Primary Sensory Cortex Research Articles

Electroacupuncture promotes the repair of the damaged spinal cord in mice by mediating neurocan-perineuronal net.

This study aimed to investigate the effect of perineuronal net (PNN) and neurocan (NCAN) on spinal inhibitory parvalbumin interneuron (PV-IN), and the mechanism of electroacupuncture (EA) in promoting spinal cord injury (SCI) repair through neurocan in PNN. A mouse model of SCI was established. Sham-operated mice or SCI model mice were treated with chondroitin sulfate ABC (ChABC) enzyme or control vehicle for 2 weeks (i.e., sham+veh group, sham+ChABC group, SCI+veh group, and SCI+ChABC group, respectively), and then spinal cord tissues were taken from the T10 lesion epicenter for RNA sequencing (RNA-seq). MSigDB Hallmark and C5 databases for functional analysis, analysis strategies such as differential expression gene analysis (DEG), Kyoto Encyclopedia of Genes and Genomes (KEGG), gene set enrichment analysis (GSEA), and protein-protein interaction (PPI). According to the results of RNA-seq analysis, the expression of NCAN was knocked down or overexpressed by virus intervention, or/and EA intervention. Polymerase chain reaction (PCR), immunofluorescence, western blot, electrophysiological, and behavioral tests were performed. After the successful establishment of SCI model, the motor dysfunction of lower limbs, and the expression of PNN core glycan protein at the epicenter of SCI were reduced. RNA-seq and PCR showed that PNN core proteoglycans except NCAN showed the same expression trend in normal and injured spinal cord treated with ChABC. KEGG and GSEA showed that PNN is mainly associated with inhibitory GABA neuronal function in injured spinal cord tissue, and PPI showed that NCAN in PNN can be associated with inhibitory neuronal function through parvalbumin (PV). Calcium imaging showed that local parvalbumin interneuron (PV-IN) activity decreased after PNN destruction, whether due to ChABC treatment or surgical bruising of the spinal cord. Overexpression of neurocan in injured spinal cord can enhance local PV-IN activity. PCR and western blot suggested that overexpression or knockdown of neurocan could up-regulate or down-regulate the expression of GAD. At the same time, the activity of PV-IN in the primary motor cortex (M1) and the primary sensory cortex of lower (S1HL) extremity changed synchronously. In addition, overexpression of neurocan improved the electrical activity of the lower limb and promoted functional repair of the paralyzed hind limb. EA intervention reversed the down-regulation of neurocan, enhanced the expression of PNN in the lesioned area, M1 and S1HL. Neurocan in PNN can regulate the activity of PV-IN, and EA can promote functional recovery of mice with SCI by upregulating neurocan expression in PNN.

CNSC-12. PATHOLOGY SPECIFIC, PHARMACOLOGICALLY REVERSIBLE LOSS OF NEURONAL FUNCTION IN HUMAN GLIOMAS

Abstract Prior evidence has demonstrated that neuronal activity is preserved within glioma-infiltrated cortex and maintains the ability to engage in task specific computations albeit with information loss. These findings support a potential therapeutic target to rescue cognitive impairments seen in nearly all afflicted patients if neuronal activity can be recovered. We developed an in vivo human behavioral and electrophysiological model to assess neuronal population tuning responses within primary sensory cortex including the decodability of stimuli and task-related changes in population spiking in a cohort of 14 human patients undergoing awake resection. We placed high-density electrode arrays to record human local field potentials from gliomas projecting to the cortical surface. We next designed a static sensory detection threshold task, stimulating with a tachometer at two different face and hand sites totaling 11,200 trials while recording from macroelectrode cortical contacts over both tumor-infiltrated (50 electrodes) and normal appearing cortex (52 electrodes). In tumor-infiltrated cortex, the ability to decode the site of stimulation using the oscillatory power in both theta (4-8 Hz) and gamma (32-70 Hz) bands was reduced compared to normal appearing cortex. However, tumor-infiltrated cortex-maintained selectivity between hand and face stimulation. Targeted next-generation tumor sequencing uncovered novel molecular targets of glioma-neuronal integration. The degree of loss of selectivity correlated with WHO grade and pathology. WHO grade 4 tumors and oligodendrogliomas compared to astrocytomas demonstrating greater loss of selectivity. Gabaergic agonist has been postulated to restore neuronal selectivity in aging and neurodegenerative disease. Therefore, we next computed GABA agonist dose (estimated by time off Propofol and beginning of behavioral testing). Higher concentrations of GABA agonist correlated with improved theta band selectivity and decodability. These results suggest that loss of neuronal computations in glioma-infiltrated cortex is caused by loss of neuronal selectivity and is both tumor selective and pharmacologically reversible.

