Cortical Areas Research Articles

Aging drives cerebrovascular network remodeling and functional changes in the mouse brain

Aging is frequently associated with compromised cerebrovasculature and pericytes. However, we do not know how normal aging differentially impacts vascular structure and function in different brain areas. Here we utilize mesoscale microscopy methods and in vivo imaging to determine detailed changes in aged murine cerebrovascular networks. Whole-brain vascular tracing shows an overall ~10% decrease in vascular length and branching density with ~7% increase in vascular radii in aged brains. Light sheet imaging with 3D immunolabeling reveals increased arteriole tortuosity of aged brains. Notably, vasculature and pericyte densities show selective and significant reductions in the deep cortical layers, hippocampal network, and basal forebrain areas. We find increased blood extravasation, implying compromised blood-brain barrier function in aged brains. Moreover, in vivo imaging in awake mice demonstrates reduced baseline and on-demand blood oxygenation despite relatively intact neurovascular coupling. Collectively, we uncover regional vulnerabilities of cerebrovascular network and physiological changes that can mediate cognitive decline in normal aging.

Decreased resting-state brain function in older adults predicts enlarged representational momentum.

Representational momentum (RM) refers to the phenomenon in which an observer's judgment of the final location of a previously viewed moving target is often displaced forward in the direction of motion. This phenomenon is an adaptive mechanism that compensates for neural processing delays and is closely associated with visual cortex function. However, the impact of age-related decline of visual cortex function on the manifestations of RM remains unclear. The present study examined differences in the RM effect between older (N = 82) and younger adults (N = 74) using a cursor-positioning task. Additionally, resting-state functional magnetic resonance imaging was used to explore the potential neural substrates that underlie these differences, employing amplitude of low-frequency fluctuation (ALFF, reflecting the intensity of neural activity) and regional homogeneity (ReHo, reflecting the synchronization of neural activity) as indicators. Our findings indicate a significant increase in RM among older adults compared with younger adults. Neuroimaging data revealed a significant decrease in ALFF and ReHo within extensive regions of the visual cortex in older adults, validating age-related differences in this cortical area. More importantly, ALFF values in the bilateral visual area 3 and ReHo values in the bilateral visual area 2 in older adults exhibited a strong negative correlation with their RM effects. These results suggest that larger RM in older adults may be functional compensation for aging of the visual cortex. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Spatial dynamics of mammalian brain development and neuroinflammation by multimodal tri-omics mapping.

The ability to spatially map multiple layers of the omics information over different time points allows for exploring the mechanisms driving brain development, differentiation, arealization, and alterations in disease. Herein we developed and applied spatial tri-omic sequencing technologies, DBiT ARP-seq (spatial ATAC-RNA-Protein-seq) and DBiT CTRP-seq (spatial CUT&Tag- RNA-Protein-seq) together with multiplexed immunofluorescence imaging (CODEX) to map spatial dynamic remodeling in brain development and neuroinflammation. A spatiotemporal tri-omic atlas of the mouse brain was obtained at different stages from postnatal day P0 to P21, and compared to the regions of interest in the human developing brains. Specifically, in the cortical area, we discovered temporal persistence and spatial spreading of chromatin accessibility for the layer-defining transcription factors. In corpus callosum, we observed dynamic chromatin priming of myelin genes across the subregions. Together, it suggests a role for layer specific projection neurons to coordinate axonogenesis and myelination. We further mapped the brain of a lysolecithin (LPC) neuroinflammation mouse model and observed common molecular programs in development and neuroinflammation. Microglia, exhibiting both conserved and distinct programs for inflammation and resolution, are transiently activated not only at the core of the LPC lesion, but also at distal locations presumably through neuronal circuitry. Thus, this work unveiled common and differential mechanisms in brain development and neuroinflammation, resulting in a valuable data resource to investigate brain development, function and disease.

Corticospinal premotor fibers facilitate complex motor control after stroke.

