Search

We appraise other people's emotions by combining multiple sources of information, including somatic facial/body reactions and the surrounding context. Wealthy literature revealed how people take into account contextual information in the interpretation of facial expressions, but the mechanisms mediating such influence still need to be duly investigated. Across two experiments, we mapped the neural representations of distinct (but comparably unpleasant) negative states, pain, and disgust, as conveyed by naturalistic facial expressions or contextual sentences. Negative expressions led to shared activity in the fusiform gyrus and superior temporal sulcus. Instead, pain contexts recruited the supramarginal, postcentral, and insular cortex, whereas disgust contexts triggered the temporoparietal cortex and hippocampus/amygdala. When pairing the two sources of information together, we found a higher likelihood of classifying an expression according to the sentence preceding it. Furthermore, networks specifically involved in processing contexts were re-enacted whenever a face followed said context. Finally, the perigenual medial prefrontal cortex (mPFC) showed increased activity for consistent (vs inconsistent) face-context pairings, suggesting that it integrates state-specific information from the two sources. Overall, our study reveals the heterogeneous nature of face-context information integration, which operates both according to a state-general and state-specific principle, with the latter mediated by the perigenual medial prefrontal cortex. [ABSTRACT FROM AUTHOR]

Human visual cortex contains regions selectively involved in perceiving and recognizing ecologically important visual stimuli such as people and places. Located in the ventral temporal lobe, these regions are organized consistently relative to cortical folding, a phenomenon thought to be inherited from how centrally or peripherally these stimuli are viewed with the retina.While this eccentricity theory of visual cortex has been one of the best descriptions of its functional organization, whether or not it accurately describes visual processing in all category-selective regions is not yet clear. Through a combination of behavioral and functional MRI measurements in 27 participants (17 females), we demonstrate that a limb-selective region neighboring well-studied face-selective regions shows tuning for the visual periphery in a cortical region originally thought to be centrally biased. We demonstrate that the spatial computations performed by the limb-selective region are consistent with visual experience and in doing so, make the novel observation that there may in fact be two eccentricity gradients, forming an eccentricity reversal across high-level visual cortex. These data expand the current theory of cortical organization to provide a unifying principle that explains the broad functional features of many visual regions, showing that viewing experience interacts with innate wiring principles to drive the location of cortical specialization. [ABSTRACT FROM AUTHOR]

From a young age, children have advanced social perceptual and reasoning abilities. However, the neural development of these abilities is still poorly understood. To address this gap, we used fMRI data collected while 122 3–12-year-old children (64 females) and 33 adults (20 females) watched an engaging and socially rich movie to investigate how the cortical basis of social processing changes throughout development. We labeled the movie with visual and social features, including motion energy, presence of a face and a social interaction, theory of mind (ToM) events, valence, and arousal. Using a voxel-wise encoding model trained on these features, we found that models based on visual (motion energy) and social (faces, social interaction, ToM, valence, and arousal) features can both predict brain activity in children as young as 3 years old across the cortex, with particularly high predictivity in motion-selective middle temporal region and the superior temporal sulcus (STS). Furthermore, models based on individual social features showed that while there may be some development throughout childhood, social interaction information in the STS is present in children as young as 3 years old and appears adult-like by age 7. The current study, for the first time, links neural activity in children to predefined social features in a narrative movie and suggests social interaction perception is supported by early developing neural responses in the STS. [ABSTRACT FROM AUTHOR]

Interhemispheric anatomical differences have long been thought to be related to language lateralization. Previous studies have explored whether asymmetries in the diffusion characteristics of white matter language tracts are consistent with language lateralization. These studies, typically with smaller cohorts, yielded mixed results. This study investigated whether connectomic analysis of quantitative anisotropy (QA) and shape features of white matter tracts across the whole brain are associated with language lateralization. We analyzed 1,040 healthy individuals (562 females) from the Human Connectome Project database. Hemispheric language dominance for each participant was quantified using a laterality quotient (LQ) derived from fMRI activation in regions of interest (ROIs) associated with a language comprehension task compared against amath task. A linear regression model was used to examine the relationship between structural asymmetry and functional lateralization. Connectometry revealed a significant negative correlation between LQs and QA of corpus callosum tracts, indicating that higher QA in these regions is associated with bilateral and right hemisphere language representation in frontal and temporal regions. Left language laterality in the temporal lobe was significantly associated with longer right inferior fronto-occipital fasciculus (IFOF) and forceps minor tracts. These results suggest that diffusion measures of microstructural architecture as well as geometrical features of reconstructed white matter tracts play a role in language lateralization. People with increased dependence on the right or both frontal hemispheres for language processing may have more developed commissural fibers, which may support more efficient interhemispheric communication. [ABSTRACT FROM AUTHOR]

Area TE is required for normal learning of visual categories based on perceptual similarity. To evaluate whether category learning changes neural activity in area TE, we trained two monkeys (both male) implanted with multielectrode arrays to categorize natural images of cats and dogs. Neural activity during a passive viewing task was compared pre- and post-training. After the category training, the accuracy of abstract category decoding improved. Single units became more category selective, the proportion of single units with category selectivity increased, and units sustained their category-specific responses for longer. Visual category learning thus appears to enhance category separability in area TE by driving changes in the stimulus selectivity of individual neurons and by recruiting more units to the active network. [ABSTRACT FROM AUTHOR]

The human auditory cortex is organized according to the timing and spectral characteristics of speech sounds during speech perception. During listening, the posterior superior temporal gyrus is organized according to onset responses, which segment acoustic boundaries in speech, and sustained responses, which further process phonological content. When we speak, the auditory system is actively processing the sound of our own voice to detect and correct speech errors in real time. This manifests in neural recordings as suppression of auditory responses during speech production compared with perception, but whether this differentially affects the onset and sustained temporal profiles is not known. Here, we investigated this question using intracranial EEG recorded from seventeen pediatric, adolescent, and adult patients with medication-resistant epilepsy while they performed a reading/listening task. We identified onset and sustained responses to speech in the bilateral auditory cortex and observed a selective suppression of onset responses during speech production. We conclude that onset responses provide a temporal landmark during speech perception that is redundant with forward prediction during speech production and are therefore suppressed. Phonological feature tuning in these “onset suppression” electrodes remained stable between perception and production. Notably, auditory onset responses and phonological feature tuning were present in the posterior insula during both speech perception and production, suggesting an anatomically and functionally separate auditory processing zone that we believe to be involved in multisensory integration during speech perception and feedback control. [ABSTRACT FROM AUTHOR]

Goal-directed visual attention is a fundamental cognitive process that enables animals to selectively focus on specific regions of the visual field while filtering out irrelevant information. However, given the domain specificity of social behaviors, it remains unclear whether attention to faces versus nonfaces recruits different neurocognitive processes. In this study, we simultaneously recorded activity from temporal and frontal nodes of the attention network whilemacaques performed a goal-directed visual search task. V4 and inferotemporal (IT) visual category-selective units, selected during cue presentation, discriminated fixations on targets and distractors during the search but were differentially engaged by face and house targets. V4 and IT category-selective units also encoded fixation transitions and search dynamics. Comparedwith distractors, fixations on targets reduced spike--LFP coherence within the temporal cortex. Importantly, targetinduced desynchronization between the temporal and prefrontal cortices was only evident for face targets, suggesting that attention to faces differentially engaged the prefrontal cortex. We further revealed bidirectional theta influence between the temporal and prefrontal cortices using Granger causality, which was again disproportionate for faces. Finally, we showed that the search became more efficient with increasing target-induced desynchronization. Together, our results suggest domain specificity for attending to faces and an intricate interplay between visual attention and social processing neural networks. [ABSTRACT FROM AUTHOR]