Functional connectivity alterations in the frontoparietal network and sensorimotor network are associated with behavioral heterogeneity in blepharospasm.

Primary blepharospasm (BSP) is a clinically heterogeneous disease that manifests not only as spasmodic closure of the eyelids but also sometimes with apraxia of eyelid opening (AEO). This cross-sectional study aimed to investigate differences in the neural mechanisms of isolated BSP and BSP-associated AEO subtypes, which may reveal the pathophysiology underlying different phenotypes. A total of 29 patients manifested as isolated BSP, 17 patients manifested as BSP associated with AEO, and 28 healthy controls underwent resting-state functional near-infrared spectroscopy (fNIRS). We assessed functional connectivity (FC) between regions of interest (ROIs) in the fronto-parietal control network (PFCN) and sensorimotor network (SMN). We also examined the relationship between altered FC and behavioral data. In the FPCN, ROI- analyses showed decreased FC between the left premotor cortex and supramarginal gyrus in the BSP with AEO group compared to the isolated BSP group. In the SMN, both subgroups showed hypoconnectivity of the left premotor cortex with the right primary motor cortex, primary sensory cortex, and somatosensory association cortex. This hypoconnectivity was positively correlated with the total number of botulinum toxin A treatments, which suggests that long-term botulinum toxin A treatment may modulate motor sequence planning and coordination. These findings showed different connectivity alterations in neural networks associated with motor and cognitive control among different behavioral phenotypes of BSP. The identification of specific alterations in various networks that correspond to clinical heterogeneity may inform the identification of potential biomarkers for early diagnosis and personalized neuromodulation targets for treating different BSP subphenotypes.

Differences in Cortical Activation During Dorsiflexion and Plantarflexion in Chronic Ankle Instability: A Task-fMRI Study.

Chronic ankle instability is a common sports injury that often presents with increased plantarflexion and restricted dorsiflexion. The cumulative effect of peripheral injuries may induce neuroplasticity in the central nervous system. However, the relationship between dorsiflexion or plantarflexion and the central nervous system in patients with chronic ankle instability remains unknown. (1) Is there a difference in region and voxel (volume pixel) of cortical activation during plantarflexion and dorsiflexion between patients with chronic ankle instability and a control group with normal ankle function? (2) Is there a correlation between activation of sensorimotor-related brain regions and three clinical measurement scales of ankle function and disease severity in patients with chronic ankle instability? Between December 2020 and May 2022, we treated 400 patients who had chronic ankle instability. Ten percent (40 patients; mean ± standard deviation age 29 ± 7 years; 17 male patients) were randomly selected to participate in this study. We recruited 42 volunteers with normal ankle function (mean age 28 ± 5 years; 21 male participants) matched by age and education level. A total of 2.5% (1 of 40) of patients with bilateral chronic ankle instability and 30% (12 of 40) with left-sided chronic ankle injury did not meet our inclusion criteria and were excluded from the study. The control group underwent MRI with good image quality. Finally, 27 patients with chronic ankle instability (mean age 26 ± 5 years; 10 male patients) and 42 participants with normal ankle function were enrolled. Ankle function and disease severity were assessed using three clinical scales: the Cumberland Ankle Instability Tool, Karlsson-Peterson Ankle Function Score, and the American Orthopedic Foot and Ankle Society Score. A uniplanar and nonweightbearing ankle dorsiflexion-plantarflexion paradigm (a recognized model or pattern) was performed using a short-block design during the functional MRI scan. This experimental design included a series of on-off periods consisting of movement and a rest period. From 15° of plantarflexion to 15° of dorsiflexion, the manipulator allowed 30° of ankle rotation. The cerebral excitability patterns between patients with chronic ankle instability and controls were analyzed using t-tests. We retained voxels with p values less than 0.05 in a voxel-level family-wise error correction. Clusters with voxel numbers greater than 10 were retained. The Cohen d coefficient was used to calculate between-group effect sizes. Spearman analysis was performed to explore the correlation between activation regions and the three clinical assessment scales. In the patient group, cortical activation was greater during plantarflexion than during dorsiflexion, which was different from that in the control group. The between-group comparison showed that patients with chronic ankle instability had reduced activation in the ipsilateral precuneus (cluster size = 35 voxels [95% CI -0.23 to 0.07]; p < 0.001) during dorsiflexion, whereas during plantarflexion, chronic ankle instability caused increased activation in the ipsilateral superior temporal gyrus (cluster size = 90 voxels [95% CI -0.73 to -0.13]; p < 0.001), precuneus (cluster size = 18 voxels [95% CI -0.56 to -0.19]; p < 0.001), supplementary motor area (cluster size = 57 voxels [95% CI -0.31 to 0.00]; p < 0.001), superior frontal gyrus (cluster size = 43 voxels [95% CI -0.82 to -0.29]; p < 0.001), medial part of the superior frontal gyrus (cluster size = 39 voxels [95% CI 0.41 to 0.78]; p < 0.001), and contralateral postcentral gyrus (cluster size = 100 voxels [95% CI -0.32 to 0.02]; p < 0.001). Patients with chronic ankle instability showed a large effect size compared with controls (Cohen d > 0.8). During plantarflexion, the number of activated voxels in the supplementary motor area had a modest, positive correlation with the Karlsson-Peterson Ankle Function Score (r = 0.52; p = 0.01), and the number of activated voxels in the primary motor cortex (M1) and primary sensory cortex (S1) had a weak, positive correlation with the American Orthopedic Foot and Ankle Society Score in patients with chronic ankle instability (M1: r = 0.45; p = 0.02, S1: r = 0.49; p = 0.01). Compared with volunteers with normal ankle function, patients with chronic ankle instability had increased cortical activation during plantarflexion and decreased cortical activation during dorsiflexion. We analyzed the central neural mechanisms of chronic ankle instability in patients with sports injuries and provided a theoretical basis for the development of new central and peripheral interventions in the future. Because there was a positive correlation between the neural activity in sensorimotor-related regions during plantarflexion and clinical severity, clinicians might one day be able to help patients who have chronic ankle instability with neuromuscular rehabilitation by applying electrical stimulation to specific targets (such as S1M1 and the supplementary motor area) or by increasing activation of sensorimotor neurons through ankle movement.