The corticospinal tract (CST) is considered the most important motor output pathway comprising fibers from the primary motor cortex (M1) and various premotor areas. Damage to its descending fibers after stroke commonly leads to motor impairment. While premotor areas are thought to critically support motor recovery after stroke, the functional role of their corticospinal output for different aspects of post-stroke motor control remains poorly understood. We assessed the differential role of CST fibers originating from premotor areas and M1 in the control of basal (single-joint muscle synergies and strength) and complex motor control (involving inter-joint coordination and visuomotor integration) using a novel diffusion imaging approach in chronic stroke patients. While M1 sub-tract anisotropy was positively correlated with basal and complex motor skills, anisotropy of PMd, PMv, and SMA sub-tracts was exclusively associated with complex motor tasks. Interestingly, patients featuring persistent motor deficits showed an additional positive association between premotor sub-tract integrity and basal motor control. While descending M1 output seems to be a prerequisite for any form of upper limb movements, complex motor skills critically depend on output from premotor areas after stroke. The additional involvement of premotor tracts in basal motor control in patients with persistent deficits emphasizes their compensatory capacity in post-stroke motor control. In summary, our findings highlight the pivotal role of descending corticospinal output from premotor areas for motor control after stroke, which thus serve as prime candidates for future interventions to amplify motor recovery.

Eigenvector centrality mapping reveals volatility of functional brain dynamics in anti-NMDA receptor encephalitis

Anti-N-methyl-D-aspartate receptor encephalitis (NMDARE) causes long-lasting cognitive deficits associated with altered functional connectivity. Eigenvector centrality (EC) mapping represents a powerful new method for data-driven voxel-wise and time-resolved estimation of network importance - beyond changes in classical 'static' functional connectivity. To assess changes in functional brain network organization, we applied EC mapping in 73 patients with NMDARE and 73 matched healthy controls. Areas with significant group differences were further investigated using (i) spatial clustering analyses, (ii) time series correlation to assess synchronicity between the hippocampus and cortical brain regions, and (iii) correlation with cognitive and clinical parameters. Dynamic, time-resolved EC showed significantly higher variability in 13 cortical areas (p(FWE)<0.05) in patients with NMDARE compared to HC. Areas with dynamic EC group differences were spatially organized in centrality clusters resembling resting-state networks. Importantly, variability of dynamic EC in the frontotemporal cluster was associated with impaired verbal episodic memory in patients (r=-0.25, p=0.037). EC synchronicity between the hippocampus and the medial prefrontal cortex was reduced in patients compared to HC (p(FWE)<0.05, t(max)=3.76), and associated with verbal episodic memory in patients (r=0.28, p=0.019). Static EC analyses showed group differences in only one brain region (left intracalcarine cortex). Widespread changes in network dynamics and reduced hippocampal-medial prefrontal synchronicity were associated with verbal episodic memory deficits and may thus represent a functional neural correlate of cognitive dysfunction in NMDARE. Importantly, dynamic EC detected substantially more network alterations than traditional static approaches, highlighting the potential of this method to explain long-term deficits in NMDARE.

Association between twin status with cognitive, behavioral development and brain structure in early adolescence: a retrospective cohort analysis based on the Adolescent Brain Cognitive Development Study.

Twin births are related with maternal and fetal adverse outcomes. Little was known about the comparability of the cognitive, behavioral development and brain structure between twins and singletons in early adolescence. This retrospective cohort study was based on data from the United States population-based, prospective, longitudinal observational Adolescent Brain Cognitive Development study. Children with complete twin status information were enrolled, and the exposure variable was twin status. Primary outcomes were cognitive, behavioral development and brain structure in early adolescence. Cognitive and behavioral outcomes were assessed by using the NIH Toolbox and Child Behavioral Checklist, respectively. Brain structure was evaluated by the cortical thickness, area, and volume extracted from the magnetic resonance imaging (MRI) data. Subgroup analyses were conducted by prematurity, birth weight, with sibling, genetic profiles, and twin types (zygosity). From 1st September 2016 to 15th November 2018, 11545 children (9477 singletons and 2068 twins) aged 9-10years were enrolled. Twins showed mildly lower cognitive performance (|t|> 5.104, P-values < 0.001, False Discovery Rate [FDR] < 0.001), better behavioral outcome (|t|> 2.441, P-values < 0.015, FDR < 0.042), such as lower scores for multiple psychiatric disorders and behavioral issues, and smaller cortical volume (t = - 3.854, P-values < 0.001, FDR < 0.001) and cortical area (t = - 3.872, P-values < 0.001, FDR < 0.001). The observed differences still held when stratified for prematurity, birth weight, presence of siblings, genetic profiles, and twin types (zygosity). Furthermore, analyses on the two-year follow-up data showed consistent results with baseline data. Twin status is associated with lower cognitive and better behavioral development in early adolescence accompanied by altered brain structure. Clinicians should be aware of the possible difference when generalizing results from adolescent twin samples to singletons.

