Reduced temporal and spatial stability of neural activity patterns predict cognitive control deficits in children with ADHD.

This study explores the neural underpinnings of cognitive control deficits in ADHD, focusing on overlooked aspects of trial-level variability of neural coding. We employed a novel computational approach to neural decoding on a single-trial basis alongside a cued stop-signal task which allowed us to distinctly probe both proactive and reactive cognitive control. Typically developing (TD) children exhibited stable neural response patterns for efficient proactive and reactive dual control mechanisms. However, neural coding was compromised in children with ADHD. Children with ADHD showed increased temporal variability and diminished spatial stability in neural responses in salience and frontal-parietal network regions, indicating disrupted neural coding during both proactive and reactive control. Moreover, this variability correlated with fluctuating task performance and with more severe symptoms of ADHD. These findings underscore the significance of modeling single-trial variability and representational similarity in understanding distinct components of cognitive control in ADHD, highlighting new perspectives on neurocognitive dysfunction in psychiatric disorders.

Hippocampal contributions to novel spatial learning are both age-related and age-invariant.

Older adults show declines in spatial memory, although the extent of these alterations is not uniform across the healthy older population. Here, we investigate the stability of neural representations for the same and different spatial environments in a sample of younger and older adults using high-resolution functional MRI of the medial temporal lobes. Older adults showed, on average, lower neural pattern similarity for retrieving the same environment and more variable neural patterns compared to young adults. We also found a positive association between spatial distance discrimination and the distinctiveness of neural patterns between environments. Our analyses suggested that one source for this association was the extent of informational connectivity to CA1 from other subfields, which was dependent on age, while another source was the fidelity of signals within CA1 itself, which was independent of age. Together, our findings suggest both age-dependent and independent neural contributions to spatial memory performance.

Hippocampal contributions to novel spatial learning are both age-related and age-invariant.

Older adults show declines in spatial memory, although the extent of these alterations is not uniform across the healthy older population. Here, we investigate the stability of neural representations for the same and different spatial environments in a sample of younger and older adults using high-resolution functional magnetic resonance imaging (fMRI) of the medial temporal lobe. Older adults showed, on average, lower neural pattern similarity for retrieving the same environment and more variable neural patterns compared to young adults. We also found a positive association between spatial distance discrimination and the distinctiveness of neural patterns between environments. Our analyses suggested that one source for this association was the extent of informational connectivity to CA1 from other subfields, which was dependent on age, while another source was the fidelity of signals within CA1 itself, which was independent of age. Together, our findings suggest both age-dependent and independent neural contributions to spatial memory performance.

Creativity in verbal associations is linked to semantic control.

Although memory is known to play a key role in creativity, previous studies have not isolated the critical component processes and networks. We asked participants to generate links between words that ranged from strongly related to completely unrelated in long-term memory, delineating the neurocognitive processes that underpin more unusual versus stereotypical patterns of retrieval. More creative responses to strongly associated word-pairs were associated with greater engagement of episodic memory: in highly familiar situations, semantic, and episodic stores converge on the same information enabling participants to form a personal link between items. This pattern of retrieval was associated with greater engagement of core default mode network (DMN). In contrast, more creative responses to weakly associated word-pairs were associated with the controlled retrieval of less dominant semantic information and greater recruitment of the semantic control network, which overlaps with the dorsomedial subsystem of DMN. Although both controlled semantic and episodic patterns of retrieval are associated with activation within DMN, these processes show little overlap in activation. These findings demonstrate that controlled aspects of semantic cognition play an important role in verbal creativity.

Flexing the principal gradient of the cerebral cortex to suit changing semantic task demands.

Understanding how thought emerges from the topographical structure of the cerebral cortex is a primary goal of cognitive neuroscience. Recent work has revealed a principal gradient of intrinsic connectivity capturing the separation of sensory-motor cortex from transmodal regions of the default mode network (DMN); this is thought to facilitate memory-guided cognition. However, studies have not explored how this dimension of connectivity changes when conceptual retrieval is controlled to suit the context. We used gradient decomposition of informational connectivity in a semantic association task to establish how the similarity in connectivity across brain regions changes during familiar and more original patterns of retrieval. Multivoxel activation patterns at opposite ends of the principal gradient were more divergent when participants retrieved stronger associations; therefore, when long-term semantic information is sufficient for ongoing cognition, regions supporting heteromodal memory are functionally separated from sensory-motor experience. In contrast, when less related concepts were linked, this dimension of connectivity was reduced in strength as semantic control regions separated from the DMN to generate more flexible and original responses. We also observed fewer dimensions within the neural response towards the apex of the principal gradient when strong associations were retrieved, reflecting less complex or varied neural coding across trials and participants. In this way, the principal gradient explains how semantic cognition is organised in the human cerebral cortex: the separation of DMN from sensory-motor systems is a hallmark of the retrieval of strong conceptual links that are culturally shared.

