Somatosensory Cortical Regions Research Articles

Beyond life: Exploring hemodynamic patterns in postmortem mice brains.

We utilize Laser Speckle Contrast Imaging (LSCI) for visualizing cerebral blood flow in mice during and post-cardiac arrest. Analyzing LSCI images, we noted temporal blood flow variations across the brain surface for hours postmortem. Fast Fourier Transform (FFT) analysis depicted blood flow and microcirculation decay post-death. Continuous Wavelet Transform (CWT) identified potential cerebral hemodynamic synchronization patterns. Additionally, non-negative matrix factorization (NMF) with four components segmented LSCI images, revealing structural subcomponent alterations over time. This integrated approach of LSCI, FFT, CWT, and NMF offers a comprehensive tool for studying cerebral blood flow dynamics, metaphorically capturing the 'end of the tunnel' experience. Results showed primary postmortem hemodynamic activity in the olfactory bulbs, followed by blood microflow relocations between somatosensory and visual cortical regions via the superior sagittal sinus. This method opens new avenues for exploring these phenomena, potentially linking neuroscientific insights with mysteries surrounding consciousness and perception at life's end.

Motor, somatosensory, and executive cortical areas elicit monosynaptic and polysynaptic neuronal activity in the auditory midbrain

We recently reported that the central nucleus of the inferior colliculus (the auditory midbrain) is innervated by glutamatergic pyramidal cells originating not only in auditory cortex (AC), but also in multiple ‘non-auditory’ regions of the cerebral cortex. Here, in anaesthetised rats, we used optogenetics and electrical stimulation, combined with recording in the inferior colliculus to determine the functional influence of these descending connections. Specifically, we determined the extent of monosynaptic excitation and the influence of these descending connections on spontaneous activity in the inferior colliculus.A retrograde virus encoding both green fluorescent protein (GFP) and channelrhodopsin (ChR2) injected into the central nucleus of the inferior colliculus (ICc) resulted in GFP expression in discrete groups of cells in multiple areas of the cerebral cortex. Light stimulation of AC and primary motor cortex (M1) caused local activation of cortical neurones and increased the firing rate of neurones in ICc indicating a direct excitatory input from AC and M1 to ICc with a restricted distribution. In naïve animals, electrical stimulation at multiple different sites within M1, secondary motor, somatosensory, and prefrontal cortices increased firing rate in ICc. However, it was notable that stimulation at some adjacent sites failed to influence firing at the recording site in ICc. Responses in ICc comprised singular spikes of constant shape and size which occurred with a short, and fixed latency (∼ 5 ms) consistent with monosynaptic excitation of individual ICc units. Increasing the stimulus current decreased the latency of these spikes, suggesting more rapid depolarization of cortical neurones, and increased the number of (usually adjacent) channels on which a monosynaptic spike was seen, suggesting recruitment of increasing numbers of cortical neurons. Electrical stimulation of cortical regions also evoked longer latency, longer duration increases in firing activity, comprising multiple units with spikes occurring with significant temporal jitter, consistent with polysynaptic excitation. Increasing the stimulus current increased the number of spikes in these polysynaptic responses and increased the number of channels on which the responses were observed, although the magnitude of the responses always diminished away from the most activated channels. Together our findings indicate descending connections from motor, somatosensory and executive cortical regions directly activate small numbers of ICc neurones and that this in turn leads to extensive polysynaptic activation of local circuits within the ICc.