Cerebral Synchronization Between Mothers and Their Newborns During Breastfeeding.

Introduction: Breastfeeding is a fundamental biological function in mammals, allowing the progeny to develop in a physiological way. A physical and emotional dialog between mothers and offspring during breastfeeding has been described as part of the attachment relationship, and a synchronicity between maternal and neonatal brains can be hypothesized. This study aimed to assess if neonatal and maternal cortical areas activated during breastfeeding are functionally synchronized since the second day of life. Materials and Methods: Twenty mothers and their term newborns were enrolled. Cortical activation during breastfeeding was identified by multichannel near-infrared spectroscopy, which detects changes in haemoglobin concentration from multiple cortical regions. Functional activity was simultaneously detected (hyperscanning) in mothers and newborns' frontal and motor/primary somatosensory cortical areas during the first 5 minutes of breastfeeding. Cluster analysis and Student's t test were used to detect oxygenated haemoglobin increase, as cortical activation estimate. Wavelet transform coherence (WTC) analysis was used to identify a possible synchronization between maternal and neonatal activated cortical regions. Results: Mothers showed an activation of the central motor/primary somatosensory cortex, above the sagittal fissure. In newborns, the bilateral frontal cortex was activated. WTC analysis revealed two different cyclical synchronizations between mothers and infants' activated cortical regions. Conclusions: Such evidence may reflect a very early common sharing of experiences, possibly associated with reciprocal dynamic motor adjustments, hormonal coregulation, and somatic stimulations and sensations. The observed cyclical neural synchronization, between the mother and her newborn's cortex during breastfeeding, may play an important role in promoting their bonding.

Widespread receptive field remapping in early primate visual cortex

Predictive remapping of receptive fields (RFs) is thought to be one of the critical mechanisms for enforcing perceptual stability during eye movements. While RF remapping has been observed in several cortical areas, its role in early visual cortex and its consequences on the tuning properties of neurons have been poorly understood. Here, we track remapping RFs in hundreds of neurons from visual area V2 while subjects perform a cued saccade task. We find that remapping is widespread in area V2 across neurons from all recorded cortical layers and cell types. Furthermore, our results suggest that remapping RFs not only maintain but also transiently enhance their feature selectivity due to untuned suppression. Taken together, these findings shed light on the dynamics and prevalence of remapping in the early visual cortex, forcing us to revise current models of perceptual stability during saccadic eye movements.

Scalp acupuncture targets for neurological disorders：evidence from neuroimaging studies (part 2).