Context free and context-dependent conceptual representation in the brain.

How concepts are coded in the brain is a core issue in cognitive neuroscience. Studies have focused on how individual concepts are processed, but the way in which conceptual representation changes to suit the context is unclear. We parametrically manipulated the association strength between words, presented in pairs one word at a time using a slow event-related fMRI design. We combined representational similarity analysis and computational linguistics to probe the neurocomputational content of these trials. Individual word meaning was maintained in supramarginal gyrus (associated with verbal short-term memory) when items were judged to be unrelated, but not when a linking context was retrieved. Context-dependent meaning was instead represented in left lateral prefrontal gyrus (associated with controlled retrieval), angular gyrus, and ventral temporal lobe (regions associated with integrative aspects of memory). Analyses of informational connectivity, examining the similarity of activation patterns across trials between sites, showed that control network regions had more similar multivariate responses across trials when association strength was weak, reflecting a common controlled retrieval state when the task required more unusual associations. These findings indicate that semantic control and representational sites amplify contextually relevant meanings in trials judged to be related.

A tale of two gradients: differences between the left and right hemispheres predict semantic cognition.

Decomposition of whole-brain functional connectivity patterns reveals a principal gradient that captures the separation of sensorimotor cortex from heteromodal regions in the default mode network (DMN). Functional homotopy is strongest in sensorimotor areas, and weakest in heteromodal cortices, suggesting there may be differences between the left and right hemispheres (LH/RH) in the principal gradient, especially towards its apex. This study characterised hemispheric differences in the position of large-scale cortical networks along the principal gradient, and their functional significance. We collected resting-state fMRI and semantic, working memory and non-verbal reasoning performance in 175 + healthy volunteers. We then extracted the principal gradient of connectivity for each participant, tested which networks showed significant hemispheric differences on the gradient, and regressed participants' behavioural efficiency in tasks outside the scanner against interhemispheric gradient differences for each network. LH showed a higher overall principal gradient value, consistent with its role in heteromodal semantic cognition. One frontotemporal control subnetwork was linked to individual differences in semantic cognition: when it was nearer heteromodal DMN on the principal gradient in LH, participants showed more efficient semantic retrieval-and this network also showed a strong hemispheric difference in response to semantic demands but not working memory load in a separate study. In contrast, when a dorsal attention subnetwork was closer to the heteromodal end of the principal gradient in RH, participants showed better visual reasoning. Lateralization of function may reflect differences in connectivity between control and heteromodal regions in LH, and attention and visual regions in RH.

Partially overlapping spatial environments trigger reinstatement in hippocampus and schema representations in prefrontal cortex.

When we remember a city that we have visited, we retrieve places related to finding our goal but also non-target locations within this environment. Yet, understanding how the human brain implements the neural computations underlying holistic retrieval remains unsolved, particularly for shared aspects of environments. Here, human participants learned and retrieved details from three partially overlapping environments while undergoing high-resolution functional magnetic resonance imaging (fMRI). Our findings show reinstatement of stores even when they are not related to a specific trial probe, providing evidence for holistic environmental retrieval. For stores shared between cities, we find evidence for pattern separation (representational orthogonalization) in hippocampal subfield CA2/3/DG and repulsion in CA1 (differentiation beyond orthogonalization). Additionally, our findings demonstrate that medial prefrontal cortex (mPFC) stores representations of the common spatial structure, termed schema, across environments. Together, our findings suggest how unique and common elements of multiple spatial environments are accessed computationally and neurally.

Distinct and common neural coding of semantic and non-semantic control demands.

The flexible retrieval of knowledge is critical in everyday situations involving problem solving, reasoning and social interaction. Current theories emphasise the importance of a left-lateralised semantic control network (SCN) in supporting flexible semantic behaviour, while a bilateral multiple-demand network (MDN) is implicated in executive functions across domains. No study, however, has examined whether semantic and non-semantic demands are reflected in a common neural code within regions specifically implicated in semantic control. Using functional MRI and univariate parametric modulation analysis as well as multivariate pattern analysis, we found that semantic and non-semantic demands gave rise to both similar and distinct neural responses across control-related networks. Though activity patterns in SCN and MDN could decode the difficulty of both semantic and verbal working memory decisions, there was no shared common neural coding of cognitive demands in SCN regions. In contrast, regions in MDN showed common patterns across manipulations of semantic and working memory control demands, with successful cross-classification of difficulty across tasks. Therefore, SCN and MDN can be dissociated according to the information they maintain about cognitive demands.