Words offer a unique opportunity to separate the processing mechanisms of object subcomponents from those of the whole object, because the phonological or semantic information provided by the word subcomponents (i.e., sublexical information) can conflict with that provided by the whole word (i.e., lexical information). Previous studies have revealed some of the specific brain regions and temporal information involved in sublexical information processing. However, a comprehensive spatiotemporal neural network for sublexical processing remains to be fully elucidated due to the low temporal or spatial resolutions of previous neuroimaging studies. In this study, we recorded stereoelectroencephalography signals with high spatial and temporal resolutions from a large sample of 39 epilepsy patients (both sexes) during a Chinese character oral reading task. We explored the activated brain regions and their connectivity related to three sublexical effects: phonological regularity (whether the whole character's pronunciation aligns with its phonetic radical), phonological consistency (whether characters with the same phonetic radical share the same pronunciation), and semantic transparency (whether the whole character's meaning aligns with its semantic radical). The results revealed that sublexical effects existed in the inferior frontal gyrus, precentral and postcentral gyri, temporal lobe, and middle occipital gyrus. Additionally, connectivity from the middle occipital gyrus to the postcentral gyrus and from postcentral gyrus to the fusiform gyrus was associated with the sublexical effects. These findings provide valuable insights into the spatiotemporal dynamics of sublexical processing and object recognition in the brain. [ABSTRACT FROM AUTHOR]

Estimating the direction of functional connectivity (FC) can help further elucidate complex brain function. However, the estimation of directed FC at the voxel level in fMRI data, and evaluating its performance, has yet to be done. We therefore developed a novel directed seed-based connectivity analysis (SCA) method based on normalized pairwise Granger causality that provides greater detail and accuracy over ROI-based methods. We evaluated its performance against 145 cortical retrograde tracer injections in male and female marmosets that were used as ground truth cellular connectivity on a voxel-by-voxel basis. The receiver operating characteristic (ROC) curve was calculated for each injection, and we achieved area under the ROC curve of 0.95 for undirected and 0.942 for directed SCA in the case of high cell count threshold. This indicates that SCA can reliably estimate the strong cellular connections between voxels in fMRI data. We then used our directed SCA method to analyze the human default mode network (DMN) and found that dlPFC (dorsolateral prefrontal cortex) and temporal lobe were separated from other DMN regions, forming part of the languagenetwork that works together with the core DMN regions. We also found that the cerebellum (Crus I-II) was strongly targeted by the posterior parietal cortices and dlPFC, but reciprocal connections were not observed. Thus, the cerebellum may not be a part of, but instead a target of, the DMN and language-network. Summarily, our novel directed SCA method, visualized with a new functional flat mapping technique, opens a new paradigm for whole-brain functional analysis. [ABSTRACT FROM AUTHOR]

Primates, as social beings, have evolved complex brain mechanisms to navigate intricate social environments. This review explores the neural bases of body perception in both human and nonhuman primates, emphasizing the processing of social signals conveyed by body postures, movements, and interactions. Early studies identified selective neural responses to body stimuli in macaques, particularly within and ventral to the superior temporal sulcus (STS). These regions, known as body patches, represent visual features that are present in bodies but do not appear to be semantic body detectors. They provide information about posture and viewpoint of the body. Recent research using dynamic stimuli has expanded the understanding of the body-selective network, highlighting its complexity and the interplay between static and dynamic processing. In humans, body-selective areas such as the extrastriate body area (EBA) and fusiform body area (FBA) have been implicated in the perception of bodies and their interactions. Moreover, studies on social interactions reveal that regions in the human STS are also tuned to the perception of dyadic interactions, suggesting a specialized social lateral pathway. Computational work developed models of body recognition and social interaction, providing insights into the underlying neural mechanisms. Despite advances, significant gaps remain in understanding the neural mechanisms of body perception and social interaction. Overall, this review underscores the importance of integrating findings across species to comprehensively understand the neural foundations of body perception and the interaction between computational modeling and neural recording. [ABSTRACT FROM AUTHOR]

From a glimpse of a face, people form trait impressions that operate as facial stereotypes, which are largely inaccurate yet nevertheless drive social behavior. Behavioral studies have long pointed to dimensions of trustworthiness and dominance that are thought to underlie face impressions due to their evolutionarily adaptive nature. Using human neuroimaging (N = 26, 19 female, 7 male), we identify a two-dimensional representation of faces' inferred traits in the middle temporal gyrus (MTG), a region involved in domain-general conceptual processing including the activation of social concepts. The similarity of neural-response patterns for any given pair of faces in the bilateral MTG was predicted by their proximity in trustworthiness-dominance space, an effect that could not be explained by mere visual similarity. This MTG trait-space representation occurred automatically, was relatively invariant across participants, and did not depend on the explicit endorsement of face impressions (i.e., beliefs that face impressions are valid and accurate). In contrast, regions involved in high-level social reasoning (the bilateral temporoparietal junction and posterior superior temporal sulcus; TPJ-pSTS) and entity-specific social knowledge (the left anterior temporal lobe; ATL) also exhibited this trait-space representation but only among participants who explicitly endorsed forming these impressions. Together, the findings identify a two-dimensional neural representation of face impressions and suggest that multiple implicit and explicit mechanisms give rise to biases based on facial appearance. While the MTG implicitly represents a multidimensional trait space for faces, the TPJ-pSTS and ATL are involved in the explicit application of this trait space for social evaluation and behavior. [ABSTRACT FROM AUTHOR]

The macaque middle temporal (MT) area is well known for its visual motion selectivity and relevance to motion perception, but the possibility of it also reflecting higher-level cognitive functions has largely been ignored. We tested for effects of task performance distinct from sensory encoding by manipulating subjects' temporal evidence-weighting strategy during a direction discrimination task while performing electrophysiological recordings from groups of MT neurons in rhesus macaques (one male, one female). This revealed multiple components of MT responses that were, surprisingly, not interpretable as behaviorally relevant modulations of motion encoding, or as bottom-up consequences of the readout of motion direction from MT. The time-varying motion-driven responses of MT were strongly affected by our strategic manipulation-but with time courses opposite the subjects' temporal weighting strategies. Furthermore, large choice-correlated signals were represented in population activity distinct from its motion responses, with multiple phases that lagged psychophysical readout and even continued after the stimulus (but which preceded motor responses). In summary, a novel experimental manipulation of strategy allowed us to control the time course of readout to challenge the correlation between sensory responses and choices, and population-level analyses of simultaneously recorded ensembles allowed us to identify strong signals that were so distinct from direction encoding that conventional, single-neuron-centric analyses could not have revealed or properly characterized them. Together, these approaches revealed multiple cognitive contributions to MT responses that are task related but not functionally relevant to encoding or decoding of motion for psychophysical direction discrimination, providing a new perspective on the assumed status of MT as a simple sensory area.SIGNIFICANCE STATEMENT This study extends understanding of the middle temporal (MT) area beyond its representation of visual motion. Combining multineuron recordings, population-level analyses, and controlled manipulation of task strategy, we exposed signals that depended on changes in temporal weighting strategy, but did not manifest as feedforward effects on behavior. This was demonstrated by (1) an inverse relationship between temporal dynamics of behavioral readout and sensory encoding, (2) a choice-correlated signal that always lagged the stimulus time points most correlated with decisions, and (3) a distinct choice-correlated signal after the stimulus. These findings invite re-evaluation of MT for functions outside of its established sensory role and highlight the power of experimenter-controlled changes in temporal strategy, coupled with recording and analysis approaches that transcend the single-neuron perspective.

