Cortical Regions Research Articles

Temporal coherence shapes cortical responses to speech mixtures in a ferret cocktail party

Perceptual segregation of complex sounds such as speech and music simultaneously emanating from multiple sources is a remarkable ability that is common in humans and other animals alike. Unlike animal physiological experiments with simplified sounds or human investigations with spatially broad imaging techniques, this study combines insights from animal single-unit recordings with segregation of speech-like sound mixtures. Ferrets are trained to attend to a female voice and detect a target word, both in presence and absence of a concurrent equally salient male voice. Recordings are made in primary and secondary auditory cortical fields, and in frontal cortex. During task performance, representation of the female words becomes enhanced relative to the male in all, but especially in higher cortical regions. Analysis of the temporal and spectral response characteristics during task performance reveals how speech segregation gradually emerges in the auditory cortex. A computational model evaluated on the same voice mixtures replicates and extends these results to different attentional targets (attention to female or male voices). These findings underscore the role of the principle of temporal coherence whereby attention to a target voice binds together all neural responses coherently modulated with the target, thus ultimately forming and extracting a common auditory stream.

Long-term effects of a double hit murine model for schizophrenia on parvalbumin expressing cells and plasticity-related molecules in the thalamic reticular nucleus and the habenula

The exposure to aversive experiences during early-life affects brain maturation and induces changes in behavior. Additionally, when these experiences coincide with subtle neurodevelopmental alterations, they may contribute to the emergence of psychiatric disorders, such as schizophrenia. Studies in patients and animal models have identified changes in parvalbumin (PV) expressing inhibitory neurons, highlighting their significance in the etiology of this disorder. Most studies have been focused on the cortex, but PV+ neurons also provide inhibitory input to diencephalic regions, particularly to the thalamus (through cells in the thalamic reticular nucleus, TRN) and the habenula. Remarkably, alterations in both nuclei have been described in schizophrenia. Some of these changes in PV+ cells may be mediated by perineuronal nets (PNN), specialized regions of the extracellular matrix that often surround them and regulate their synaptic input and activity. Interestingly, the physiological maturation and integration of PV+ neurons, which involves the assembly of PNN, occurs during early postnatal life. Plasticity molecules associated to inhibitory neurons, such as PSA-NCAM, or NMDA receptors (NMDAR) can also influence the structure and function of these cells. Growing evidence also indicates that glial cells regulate the physiology of PV+ neurons by influencing their maturation and modulating their synaptic connectivity. To explore the impact of early-life aversive experiences and concomitant subtle neurodevelopmental alterations on diencephalic PV+ cells, we analyzed adult male mice subjected to a double-hit model (DHM) of schizophrenia, combining a single injection of an NMDAR antagonist at P7 and post-weaning social isolation. We observed that exploratory behavior, PV+ neurons and their associated PNN, as well as PSA-NCAM and NMDAR expression and glial cells, in the TRN and the habenula were affected by the DHM or one of its factors. To our knowledge, this is the first report on such alterations in these diencephalic structures in an animal model combining neurodevelopmental alterations and early-life stress during adolescence. Our findings complement previous work on PV+ neurons in cortical regions and underscore the importance of studying diencephalic inhibitory networks and their intricate interactions with aversive experiences and neurodevelopmental alterations during early life in the context of schizophrenia.

Identification of the proliferative activity of germline progenitor cells in the adult ovary of the bat Artibeus jamaicensis.

Until a few years ago, it was assumed that oocyte renewal did not take place in the ovary of adult organisms; however, the existence of germline progenitor cells (GPCs), which renew the ovarian follicular reserve, has now been documented in mammals. Specifically, in the adult ovary of bats, the presence of cells located in the cortical region with characteristics similar to GPCs, called adult cortical germ cells (ACGC), has been observed. One of the requirements that a GPC must fulfil is to be able to proliferate mitotically, so the evaluation of cell proliferation in ACGC is of utmost importance in order to be able to relate them to a parental lineage. Currently, there are several methods to determine cell proliferation, including BrdU labelling or the use of endogenous proliferation markers. Thus, the aim of this work was to evaluate the proliferative activity of ACGC in the adult ovary of the bat Artibeus jamaicensis, using different proliferation markers and correlating these with the protein expression of the transcription factor Oct4 and the germ line marker Ddx4. We found that the expression pattern of the proliferation markers BrdU, PCNA, Ki-67 and pH3 occurs at different times of the cell cycle, so co-localization of two or more of these markers allows us to identify proliferating cells. This allowed us to identify ACGC with proliferative capacity in the adult ovary of A. jamaicensis, suggesting that GPCs renew the follicle reserve during the adult life of the organism.

