahippocampal and cerebellar cortices, as well as regions across the left-lateralized language network. These results extend the existing literature on the development of verbal working memory processing by showing region and sex-specific effects of testosterone, and are the first results to link endogenous testosterone levels to the neural oscillatory activity serving verbal working memory, above and beyond the effects of chronological age.

Aperiodic component of EEG power spectrum and cognitive performance are modulated by education in aging.

Recent studies have shown a growing interest in the so-called "aperiodic" component of the EEG power spectrum, which describes the overall trend of the whole spectrum with a linear or exponential function. In the field of brain aging, this aperiodic component is associated both with age-related changes and performance on cognitive tasks. This study aims to elucidate the potential role of education in moderating the relationship between resting-state EEG features (including aperiodic component) and cognitive performance in aging. N = 179 healthy participants of the "Leipzig Study for Mind-Body-Emotion Interactions" (LEMON) dataset were divided into three groups based on age and education. Older adults exhibited lower exponent, offset (i.e. measures of aperiodic component), and Individual Alpha Peak Frequency (IAPF) as compared to younger adults. Moreover, visual attention and working memory were differently associated with the aperiodic component depending on education: in older adults with high education, higher exponent predicted slower processing speed and less working memory capacity, while an opposite trend was found in those with low education. While further investigation is needed, this study shows the potential modulatory role of education in the relationship between the aperiodic component of the EEG power spectrum and aging cognition.

Extent of magnitude representation deficit and relationship with arithmetic skills in children with 22q11.2DS.

BACKGROUND: Previous studies have produced conflicting results concerning the extent of magnitude representation deficit and its relationship with arithmetic achievement in children with 22q11.2 deletion syndrome. More specifically, it remains unclear whether deficits are restricted to visuospatial content or are more general and whether they could explain arithmetical impairment. METHODS: Fifteen 5- to 12-year-old children with 22q11.2 deletion syndrome and 23 age-matched healthy controls performed a non-symbolic magnitude comparison task. Depending on the trial, participants had to compare stimuli with high or low visuospatial load (visuospatial stimuli or temporal sequence of visual stimuli). The participants also completed a battery of arithmetic skills (ZAREKI-R) and a battery of global cognitive functioning (WISC-V or WPPSI-IV), from which working memory and visuospatial indices were derived. RESULTS: Children with 22q11.2DS responded as fast as healthy controls did but received fewer correct responses, irrespective of visuospatial load. In addition, their performance in the non-symbolic magnitude comparison task did not correlate with the ZAREKI total score, while the working memory index did. CONCLUSION: Children with 22q11.2DS might suffer from a global magnitude representation deficit rather than a specific deficit due to visuospatial load. However, this deficit alone does not seem to be related to arithmetic achievement. Working memory might be a better concern of interest in favoring arithmetic skills in patients with 22q11.2 deletion syndrome. TRIAL REGISTRATION: Clinicaltrials, NCT04373226 . Registered 16 September 2020.

Writing about a stressful experience can impair visual working memory.

Acute stress has been well-established to impair working memory. However, less is known about how writing about an unresolved stressor may influence working memory or working memory processes. We addressed these issues in the present study (N = 282) by randomly assigning participants to write about an unresolved stressful experience (stressful writing condition or the events of the previous day). We then both measured performance on a change detection task and used computational modeling to estimate the processes underlying performance: attention, capacity, and guessing bias. We found that, relative to the control condition, writing about a stressful experience impaired change detection task performance and significantly impaired task attention. These results show that the effects of writing about an unresolved stressor may mimic the effects of acute stress on working memory, rather than conforming to expectations from mood-as-information theory.

Neural dysfunction underlying working memory processing at different stages of the illness course in schizophrenia: a comparative meta-analysis.