Decreased neuronal specificity of the brain in response to cognitive demands (i.e., neural dedifferentiation) has been implicated in age-related cognitive decline. Investigations into functional connectivity analogs of these processes have focused primarily on measuring segregation of nonoverlapping networks at rest. Here, we used an edge-centric network approach to derive entropy, a measure of specialization, from spatially overlapping communities during cognitive task fMRI. Using Human Connectome Project Lifespan data (713 participants, 36-100 years old, 55.7% female), we characterized a pattern of nodal despecialization differentially affecting the medial temporal lobe and limbic, visual, and subcortical systems. At the whole-brain level, global entropy moderated declines in fluid cognition across the lifespan and uniquely covaried with age when controlling for the network segregation metric modularity. Importantly, relationships between both metrics (entropy and modularity) and fluid cognition were age dependent, although entropy's relationship with cognition was specific to older adults. These results suggest entropy is a potentially important metric for examining how neurological processes in aging affect functional specialization at the nodal, network, and whole-brain level. [ABSTRACT FROM AUTHOR]

Humans need social closeness to prosper. There is evidence that empathy can induce social closeness. However, it remains unclear how empathy-related social closeness is formed and how stable it is as time passes. We applied an acquisition-extinction paradigm combined with computational modeling and fMRI, to investigate the formation and stability of empathy-related social closeness. Female participants observed painful stimulation of another person with high probability (acquisition) and low probability (extinction) and rated their closeness to that person. The results of two independent studies showed increased social closeness in the acquisition block that resisted extinction in the extinction block. Providing insights into underlying mechanisms, reinforcement learning modeling revealed that the formation of social closeness is based on a learning signal (prediction error) generated from observing another's pain, whereas maintaining social closeness is based on a learning signal generated from observing another's pain relief. The results of a reciprocity control study indicate that this feedback recalibration is specific to learning of empathy-related social closeness. On the neural level, the recalibration of the feedback signal was associated with neural responses in anterior insula and adjacent inferior frontal gyrus and the bilateral superior temporal sulcus/temporoparietal junction. Together, these findings show that empathy-related social closeness generated in bad times, that is, empathy with the misfortune of another person, transfers to good times and thus may form one important basis for stable social relationships. [ABSTRACT FROM AUTHOR]

Humans have the remarkable ability to vividly retrieve sensory details of past events. According to the theory of sensory reinstatement, during remembering, brain regions specialized for processing specific sensory stimuli are reactivated to support content-specific retrieval. Recently, several studies have emphasized transformations in the spatial organization of these reinstated activity patterns. Specifically, studies of scene stimuli suggest a clear anterior shift in the location of retrieval activations compared with the activity observed during perception. However, it is not clear that such transformations occur universally, with inconsistent evidence for other important stimulus categories, particularly faces. One challenge in addressing this question is the careful delineation of face-selective cortices, which are interdigitated with other selective regions, in configurations that spatially differ across individuals. Therefore, we conducted a multisession neuroimaging study to first carefully map individual participants' (nine males and seven females) face-selective regions within ventral temporal cortex (VTC), followed by a second session to examine the activity patterns within these regions during face memory encoding and retrieval. While face-selective regions were expectedly engaged during face perception at encoding, memory retrieval engagement exhibited a more selective and constricted reinstatement pattern within these regions, but did not show any consistent direction of spatial transformation (e.g., anteriorization). We also report on unique human intracranial recordings from VTC under the same experimental conditions. These findings highlight the importance of considering the complex configuration of category-selective cortex in elucidating principles shaping the neural transformations that occur from perception to memory. [ABSTRACT FROM AUTHOR]

The default mode network (DMN) typically deactivates to external tasks, yet supports semantic cognition. It comprises medial temporal (MT), core, and frontotemporal (FT) subsystems, but its functional organization is unclear: the requirement for perceptual coupling versus decoupling, input modality (visual/verbal), type of information (social/spatial), and control demands all potentially affect its recruitment. We examined the effect of these factors on activation and deactivation of DMN subsystems during semantic cognition, across four task-based human functional magnetic resonance imaging (fMRI) datasets, and localized these responses in whole-brain state space defined by gradients of intrinsic connectivity. FT showed activation consistent with a central role across domains, tasks, and modalities, although it was most responsive to abstract, verbal tasks; this subsystem uniquely showed more "tuned" states characterized by increases in both activation and deactivation when semantic retrieval demands were higher. MT also activated to both perceptually coupled (scenes) and decoupled (autobiographical memory) tasks and showed stronger responses to picture associations, consistent with a role in scene construction. Core DMN consistently showed deactivation, especially to externally oriented tasks. These diverse contributions of DMN subsystems to semantic cognition were related to their location on intrinsic connectivity gradients: activation was closer to the sensory-motor cortex than deactivation, particularly for FT and MT, while activation for core DMN was distant from both visual cortex and cognitive control. These results reveal distinctive yet complementary DMN responses: MT and FT support different memory-based representations that are accessed externally and internally, while deactivation in core DMN is associated with demanding, external semantic tasks. [ABSTRACT FROM AUTHOR]

The visual perception of individuals is thought to be mediated by a network of regions in the occipitotemporal cortex that supports specialized processing of faces, bodies, and actions. In comparison, we know relatively little about the neural mechanisms that support the perception of multiple individuals and the interactions between them. The present study sought to elucidate the visual processing of social interactions by identifying which regions of the social perception network represent interpersonal synchrony. In an fMRI study with 32 human participants (26 female, 6 male), we used multivoxel pattern analysis to investigate whether activity in face-selective, body-selective, and interaction-sensitive regions across the social perception network supports the decoding of synchronous versus asynchronous head-nodding and head-shaking. Several regions were found to support significant decoding of synchrony/asynchrony, including extrastriate body area (EBA), face-selective and interaction-sensitive mid/posterior right superior temporal sulcus, and occipital face area. We also saw robust cross-classification across actions in the EBA, suggestive of movement-invariant representations of synchrony/asynchrony. Exploratory whole-brain analyses also identified a region of the right fusiform cortex that responded more strongly to synchronous than to asynchronous motion. Critically, perceiving interpersonal synchrony/asynchrony requires the simultaneous extraction and integration of dynamic information from more than one person. Hence, the representation of synchrony/asynchrony cannot be attributed to augmented or additive processing of individual actors. Our findings therefore provide important new evidence that social interactions recruit dedicated visual processing within the social perception network that extends beyond that engaged by the faces and bodies of the constituent individuals. [ABSTRACT FROM AUTHOR]

Human neuroimaging studies of episodic memory retrieval routinely observe the engagement of specific cortical regions beyond the medial temporal lobe. Of these, medial parietal cortex (MPC) is of particular interest given its distinct functional characteristics during different retrieval tasks. Specifically, while recognition and autobiographical recall tasks are both used to probe episodic retrieval, these paradigms consistently drive distinct spatial patterns of response within MPC. However, other studies have emphasized alternate MPC functional dissociations in terms of brain network connectivity profiles or stimulus category selectivity. As the unique contributions of MPC to episodic memory remain unclear, adjudicating between these different accounts can provide better consensus regarding MPC function. Therefore, we used a precision-neuroimaging dataset (7T functional magnetic resonance imaging) to examine how MPC regions are differentially engaged during recognition memory and how these task-related dissociations may also reflect distinct connectivity and stimulus category functional profiles. We observed interleaved, though spatially distinct, subregions of MPC where responses were sensitive to either recognition decisions or the semantic representation of stimuli. In addition, this dissociation was further accentuated by functional subregions displaying distinct profiles of connectivity with the hippocampus during task and rest. Finally, we show that recent observations of dissociable person and place selectivity within the MPC reflect category-specific responses from within identified semantic regions that are sensitive to mnemonic demands. Together, by examining precision functional mapping within individuals, these data suggest that previously distinct observations of functional dissociation within MPC conform to a common principle of organization throughout hippocampal–neocortical memory systems. [ABSTRACT FROM AUTHOR]

The human medial temporal lobe (MTL) plays a crucial role in recognizing visual objects, a key cognitive function that relies on the formation of semantic representations. Nonetheless, it remains unknown how visual information of general objects is translated into semantic representations in the MTL. Furthermore, the debate about whether the human MTL is involved in perception has endured for a long time. To address these questions, we investigated three distinct models of neural object coding--semantic coding, axisbased feature coding, and region-based feature coding--in each subregion of the human MTL, using high-resolution fMRI in two male and six female participants. Our findings revealed the presence of semantic coding throughout the MTL, with a higher prevalence observed in the parahippocampal cortex (PHC) and perirhinal cortex (PRC), while axis coding and region coding were primarily observed in the earlier regions of the MTL. Moreover, we demonstrated that voxels exhibiting axis coding supported the transition to region coding and contained information relevant to semantic coding. Together, by providing a detailed characterization of neural object coding schemes and offering a comprehensive summary of visual coding information for each MTL subregion, our results not only emphasize a clear role of the MTL in perceptual processing but also shed light on the translation of perceptiondriven representations of visual features into memory-driven representations of semantics along the MTL processing pathway. [ABSTRACT FROM AUTHOR]