White matter connectivity of subthalamic nucleus and globus pallidus interna targets for deep brain stimulation.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) and globus pallidus interna (GPi) have differential therapeutic effects for Parkinson's disease (PD) that drive patient selection. For example, GPi DBS is preferred for dystonic features and dyskinesia, whereas STN DBS has shown faster tremor control and medication reduction. Connectivity studies comparing these two targets, using patient-specific data, are still lacking. The objective was to find STN and GPi structural connectivity patterns in order to better understand differences in DBS-activated brain circuits between these two stimulation targets and to guide optimal contact selection. The authors simulated DBS activation along the main axis of both the STN and GPi by using volume of activated tissue (VAT) modeling with known average stimulation parameters (2.8 V and 60 μsec for STN; 3.3 V and 90 μsec for GPi). The authors modeled VATs in the anterior, middle, and posterior STN and the anterior, midanterior, midposterior, and posterior GPi. The authors generated maps of the connections shared by the patients for each VAT by using probabilistic tractography of diffusion-weighted imaging data obtained in 46 PD patients who underwent DBS (26 with STN and 20 with GPi targeting), and differences between VATs for whole-brain and distal regions of interest (prefrontal cortex, supplementary motor area, primary motor cortex, primary sensory cortex, caudate, motor thalamus, and cerebellum) were generated from structural atlases. Differences between maps were quantified and compared. VATs across the STN and GPi had different structural connectivity patterns. The authors found significant connectivity differences between VATs for all regions of interest. Posterior and middle STN showed stronger connectivity to the primary motor cortex and supplementary motor area (SMA) (p < 0.001). Posterior STN had the strongest connectivity to the primary sensory cortex and motor thalamus (p < 0.001). Posterior GPi showed stronger connectivity to the primary motor cortex (p < 0.001). Connectivity to the SMA was similar for the posterior and midposterior GPi (p > 0.05), which was greater than that for the anterior GPi (p < 0.001). When both nuclei were compared, posterior and middle STN had stronger connectivity to the SMA, cerebellum, and motor thalamus than GPi (all p < 0.001). Posterior GPi and STN had similar connectivity to the primary sensory cortex. On patient-specific imaging, structural connectivity differences existed between GPi and STN DBS, as measured with standardized electrical field modeling of the DBS targets. These connectivity differences may correlate with the differential clinical benefits obtained by targeting each of the two nuclei with DBS for PD. Prospective work is needed to relate these differences to clinical outcomes and to inform targeting and programming.