Schizophrenia, as a chronic and persistent disorder, exhibits working memory deficits across various stages of the disorder, yet the neural mechanisms underlying these deficits remain elusive with inconsistent neuroimaging findings. We aimed to compare the brain functional changes of working memory in patients at different stages: clinical high risk, first-episode psychosis, and long-term schizophrenia, using meta-analyses of functional magnetic resonance imaging studies. Following a systematic literature search, 56 whole-brain task-based functional magnetic resonance imaging studies (15 for clinical high risk, 16 for first-episode psychosis, and 25 for long-term schizophrenia) were included. The separate and pooled neurofunctional mechanisms among clinical high risk, first-episode psychosis, and long-term schizophrenia were generated by Seed-based d Mapping toolbox. The clinical high risk and first-episode psychosis groups exhibited overlapping hypoactivation in the right inferior parietal lobule, right middle frontal gyrus, and left superior parietal lobule, indicating key lesion sites in the early phase of schizophrenia. Individuals with first-episode psychosis showed lower activation in left inferior parietal lobule than those with long-term schizophrenia, reflecting a possible recovery process or more neural inefficiency. We concluded that SCZ represent as a continuum in the early stage of illness progression, while the neural bases are inversely changed with the development of illness course to long-term course.

Perirhinal cortex learns a predictive map of the task environment.

Goal-directed tasks involve acquiring an internal model, known as a predictive map, of relevant stimuli and associated outcomes to guide behavior. Here, we identified neural signatures of a predictive map of task behavior in perirhinal cortex (Prh). Mice learned to perform a tactile working memory task by classifying sequential whisker stimuli over multiple training stages. Chronic two-photon calcium imaging, population analysis, and computational modeling revealed that Prh encodes stimulus features as sensory prediction errors. Prh forms stable stimulus-outcome associations that can progressively be decoded earlier in the trial as training advances and that generalize as animals learn new contingencies. Stimulus-outcome associations are linked to prospective network activity encoding possible expected outcomes. This link is mediated by cholinergic signaling to guide task performance, demonstrated by acetylcholine imaging and systemic pharmacological perturbation. We propose that Prh combines error-driven and map-like properties to acquire a predictive map of learned task behavior.

Shared structure facilitates working memory of multiple sequences.

Daily experiences often involve the processing of multiple sequences, yet storing them challenges the limited capacity of working memory (WM). To achieve efficient memory storage, relational structures shared by sequences would be leveraged to reorganize and compress information. Here, participants memorized a sequence of items with different colors and spatial locations and later reproduced the full color and location sequences one after another. Crucially, we manipulated the consistency between location and color sequence trajectories. First, sequences with consistent trajectories demonstrate improved memory performance and a trajectory correlation between reproduced color and location sequences. Second, sequences with consistent trajectories show neural reactivation of common trajectories, and display spontaneous replay of color sequences when recalling locations. Finally, neural reactivation correlates with WM behavior. Our findings suggest that a shared common structure is leveraged for the storage of multiple sequences through compressed encoding and neural replay, together facilitating efficient information organization in WM.

When we memorize a grocery list before heading into the store, we make use of our working memory. This type of neural process allows us to temporarily store the knowledge needed for a task, yet its capacity is limited. Having to recall more than one type of information at the same time, in particular, can quickly create challenges. Exactly how the brain maximizes the use of this limited working memory space remains unclear. One possible strategy would be to take advantage of the patterns or connections that exist between seemingly unrelated pieces of information ­ for example, by remembering to buy apples, oranges and bananas under one broader 'fruit' category. To explore if this may be the case, Qiaoli Huang and Huan Luo designed a memory task in which two types of information were either connected through an underlying pattern (aligned trajectory condition) or completely independent (misaligned trajectory condition). Participants watched three colored dots appearing on screen one after the other, in such a way that they seemed to 'travel' around an imaginary circle. The volunteers were then asked to recall, in order, the location and color of each dot. Performance increased when color and location information were structured in the same way ­ that is, when both emerged from the three dots traveling around a circle or a color wheel with the same trajectory. Recording the brain activity of the participants 'live' as they performed the task indicates that, in the aligned trajectory condition, the brain 'compresses' both types of information and extracts their common structure. Even when participants were asked to recall only the location of the dots, their brain also spontaneously replayed the related color information. Taken together, these findings provide new insights into how working memory aids in multitasking, a crucial aspect of our daily lives, and lay the groundwork for further exploration of this capability.

Effect of transcranial direct current stimulation with concurrent cognitive performance targeting posterior parietal cortex vs prefrontal cortex on working memory in schizophrenia: a randomized clinical trial.