Scalp acupuncture is a method of treating diseases by dividing and stimulating the corresponding function-oriented cortical scalp areas. It is a commonly used therapy for neurological disorders. However, the specific target selection for scalp acupuncture remains to be explored. This manuscript aims to initiate an attempt to develop/identify scalp acupuncture targets based on neuroimaging findings and noninvasive brain stimulation. Neurosynth-based meta-analysis of neuroimaging studies was conducted to identify brain stimulation targets of neurological disorders. The identified target regions were further projected to the scalp. The traditional acupoints and 10-20 EEG system were referenced for the localization of these targets. In this study, the "mild cognitive impairment" (MCI), "Alzheimer's disease" (AD) and "dementia" were used as the retrieval terms respectively, and a unity detection method was used to generate brain maps, with the default FDR (false discovery rate, P<0.01) threshold of Neurosynth set for subsequent exploration of various disease-related brain regions. The literature search was conducted on July 30, 2022. The localization and manipulation suggestions of neuroimage-based scalp acupuncture targets for MCI, AD, and dementia were introduced in the present paper (part 2). Here are 3 target examples for each of these 3 diseases due to word limitation. 1) MCI：Based on the 81 papers retrieved, we identified 6 potential scalp acupuncture points for MCI, their corresponding brain regions, brain functions and the possible resultant effects of the scalp target acupoint stimulation respectively are as below. MCI1：the orbital part of the left inferior frontal gyrus (left Brodmann area ［BA］47), related to semantic coding, working memory and episodic memory, improving semantic coding and memory function；MCI2：the anterior motor area/left anterior central gyrus (left BA6), the motor center area, improving MCI motor function；MCI3：the left medial temporal gyrus (left BA21), related to the processing of speech, visual space, language and word understanding, improving language and memory. 2) AD：Based on the 196 papers retrieved, we found 6 potential scalp acupuncture targets for AD, their corresponding brain regions and brain functions of the 3 example targets respectively are as below. AD1：the left medial temporal gyrus (left BA21), participating in language and semantic processing, sentence and word generation, intent expression, deductive reasoning；AD2：the left angular gyrus (left BA39), related to semantic processing, word reading and comprehension, memory retrieval, attention and spatial cognition, reasoning, etc.；AD3：the left fusiform/suboccipital gyrus (left BA37), related to semantic classification, text generation, sign language, phonology processing, etc. 3) Dementia：Based on the 142 papers retrieved, we found 4 potential scalp acupuncture targets for dementia, their corresponding brain regions, brain functions and the possible targets of the proposed scalp stimulation respectively are as below. D1 and D2：the left inferior frontal gyrus (i.e., left BA46, and left BA47, respectively), being closely related to working memory, emotional response regulation, melody and other processing processes, may be suitable for treating memory decline and advanced executive dysfunction in patients with dementia；D3：the left medial temporal gyrus (left BA21), an important brain region for various sensory integration, cognitive processing and memory functions, and emotional processing, may be suitable for temporal dementia. We identified scalp acupuncture targets for several common neurological disorders based on neuroimaging findings and noninvasive brain stimulation. The proposed targets may also be used for treating these disorders using nerve/brain stimulation methods.

Implications of altered pyramidal cell morphology on clinical symptoms of neurodevelopmental disorders.

The prevalence of pyramidal cells (PCs) in the mammalian cerebral cortex underscore their value as they play a crucial role in various brain functions, ranging from cognition, sensory processing, to motor output. PC morphology significantly influences brain connectivity and plays a critical role in maintaining normal brain function. Pathological alterations to PC morphology are thought to contribute to the aetiology of neurodevelopmental disorders such as autism spectrum disorder (ASD) and schizophrenia. This review explores the relationship between abnormalities in PC morphology in key cortical areas and the clinical manifestations in schizophrenia and ASD. We focus largely on human postmortem studies and provide evidence that dendritic segment length, complexity and spine density are differentially affected in these disorders. These morphological alterations can lead to disruptions in cortical connectivity, potentially contributing to the cognitive and behavioural deficits observed in these disorders. Furthermore, we highlight the importance of investigating the functional and structural characteristics of PCs in these disorders to illuminate the underlying pathogenesis and stimulate further research in this area.

Functional and structural brain connectivity in disorders of consciousness.

Brain connectivity, allowing information to be shared between distinct cortical areas and thus to be processed in an integrated way, has long been considered critical for consciousness. However, the relationship between functional intercortical interactions and the structural connections thought to underlie them is poorly understood. In the present work, we explore both functional (with an EEG-based metric: the median weighted symbolic mutual information in the theta band) and structural (with a brain MRI-based metric: fractional anisotropy) connectivities in a cohort of 78 patients with disorders of consciousness. Both metrics could distinguish patients in a vegetative state from patients in minimally conscious state. Crucially, we discovered a significant positive correlation between functional and structural connectivities. Furthermore, we showed that this structure-function relationship is more specifically observed when considering structural connectivity within the intra- and inter-hemispheric long-distance cortico-cortical bundles involved in the Global Neuronal Workspace (GNW) theory of consciousness, thus supporting predictions of this model. Altogether, these results support the interest of multimodal assessments of brain connectivity in refining the diagnostic evaluation of patients with disorders of consciousness.