Atypical Activation of Laryngeal Somatosensory-Motor Cortex During Vocalization in People With Unexplained Chronic Cough

Unexplained chronic cough is common and has substantial negative quality-of-life implications, yet its causes are not well understood. A better understanding of how peripheral and central neural processes contribute to chronic cough is essential for treatment design. To determine if people with chronic cough exhibit signs of abnormal neural processing over laryngeal sensorimotor cortex during voluntary laryngeal motor activity such as vocalization. This was a cross-sectional study of a convenience sample of participants with chronic cough and healthy participants. Testing was performed in an acoustically and electromagnetically shielded chamber. In a single visit, electroencephalographic (EEG) signals were recorded from participants with chronic cough and healthy participants during voice production. The chronic cough group participants presented with unexplained cough of 8 weeks or longer duration with prior medical evaluation including negative results of chest imaging. None of the participants had a history of any neurologic disease known to impair vocalization or swallowing. Data collection for the healthy control group occurred from February 2 to June 28, 2018, and for the chronic cough group, from November 22, 2021, to June 21, 2022. Data analysis was performed from May 1 to October 30, 2022. Participants with or without chronic cough. Event-related spectral perturbation over the laryngeal area of somatosensory-motor cortex from 0 to 30 Hz (ie, θ, α, and β bands) and event-related coherence as a measure of synchronous activity between somatosensory and motor cortical regions. The chronic cough group comprised 13 participants with chronic cough (mean [SD] age, 63.5 [7.8] years; 9 women and 4 men) and the control group, 10 healthy age-matched individuals (mean [SD] age, 60.3 [13.9] years; 6 women and 4 men). In the chronic cough group, the typical movement-related desynchronization over somatosensory-motor cortex during vocalization was significantly reduced across θ, α, and β frequency bands when compared with the control group. This cross-sectional study found that the typical movement-related suppression of brain oscillatory activity during vocalization is weak or absent in people with chronic cough. Thus, chronic cough affects sensorimotor cortical activity during the asymptomatic voluntary activation of laryngeal muscles.

Transient disruption of functional connectivity and depression of neural fluctuations in a mouse model of acute septic encephalopathy.

Septic encephalopathy leads to major and costly burdens for a large percentage of admitted hospital patients. Elderly patients are at an increased risk, especially those with dementia. Current treatments are aimed at sedation to combat mental status changes and are not aimed at the underlying cause of encephalopathy. Indeed, the underlying pathology linking together peripheral infection and altered neural function has not been established, largely because good, acutely accessible readouts of encephalopathy in animal models do not exist. Behavioral testing in animals lasts multiple days, outlasting the time frame of acute encephalopathy. Here, we propose optical fluorescent imaging of neural functional connectivity (FC) as a readout of encephalopathy in a mouse model of acute sepsis. Imaging and basic behavioral assessment were performed at baseline, Hr8, Hr24, and Hr72 following injection of either lipopolysaccharide or phosphate buffered saline. Neural FC strength decreased at Hr8 and returned to baseline by Hr72 in motor, somatosensory, parietal, and visual cortical regions. Additionally, neural fluctuations transiently declined at Hr8 and returned to baseline by Hr72. Both FC strength and fluctuation tone correlated with neuroscore indicating this imaging methodology is a sensitive and acute readout of encephalopathy.

Multisensory Rather than Unisensory Representations Contribute to Statistical Context Learning in Tactile Search.

Using a combination of behavioral and EEG measures in a tactile odd-one-out search task with collocated visual items, we investigated the mechanisms underlying facilitation of search by repeated (vs. nonrepeated) spatial distractor-target configurations ("contextual cueing") when either the tactile (same-modality) or the visual array (different-modality) context was predictive of the location of the tactile singleton target. Importantly, in both conditions, the stimulation was multisensory, consisting of tactile plus visual items, although the target was singled out in the tactile modality and so the visual items were task-irrelevant. We found that when the predictive context was tactile, facilitation of search RTs by repeated configurations was accompanied by, and correlated with, enhanced lateralized ERP markers of pre-attentive (N1, N2) and, respectively focal-attentional processing (contralateral delay activity) not only over central ("somatosensory"), but also posterior ("visual") electrode sites, although the ERP effects were less marked over visual cortex. A similar pattern-of facilitated RTs and enhanced lateralized (N2 and contralateral delay activity) ERP components-was found when the predictive context was visual, although the ERP effects were less marked over somatosensory cortex. These findings indicate that both somatosensory and visual cortical regions contribute to the more efficient processing of the tactile target in repeated stimulus arrays, although their involvement is differentially weighted depending on the sensory modality that contains the predictive information.