In situ optical feedback in brain tumor biopsy - a multipara-metric analysis

Abstract Introduction Brain tumor needle biopsy interventions are inflicted with non-diagnostic or biased sampling in up to 25% and hemorrhage, including asymptomatic cases, in up to 60%. To identify diagnostic tissue and sites with increased microcirculation, intraoperative optical techniques have been suggested. The aim of this study was to investigate the clinical implications of in situ optical guidance in frameless navigated tumor biopsies. Methods Real-time feedback on protoporphyrin IX (PpIX) fluorescence, microcirculation, and gray-whiteness was given before tissue sampling (272 positions) in 20 patients along 21 trajectories in total. The primary variables of investigation were fluorescence in relation to neuropathological findings and gadolinium (Gd) enhancement, increased cerebral microcirculation in relation to bleeding incidence, number of trajectories, and impact on operation time. Results PpIX fluorescence was detected in Glioblastoma IDH-wildtype CNS WHO grade 4 (n=12), Primary diffuse large B-cell lymphoma (n=3), astrocytoma IDH-mutated CNS WHO grade 4 (n=1) (Ki67 indices ≥15%). For two patients, no PpIX fluorescence or Gd was found, although samples contained tumorous tissue (Ki67 index 6%). Increased microcirculation was found along nine trajectories (34 sites), located in cortical, tumorous, or tentorium regions. Postoperative bleedings (n=10, nine asymptomatic) were related to skull opening or tissue sampling. The present study strengthens the proposed independence from intraoperative neuropathology as PpIX fluorescence is detected. Objective real-time feedback resulted in fewer trajectories compared to previous studies indicating reduced operation time. Conclusions The integrated optical guidance system provides real-time feedback in situ, increasing certainty and precision of diagnostic tissue before sampling during frameless brain tumor biopsies.

Selective expansion of motor cortical projections in the evolution of vocal novelty.

Deciphering how cortical architecture evolves to drive behavioral innovations is a long-standing challenge in neuroscience and evolutionary biology. Here, we leverage a striking behavioral novelty in the Alston's singing mouse ( Scotinomys teguina ), compared to the laboratory mouse ( Mus musculus ), to quantitatively test models of motor cortical evolution. We used bulk tracing, serial two-photon tomography, and high-throughput DNA sequencing of over 76,000 barcoded neurons to discover a specific and substantial expansion ( ∼ 200%) of orofacial motor cortical (OMC) projections to the auditory cortical region (AudR) and the midbrain periaqueductal gray (PAG), both implicated in vocal behaviors. Moreover, analysis of individual OMC neurons' projection motifs revealed preferential expansion of exclusive projections to AudR. Our results imply that selective expansion of ancestral motor cortical projections can underlie behavioral divergence over short evolutionary timescales, suggesting potential mechanisms for the evolution of enhanced cortical control over vocalizations-a crucial preadaptation for human language.

Cortex-wide characterization of decision-making neural dynamics during spatial navigation.

Decision-making during freely moving behaviors involves complex interactions among many cortical and subcortical regions. However, the spatiotemporal coordination across regions to generate a decision is less understood. Using a head-mounted widefield microscope, cortex-wide calcium dynamics were recorded in mice expressing GCaMP7f as they navigated an 8-maze using two paradigms. The first was an alternating pattern that required short term memory of the previous trial to make the correct decision and the second after a rule change to a fixed path in which rewards were delivered only on the left side. Identification of cortex-wide activation states revealed differences between the two paradigms. There was a higher probability for a visual/retrosplenial cortical state during the alternating paradigm and higher probability of a secondary motor and posterior parietal state during left-only. Three state sequences (motifs) illustrated both anterior and posterior activity propagations across the cortex. The anterior propagating motifs had the highest probability around the decision and propagating motifs peaked following the decision. The latter, likely reflecting internal feedback to influence future actions, were more common in the left-only paradigm. Therefore, the probabilities and sequences of cortical states differ when working memory is required versus a fixed trajectory reward paradigm.

Neural Correlates of Psychedelic, Sleep, and Sedated States Support Global Theories of Consciousness.