The nervous system is under tight energy constraints and must represent information efficiently. This is particularly relevant in the dorsal part of the medial superior temporal area (MSTd) in primates where neurons encode complex motion patterns to support a variety of behaviors. A sparse decomposition model based on a dimensionality reduction principle known as non-negative matrix factorization (NMF) was previously shown to account for a wide range of monkey MSTd visual response properties. This model resulted in sparse, parts-based representations that could be regarded as basis flow fields, a linear superposition of which accurately reconstructed the input stimuli. This model provided evidence that the seemingly complex response properties of MSTd may be a by-product of MSTd neurons performing dimensionality reduction on their input. However, an open question is how a neural circuit could carry out this function. In the current study, we propose a spiking neural network (SNN) model of MSTd based on evolved spike-timing-dependent plasticity and homeostatic synaptic scaling (STDP-H) learning rules. We demonstrate that the SNN model learns compressed and efficient representations of the input patterns similar to the patterns that emerge from NMF, resulting in MSTd-like receptive fields observed in monkeys. This SNN model suggests that STDP-H observed in the nervous system may be performing a similar function as NMF with sparsity constraints, which provides a test bed for mechanistic theories of how MSTd may efficiently encode complex patterns of visual motion to support robust self-motion perception.SIGNIFICANCE STATEMENT The brain may use dimensionality reduction and sparse coding to efficiently represent stimuli under metabolic constraints. Neurons in monkey area MSTd respond to complex optic flow patterns resulting from self-motion. We developed a spiking neural network model that showed MSTd-like response properties can emerge from evolving spike-timing-dependent plasticity with STDP-H parameters of the connections between then middle temporal area and MSTd. Simulated MSTd neurons formed a sparse, reduced population code capable of encoding perceptual variables important for self-motion perception. This model demonstrates that complex neuronal responses observed in MSTd may emerge from efficient coding and suggests that neurobiological plasticity, like STDP-H, may contribute to reducing the dimensions of input stimuli and allowing spiking neurons to learn sparse representations.

A correction to an article "Menopause status and within-group differences in chronological age affect the functional neural correlates of spatial context memory in middle-aged females" is presented in February 20, 2024 issue.

Direct human brain recordings have confirmed the presence of high-frequency oscillatory events, termed ripples, during awake behavior. While many prior studies have focused on medial temporal lobe (MTL) ripples during memory retrieval, here we investigate ripples during memory encoding. Specifically, we ask whether ripples during encoding predict whether and how memories are subsequently recalled. Detecting ripples from MTL electrodes implanted in 116 neurosurgical participants (n = 61 male) performing a verbal episodic memory task, we find that encoding ripples do not distinguish recalled from not recalled items in any MTL region, even as high-frequency activity during encoding predicts recall in these same regions. Instead, hippocampal ripples increase during encoding of items that subsequently lead to recall of temporally and semantically associated items during retrieval, a phenomenon known as clustering. This subsequent clustering effect arises specifically when hippocampal ripples co-occur during encoding and retrieval, suggesting that ripples mediate both encoding and reinstatement of episodic memories. [ABSTRACT FROM AUTHOR]

Humor comprehension (i.e., getting a joke) and humor appreciation (i.e., enjoying a joke) are distinct, cognitively complex processes. Functional magnetic resonance imaging (fMRI) investigations have identified several key cortical regions but have overlooked subcortical structures that have theoretical importance in humor processing. The dorsal striatum (DS) contributes to working memory, ambiguity processing, and cognitive flexibility, cognitive functions that are required to accurately recognize humorous stimuli. The ventral striatum (VS) is critical in reward processing and enjoyment. We hypothesized that the DS and VS play important roles in humor comprehension and appreciation, respectively. We investigated the engagement of these regions in these distinct processes using fMRI. Twenty-six healthy young male and female human adults completed two humor-elicitation tasks during a 3 tesla fMRI scan consisting of a traditional behavior-based joke task and a naturalistic audiovisual sitcom paradigm (i.e., Seinfeld viewing task). Across both humor-elicitation methods, whole-brain analyses revealed cortical activation in the inferior frontal gyrus, the middle frontal gyrus, and the middle temporal gyrus for humor comprehension, and the temporal cortex for humor appreciation. Additionally, with region of interest analyses, we specifically examined whether DS and VS activation correlated with these processes. Across both tasks, we demonstrated that humor comprehension implicates both the DS and the VS, whereas humor appreciation only engages the VS. These results establish the role of the DS in humor comprehension, which has been previously overlooked, and emphasize the role of the VS in humor processing more generally. [ABSTRACT FROM AUTHOR]

α7 nicotinic acetylcholine receptors (nAChRs) are widely expressed in the brain where they promote fast cholinergic synaptic transmission and serve important neuromodulatory functions. However, their high permeability to Ca2+ also predisposes them to contribute to disease states. Here, using transfected HEK-tsa cells and primary cultured hippocampal neurons from male and female rats, we demonstrate that two proteins called Ly6h and NACHO compete for access to α7 subunits, operating together but in opposition to maintain α7 assembly and activity within a narrow range that is optimal for neuronal function and viability. Using mixed gender human temporal cortex and cultured hippocampal neurons from rats we further show that this balance is perturbed during Alzheimers disease (AD) because of amyloid β (Aβ)-driven reduction in Ly6h, with severe reduction leading to increased phosphorylated tau and α7-mediated neurotoxicity. Ly6h release into human CSF is also correlated with AD severity. Thus, Ly6h links cholinergic signaling, Aβ and phosphorylated tau and may serve as a novel marker for AD progression.SIGNIFICANCE STATEMENT One of the earliest and most persistent hypotheses regarding Alzheimers disease (AD) attributes cognitive impairment to loss of cholinergic signaling. More recently, interest has focused on crucial roles for amyloid β (Aβ) and phosphorylated tau in Alzheimers pathogenesis. Here, we demonstrate that these elements are linked by Ly6h and its counterpart, NACHO, functioning in opposition to maintain assembly of nicotinic acetylcholine receptors (nAChRs) within the physiological range. Our data suggests that Aβ shifts the balance away from Ly6h and toward NACHO, resulting in increased assembly of Ca2+-permeable nAChRs and thus a conversion of basal cholinergic to neurotoxic signaling.

Tau deposition begins in the medial temporal lobe (MTL) in aging and Alzheimer's disease (AD), and MTL neural dysfunction is commonly observed in these groups. However, the association between tau and MTL neural activity has not been fully characterized. We investigated the effects of tau on repetition suppression, the reduction of activity for repeated stimulus presentations compared to novel stimuli. We used task-based functional MRI (fMRI) to assess MTL subregional activity in 21 young adults (YA) and 45 cognitively normal human older adults (OA; total sample: 37 females, 29 males). AD pathology was measured with position emission tomography (PET), using 18F-Flortaucipir for tau and 11C-Pittsburgh compound B (PiB) for amyloid-β (Aβ). The MTL was segmented into six subregions using high-resolution structural images. We compared the effects of low tau pathology, restricted to entorhinal cortex and hippocampus (Tau- OA), to high tau pathology, also occurring in temporal and limbic regions (Tau+ OA). Low levels of tau (Tau- OA vs YA) were associated with reduced repetition suppression activity specifically in anterolateral entorhinal cortex (alEC) and hippocampus, the first regions to accumulate tau. High tau pathology (Tau+ vs Tau- OA) was associated with widespread reductions in repetition suppression across MTL. Further analyses indicated that reduced repetition suppression was driven by hyperactivity to repeated stimuli, rather than decreased activity to novel stimuli. Increased activation was associated with entorhinal tau, but not Aβ. These findings reveal a link between tau deposition and neural dysfunction in MTL, in which tau-related hyperactivity prevents deactivation to repeated stimuli, leading to reduced repetition suppression.SIGNIFICANCE STATEMENT Abnormal neural activity occurs in the medial temporal lobe (MTL) in aging and Alzheimer's disease (AD). Because tau pathology first deposits in the MTL in aging, this altered activity may be due to local tau pathology, and distinct MTL subregions may be differentially vulnerable. We demonstrate that in older adults (OAs) with low tau pathology, there are focal alterations in activity in MTL subregions that first develop tau pathology, while OAs with high tau pathology have aberrant activity throughout MTL. Tau was associated with hyperactivity to repeated stimulus presentations, leading to reduced repetition suppression, the discrimination between novel and repeated stimuli. Our data suggest that tau deposition is related to abnormal activity in MTL before the onset of cognitive decline.