Thalamo-cortical circuits associated with trait- and state-repetitive negative thinking in major depressive disorder

BackgroundRepetitive negative thinking (RNT), often referred to as rumination in the mood disorders literature, is a symptom dimension associated with poor prognosis and suicide in major depressive disorder (MDD). Given the transdiagnostic nature of RNT, this study aimed to evaluate the hypothesis that neurobiological substrates of RNT in MDD may share the brain mechanisms underlying obsessions, particularly those involving cortico-striatal-thalamic-cortical (CSTC) circuits. MethodsThirty-nine individuals with MDD underwent RNT induction during fMRI. Trait-RNT was measured by the Ruminative Response Scale (RRS) and state-RNT was measured by a visual analogue scale. We employed a connectome-wide association analysis examining the association between RNT intensity with striatal and thalamic connectivity. ResultsA greater RRS score was associated with hyperconnectivity of the right mediodorsal thalamus with prefrontal cortex, including lateral orbitofrontal cortex, along with Wernicke's area and posterior default mode network nodes (t = 4.66–6.70). A greater state-RNT score was associated with hyperconnectivity of the right laterodorsal thalamus with bilateral primary sensory and motor cortices, supplementary motor area, and Broca's area (t = 4.51–6.57). Unexpectedly, there were no significant findings related to the striatum. ConclusionsThe present results suggest RNT in MDD is subserved by abnormal connectivity between right thalamic nuclei and cortical regions involved in both visceral and higher order cognitive processing. Emerging deep-brain neuromodulation methods may be useful to establish causal relationships between dysfunction of right thalamic-cortical circuits and RNT in MDD.

Directed functional connectivity of the sensorimotor system in young and older individuals.

Studies in the sensorimotor system of older versus young individuals have shown alterations in functional connectivity and organization. Our objective was to explore the implications of these differences in terms of local organizations, and to identify processes that correlate with neuropsychological parameters. Using a novel multivariate analysis method on resting-state functional MRI data obtained from 50 young and 31 older healthy individuals, we identified directed 4-node functional pathways within the sensorimotor system and examined their correlations with neuropsychological assessments. In young individuals, the functional pathways were unidirectional, flowing from the primary motor and sensory cortices to higher motor and visual regions. In older individuals, the functional pathways were more complex. They originated either from the calcarine sulcus or the insula and passed through mutually coupled high-order motor areas before reaching the primary sensory and motor cortices. Additionally, the pathways in older individuals that resembled those found in young individuals exhibited a positive correlation with years of education. The flow pattern of young individuals suggests efficient and fast information transfer. In contrast, the mutual coupling of high-order motor regions in older individuals suggests an inefficient and slow transfer, a less segregated and a more integrated organization. The differences in the number of sensorimotor pathways and of their directionality suggests reduced efferent degenerated pathways and increased afferent compensated pathways. Furthermore, the positive effect of years of education may be associated with the Cognitive Reserve Hypothesis, implying that cognitive reserve could be maintained through specific information transfer pathways.

Beyond sense-specific processing: decoding texture in the brain from touch and sonified movement

Texture, a fundamental object attribute, is perceived through multisensory information including touch and auditory cues. Coherent perceptions may rely on shared texture representations across different senses in the brain. To test this hypothesis, we delivered haptic textures coupled with a sound synthesizer to generate real-time textural sounds. Participants completed roughness estimation tasks with haptic, auditory, or bimodal cues in an MRI scanner. Somatosensory, auditory, and visual cortices were all activated during haptic and auditory exploration, challenging the traditional view that primary sensory cortices are sense-specific. Furthermore, audio-tactile integration was found in secondary somatosensory (S2) and primary auditory cortices. Multivariate analyses revealed shared spatial activity patterns in primary motor and somatosensory cortices, for discriminating texture across both modalities. This study indicates that primary areas and S2 have a versatile representation of multisensory textures, which has significant implications for how the brain processes multisensory cues to interact more efficiently with our environment.

Evaluating Dual Task Neurological Costs with Functional Near-Infrared Spectroscopy: A Preliminary Report in Healthy Athletes.