Dynamic spatial representation of self and others’ actions in the macaque frontal cortex

Modulation of neuronal firing rates by the spatial locations of physical objects is a widespread phenomenon in the brain. However, little is known about how neuronal responses to the actions of biological entities are spatially tuned and whether such spatially tuned responses are affected by social contexts. These issues are of key importance for understanding the neural basis of embodied social cognition, such as imitation and perspective-taking. Here, we show that spatial representation of actions can be dynamically changed depending on others' social relevance and agents of action. Monkeys performed a turn-taking choice task with a real monkey partner sitting face-to-face or a filmed partner in prerecorded videos. Three rectangular buttons (left, center, and right) were positioned in front of the subject and partner as their choice targets. We recorded from single neurons in two frontal nodes in the social brain, the ventral premotor cortex (PMv) and the medial prefrontal cortex (MPFC). When the partner was filmed rather than real, spatial preference for partner-actions was markedly diminished in MPFC, but not PMv, neurons. This social context-dependent modulation in the MPFC was also evident for self-actions. Strikingly, a subset of neurons in both areas switched their spatial preference between self-actions and partner-actions in a diametrically opposite manner. This observation suggests that these cortical areas are associated with coordinate transformation in ways consistent with an actor-centered perspective-taking coding scheme. The PMv may subserve such functions in context-independent manners, whereas the MPFC may do so primarily in social contexts.

Sex Differences in the Effect of Brain-derived Neurotrophic Factor (BDNF) Val66Met Polymorphism on Baseline EEG Connectivity

Dependent on Val66Met polymorphism in BDNF gene secretion of neurotrophin affects morphological and functional changes in the developing and mature nervous system, in particular, may contribute to associated with white matter degradation changes in connectivity observed with aging. It was also shown that the associated with Val66Met polymorphism differences in connectivity between cortical structures are moderated by the sex of the subjects. However, there are no studies examining the effect of polymorphism on connectivity, taking into account age and gender differences. In this regard, the present study examined the associations of the Val66Met polymorphism of the BDNF gene with the characteristics of delayed phase synchronization based on EEG data in 223 younger (from 18 to 35 years old) and 134 older (over 55 years old) men and women. The analysis included connections between 84 cortical areas, identified on the basis of 42 Brodmann areas located in the left and right hemispheres. A statistically significant effect, including the factor of polymorphism, was the SEX × GENOTYPE interaction when considering associations at the frequency of the α1-rhythm: in Val/Met men, the strength of thirty-three connections was higher compared to Val/Val. Strengthening of connections was observed mainly between the parahippocampal regions of different hemispheres. At the frequency of the gamma rhythm, associated with the genotype differences in connectivity depended on gender and age. In young subjects, the scores of connectivity in Val/Val women were lower in comparison with men, however, no differences between Val/Val and Met carriers were found in any age group. The combined effect of sex and BDNF genotype on the baseline EEG parameters of brain connectivity may be a background for further study of the role of these factors in the formation of basic characteristics of brain activity.

EEG-Correlates of Competition and Cooperation

The aim was to investigate the peculiarities and localization of the current source density of α- and θ-frequency bands accompanying competition and cooperation with another player, as well as individual figure building in a computer game. The sample included forty-two volunteers (24 females) between the ages of 18 and 47. Analysis of differences in the current source density of 127 channel EEG under different game conditions was performed in the eLoreta program. During competition, the θ-current source density in the anterior cingulate cortex and medial prefrontal cortex was greater than during cooperation. According to the literature on functional correlates of θ-rhythm, it can be suggested that the greater increase in medial frontal θ-rhythm detected during competition may be related to focused attention and cognitive control processes. The alpha current source density in the parietal and visual cortex areas during interactive game modes (cooperation and competition) was lower compared to the individual mode. During cooperation the α-current source density was lower compared to the competition mode. The greatest decrease of the α-current source density in the cooperation mode is consistent with idea of a relation between α-rhythm decrease and the processes of understanding the other person’s intentions.