Working memory deficits are linked to irregularities in the dorsolateral prefrontal cortex (DLPFC) and the posterior parietal cortex (PPC) in schizophrenia, effective intervention strategies are lacking. We evaluated the differential efficacy and underlying neuromechanisms of targeting transcranial direct current stimulation (tDCS) at the DLPFC and the PPC with concurrent cognitive performance for working memory in schizophrenia. In a randomized and double-blind clinical trial, sixty clinically stable schizophrenic patients with below-average working memory were randomly assigned to active DLPFC, active PPC, and sham tDCS groups. Two sessions of tDCS during N-back task were delivered daily for five days. The primary outcome was changes in spatial span test scores from baseline to week 1. The secondary outcomes included changes in scores of color delay-estimation task, other cognitive tasks, and mismatch negativity (biomarker of N-methyl-d-aspartate receptor functioning). Compared with the active DLPFC group, the active PPC group demonstrated significantly greater improvement in spatial span test scores (p = 0.008, d = 0.94) and an augmentation in color delay-estimation task capacity at week 1; the latter sustained to week 2. Compared with the sham tDCS group, the active PPC group did not show a significant improvement in spatial span test scores at week 1 and 2; however, significant enhancement was observed in their color delay-estimation task capacity at week 2. Additionally, mismatch negativity amplitude was enhanced, and changes in theta band measures were positively correlated with working memory improvement in the active PPC group, while no such correlations were observed in the active DLPFC group or the sham tDCS group. Our results suggest that tDCS targeting the PPC relative to the DLPFC during concurrent cognitive performance may improve working memory in schizophrenia, meriting further investigation. The improvement in working memory appears to be linked to enhanced N-methyl-d-aspartate receptor functioning.

Selective recruitment of the cerebellum evidenced by task-dependent gating of inputs.

Functional magnetic resonance imaging (fMRI) studies have documented cerebellar activity across a wide array of tasks. However, the functional contribution of the cerebellum within these task domains remains unclear because cerebellar activity is often studied in isolation. This is problematic, as cerebellar fMRI activity may simply reflect the transmission of neocortical activity through fixed connections. Here, we present a new approach that addresses this problem. Rather than focus on task-dependent activity changes in the cerebellum alone, we ask if neocortical inputs to the cerebellum are gated in a task-dependent manner. We hypothesize that input is upregulated when the cerebellum functionally contributes to a task. We first validated this approach using a finger movement task, where the integrity of the cerebellum has been shown to be essential for the coordination of rapid alternating movements but not for force generation. While both neocortical and cerebellar activity increased with increasing speed and force, the speed-related changes in the cerebellum were larger than predicted by an optimized cortico-cerebellar connectivity model. We then applied the same approach in a cognitive domain, assessing how the cerebellum supports working memory. Enhanced gating was associated with the encoding of items in working memory, but not with the manipulation or retrieval of the items. Focusing on task-dependent gating of neocortical inputs to the cerebellum offers a promising approach for using fMRI to understand the specific contributions of the cerebellum to cognitive function.

The combination operation of grouping and ensemble coding for structured biological motion crowds in working memory.

Massive studies have explored biological motion (BM) crowds processing for their remarkable social significance, primarily focused on uniformly distributed ones. However, real-world BM crowds often exhibit hierarchical structures rather than uniform arrangements. How such structured BM crowds are processed remains a subject of inquiry. This study investigates the representation of structured BM crowds in working memory (WM), recognizing the pivotal role WM plays in our social interactions involving BM. We propose the group-based ensemble hypothesis and test it through a member identification task. Participants were required to discern whether a presented BM belonged to a prior memory display of eight BM, each with distinct walking directions. Drawing on prominent Gestalt principles as organizational cues, we constructed structured groups within BM crowds by applying proximity and similarity cues in Experiments 1 and 2, respectively. In Experiment 3, we deliberately weakened the visibility of stimuli structures by increasing the similarity between subsets, probing the robustness of results. Consistently, our findings indicate that BM aligned with the mean direction of the subsets was more likely to be recognized as part of the memory stimuli. This suggests that WM inherently organizes structured BM crowds into separate ensembles based on organizational cues. In essence, our results illuminate the simultaneous operation of grouping and ensemble encoding mechanisms for BM crowds within WM.

Multiscale chemogenetic dissection of fronto-temporal top-down regulation for object memory in primates.