Understanding neural mechanisms of consciousness remains a challenging question in neuroscience. A central debate in the field concerns whether consciousness arises from global interactions that involve multiple brain regions or focal neural activity, such as in sensory cortex. Additionally, global theories diverge between the Global Neuronal Workspace (GNW) hypothesis, which emphasizes frontal and parietal areas, and the Integrated Information Theory (IIT), which focuses on information integration within posterior cortical regions. To disentangle the global vs. local and frontoparietal vs. posterior dilemmas, we measured global functional connectivity and local neural synchrony with functional magnetic resonance imaging (fMRI) data across a spectrum of conscious states in humans induced by psychedelics, sleep, and deep sedation. We found that psychedelic states are associated with increased global functional connectivity and decreased local neural synchrony. In contrast, non-REM sleep and deep sedation displayed the opposite pattern, suggesting that consciousness arises from global brain network interactions rather than localized activity. This mirror-image pattern between enhanced and diminished states was observed in both anterior-posterior (A-P) and posterior-posterior (P-P) brain regions but not within the anterior part of the brain alone. Moreover, anterior transmodal regions played a key role in A-P connectivity, while both posterior transmodal and posterior unimodal regions were critical for P-P connectivity. Overall, these findings provide empirical evidence supporting global theories of consciousness in relation to varying states of consciousness. They also bridge the gap between two prominent theories, GNW and IIT, by demonstrating how different theories can converge on shared neuronal mechanisms.

Topography of putative bidirectional interaction between hippocampal sharp wave ripples and neocortical slow oscillations.

Systems consolidation relies on coordination between hippocampal sharp-wave ripples (SWRs) and neocortical UP/DOWN states during sleep. However, whether this coupling exists across neocortex and the mechanisms enabling it remain unknown. By combining electrophysiology in mouse hippocampus (HPC) and retrosplenial cortex (RSC) with widefield imaging of dorsal neocortex, we found spatially and temporally precise bidirectional hippocampo-neocortical interaction. HPC multi-unit activity and SWR probability was correlated with UP/DOWN states in mouse default mode network, with highest modulation by RSC in deep sleep. Further, some SWRs were preceded by the high rebound excitation accompanying DMN DOWN→UP transitions, while large-amplitude SWRs were often followed by DOWN states originating in RSC. We explain these electrophysiological results with a model in which HPC and RSC are weakly coupled excitable systems capable of bi-directional perturbation and suggest RSC may act as a gateway through which SWRs can perturb downstream cortical regions via cortico-cortical propagation of DOWN states.

Insights from the Evolving Model of Two Cortical Visual Pathways.

The two cortical visual pathways framework has had a profound influence on theories and empirical studies of the visual system for over 40 years. By grounding physiological responses and behavior in neuroanatomy, the framework provided a critical guide for understanding vision. Although the framework has evolved over time, as our understanding of the physiology and neuroanatomy expanded, cortical visual processing is still often conceptualized as two separate pathways emerging from the primary visual cortex that support distinct behaviors ("what" vs. "where/how"). Here, we take a historical perspective and review the continuing evolution of the framework, discussing key and often overlooked insights. Rather than a functional and neuroanatomical bifurcation into two independent serial, hierarchical pathways, the current evidence points to two highly recurrent heterarchies with heterogeneous connections to cortical regions and subcortical structures that flexibly support a wide variety of behaviors. Although many of the simplifying assumptions of the framework are belied by the evidence gathered since its initial proposal, the core insight of grounding function and behavior in neuroanatomy remains fundamental. Given this perspective, we highlight critical open questions and the need for a better understanding of neuroanatomy, particularly in the human.

Distributed network flows generate localized category selectivity in human visual cortex.

A central goal of neuroscience is to understand how function-relevant brain activations are generated. Here we test the hypothesis that function-relevant brain activations are generated primarily by distributed network flows. We focused on visual processing in human cortex, given the long-standing literature supporting the functional relevance of brain activations in visual cortex regions exhibiting visual category selectivity. We began by using fMRI data from N = 352 human participants to identify category-specific responses in visual cortex for images of faces, places, body parts, and tools. We then systematically tested the hypothesis that distributed network flows can generate these localized visual category selective responses. This was accomplished using a recently developed approach for simulating - in a highly empirically constrained manner - the generation of task-evoked brain activations by modeling activity flowing over intrinsic brain connections. We next tested refinements to our hypothesis, focusing on how stimulus-driven network interactions initialized in V1 generate downstream visual category selectivity. We found evidence that network flows directly from V1 were sufficient for generating visual category selectivity, but that additional, globally distributed (whole-cortex) network flows increased category selectivity further. Using null network architectures we also found that each region's unique intrinsic "connectivity fingerprint" was key to the generation of category selectivity. These results generalized across regions associated with all four visual categories tested (bodies, faces, places, and tools), and provide evidence that the human brain's intrinsic network organization plays a prominent role in the generation of functionally relevant, localized responses.