Seeing social touch triggers a strong social-affective response that involves multiple brain networks, including visual, social perceptual, and somatosensory systems. Previous studies have identified the specific functional role of each system, but little is known about the speed and directionality of the information flow. Is this information extracted via the social perceptual system or from simulation from somatosensory cortex? To address this, we examined the spatiotemporal neural processing of observed touch. Twenty-one human participants (seven males) watched 500-ms video clips showing social and nonsocial touch during electroencephalogram (EEG) recording. Visual and social-affective features were rapidly extracted in the brain, beginning at 90 and 150 ms after video onset, respectively. Combining the EEG data with functional magnetic resonance imaging (fMRI) data from our prior study with the same stimuli reveals that neural information first arises in early visual cortex (EVC), then in the temporoparietal junction and posterior superior temporal sulcus (TPJ/pSTS), and finally in the somatosensory cortex. EVC and TPJ/pSTS uniquely explain EEG neural patterns, while somatosensory cortex does not contribute to EEG patterns alone, suggesting that social-affective information may flow from TPJ/pSTS to somatosensory cortex. Together, these findings show that social touch is processed quickly, within the timeframe of feedforward visual processes, and that the social-affective meaning of touch is first extracted by a social perceptual pathway. Such rapid processing of social touch may be vital to its effective use during social interaction. [ABSTRACT FROM AUTHOR]

Infant stimuli elicit widespread neural and behavioral response in human adults, and such massive allocation of resources attests to the evolutionary significance of the primary attachment. Here, we examined whether attachment reminders also trigger cross-brain concordance and generate greater neural uniformity, as indicated by intersubject correlation. Human mothers were imaged twice in oxytocin/placebo administration design, and stimuli included four ecological videos of a standard unfamiliar mother and infant: two infant/mother alone (Alone) and two mother-infant dyadic contexts (Social). Theory-driven analysis measured cross-brain synchrony in preregistered nodes of the parental caregiving network (PCN), which integrates subcortical structures underpinning mammalian mothering with cortical areas implicated in simulation, mentalization, and emotion regulation, and data-driven analysis assessed brain-wide concordance using whole-brain parcellation. Results demonstrated widespread cross-brain synchrony in both the PCN and across the neuroaxis, from primary sensory/somatosensory areas, through insular-cingulate regions, to temporal and prefrontal cortices. The Social context yielded significantly more cross-brain concordance, with PCNs striatum, parahippocampal gyrus, superior temporal sulcus, ACC, and PFC displaying cross-brain synchrony only to mother-infant social cues. Moment-by-moment fluctuations in mother-infant social synchrony, ranging from episodes of low synchrony to tightly coordinated positive bouts, were tracked online by cross-brain concordance in the preregistered ACC. Findings indicate that social attachment stimuli, representing evolutionary-salient universal cues that require no verbal narrative, trigger substantial interbrain concordance and suggest that the mother-infant bond, an icon standing at the heart of human civilization, may function to glue brains into a unified experience and bind humans into social groups. [ABSTRACT FROM AUTHOR]

It has been postulated that the brain is organized by “metamodal,” sensory-independent cortical modules capable of performing tasks (e.g., word recognition) in both “standard” and novel sensory modalities. Still, this theory has primarily been tested in sensory-deprived individuals, with mixed evidence in neurotypical subjects, thereby limiting its support as a general principle of brain organization. Critically, current theories of metamodal processing do not specify requirements for successful metamodal processing at the level of neural representations. Specification at this level may be particularly important in neurotypical individuals, where novel sensory modalities must interface with existing representations for the standard sense. Here we hypothesized that effective metamodal engagement of a cortical area requires congruence between stimulus representations in the standard and novel sensory modalities in that region. To test this, we first used fMRI to identify bilateral auditory speech representations. We then trained 20 human participants (12 female) to recognize vibrotactile versions of auditory words using one of two auditory-to-vibrotactile algorithms. The vocoded algorithm attempted to match the encoding scheme of auditory speech while the token-based algorithm did not. Crucially, using fMRI, we found that only in the vocoded group did trained-vibrotactile stimuli recruit speech representations in the superior temporal gyrus and lead to increased coupling between them and somatosensory areas. Our results advance our understanding of brain organization by providing new insight into unlocking the metamodal potential of the brain, thereby benefitting the design of novel sensory substitution devices that aim to tap into existing processing streams in the brain. [ABSTRACT FROM AUTHOR]

Microstimulation can modulate the activity of individual neurons to affect behavior, but the effects of stimulation on neuronal spiking are complex and remain poorly understood. This is especially challenging in the human brain where the response properties of individual neurons are sparse and heterogeneous. Here we use microelectrode arrays in the human anterior temporal lobe in 6 participants (3 female) to examine the spiking responses of individual neurons to microstimulation delivered through multiple distinct stimulation sites. We demonstrate that individual neurons can be driven with excitation or inhibition using different stimulation sites, which suggests an approach for providing direct control of spiking activity at the single-neuron level. Spiking responses are inhibitory in neurons that are close to the site of stimulation, while excitatory responses are more spatially distributed. Together, our data demonstrate that spiking responses of individual neurons can be reliably identified and manipulated in the human cortex. [ABSTRACT FROM AUTHOR]

The human ventral temporal cortex (VTC) is highly connected to integrate visual perceptual inputs with feedback from cognitive and emotional networks. In this study, we used electrical brain stimulation to understand how different inputs from multiple brain regions drive unique electrophysiological responses in the VTC. We recorded intracranial EEG data in 5 patients (3 female) implanted with intracranial electrodes for epilepsy surgery evaluation. Pairs of electrodes were stimulated with single-pulse electrical stimulation, and corticocortical evoked potential responses were measured at electrodes in the collateral sulcus and lateral occipitotemporal sulcus of the VTC. Using a novel unsupervised machine learning method, we uncovered 2-4 distinct response shapes, termed basis profile curves (BPCs), at each measurement electrode in the 11-500 ms after stimulation interval. Corticocortical evoked potentials of unique shape and high amplitude were elicited following stimulation of several regions and classified into a set of four consensus BPCs across subjects. One of the consensus BPCs was primarily elicited by stimulation of the hippocampus; another by stimulation of the amygdala; a third by stimulation of lateral cortical sites, such as the middle temporal gyrus; and the final one by stimulation of multiple distributed sites. Stimulation also produced sustained high-frequency power decreases and low-frequency power increases that spanned multiple BPC categories. Characterizing distinct shapes in stimulation responses provides a novel description of connectivity to the VTC and reveals significant differences in input from cortical and limbic structures. [ABSTRACT FROM AUTHOR]