Visual object memory is a fundamental element of various cognitive abilities, and the underlying neural mechanisms have been extensively examined especially in the anterior temporal cortex of primates. However, both macroscopic large-scale functional network in which this region is embedded and microscopic neuron-level dynamics of top-down regulation it receives for object memory remains elusive. Here, we identified the orbitofrontal node as a critical partner of the anterior temporal node for object memory by combining whole-brain functional imaging during rest and a short-term object memory task in male macaques. Focal chemogenetic silencing of the identified orbitofrontal node downregulated both the local orbitofrontal and remote anterior temporal nodes during the task, in association with deteriorated mnemonic, but not perceptual, performance. Furthermore, imaging-guided neuronal recordings in the same monkeys during the same task causally revealed that orbitofrontal top-down modulation enhanced stimulus-selective mnemonic signal in individual anterior temporal neurons while leaving bottom-up perceptual signal unchanged. Furthermore, similar activity difference was also observed between correct and mnemonic error trials before silencing, suggesting its behavioral relevance. These multifaceted but convergent results provide a multiscale causal understanding of dynamic top-down regulation of the anterior temporal cortex along the ventral fronto-temporal network underpinning short-term object memory in primates.

Comparable cerebral cortex activity and gait performance in elderly hypertensive and healthy individuals during dual-task walking: A fNIRS study.

BACKGROUND: Hypertension increases the risk of cognitive impairment and related dementia, causing impaired executive function and unusual gait parameters. However, the mechanism of neural function illustrating this is unclear. Our research aimed to explore the differences of cerebral cortex activation, gait parameters, and working memory performance between healthy older adults (HA) and older hypertensive (HT) patients when performing cognitive and walking tasks. METHOD: A total of 36 subjects, including 12 healthy older adults and 24 older hypertensive patients were asked to perform series conditions including single cognitive task (SC), single walking task (SW), and dual-task (DT), wearing functional near-infrared spectroscopy (fNIRS) equipment and Intelligent Device for Energy Expenditure and Activity equipment to record cortical hemodynamic reactions and various gait parameters. RESULTS: The left somatosensory cortex (L-S1) and bilateral supplementary motor area (SMA) showed higher cortical activation (p < .05) than HA when HT performed DT. The intragroup comparison showed that HT had higher cortical activation (p < .05) when performing DT as SW. The cognitive performance of HT was significantly worse (p < .05) than HA when executing SC. The activation of the L-S1, L-M1, and bilateral SMA in HT were significantly higher during SW (p < .05). CONCLUSION: Hypertension can lead to cognitive impairment in the elderly, including executive function and walking function decline. As a result of these functional declines, elderly patients with hypertension are unable to efficiently allocate brain resources to support more difficult cognitive interference tasks and need to meet more complex task demands by activating more brain regions.

Mechanisms of visual working memory processing task-irrelevant information retrieved from visual long-term memory.

Visual working memory (VWM) can selectively filter task-irrelevant information from incoming visual stimuli. However, whether a similar filtering process applies to task-irrelevant information retrieved from visual long-term memory (VLTM) remains elusive. We assume a "resource-limited retrieval mechanism" in VWM in charge of the retrieval of irrelevant VLTM information. To make a comprehensive understanding of this mechanism, we conducted three experiments using both a VLTM learning task and a VWM task combined with pupillometry. The presence of a significant pupil light response (PLR) served as empirical evidence that VLTM information can indeed make its way into VWM. Notably, task-relevant VLTM information induced a sustained PLR, contrasting with the transient PLR observed for task-irrelevant VLTM information. Importantly, the transience of the PLR occurred under conditions of low VWM load, but this effect was absent under conditions of high load. Collectively, these results show that task-irrelevant VLTM information can enter VWM and then fade away only under conditions of low VWM load. This dynamic underscores the resource-limited retrieval mechanism within VWM, exerting control over the entry of VLTM information.

High-frequency assessment of mood, personality, and cognition in healthy younger, healthy older and adults with cognitive impairment.

Increased variability in cognitive scores, mood or personality traits can be indicative of underlying neurological disorders. Whether variability in cognition is due to changes in mood or personality is unknown. A total of 66 younger adults, 51 healthy older adults and 38 participants with cognitive impairment completed 21 daily sessions of attention, working memory, mood, and personality assessment. Group differences in mean performance and variability were examined using Bayesian mixed effects location scale models. Variability in attention decreased from younger to older adults and then increased again in cognitive impairment. Younger adults were more variable in agreeableness, openness and conscientiousness compared to older adults. The clinically impaired group differed from the healthy older adults in terms of variability on attention, openness, and conscientiousness. Healthy aging results in greater stability in personality traits over short intervals yet this stability is not redundant with increased stability in cognitive scores.