Microglia Activation Tracking across Brain Regions over the Development of Neuropathic Pain

Neuropathic pain is a chronic, debilitating condition associated with impaired cognitive, affective and sensory dimensions. One of the mechanisms underlying neuropathic pain is neuroinflammation. Microglia are resident macrophages in the central nervous system and plays an important role in setting neuroinflammation during chronic pain conditions. Microglial mechanisms of pain have been broadly studied in the spinal cord. However, brain mapping of microglial activation over the development of neuropathic pain has not been performed. Adult male and female Sprague-Dawley rats (n=4-6/group) were submitted to a chronic constriction injury (CCI) model of neuropathic pain. After mechanical allodynia assessment by von Frey tests, the whole brain tissue was collected prior the surgery (day 0), or after 7 and 28 days. Microglia activation was assessed by CD11b densitometry using immunohistochemistry in brain regions associated with pain (sensory, affective, motor, and reward system areas). Male rats show a strongly activated microglia in somatosensory cortical regions (Insular and dorsolateral-prefrontal cortex) at 7 but not 28 days. However, it shows a sustained CD11b activation in mediodorsal thalamic nuclei and parabrachial nucleus at 7 and 28 days after CCI surgery. Central medial and paraventricular thalamic nucleus show microglia activation only at 28 days. Affective associated regions (anterior cingulate cortex, medial prefrontal cortex and central amygdala) also shown a sustained microglia activation. Brain reward system regions like the ventral tegmental area, nucleus accumbens and substantia nigra displays microglia activation at 7 and 28 days. Neuropathic pain induces widespread microglia activation across the brain. Microglia activation in somatosensory cortex occurs at 7 but not 28 days whilst affective-motivational regions display a sustained or stronger activation. Sensory regions microglia activation could develop rather than maintain neuropathic pain. Long-lasting effective disorders may be associated with microglial activation in affective-motivational encoding regions. NARSAD - YOUNG INVESTIGATOR GRANT from BRAIN & BEHAVIOR RESEARCH FOUNDATION.

Timed Up and Go in People with Subjective Cognitive Decline Is Associated with Faster Cognitive Deterioration and Cortical Thickness

Introduction: Early markers of neurodegeneration provide an opportunity to detect, monitor, and initiate interventions in individuals who have an increased risk of developing dementia. Here, we investigated whether the Timed Up and Go (TUG) test is associated with early brain neurodegeneration and whether the TUG test could be a marker of cognitive decline in people with subjective cognitive decline (SCD). Methods: This is a longitudinal analysis of the Dementia Disease Initiation Study, a prospective, community-based, cohort study from Norway, designed to investigate early markers of cognitive impairment and dementia. Participants were classified as SCD and healthy controls (HC). The main studied variables were the TUG test and cognition as measured by the Mini-Mental State Examination and the Consortium to Establish a Registry for Alzheimer’s Disease memory composite score. Additionally, we investigated the cross-sectional association of brain morphology with the TUG using 1.5T-MRI. Results: The sample included 45 participants (SCD = 21, HC = 24) followed during a mean time of 1.50 ± 0.70 years. At baseline, the cognitive performance did not differ between the groups, but TUG was longer in SCD. Slower baseline TUG was associated with a faster cognitive decline in both groups and it was also associated with reduced cortical thickness especially in motor, executive, associative, and somatosensory cortical regions in people with SCD. Discussion/Conclusion: TUG predicted cognitive change in individuals with SCD, and there was a negative association between TUG and cortical thickness. TUG is a promising cheap and noninvasive marker of early cognitive decline and may help initiate interventions in individuals who have an increased risk of dementia.

Thalamic altered spontaneous activity and connectivity in obstructive sleep apnea syndrome.