Heading perception in primates depends heavily on visual optic-flow cues. Yet during self-motion, heading percepts remain stable, even though smooth-pursuit eye movements often distort optic flow. According to theoretical work, self-motion can be represented accurately by compensating for these distortions in two ways: via retinal mechanisms or via extraretinal efference-copy signals, which predict the sensory consequences of movement. Psychophysical evidence strongly supports the efference-copy hypothesis, but physiological evidence remains inconclusive. Neurons that signal the true heading direction during pursuit are found in visual areas of monkey cortex, including the dorsal medial superior temporal area (MSTd). Here we measured heading tuning in MSTd using a novel stimulus paradigm, in which we stabilize the optic-flow stimulus on the retina during pursuit. This approach isolates the effects on neuronal heading preferences of extraretinal signals, which remain active while the retinal stimulus is prevented from changing. Our results from 3 female monkeys demonstrate a significant but small influence of extraretinal signals on the preferred heading directions of MSTd neurons. Under our stimulus conditions, which are rich in retinal cues, we find that retinal mechanisms dominate physiological corrections for pursuit eye movements, suggesting that extraretinal cues, such as predictive efference-copy mechanisms, have a limited role under naturalistic conditions.SIGNIFICANCE STATEMENT Sensory systems discount stimulation caused by an animal's own behavior. For example, eye movements cause irrelevant retinal signals that could interfere with motion perception. The visual system compensates for such self-generated motion, but how this happens is unclear. Two theoretical possibilities are a purely visual calculation or one using an internal signal of eye movements to compensate for their effects. The latter can be isolated by experimentally stabilizing the image on a moving retina, but this approach has never been adopted to study motion physiology. Using this method, we find that extraretinal signals have little influence on activity in visual cortex, whereas visually based corrections for ongoing eye movements have stronger effects and are likely most important under real-world conditions.

During rest, intrinsic neural dynamics manifest at multiple timescales, which progressively increase along visual and somatosensory hierarchies. Theoretically, intrinsic timescales are thought to facilitate processing of external stimuli at multiple stages. However, direct links between timescales at rest and sensory processing, as well as translation to the auditory system are lacking. Here, we measured intracranial EEG in 11 human patients with epilepsy (4 women), while listening to pure tones. We show that, in the auditory network, intrinsic neural timescales progressively increase, while the spectral exponent flattens, from temporal to entorhinal cortex, hippocampus, and amygdala. Within the neocortex, intrinsic timescales exhibit spatial gradients that follow the temporal lobe anatomy. Crucially, intrinsic timescales at baseline can explain the latency of auditory responses: as intrinsic timescales increase, so do the single-electrode response onset and peak latencies. Our results suggest that the human auditory network exhibits a repertoire of intrinsic neural dynamics, which manifest in cortical gradients with millimeter resolution and may provide a variety of temporal windows to support auditory processing. [ABSTRACT FROM AUTHOR]

Rapidly recognizing and understanding others' social interactions is an important ability that relies on deciphering multiple sources of information, for example, perceiving body information and inferring others' intentions. Despite recent advances in characterizing the brain basis of this ability in adults, its developmental underpinnings are virtually unknown. Here, we used fMRI to investigate which sources of social information support superior temporal sulcus responses to interactive biological motion (i.e., 2 interacting point-light human figures) at different developmental intervals in human participants (of either sex): Children show supportive functional connectivity with key nodes of the mentalizing network, while adults show stronger reliance on regions associated with body- and dynamic social interaction/biological motion processing. We suggest that adults use efficient action-intention understanding via body and biological motion information, while children show a stronger reliance on hidden mental state inferences as a potential means of learning to better understand others' interactive behavior. [ABSTRACT FROM AUTHOR]

Distinct lines of research in both humans and animals point to a specific role of the hippocampus in both spatial and episodic memory function. The discovery of concept cells in the hippocampus and surrounding medial temporal lobe (MTL) regions suggests that the MTL maps physical and semantic spaces with a similar neural architecture. Here, we studied the emergence of such maps using MTL microwire recordings from 20 patients (9 female, 11 male) navigating a virtual environment featuring salient landmarks with established semantic meaning. We present several key findings. The array of local field potentials in the MTL contains sufficient information for above-chance decoding of subjects' instantaneous location in the environment. Closer examination revealed that as subjects gain experience with the environment the field potentials come to represent both the subjects' locations in virtual space and in high-dimensional semantic space. Similarly, we observe a learning effect on temporal sequence coding. Over time, field potentials come to represent future locations, even after controlling for spatial proximity. This predictive coding of future states, more so than the strength of spatial representations per se, is linked to variability in subjects' navigation performance. Our results thus support the conceptualization of the MTL as a memory space, representing both spatial- and nonspatial information to plan future actions and predict their outcomes. [ABSTRACT FROM AUTHOR]

Electrical stimulation of the medial temporal lobe (MTL) has the potential to uncover causal circuit mechanisms underlying memory function. However, little is known about how MTL stimulation alters information flow with frontoparietal cortical regions implicated in episodic memory. We used intracranial EEG recordings from humans (14 participants, 10 females) to investigate how MTL stimulation alters directed information flow between MTL and PFC and between MTL and posterior parietal cortex (PPC). Participants performed a verbal episodic memory task during which they were presented with words and asked to recall them after a delay of;20 s; 50 Hz stimulation was applied to MTL electrodes on selected trials during memory encoding. Directed information flow was examined using phase transfer entropy. Behaviorally, we observed that MTL stimulation reduced memory recall. MTL stimulation decreased top-down PFC→MTL directed information flow during both memory encoding and subsequent memory recall, revealing aftereffects more than 20 s after end of stimulation. Stimulation suppressed top-down PFC→MTL influences to a greater extent than PPC→MTL. Finally, MTL→PFC information flow on stimulation trials was significantly lower for successful, compared with unsuccessful, memory recall; in contrast, MTL→ventral PPC information flow was higher for successful, compared with unsuccessful, memory recall. Together, these results demonstrate that the effects of MTL stimulation are behaviorally, regionally, and directionally specific, that MTL stimulation selectively impairs directional signaling with PFC, and that causal MTL-ventral PPC circuits support successful memory recall. Findings provide new insights into dynamic casual circuits underling episodic memory and their modulation by MTL stimulation. [ABSTRACT FROM AUTHOR]

Numerosity, the set size of a group of items, helps guide human and animals' behavior and decisions. Numerosity perception is thought to be a precursor of symbolic numerical cognition. Previously, we uncovered neural populations selectively tuned to numerosities organized in a network of topographic maps in human association cortex. Here we investigate whether these numerosity maps are also involved in the processing of symbolic numbers, using 7T fMRI and a number-detection task. We recruited 7 participants (3 females) and found that the numerosity map at the temporal-occipital cortex (NTO) also responds to symbolic numbers. Furthermore, we found that numerosity-tuned neuronal populations at the NTO map in the left hemisphere are tuned to symbolic numbers. These results reveal different functions of the numerosity maps and support a link between numerosity representation and symbolic number processing in the ventral temporal-occipital cortex. [ABSTRACT FROM AUTHOR]

This study examined the effect of danger on consolidation of neutral information in two regions of the rat (male and female) medial temporal lobe: the perirhinal cortex (PRh) and basolateral amygdala complex (BLA). The neutral information was the association that forms between an auditory stimulus and a visual stimulus (labeled S2 and S1) across their pairings in sensory preconditioning. We show that, when the sensory preconditioning session is followed by a shocked context exposure, the danger shifts consolidation of the S2-S1 association from the PRh to the BLA; and does so by interacting with processes involved in encoding of the S2-S1 pairings. Specifically, we show that the initial S2-S1 pairing in sensory preconditioning is encoded in the BLA and not the PRh; whereas the later S2-S1 pairings are encoded in the PRh and not the BLA. When the sensory preconditioning session is followed by a context alone exposure, the BLA-dependent trace of the early S2-S1 pairings decays and the PRhdependent trace of the later S2-S1 pairings is consolidated in memory. However, when the sensory preconditioning session is followed by a shocked context exposure, the PRh-dependent trace of the later S2-S1 pairings is suppressed and the BLAdependent trace of the initial S2-S1 pairing is consolidated in memory. These findings are discussed with respect to mutually inhibitory interactions between the PRh and BLA, and the way that these regions support memory in other protocols, including recognition memory in people. [ABSTRACT FROM AUTHOR]