An ANN models cortical-subcortical interaction during post-stroke recovery of finger dexterity.

Finger dexterity, and finger individuation in particular, is crucial for human movement, and disruptions due to brain injury can significantly impact quality of life. Understanding the neurological mechanisms responsible for recovery is vital for effective neurorehabilitation. This study explores the role of two key pathways in finger individuation: the corticospinal tract (CST) from the primary motor cortex and premotor areas, and the subcortical reticulospinal tract (RST) from the brainstem. We aimed to investigate how the cortical-reticular network reorganizes to aid recovery of finger dexterity following lesions in these areas. To provide a potential biologically plausible answer to this question, we developed an artificial neural network (ANN) to model the interaction between a premotor planning layer, a cortical layer with excitatory and inhibitory corticospinal outputs, and reticulospinal outputs controlling finger movements. The ANN was trained to simulate normal finger individuation and strength. A simulated stroke was then applied to the corticospinal (CS) area, reticulospinal (RS) area, or both, and the recovery of finger dexterity was analyzed. In the intact model, the ANN demonstrated a near-linear relationship between the forces of instructed and uninstructed fingers, resembling human individuation patterns. Post-stroke simulations revealed that lesions in both CS and RS regions led to increased unintended force in uninstructed fingers, immediate weakening of instructed fingers, improved control during early recovery, and increased neural plasticity. Lesions in the CS region alone significantly impaired individuation, while RS lesions affected strength and to a lesser extent, individuation. The model also predicted the impact of stroke severity on finger individuation, highlighting the combined effects of CS and RS lesions. This model provides insights into the interactive role of cortical and subcortical regions in finger individuation. It suggests that recovery mechanisms involve reorganization of these networks, which may inform neurorehabilitation strategies.

Decoding reveals the neural representation of perceived and imagined musical sounds.

Vividly imagining a song or a melody is a skill that many people accomplish with relatively little effort. However, we are only beginning to understand how the brain represents, holds, and manipulates these musical "thoughts." Here, we decoded perceived and imagined melodies from magnetoencephalography (MEG) brain data (N = 71) to characterize their neural representation. We found that, during perception, auditory regions represent the sensory properties of individual sounds. In contrast, a widespread network including fronto-parietal cortex, hippocampus, basal nuclei, and sensorimotor regions hold the melody as an abstract unit during both perception and imagination. Furthermore, the mental manipulation of a melody systematically changes its neural representation, reflecting volitional control of auditory images. Our work sheds light on the nature and dynamics of auditory representations, informing future research on neural decoding of auditory imagination.

Interhemispheric axonal sprouting occurs after pial removal in mice.

White matter lacks the kind of plasticity that is present in the cortex, and subcortical injuries often result in permanent neurological deficits. Because cortical regions share common subcortical nuclei, creating new intergyral connections may allow for the bypass of subcortical damage. In this manuscript, a surgical interhemispheric bridge is created in mice, providing a model for an intercortical transpial bypass. To model this bypass, a midline craniotomy followed by interhemispheric (IH) pial removal was performed in C57BL/6 mice, allowing for the juxtaposition of the right and left prefrontal cortices. Adeno-associated virus (AAV) expressing tdTomato under a neuronal-specific promoter were injected into the right hemisphere. Animals were sacrificed two and four weeks after surgery, and axonal sprouting and glial changes were assessed in the "bypass" (BP) operation and sham surgery. Surgery did not result in any clear functional impairments. Removing the pia resulted in the formation of a physical connection between the hemispheres and the loss of the normal pial IH barrier. Cortical layer I became thinner with neuronal bodies in closer proximity than in the sham group. New interhemispheric axonal crossings were visible at two and four weeks in the BP group but not in the sham mice. These findings constitute the first step in the development of a cortico-cortico transpial bypass, allowing us to test a new way to surgically restore neurological function.