Myelin dystrophy impairs signal transmission and working memory in a multiscale model of the aging prefrontal cortex.

Normal aging leads to myelin alterations in the rhesus monkey dorsolateral prefrontal cortex (dlPFC), which are positively correlated with degree of cognitive impairment. It is hypothesized that remyelination with shorter and thinner myelin sheaths partially compensates for myelin degradation, but computational modeling has not yet explored these two phenomena together systematically. Here, we used a two-pronged modeling approach to determine how age-related myelin changes affect a core cognitive function: spatial working memory. First, we built a multicompartment pyramidal neuron model fit to monkey dlPFC empirical data, with an axon including myelinated segments having paranodes, juxtaparanodes, internodes, and tight junctions. This model was used to quantify conduction velocity (CV) changes and action potential (AP) failures after demyelination and subsequent remyelination. Next, we incorporated the single neuron results into a spiking neural network model of working memory. While complete remyelination nearly recovered axonal transmission and network function to unperturbed levels, our models predict that biologically plausible levels of myelin dystrophy, if uncompensated by other factors, can account for substantial working memory impairment with aging. The present computational study unites empirical data from ultrastructure up to behavior during normal aging, and has broader implications for many demyelinating conditions, such as multiple sclerosis or schizophrenia.

Volleyball training improves working memory in children aged 7 to 12 years old: an fNIRS study.

This study aimed to investigate the effect of a 12-wk extracurricular volleyball training on working memory from both behavioral and cerebral aspects. A total of 80 children were randomized assigned to (i) the experimental group, who engaged in extracurricular volleyball training for 60 min, thrice a week for 12 wk, and (ii) the control group, who maintained their regular daily routine. Working memory was evaluated in both groups using the N-back task before and after the intervention. Furthermore, functional near-infrared spectroscopy was employed to monitor the level of oxygenated hemoglobin in the prefrontal cortex. The experimental group performed better in the behavioral task than the control group, as evidenced by a shorter response time and a higher correct rate. The functional near-infrared spectroscopy results suggested that the activation of the left dorsolateral prefrontal cortex was significantly higher in the experimental group than in the control group. In addition, correlation analyses showed that the enhancement of left dorsolateral prefrontal cortex activation was significantly correlated with decreasing response time and improving response accuracy in the N-back task. These findings suggest that the left dorsolateral prefrontal cortex is likely the neural substrate for improved working memory performance elicited by 12-wk open skill exercise.

MRI resting-state signature of the propensity to experience meaningful coincidences: a functional coupling analysis.

The propensity to experience meaningful patterns in random arrangements and unrelated events shows considerable interindividual differences. Reduced inhibitory control (over sensory processes) and decreased working memory capacities are associated with this trait, which implies that the activation of frontal as well as posterior brain regions may be altered during rest and working memory tasks. In addition, people experiencing more meaningful coincidences showed reduced gray matter of the left inferior frontal gyrus (IFG), which is linked to the inhibition of irrelevant information in working memory and the control and integration of multisensory information. To study deviations in the functional connectivity of the IFG with posterior associative areas, the present study investigated the fMRI resting state in a large sample of n = 101 participants. We applied seed-to-voxel analysis and found that people who perceive more meaningful coincidences showed negative functional connectivity of the left IFG (i.e. pars triangularis) with areas of the left posterior associative cortex (e.g. superior parietal cortex). A data-driven multivoxel pattern analysis further indicated that functional connectivity of a cluster located in the right cerebellum with a cluster including parts of the left middle frontal gyrus, left precentral gyrus, and the left IFG (pars opercularis) was associated with meaningful coincidences. These findings add evidence to the neurocognitive foundations of the propensity to experience meaningful coincidences, which strengthens the idea that deviations of working memory functions and inhibition of sensory and motor information explain why people experience more meaning in meaningless noise.

Effects of head alignment devices on working memory and postural support during computer work.