The hierarchically organized structures of the medial temporal lobe are critically important for episodic memory function. Accumulating evidence suggests dissociable information processing pathways are maintained throughout these structures including in the medial and lateral entorhinal cortex. Cortical layers provide an additional dimension of dissociation as the primary input to the hippocampus derives from layer 2 neurons in the entorhinal cortex, whereas the deeper layers primarily receive output from the hippocampus. Here, novel high-resolution T2-prepared functional MRI methods were successfully used to mitigate susceptibility artifacts typically affecting MRI signals in this region providing uniform sensitivity across the medial and lateral entorhinal cortex. During the performance of a memory task, healthy human subjects (age 25-33 years, mean age 28.2 ± 3.3 years, 4 female) showed differential functional activation in the superficial and deep layers of the entorhinal cortex associated with task-related encoding and retrieval conditions, respectively. The methods provided here offer an approach to probe layer-specific activation in normal cognition and conditions contributing to memory impairment. [ABSTRACT FROM AUTHOR]

Body ownership and the sense of agency are two central aspects of bodily self-consciousness. While multiple neuroimaging studies have investigated the neural correlates of body ownership and agency separately, few studies have investigated the relationship between these two aspects during voluntary movement when such experiences naturally combine. By eliciting the moving rubber hand illusion with active or passive finger movements during functional magnetic resonance imaging, we isolated activations reflecting the sense of body ownership and agency, respectively, as well as their interaction, and assessed their overlap and anatomic segregation. We found that perceived hand ownership was associated with activity in premotor, posterior parietal, and cerebellar regions, whereas the sense of agency over the movements of the hand was related to activity in the dorsal premotor cortex and superior temporal cortex. Moreover, one section of the dorsal premotor cortex showed overlapping activity for ownership and agency, and somatosensory cortical activity reflected the interaction of ownership and agency with higher activity when both agency and ownership were experienced. We further found that activations previously attributed to agency in the left insular cortex and right temporoparietal junction reflected the synchrony or asynchrony of visuoproprioceptive stimuli rather than agency. Collectively, these results reveal the neural bases of agency and ownership during voluntary movement. Although the neural representations of these two experiences are largely distinct, there are interactions and functional neuroanatomical overlap during their combination, which has bearing on theories on bodily selfconsciousness. [ABSTRACT FROM AUTHOR]

The default mode network (DMN) supports memory functioning and may be sensitive to preclinical Alzheimer's pathology. Little is known, however, about the longitudinal trajectory of this network's intrinsic functional connectivity (FC). In this study, we evaluated longitudinal FC in 111 cognitively normal older human adults (ages 49-87, 46 women/65 men), 92 of whom had at least three task-free fMRI scans (n = 353 total scans). Whole-brain FC and three DMN subnetworks were assessed: (1) within-DMN, (2) between anterior and posterior DMN, and (3) between medial temporal lobe network and posterior DMN. Linear mixed-effects models demonstrated significant baseline age × time interactions, indicating a nonlinear trajectory. There was a trend toward increasing FC between ages 50-66 and significantly accelerating declines after age 74. A similar interaction was observed for whole-brain FC. APOE status did not predict baseline connectivity or change in connectivity. After adjusting for network volume, changes in within-DMN connectivity were specifically associated with changes in episodic memory and processing speed but not working memory or executive functions. The relationship with processing speed was attenuated after covarying for white matter hyperintensities (WMH) and whole-brain FC, whereas within-DMN connectivity remained associated with memory above and beyond WMH and whole-brain FC. Whole-brain and DMN FC exhibit a nonlinear trajectory, with more rapid declines in older age and possibly increases in connectivity early in the aging process. Within-DMN connectivity is a marker of episodic memory performance even among cognitively healthy older adults.SIGNIFICANCE STATEMENT Default mode network and whole-brain connectivity, measured using task-free fMRI, changed nonlinearly as a function of age, with some suggestion of early increases in connectivity. For the first time, longitudinal changes in DMN connectivity were shown to correlate with changes in episodic memory, whereas volume changes in relevant brain regions did not. This relationship was not accounted for by white matter hyperintensities or mean whole-brain connectivity. Functional connectivity may be an early biomarker of changes in aging but should be used with caution given its nonmonotonic nature, which could complicate interpretation. Future studies investigating longitudinal network changes should consider whole-brain changes in connectivity.

The human action observation network (AON) encompasses brain areas consistently engaged when we observe other’s actions. Although the core nodes of the AON are present from childhood, it is not known to what extent they are sensitive to different action features during development. Because social cognitive abilities continue to mature during adolescence, the AON response to socially-oriented actions, but not to object-related actions, may differ in adolescents and adults. To test this hypothesis, we scanned with functional magnetic resonance imaging (fMRI) male and female typically-developing teenagers (n = 28; 13 females) and adults (n = 25; 14 females) while they passively watched videos of manual actions varying along two dimensions: sociality (i.e., directed toward another person or not) and transitivity (i.e., involving an object or not). We found that action observation recruited the same fronto-parietal and occipito-temporal regions in adults and adolescents. The modulation of voxel-wise activity according to the social or transitive nature of the action was similar in both groups of participants. Multivariate pattern analysis, however, revealed that decoding accuracies in intraparietal sulcus (IPS)/superior parietal lobe (SPL) for both sociality and transitivity were lower for adolescents compared with adults. In addition, in the lateral occipital temporal cortex (LOTC), generalization of decoding across the orthogonal dimension was lower for sociality only in adolescents. These findings indicate that the representation of the content of others’ actions, and in particular their social dimension, in the adolescent AON is still not as robust as in adults. [ABSTRACT FROM AUTHOR]

The article explores the neural distinctions between actual tool use and pantomime, suggesting that these actions engage different cognitive processes and neural networks. It states that by using neuroimaging techniques and multivoxel pattern analyses, researchers demonstrate distinct activation patterns in brain areas associated with motor planning and execution.

Temporal lobe epilepsy is common, but mechanisms of seizure initiation are unclear. We evaluated seizure initiation in female and male rats that had been systemically treated with pilocarpine, a widely used model of temporal lobe epilepsy. Local field potential (LFP) recordings from many brain regions revealed variable sites of earliest recorded seizure activity, but mostly the ventral hippocampal formation. To test whether inactivation of the ventral hippocampal formation would reduce seizures, mini-osmotic pumps were used to continually and focally deliver TTX. High doses of TTX infused unilaterally into the ventral hippocampal formation blocked seizures reversibly but also reduced LFP amplitudes in remote brain regions, indicating distant effects. A lower dose did not reduce LFP amplitudes in remote brain regions but did not reduce seizures when infused unilaterally. Instead, seizures tended to initiate in the contralateral ventral hippocampal formation. Bilateral infusion of the lower dose into the ventral hippocampal formation reduced seizure frequency 85%. Similar bilateral treatment in the amygdala was not effective. Bilateral infusion of the dorsal hippocampus reduced seizure frequency, but only 17%. Together, these findings reveal that the ventral hippocampal formation is a primary bilaterally independent epileptogenic zone, and the dorsal hippocampus is a secondary epileptogenic zone in pilocarpine-treated rats. This is consistent with many human patients, and the results further validate the LFP method for identifying seizure onset zones. Finally, the findings are more consistent with a focal mechanism of ictogenesis rather than one involving a network of interdependent nodes. [ABSTRACT FROM AUTHOR]