Effects of a Single Session of Repetitive Transcranial Stimulation in Parkinson Disease

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive technique proposed for recovery of gait and balance in patients with Parkinson&amp;apos;s disease (PD). Our aim was to evaluate the effects of rTMS in PD patients by clinical evaluation and computerized gait analysis. Ten patients were recruited. Each patient was assessed before and after a single session of rTMS by: Berg Scale, Unified Parkinson Disease Rating Scale (UPDRS), 6 Minute Walking Test (6MWT), 10MWT, Time Up and Go (TUG) and spatial-temporal gait analysis by Pablo Gait Assessment sensor. We availed of STM 9000, stimulating with 2000 pulses of 20 Hz rTMS, delivered in 5-second trains with 25 seconds between trains, on the hand area of the motor cortex at 90% resting motor threshold (RMT) on each hemisphere, with 5 minutes pause between hemispheres. Eighty percent of the patient reported subjective benefits, corroborated by objective examination of the results. A significant improvement on the Berg scale was observed. Moreover, a tendence to a significant decrease of stiffness at the lower limbs was evident at UPDRS. Gait analysis showed not significant improvements of evaluated parameters. Although it is premature to draw conclusions, because of the small number of patients, underwent to a single session of rTMS, we confirm the possible beneficial effects and the safety of rTMS. Further studies are needed to validate our findings by clinical evaluation and gait analysis at short, medium, and long term. These may be different in relation to the age, duration and stage of the disease, prevalence of tremor or akinesia and rigidity.

The Pavlovian interpretation of speech and aphasia: Alexander Luria and Wilder Penfield.

This paper discusses a neglected aspect of the historiography of aphasia, the role that Pavlovian conditioning played in Alexander Luria's and Wilder Penfield's understanding of the acquisition, expression, and loss of spoken and written speech. Luria was born into a bourgeois family in Tzarist Russia and pursued his research on speech and aphasia under the Soviet regime. Luria's work was condemned in the last years of Stalin's rule, but it received international acclaim in the West after Stalin's death. Penfield was conversant with Pavlov's writing having had a working relationship with one of Pavlov's foremost students, Boris Babkin, who came to McGill University and later to the Montreal Neurological Institute after being jailed and exiled from the Soviet Union for lack of revolutionary fervor. Both Luria and Penfield, the latter as early as 1935, saw in Pavlovian conditioning mediated by specific areas of the human cerebral cortex the basic neurophysiological mechanism underlying speech and thought, and in Penfield's' case, memory, perception, self-awareness, and purposeful behavior. It is concluded that Luria and Penfield independently arrived at a general hypothesis, based on Pavlovian conditioning, that united the localization of speech, the syndromes caused by damage to speech-competent regions, and the putative neurophysiological mechanisms that they believed to underlie speech and higher cortical functions.

Exploring the Consistent Roles of Motor Areas Across Voluntary Movement and Locomotion.

Multiple cortical motor areas are critically involved in the voluntary control of discrete movement (e.g., reaching) and gait. Here, we outline experimental findings in nonhuman primates with clinical reports and research in humans that explain characteristic movement control mechanisms in the primary, supplementary, and presupplementary motor areas, as well as in the dorsal premotor area. We then focus on single-neuron activity recorded while monkeys performed motor sequences consisting of multiple discrete movements, and we consider how area-specific control mechanisms may contribute to the performance of complex movements. Following this, we explore the motor areas in cats that we have considered as analogs of those in primates based on similarities in their cortical surface topology, anatomic connections, microstimulation effects, and activity patterns. Emphasizing that discrete movement and gait modification entail similar control mechanisms, we argue that single-neuron activity in each area of the cat during gait modification is compatible with the function ascribed to the activity in the corresponding area in primates, recorded during the performance of discrete movements. The findings that demonstrate the premotor areas' contribution to locomotion, currently unique to the cat model, should offer highly valuable insights into the control mechanisms of locomotion in primates, including humans.

Developmental changes in mouse motor skill learning and cortical circuitry.