Neuroimaging Findings for the Overnight Consolidation of Learned Non-native Speech Sounds

Abstract Research over the past two decades has documented the importance of sleep to language learning. Sleep has been suggested to play a role in establishing new speech representations as well; however, the neural mechanisms corresponding to sleep-mediated effects on speech perception behavior are unknown. In this study, we trained monolingual English-speaking adults to perceive differences between the Hindi dental vs. retroflex speech contrast in the evening. We examined the blood oxygen level dependent signal using functional magnetic resonance imaging during perceptual tasks on both the trained talker and on an untrained talker shortly after training, and again the next morning. We also employed diffusion tensor imaging to determine if individual differences in white matter structure could predict variability in overnight consolidation. We found greater activity in cortical regions associated with language processing (e.g., left insula) on the second day. Fractional anisotropy values in the anterior thalamic radiation and the uncinate fasciculus was associated with the magnitude of overnight change in perceptual behavior on the generalization (untrained) talker, after controlling for differences in sleep duration and initial learning. Our findings suggest that speech-perceptual information is subject to an overnight transfer of information to the cortex. Moreover, neural structure appears to be linked to individual differences in efficiency of overnight consolidation.

Cortical activity in body balance tasks as a function of motor and cognitive demands: A systematic review.

Technological tools, like electroencephalography and functional near-infrared spectroscopy, have deepened our understanding of cortical regions involved in balance control. In this systematic literature review, we aimed to identify the prevalent cortical areas activated during balance tasks with specific motor or cognitive demands. Our search strategy encompassed terms related to balance control and cortical activity, yielding 2250 results across five databases. After screening, 67 relevant articles were included in the review. Results indicated that manipulations of visual and/or somatosensory information led to prevalent activity in the parietal, frontal and temporal regions; manipulations of the support base led to prevalent activity of the parietal and frontal regions; both balance-cognitive dual-tasking and reactive responses to extrinsic perturbations led to prevalent activity in the frontal and central regions. These findings deepen our comprehension of the cortical regions activated to manage the complex demands of maintaining body balance in the performance of tasks posing specific requirements. By understanding these cortical activation patterns, researchers and clinicians can develop targeted interventions for balance-related disorders.

Acute transcutaneous auricular vagus nerve stimulation modulates presynaptic SV2A density in healthy rat brain: An invivo microPET study.

Vagus nerve stimulation (VNS) is the subject of exploration as an adjunct treatment for neurological disorders such as epilepsy, chronic migraine, pain, and depression. A non-invasive form of VNS is transcutaneous auricular VNS (taVNS). Combining animal models and positron emission tomography (PET) may lead to a better understanding of the elusive mechanisms of taVNS. We evaluated the acute effect of electrical stimulation of the left vagus nerve via the ear on brain synaptic vesicle glycoprotein 2A (SV2A) as a measure of presynaptic density and glucose metabolism in naïve rats. Female Sprague-Dawley rats were imaged with [11C]UCB-J (n = 11) or [18F]fluorodeoxyglucose ([18F]FDG) PET (n = 13) on two separate days, (1) at baseline, and (2) after acute unilateral left taVNS or sham stimulation (30 min). We calculated the regional volume of distribution (VT) for [11C]UCB-J and standard uptake values (SUV) for [18F]FDG. We observed regional reductions of [11C]UCB-J binding in response to taVNS ranging from 36% to 59%. The changes in taVNS compared to baseline were significantly larger than those induced by sham stimulation. The differences were observed bilaterally in the frontal cortex, striatum, and midbrain. The [18F]FDG PET uptake remained unchanged following acute taVNS or sham stimulation compared to baseline values. This proof-of-concept study shows for the first time that acute taVNS for 30 min can modulate invivo synaptic SV2A density in cortical and subcortical regions of healthy rats. Preclinical disease models and PET ligands of different targets can be a powerful combination to assess the therapeutic potential of taVNS.

Biophysical contrast sources for magnetic susceptibility and R2* mapping: A combined 7 Tesla, mass spectrometry and electron paramagnetic resonance study

Iron is the most abundant trace metal in the human brain and consistently shown elevated in prevalent neurological disorders. Because of its paramagnetism, brain iron can be assessed in vivo by quantitative MRI techniques such as R2* mapping and Quantitative Susceptibility Mapping (QSM). While Inductively Coupled Plasma Mass Spectrometry (ICP-MS) has demonstrated good correlations of the total iron content to MRI parameters in gray matter, the relationship to ferritin levels as assessed by Electron Paramagnetic Resonance (EPR) has not been systematically analyzed. Therefore, we included 15 postmortem subjects (age: 26–91 years) which underwent quantitative in-situ MRI at 7 Tesla within a post-mortem interval of 24 h after death. ICP-MS and EPR were used to measure the total iron and ferritin content in 8 selected gray matter (GM) structures and the correlations to R2* and QSM were calculated. We found that R2* and QSM in the iron rich basal ganglia and the red nucleus were highly correlated with iron (R² > 0.7) and ferritin (R² > 0.6), whereas those correlations were lost in cortical regions and the hippocampus. The neuromelanin-rich substantia nigra showed a different behavior with a correlation with total iron only (R² > 0.5) but not with ferritin. Although qualitative results were similar for both qMRI techniques the observed correlation was always stronger for QSM than R2*. This study demonstrated the quantitative correlations between R2*, QSM, total iron and ferritin levels in an in-situ MRI setup and therefore aids to understand how molecular forms of iron are responsible for MRI contrast generation.