Neuroimaging, neuropsychological, and psychophysical evidence indicate that concept retrieval selectively engages specific sensory and motor brain systems involved in the acquisition of the retrieved concept. However, it remains unclear which supramodal cortical regions contribute to this process and what kind of information they represent. Here, we used representational similarity analysis of two large fMRI datasets with a searchlight approach to generate a detailed map of human brain regions where the semantic similarity structure across individual lexical concepts can be reliably detected. We hypothesized that heteromodal cortical areas typically associated with the default mode network encode multimodal experiential information about concepts, consistent with their proposed role as cortical integration hubs. In two studies involving different sets of concepts and different participants (both sexes), we found a distributed, bihemispheric network engaged in concept representation, composed of high-level association areas in the anterior, lateral, and ventral temporal lobe; inferior parietal lobule; posterior cingulate gyrus and precuneus; and medial, dorsal, ventrolateral, and orbital prefrontal cortex. In both studies, a multimodal model combining sensory, motor, affective, and other types of experiential information explained significant variance in the neural similarity structure observed in these regions that was not explained by unimodal experiential models or by distributional semantics (i.e., word2vec similarity). These results indicate that during concept retrieval, lexical concepts are represented across a vast expanse of high-level cortical regions, especially in the areas that make up the default mode network, and that these regions encode multimodal experiential information. [ABSTRACT FROM AUTHOR]

Normal aging is associated with a decline in episodic memory and also with aggregation of the β-amyloid (Aβ) and tau proteins and atrophy of medial temporal lobe (MTL) structures crucial to memory formation. Although some evidence suggests that Aβ is associated with aberrant neural activity, the relationships among these two aggregated proteins, neural function, and brain structure are poorly understood. Using in vivo human Aβ and tau imaging, we demonstrate that increased Aβ and tau are both associated with aberrant fMRI activity in the MTL during memory encoding in cognitively normal older adults. This pathological neural activity was in turn associated with worse memory performance and atrophy within the MTL. A mediation analysis revealed that the relationship with regional atrophy was explained by MTL tau. These findings broaden the concept of cognitive aging to include evidence of Alzheimer's disease-related protein aggregation as an underlying mechanism of age-related memory impairment.SIGNIFICANCE STATEMENT Alterations in episodic memory and the accumulation of Alzheimer's pathology are common in cognitively normal older adults. However, evidence of pathological effects on episodic memory has largely been limited to β-amyloid (Aβ). Because Aβ and tau often cooccur in older adults, previous research offers an incomplete understanding of the relationship between pathology and episodic memory. With the recent development of in vivo tau PET radiotracers, we show that Aβ and tau are associated with different aspects of memory encoding, leading to aberrant neural activity that is behaviorally detrimental. In addition, our results provide evidence linking Aβ- and tau-associated neural dysfunction to brain atrophy.

The Journal of Neuroscience published an article titled "New Myelination and Remyelination Molecular Insights" by Siying Cui et al. The study focused on the role of zinc-finger protein ZFP488 in regulating myelination and remyelination in the central nervous system. The researchers found that ZFP488 loss disrupted myelination and impaired remyelination in mice. This investigation contributes to our understanding of the mechanisms underlying the timing of oligodendrocyte myelination and remyelination. Another article in the journal, "How Our Brains Implicitly and Explicitly Stereotype Others" by John Chwe et al., explored how our brains shape our perceptions of others based on physical appearance. The researchers discovered that the medial temporal gyrus forms a two-dimensional plot of internal traits, such as trustworthiness and dominance, based on facial impressions. These findings highlight the need to reconsider how our judgments based on appearances can lead to social biases and real consequences for others. [Extracted from the article]

The Journal of Neuroscience published an article on the mechanisms of action of beta amyloid in Alzheimer's disease. The study found that beta amyloid disrupts synaptic activity and contributes to cell death by causing glutamatergic NMDA receptor dysfunction and dendritic spine loss. The researchers also discovered that beta amyloid interacts with a signaling system involving AKAP150 and metabotropic glutamate receptor 1, leading to the destabilization of dendritic spines. This study provides valuable insights into how beta amyloid impairs glutamatergic synapses and may inform the development of new therapeutics for Alzheimer's disease. Another article in the journal addressed the lack of research on language dysfunction in non-European populations. The study focused on Chinese language dysfunction in temporal lobe epilepsy and identified the left anterior inferior temporal gyrus as important for Chinese fluency. This research highlights the need for better representation of non-European languages in studies on language and language deficits in disease. [Extracted from the article]

As humans are social beings, human behavior and cognition are fundamentally shaped by information provided by peers, making human subjective value for rewards prone to be manipulated by perceived social information. Even subtle nonverbal social information, such as others' eye gazes, can influence value assignment, such as food value. In this study, we investigate the neural underpinnings of how gaze cues modify participants' food value (both genders) by means of functional magnetic resonance imaging. During the gaze-cuing task, food items were repeatedly presented either while others looked at them or while they were ignored by others. We determined participants' food values by assessing their willingness to pay before and after a standard gaze-cuing training. Results revealed that participants were willing to pay significantly more for food items that were attended to by others compared with the unattended to food items. Neural data showed that differences in subjective values between the two conditions were accompanied by enhanced activity in the inferior frontal gyrus, middle temporal gyrus, and caudate after food items were attended to. Furthermore, the functional connectivity between the caudate and the angular gyrus precisely predicted the individual differences in the preference shift. Our results unveil the key neural mechanism underlying the influence of social cues on the subjective value of food and highlight the crucial role of social context in shaping subjective value for food rewards in human. [ABSTRACT FROM AUTHOR]

Altered amygdala development is implicated in the neurobiology of autism, but little is known about the coordinated development of the brain regions directly connected with the amygdala. Here we investigated the volumetric development of an amygdala-connected network, defined as the set of brain regions with monosynaptic connections with the amygdala, in autism from early to middle childhood. A total of 950 longitudinal structural MRI scans were acquired from 282 children (93 female) with autism and 128 children with typical development (61 female) at up to four time points (mean ages: 39, 52, 64, and 137 months, respectively). Volumes from 32 amygdala-connected brain regions were examined using mixed effects multivariate distance matrix regression. The Social Responsiveness Scale-2 was administered to assess degree of autistic traits and social impairments. The amygdala-connected network exhibited persistent diagnostic differences (p values ≤ 0.03) that increased over time (p values ≤ 0.02). These differences were most prominent in autistics with more impacted social functioning at baseline. This pattern was not observed across regions without monosynaptic amygdala connection. We observed qualitative sex differences. In males, the bilateral subgenual anterior cingulate cortices were most affected, while in females the left fusiform and superior temporal gyri were most affected. In conclusion, (1) autism is associated with widespread alterations to the development of brain regions connected with the amygdala, which were associated with autistic social behaviors; and (2) autistic males and females exhibited different patterns of alterations, adding to a growing body of evidence of sex differences in the neurobiology of autism. [ABSTRACT FROM AUTHOR]

Speech perception in noisy environments is enhanced by seeing facial movements of communication partners. However, the neural mechanisms by which audio and visual speech are combined are not fully understood. We explore MEG phase-locking to auditory and visual signals in MEG recordings from 14 human participants (6 females, 8 males) that reported words from single spoken sentences. We manipulated the acoustic clarity and visual speech signals such that critical speech information is present in auditory, visual, or both modalities. MEG coherence analysis revealed that both auditory and visual speech envelopes (auditory amplitude modulations and lip aperture changes) were phase-locked to 2-6 Hz brain responses in auditory and visual cortex, consistent with entrainment to syllable-rate components. Partial coherence analysis was used to separate neural responses to correlated audio-visual signals and showed non-zero phase-locking to auditory envelope in occipital cortex during audio-visual (AV) speech. Furthermore, phase-locking to auditory signals in visual cortex was enhanced for AV speech compared with audioonly speech that was matched for intelligibility. Conversely, auditory regions of the superior temporal gyrus did not show abovechance partial coherence with visual speech signals during AV conditions but did show partial coherence in visual-only conditions. Hence, visual speech enabled stronger phase-locking to auditory signals in visual areas, whereas phase-locking of visual speech in auditory regions only occurred during silent lip-reading. Differences in these cross-modal interactions between auditory and visual speech signals are interpreted in line with cross-modal predictive mechanisms during speech perception. [ABSTRACT FROM AUTHOR]