Dual task assessments, which simultaneously challenge and assess cognitive and motor performance, have been used to improve the assessment of athletes with sports-related concussions (SRC). Our lab created a Dual Task Screen (DTS) to evaluate athletes with SRCs, and we have established that it is a valid behavioral measure, as it consistently elicits poorer behavioral performance under dual, compared to single, task conditions. Here, we used a Neuroimaging-Compatible (NC) version of the DTS, named the NC-DTS, which uses portable functional near-infrared spectroscopy (fNIRS) to assess behavioral performance and neural recruitment during single and dual tasks. Our study objective was to evaluate healthy athletes and establish whether the NC-DTS is a valid dual task neurological assessment that can elicit different patterns of neural recruitment during dual versus single task conditions. Twenty-five healthy collegiate athletes completed the NC-DTS in a single laboratory visit. The NC-DTS includes a lower and upper extremity subtask; both include single motor, single cognitive, and dual task conditions. The NC-DTS was administered in a block design, where conditions (i.e., single motor, single cognitive, and dual task) were repeated five times to generate average behavioral performance and task-dependent neural recruitment in superficial cortical regions including: prefrontal cortex, bilateral primary motor and sensory cortices, and posterior parietal cortex. Neural recruitment was measured with fNIRS and quantified using oxygenated hemoglobin (HbO) and deoxygenated hemoglobin (HbR) metrics. A single-tailed, within subject t-test was used to compare average dual task behavioral performance to average single task behavioral performance. Pairwise comparisons, that were family-wise-error (FWE) corrected, were used to compare localized neural recruitment during dual versus single task conditions. As observed in previous studies, the NC-DTS elicited significantly poorer behavioral performance under dual, compared to single, task conditions. Additionally, dual task conditions of the NC-DTS elicited significantly greater neural recruitment in regions of the brain associated with attention allocation and task-specific demands in three of four comparisons. These preliminary results suggest that the NC-DTS is a valid dual task neurological assessment which warrants future work using the NC-DTS to evaluate athletes with SRCs.

Role of TRPV1 in electroacupuncture-mediated signal to the primary sensory cortex during regulation of the swallowing function.

Electroacupuncture (EA) at the Lianquan (CV23) could alleviate swallowing dysfunction. However, current knowledge of its neural modulation focused on the brain, with little evidence from the periphery. Transient receptor potential channel vanilloid subfamily 1 (TRPV1) is an ion channel predominantly expressed in sensory neurons, and acupuncture can trigger calcium ion (Ca2+ ) wave propagation through active TRPV1 to deliver signals. The present study aimed to investigate whether TRPV1 mediated the signal of EA to the primary sensory cortex (S1) during regulation of swallowing function. Blood perfusion was evaluated by laser speckle contrast imaging (LSCI), and neuronal activity was evaluated by fiber calcium recording and c-Fos staining. The expression of TRPV1 was detected by RNA-seq analysis, immunofluorescence, and ELISA. In addition, the swallowing function was assessed by in vivo EMG recording and water consumption test. EA treatment potentiated blood perfusion and neuronal activity in the S1, and this potentiation was absent after injecting lidocaine near CV23. TRPV1 near CV23 was upregulated by EA-CV23. The blood perfusion at CV23 was decreased in the TRPV1 hypofunction mice, while the blood perfusion and the neuronal activity of the S1 showed no obvious change. These findings were also present in post-stroke dysphagia (PSD) mice. The TRPV1 at CV23 after EA treatment might play a key role in mediating local blood perfusion but was not involved in transferring EA signals to the central nervous system (CNS). These findings collectively suggested that TRPV1 may be one of the important regulators involved in the mechanism of EA treatment for improving swallowing function in PSD.

Sensory Gating during Voluntary Finger Movement in Amyotrophic Lateral Sclerosis with Sensory Cortex Hyperexcitability.

Cortical responses in somatosensory evoked potentials (SEP) are enhanced in patients with amyotrophic lateral sclerosis (ALS). This study investigated whether sensory gating is involved in the pathophysiology of sensory cortical hyperactivity in ALS patients. The median nerve SEP was recorded at rest and during voluntary finger movements in 14 ALS patients and 13 healthy control subjects. The parietal N20, P25, and frontal N30 were analyzed, and sensory gating was assessed by measuring the amplitude of each component during finger movement. The amplitudes of the N20 onset-peak, N20 peak-P25 peak, and N30 onset-peak were higher in ALS patients than in controls. Nonetheless, there were no significant differences in the amplitude reduction ratio of SEPs between patients and controls. There was a significant correlation between the baseline amplitudes of the N20 onset-peak or N20 peak-P25 peak and their gating ratios in patients with ALS. Our findings indicate that the excitability of the primary sensory cortex and secondary motor cortex is enhanced in ALS, while sensory gating is preserved in the early stages of ALS. This result suggests that enhanced SEP is caused by the hyperexcitability of the primary sensory and secondary motor cortices but not by the dysfunction of inhibitory mechanisms during voluntary movements.