Both Default and Multiple-Demand Regions Represent Semantic Goal Information.

We used a semantic feature-matching task combined with multivoxel pattern decoding to test contrasting accounts of the role of the default mode network (DMN) in cognitive flexibility. By one view, DMN and multiple-demand cortex have opposing roles in cognition, with DMN and multiple-demand regions within the dorsal attention network (DAN) supporting internal and external cognition, respectively. Consequently, while multiple-demand regions can decode current goal information, semantically relevant DMN regions might decode conceptual similarity regardless of task demands. Alternatively, DMN regions, like multiple-demand cortex, might show sensitivity to changing task demands, since both networks dynamically alter their patterns of connectivity depending on the context. Our task required human participants (any sex) to integrate conceptual knowledge with changing task goals, such that successive decisions were based on different features of the items (color, shape, and size). This allowed us to simultaneously decode semantic category and current goal information using whole-brain searchlight decoding. As expected, multiple-demand cortex, including DAN and frontoparietal control network, represented information about currently relevant conceptual features. Similar decoding results were found in DMN, including in angular gyrus and posterior cingulate cortex, indicating that DMN and multiple-demand regions can support the same function rather than being strictly competitive. Semantic category could be decoded in lateral occipital cortex independently of task demands, but not in most regions of DMN. Conceptual information related to the current goal dominates the multivariate response within DMN, which supports flexible retrieval by modulating its response to suit the task demands, alongside regions of multiple-demand cortex.SIGNIFICANCE STATEMENT We tested contrasting accounts of default mode network (DMN) function using multivoxel pattern analysis. By one view, semantically relevant parts of DMN represent conceptual similarity, regardless of task context. By an alternative view, DMN tracks changing task demands. Our semantic feature-matching task required participants to integrate conceptual knowledge with task goals, such that successive decisions were based on different features of the items. We demonstrate that DMN regions can decode the current goal, as it is applied, alongside multiple-demand regions traditionally associated with cognitive control, speaking to how DMN supports flexible cognition.

Neural Activity Is Dynamically Modulated by Memory Load During the Maintenance of Spatial Objects.

Visuospatial working memory (WM) is a fundamental but severely limited ability to temporarily remember selected stimuli. Several studies have investigated the underlying neural mechanisms of maintaining various visuospatial stimuli simultaneously (i.e., WM load, the number of representations that need to be maintained in WM). However, two confounding factors, namely verbal representation and encoding load (the number of items that need to be encoded into WM), have not been well controlled in previous studies. In this study, we developed a novel delayed-match-to-sample task (DMST) controlling for these two confounding factors and recorded scalp EEG signals during the task. We found that behavioral performance deteriorated severely as memory load increased. Neural activity was modulated by WM load in a dynamic manner. Specifically, higher memory load induced stronger amplitude in occipital and central channel-clusters during the early delay period, while the inverse trend was observed in central and frontal channel-clusters during late delay. In addition, the same inverse memory load effect, that was lower memory load induced stronger amplitude, was observed in occipital channel-cluster alpha power during late delay. Finally, significant correlations between neural activity and individual reaction time showed a role of late-delay central and frontal channel-cluster amplitude in predicting behavioral performance. Because the occipital cortex is important for visual information maintenance, the decrease in alpha oscillation was consistent with the cognitive role that is "gating by inhibition." Together, our results from a well-controlled DMST suggest that WM load not exerted constant but dynamic effect on neural activity during maintenance of visuospatial objects.

Reduced Fidelity of Neural Representation Underlies Episodic Memory Decline in Normal Aging.

Emerging studies have emphasized the importance of the fidelity of cortical representation in forming enduring episodic memory. No study, however, has examined whether there are age-related reductions in representation fidelity that can explain memory declines in normal aging. Using functional MRI and multivariate pattern analysis, we found that older adults showed reduced representation fidelity in the visual cortex, which accounted for their decreased memory performance even after controlling for the contribution of reduced activation level. This reduced fidelity was specifically due to older adults' poorer item-specific representation, not due to their lower activation level and variance, greater variability in neuro-vascular coupling, or decreased selectivity of categorical representation (i.e., dedifferentiation). Older adults also showed an enhanced subsequent memory effect in the prefrontal cortex based on activation level, and their prefrontal activation was associated with greater fidelity of representation in the visual cortex and better memory performance. The fidelity of cortical representation thus may serve as a promising neural index for better mechanistic understanding of the memory declines and its compensation in normal aging.