Motor learning aptitude is developmentally regulated, peaking at P30-P45 for the cortically-dependent accelerating rotarod taskMice learn by shifting from hopping to walking gait, with the gait shift in forelimbs preceding the shift in hindlimbsInhibitory responses in task-active neurons are stronger than task-inactive neurons from parvalbumin-expressing fast-spiking neurons on the first training dayOther interneuron connections from somatostatin-expressing interneurons are unchanged. Plasticity in sensory cortex is restricted to a limited developmental window. Learning motor skills requires motor cortex plasticity, but it is unknown whether there are changes in learning aptitude over development and whether the synaptic mechanisms of plasticity vary across cortical areas. Here, we define the developmental trajectory of motor learning aptitude for the accelerating rotarod task in mice. We find that learning peaks at P30-P45, with mice learning to shift from hopping to walking gait to stay on the rotarod longer. Further, the gait shift in forelimbs precedes hindlimbs. We then find, using recordings targeted to task-active neurons, that inhibitory responses from specific subtypes of interneurons (parvalbumin-expressing) are stronger in active cells, while other interneuron connections (somatostatin-expressing) are unchanged. These results suggest early changes in PV-mediated inhibition support motor skill acquisition.

Amygdala and cortex relationships during learning of a sensory discrimination task.

During learning of a sensory discrimination task, cortical and sub-cortical regions display complex spatiotemporal dynamics. During learning, both amygdala and cortex link stimulus information to its appropriate association, for example a reward. In addition, both structures are also related to non-sensory parameters such as body movements and licking during the reward period. However, the emergence of cortico-amygdala relationships during learning is largely unknown. To study this, we combined wide-field cortical imaging with fiber photometry to simultaneously record cortico-amygdala population dynamics as male mice learn a whisker-dependent go/no-go task. We were able to simultaneously record neuronal populations from the posterior cortex and either the basolateral amygdala (BLA) or central medial amygdala (CEM). Prior to learning, somatosensory and associative cortex responded during sensation, while amygdala areas did not show significant responses. As mice became experts, amygdala responses emerged early during the sensation period, increasing in CEM, while decreasing in BLA. Interestingly, amygdala and cortical responses were associated with task-related body movement, displaying significant responses ∼200 ms before movement initiation which led to licking for the reward. A correlation analysis between cortex and amygdala revealed negative and positive correlation with BLA and CEM respectively, only in the expert case. These results imply that learning induces an involvement of cortex and amygdala which may aid to link sensory stimuli with appropriate associations.Significance Statement Levitan and Gilad study neuronal dynamics in cortex and amygdala as mice learn a sensory discrimination task. They find that amygdala areas display opposing responses only after the mice learn the task. In contrast cortical areas display responses both before and after learning. These results imply that learning induces an involvement of amygdala and cortical areas in order to optimally link sensory stimuli with appropriate associations.

Functional connectivity associations with menstrual pain characteristics in adolescents: an investigation of the triple network model.

Menstrual pain is associated with deficits in central pain processing, yet neuroimaging studies to date have all been limited by focusing on group comparisons of adult women with vs without menstrual pain. This study aimed to investigate the role of the triple network model (TNM) of brain networks in adolescent girls with varied menstrual pain severity ratings. One hundred participants (ages 13-19 years) completed a 6-min resting state functional magnetic resonance imaging (fMRI) scan and rated menstrual pain severity, menstrual pain interference, and cumulative menstrual pain exposure. Imaging analyses included age and gynecological age (years since menarche) as covariates. Menstrual pain severity was positively associated with functional connectivity between the cingulo-opercular salience network (cSN) and the sensory processing regions, limbic regions, and insula, and was also positively associated with connectivity between the left central executive network (CEN) and posterior regions. Menstrual pain interference was positively associated with connectivity between the cSN and widespread brain areas. In addition, menstrual pain interference was positively associated with connectivity within the left CEN, whereas connectivity both within the right CEN and between the right CEN and cortical areas outside the network (including the insula) were negatively associated with menstrual pain interference. Cumulative menstrual pain exposure shared a strong negative association with connectivity between the default mode network and other widespread regions associated with large-scale brain networks. These findings support a key role for the involvement of TNM brain networks in menstrual pain characteristics and suggest that alterations in pain processing exist in adolescents with varying levels of menstrual pain.