Robust multisensory deviance detection in the mouse parietal associative area

Context modulates how information is processed in the mammalian brain. For example, brain responses are amplified to contextually unusual stimuli. This phenomenon, known as "deviance detection,"1,2 is well documented in early, primary sensory cortex, where large responses are generated to simple stimuli that deviate from their context in low-order properties, such as line orientation, size, or pitch.2,3,4,5 However, the extent to which neural deviance detection manifests (1) in broader cortical networks and (2) to simple versus complex stimuli, which deviate only in their higher-order, multisensory properties, is not known. Consistent with a predictive processing framework,6,7 we hypothesized that deviance detection manifests in a hierarchical manner across cortical networks,8,9 emerging later and further downstream when stimulus deviance is complex. To test this, we examined brain responses of awake mice to simple unisensory deviants (e.g., visual line gratings, deviating from context in their orientation alone) versus complex multisensory deviants (i.e., audiovisual pairs, deviating from context only in their audiovisual pairing but not visual or auditory content alone). We find that mouse parietal associative area-a higher cortical region-displays robust multisensory deviance detection. In contrast, primary visual cortex exhibits strong unisensory visual deviance detection but weaker multisensory deviance detection. These results suggest that deviance detection signals in the cortex may be conceptualized as "prediction errors," which are primarily fed forward-or downstream-in cortical networks.6,7.

Temporal Unfolding of Racial Ingroup Bias in Neural Responses to Perceived Dynamic Pain in Others.

In this study, we investigated how empathic neural responses unfold over time in different empathy networks when viewing same-race and other-race individuals in dynamic painful conditions. We recorded magnetoencephalography signals from Chinese adults when viewing video clips showing a dynamic painful (or non-painful) stimulation to Asian and White models' faces to trigger painful (or neutral) expressions. We found that perceived dynamic pain in Asian models modulated neural activities in the visual cortex at 100ms-200ms, in the orbitofrontal and subgenual anterior cingulate cortices at 150ms-200ms, in the anterior cingulate cortex around 250ms-350ms, and in the temporoparietal junction and middle temporal gyrus around 600ms after video onset. Perceived dynamic pain in White models modulated activities in the visual, anterior cingulate, and primary sensory cortices after 500ms. Our findings unraveled earlier dynamic activities in multiple neural circuits in response to same-race (vs other-race) individuals in dynamic painful situations.

Interneuron-Targeted Disruption of SYNGAP1 Alters Sensory Representations in the Neocortex and Impairs Sensory Learning.

SYNGAP1 haploinsufficiency in humans leads to severe neurodevelopmental disorders characterized by intellectual disability, autism, epilepsy, and sensory processing deficits. However, the circuit mechanisms underlying these disorders are not well understood. In mice, a decrease of SynGAP levels results in cognitive deficits by interfering with the development of excitatory glutamatergic connections. Recent evidence suggests that SynGAP also plays a crucial role in the development and function of GABAergic inhibitory interneurons. Nevertheless, it remains uncertain whether and to what extent the expression of SYNGAP1 in inhibitory interneurons contributes to cortical circuit function and related behaviors. The activity of cortical neurons has not been measured simultaneously with behavior. To address these gaps, we recorded from layer 2/3 neurons in the primary whisker somatosensory cortex (wS1) of mice while they learned to perform a whisker tactile detection task. Our results demonstrate that mice with interneuron-specific SYNGAP1 haploinsufficiency exhibit learning deficits characterized by heightened behavioral responses in the absence of relevant sensory input and premature responses to unrelated sensory stimuli not associated with reward acquisition. These behavioral deficits are accompanied by specific circuit abnormalities within wS1. Interneuron-specific SYNGAP1 haploinsufficiency increases detrimental neuronal correlations directly related to task performance and enhances responses to irrelevant sensory stimuli unrelated to the reward acquisition. In summary, our findings indicate that a reduction of SynGAP in inhibitory interneurons impairs sensory representation in the primary sensory cortex by disrupting neuronal correlations, which likely contributes to the observed cognitive deficits in mice with pan-neuronal SYNGAP1 haploinsufficiency.SIGNIFICANCE STATEMENT SYNGAP1 haploinsufficiency leads to severe neurodevelopmental disorders. The exact nature of neural circuit dysfunction caused by SYNGAP1 haploinsufficiency remains poorly understood. SynGAP plays a critical role in the function of GABAergic inhibitory interneurons as well as glutamatergic pyramidal neurons in the neocortex. Whether and how decreasing SYNGAP1 level in inhibitory interneurons disrupts a behaviorally relevant circuit remains unclear. We measure neural activity and behavior in mice learning a perceptual task. Mice with interneuron-targeted disruption of SYNGAP1 display increased detrimental neuronal correlations and elevated responses to irrelevant sensory inputs, which are related to impaired task performance. These results show that cortical interneuron dysfunction contributes to sensory deficits in SYNGAP1 haploinsufficiency with important implications for identifying therapeutic targets.