The most common risk factor of computer workers is poor head and neck posture. Therefore, upright seated posture has been recommended repeatedly. However, maintaining an upright seated posture is challenging during computer work and induces various complaints, such as fatigue and discomfort, which can interfere working performance. Therefore, it is necessary to maintain an upright posture without complaints or intentional efforts during long-term computer work. Alignment devices are an appropriate maneuver to support postural control for maintaining head-neck orientation and reduce head weight. This study aimed to demonstrate the effects of workstations combined with alignment device on head-neck alignment, muscle properties, comfort and working memory ability in computer workers. Computer workers (n = 37) participated in a total of three sessions (upright computer (CPT_U), upright support computer (CPT_US), traction computer (CPT_T) workstations). The craniovertebral angle, muscles tone and stiffness, visual analog discomfort scale score, 2-back working memory performance, and electroencephalogram signals were measured. All three workstations had a substantial effect on maintaining head-neck alignment (p< 0.001), but only CPT_US showed significant improvement on psychological comfort (p = 0.04) and working memory performance (p = 0.024), which is consistent with an increase in delta power. CPT_U showed the increased beta 2 activity, discomfort, and false rates compared to CPT_US. CPT_T showed increased alpha and beta 2 activity and decreased delta activity, which are not conductive to working memory performance. In conclusion, CPT_US can effectively induce efficient neural oscillations without causing any discomfort by increasing delta and decreasing beta 2 activity for working memory tasks.

The effects of moderate-intensity aerobic exercise on cognitive function in individuals with stroke-induced mild cognitive impairment: a randomized controlled pilot study.

OBJECTIVE: To assess the impact of moderate-intensity aerobic exercise on working memory in stroke-induced mild cognitive impairment (MCI). DESIGN: Randomized, double-blind controlled study. SUBJECTS AND METHODS: Twenty MCI patients from the Fifth Affiliated Hospital of Guangzhou Medical University (December 2021 to February 2023), aged 34-79, 2-12 months post-stroke, were divided into an experimental group (EG) and a control group (CG), each with 10 participants. The EG underwent standard rehabilitation plus 40 minutes of aerobic exercise, while the CG received only standard therapy, 5 times weekly for 2 weeks. Working memory was tested using the n-back task, and overall cognitive function was measured with the MOCA and MMSE Scales before and after the intervention. RESULTS: The EG showed higher 3-back correctness (71.80 ± 14.53 vs 56.50 ± 13.66), MOCA scores (27.30 ± 1.57 vs 24.00 ± 3.13), and improved visuospatial/executive (4.60 ± 0.52 vs 3.30 ± 1.06) and delayed recall (4.30 ± 0.82 vs 3.00 ± 1.56) on the MOCA scale compared with the CG. CONCLUSION: Moderate-intensity aerobic exercise may enhance working memory, visuospatial/executive, and delayed recall functions in stroke-induced MCI patients.

Task and stimulus coding in the multiple-demand network.

In the human brain, a multiple-demand (MD) network plays a key role in cognitive control, with core components in lateral frontal, dorsomedial frontal and lateral parietal cortex, and multivariate activity patterns that discriminate the contents of many cognitive activities. In prefrontal cortex of the behaving monkey, different cognitive operations are associated with very different patterns of neural activity, while details of a particular stimulus are encoded as small variations on these basic patterns (Sigala et al, 2008). Here, using the advanced fMRI methods of the Human Connectome Project and their 360-region cortical parcellation, we searched for a similar result in MD activation patterns. In each parcel, we compared multivertex patterns for every combination of three tasks (working memory, task-switching, and stop-signal) and two stimulus classes (faces and buildings). Though both task and stimulus category were discriminated in every cortical parcel, the strength of discrimination varied strongly across parcels. The different cognitive operations of the three tasks were strongly discriminated in MD regions. Stimulus categories, in contrast, were most strongly discriminated in a large region of primary and higher visual cortex, and intriguingly, in both parietal and frontal lobe regions adjacent to core MD regions. In the monkey, frontal neurons show a strong pattern of nonlinear mixed selectivity, with activity reflecting specific conjunctions of task events. In our data, however, there was limited evidence for mixed selectivity; throughout the brain, discriminations of task and stimulus combined largely linearly, with a small nonlinear component. In MD regions, human fMRI data recapitulate some but not all aspects of electrophysiological data from nonhuman primates.