Exploring the links among brain iron accumulation, cognitive performance, and dietary intake in older adults: A longitudinal MRI study

This study evaluated longitudinal brain iron accumulation in older adults, its association with cognition, and the role of specific nutrients in mitigating iron accumulation. MRI-based, quantitative susceptibility mapping estimates of brain iron concentration were acquired from seventy-two healthy older adults (47 women, ages 60–86) at a baseline timepoint (TP1) and a follow-up timepoint (TP2) 2.5–3.0 years later. Dietary intake was evaluated at baseline using a validated questionnaire. Cognitive performance was assessed at TP2 using the uniform data set (Version 3) neuropsychological tests of episodic memory (MEM) and executive function (EF). Voxel-wise, linear mixed-effects models, adjusted for longitudinal gray matter volume alterations, age, and several non-dietary lifestyle factors revealed brain iron accumulation in multiple subcortical and cortical brain regions, which was negatively associated with both MEM and EF performance at T2. However, consumption of specific dietary nutrients at TP1 was associated with reduced brain iron accumulation. Our study provides a map of brain regions showing iron accumulation in older adults over a short 2.5-year follow-up and indicates that certain dietary nutrients may slow brain iron accumulation.

Transient CSF1R inhibition ameliorates behavioral deficits in Cntnap2 knockout and valproic acid-exposed mouse models of autism

Microglial abnormality and heterogeneity are observed in autism spectrum disorder (ASD) patients and animal models of ASD. Microglial depletion by colony stimulating factor 1-receptor (CSF1R) inhibition has been proved to improve autism-like behaviors in maternal immune activation mouse offspring. However, it is unclear whether CSF1R inhibition has extensive effectiveness and pharmacological heterogeneity in treating autism models caused by genetic and environmental risk factors. Here, we report pharmacological functions and cellular mechanisms of PLX5622, a small-molecule CSF1R inhibitor, in treating Cntnap2 knockout and valproic acid (VPA)-exposed autism model mice. For the Cntnap2 knockout mice, PLX5622 can improve their social ability and reciprocal social behavior, slow down their hyperactivity in open field and repetitive grooming behavior, and enhance their nesting ability. For the VPA model mice, PLX5622 can enhance their social ability and social novelty, and alleviate their anxiety behavior, repetitive and stereotyped autism-like behaviors such as grooming and marble burying. At the cellular level, PLX5622 restores the morphology and/or number of microglia in the somatosensory cortex, striatum, and hippocampal CA1 regions of the two models. Specially, PLX5622 corrects neurophysiological abnormalities in the striatum of the Cntnap2 knockout mice, and in the somatosensory cortex, striatum, and hippocampal CA1 regions of the VPA model mice. Incidentally, microglial dynamic changes in the VPA model mice are also reported. Our study demonstrates that microglial depletion and repopulation by transient CSF1R inhibition is effective, and however, has differential pharmacological functions and cellular mechanisms in rescuing behavioral deficits in the two autism models.

Changes in cortical manifold structure following stroke and its relation to behavioral recovery in the male macaque

Stroke, a major cause of disability, disrupts brain function and motor skills. Previous research has mainly focused on reorganization of the motor system post-stroke, but the effects on other brain areas and their influence on recovery is poorly understood. Here, we use functional neuroimaging in a nonhuman primate model (23 male Cynomolgus Macaques), we explore how ischemic stroke affects whole-brain cortical architecture and its relation to spontaneous behavioral recovery. By projecting patterns of cortical functional connectivity onto a low-dimensional manifold space, we find that several regions in both sensorimotor cortex and higher-order transmodal cortex exhibit significant shifts in their manifold embedding from pre- to post-stroke. Furthermore, we observe that changes in default mode and limbic network regions, and not preserved sensorimotor cortical regions, are associated with animal behavioral recovery post-stroke. These results establish the whole-brain functional changes associated with stroke, and suggest an important role for higher-order transmodal cortex in post-stroke outcomes.