Frequency-specific directed interactions between whole-brain regions during sentence processing using multimodal stimulus

Neural oscillations subserve a broad range of speech processing and language comprehension functions. Using an electroencephalogram (EEG), we investigated the frequency-specific directed interactions between whole-brain regions while the participants processed Chinese sentences using different modality stimuli (i.e., auditory, visual, and audio-visual). The results indicate that low-frequency responses correspond to the process of information flow aggregation in primary sensory cortices in different modalities. Information flow dominated by high-frequency responses exhibited characteristics of bottom-up flow from left posterior temporal to left frontal regions. The network pattern of top-down information flowing out of the left frontal lobe was presented by the joint dominance of low- and high-frequency rhythms. Overall, our results suggest that the brain may be modality-independent when processing higher-order language information.

Reduced somatosensory evoked potentials and paired-pulse inhibition in the primary somatosensory cortex of athletes with chronic pain.

Chronic pain impedes athletic training and performance. However, it is challenging to identify the precise causes of chronic pain for effective treatment. To examine possible neuroplastic changes in sensory transmission and cortical processing, we compared somatosensory evoked potentials (SEPs) and paired-pulse inhibition (PPI) in primary sensory cortex (S1) between athletes with chronic pain and control athletes. Sixty-six intercollegiate athletes (39 males and 27 females) were recruited for this study, 45 control athletes and 21 reporting persistent pain for > 3months. Sensory-evoked potentials were induced in S1 by constant-current square-wave pulses (0.2-ms duration) delivered to the right median nerve, while PPI was induced by paired stimulation at interstimulus intervals of 30 and 100ms (PPI-30 and PPI-100ms, respectively). All participants were randomly presented with total 1,500 (each 500 stimuli) single stimuli and stimulus pairs at 2Hz. Both N20 amplitude and PPI-30ms were significantly lower in athletes with chronic pain compared to control athletes, while P25 amplitude and PPI-100ms did not differ significantly between groups. Chronic pain in athletes is associated with substantially altered excitatory-inhibitory balance within the primary somatosensory cortex, possibly due to reduced thalamocortical excitatory transmission and suppressed cortical inhibitory transmission.

Binge drinking is associated with higher cortisol and lower hippocampal and prefrontal gray matter volume: Prospective association with future alcohol intake

BackgroundCortisol is a significant driver of the biological stress response that is potently activated by acute alcohol intake and increased with binge drinking. Binge drinking is associated with negative social and health consequences and risk of developing alcohol use disorder (AUD). Both cortisol levels and AUD are also associated with changes in hippocampal and prefrontal regions. However, no previous research has assessed structural gray matter volume (GMV) and cortisol concurrently to examine BD effects on hippocampal and prefrontal GMV and cortisol, and their prospective relationship to future alcohol intake. MethodsIndividuals who reported binge drinking (BD: N = 55) and demographically matched non-binge moderate drinkers (MD: N = 58) were enrolled and scanned using high-resolution structural MRI. Whole brain voxel-based morphometry was used to quantify regional GMV. In a second phase, 65% of the sample volunteered to participate in prospective daily assessment of alcohol intake for 30 days post-scanning. ResultsRelative to MD, BD showed significantly higher cortisol and smaller GMV in regions including hippocampus, dorsal lateral prefrontal cortex (dlPFC), prefrontal and supplementary motor, primary sensory and posterior parietal cortex (FWE, p < 0.05). GMV in bilateral dlPFC and motor cortices were negatively associated with cortisol levels, and smaller GMV in multiple PFC regions was associated with more subsequent drinking days in BD. ConclusionThese findings indicate neuroendocrine and structural dysregulation associated with BD relative to MD. Notably, BD-associated lower GMV regions were those involved in stress, memory and cognitive control, with lower GMV in cognitive control and motor regions also predicting higher levels of future alcohol intake in BD.

Neuropathic pain following spinal cord hemisection induced by the reorganization in primary somatosensory cortex and regulated by neuronal activity of lateral parabrachial nucleus.

Neuropathic pain after spinal cord injury (SCI) remains a common and thorny problem, influencing the life quality severely. This study aimed to elucidate the reorganization of the primary sensory cortex (S1) and the regulatory mechanism of the lateral parabrachial nucleus (lPBN) in the presence of allodynia or hyperalgesia after left spinal cord hemisection injury (LHS). Through behavioral tests, we first identified mechanical allodynia and thermal hyperalgesia following LHS. We then applied two-photon microscopy to observe calcium activity in S1 during mechanical or thermal stimulation and long-term spontaneous calcium activity after LHS. By slice patch clamp recording, the electrophysiological characteristics of neurons in lPBN were explored. Finally, exploiting chemogenetic activation or inhibition of the neurons in lPBN, allodynia or hyperalgesia was regulated. The calcium activity in left S1 was increased during mechanical stimulation of right hind limb and thermal stimulation of tail, whereas in right S1 it was increased only with thermal stimulation of tail. The spontaneous calcium activity in right S1 changed more dramatically than that in left S1 after LHS. The lPBN was also activated after LHS, and exploiting chemogenetic activation or inhibition of the neurons in lPBN could induce or alleviate allodynia and hyperalgesia in central neuropathic pain. The neuronal activity changes in S1 are closely related to limb pain, which has accurate anatomical correspondence. After LHS, the spontaneously increased functional connectivity of calcium transient in left S1 is likely causing the mechanical allodynia in right hind limb and increased neuronal activity in bilateral S1 may induce thermal hyperalgesia in tail. This state of allodynia and hyperalgesia can be regulated by lPBN.

Amplified cortical neural responses as animals learn to use novel activity patterns

Cerebral cortex supports representations of the world in patterns of neural activity, used by the brain to make decisions and guide behavior. Past work has found diverse, or limited, changes in the primary sensory cortex in response to learning, suggesting that the key computations might occur in downstream regions. Alternatively, sensory cortical changes may be central to learning. We studied cortical learning by using controlled inputs we insert: we trained mice to recognize entirely novel, non-sensory patterns of cortical activity in the primary visual cortex (V1) created by optogenetic stimulation. As animals learned to use these novel patterns, we found that their detection abilities improved by an order of magnitude or more. The behavioral change was accompanied by large increases in V1 neural responses to fixed optogenetic input. Neural response amplification to novel optogenetic inputs had little effect on existing visual sensory responses. A recurrent cortical model shows that this amplification can be achieved by a small mean shift in recurrent network synaptic strength. Amplification would seem to be desirable to improve decision-making in a detection task; therefore, these results suggest that adult recurrent cortical plasticity plays a significant role in improving behavioral performance during learning.

Categorical working memory codes in human visual cortex

Working memory contents are represented in neural activity patterns across multiple regions of the cortical hierarchy. A division of labor has been proposed where more anterior regions harbor increasingly abstract and categorical representations while the most detailed representations are held in primary sensory cortices. Here, using fMRI and multivariate encoding modeling, we demonstrate that for color stimuli categorical codes are already present at the level of extrastriate visual cortex (V4 and VO1), even when subjects are neither implicitly nor explicitly encouraged to categorize the stimuli. Importantly, this categorical coding was observed during working memory, but not during perception. Thus, visual working memory is likely to rely at least in part on categorical representations. Significance statementWorking memory is the representational basis for human cognition. Recent work has demonstrated that numerous regions across the human brain can represent the contents of working memory. We use fMRI brain scanning and machine learning methods to demonstrate that different regions can represent the same content differently during working memory. Reading out the neural codes used to store working memory contents, we show that already in sensory cortex, areas V4 and VO1 represent color in a categorical format rather than a purely sensory fashion. Thereby, we provide a better understanding of how different regions of the brain might serve working memory and cognition.