Obstructive sleep apnea (OSA) syndrome is a sleep disorder characterized by excessive snoring, repetitive apneas, and nocturnal arousals, that leads to fragmented sleep and intermittent nocturnal hypoxemia. Morphometric and functional brain alterations in cortical and subcortical structures have been documented in these patients via magnetic resonance imaging (MRI), even if correlational data between the alterations in the brain and cognitive and clinical indexes are still not reported. We examined the impact of OSA on brain spontaneous activity by measuring the fractional amplitude of low-frequency fluctuations (fALFF) in resting-state functional MRI data of 20 drug-naïve patients with OSA syndrome and 20 healthy controls matched for age, gender, and body mass index. Patients showed a pattern of significantly abnormal subcortical functional activity as compared to controls, with increased activity selectively involving the thalami, specifically their intrinsic nuclei connected to somatosensory and motor-premotor cortical regions. Using these nuclei as seed regions, the subsequent functional connectivity analysis highlighted an increase in patients' thalamocortical connectivity at rest. Additionally, the correlation between fALFF and polysomnographic data revealed a possible link between OSA severity and fALFF of regions belonging to the central autonomic network. Our results suggest a hyperactivation in thalamic diurnal activity in patients with OSA syndrome, which we interpret as a possible consequence of increased thalamocortical circuitry activation during nighttime due to repeated arousals.

Cortical Hub for Flavor Sensation in Rodents.

The experience of eating is inherently multimodal, combining intraoral gustatory, olfactory, and somatosensory signals into a single percept called flavor. As foods and beverages enter the mouth, movements associated with chewing and swallowing activate somatosensory receptors in the oral cavity, dissolve tastants in the saliva to activate taste receptors, and release volatile odorant molecules to retronasally activate olfactory receptors in the nasal epithelium. Human studies indicate that sensory cortical areas are important for intraoral multimodal processing, yet their circuit-level mechanisms remain unclear. Animal models allow for detailed analyses of neural circuits due to the large number of molecular tools available for tracing and neuronal manipulations. In this review, we concentrate on the anatomical and neurophysiological evidence from rodent models toward a better understanding of the circuit-level mechanisms underlying the cortical processing of flavor. While more work is needed, the emerging view pertaining to the multimodal processing of food and beverages is that the piriform, gustatory, and somatosensory cortical regions do not function solely as independent areas. Rather they act as an intraoral cortical hub, simultaneously receiving and processing multimodal sensory information from the mouth to produce the rich and complex flavor experience that guides consummatory behavior.

Sex-Dependent Cortical Volume Changes in Patients with Degenerative Cervical Myelopathy.

Degenerative cervical myelopathy (DCM) is a progressive condition characterized by degeneration of osseocartilaginous structures within the cervical spine resulting in compression of the spinal cord and presentation of clinical symptoms. Compared to healthy controls (HCs), studies have shown DCM patients experience structural and functional reorganization in the brain; however, sex-dependent cortical differences in DCM patients remains largely unexplored. In the present study, we investigate the role of sex differences on the structure of the cerebral cortex in DCM and determine how structural differences may relate to clinical measures of neurological function. T1-weighted structural MRI scans were acquired in 85 symptomatic and asymptomatic patients with DCM and 90 age-matched HCs. Modified Japanese Orthopedic Association (mJOA) scores were obtained for patients. A general linear model was used to determine vertex-level significant differences in gray matter volume (GMV) between the following groups (1) male HCs and female HCs, (2) male patients and female patients, (3) male patients and male HCs, and (4) female patients and female HCs. Within patients, males exhibited larger GMV in motor, language, and vision related brain regions compared to female DCM patients. Males demonstrated a significant positive correlation between GMV and mJOA score, in which patients with worsening neurological symptoms exhibited decreasing GMV primarily across somatosensory and motor related cortical regions. Females exhibited a similar association, albeit across a broader range of cortical areas including those involved in pain processing. In sensorimotor regions, female patients consistently showed smaller GMV compared with male patients, independent of mJOA score. Results from the current study suggest strong sex-related differences in cortical volume in patients with DCM, which may reflect hormonal influence or differing compensation mechanisms.

Vagus nerve stimulation induces widespread cortical and behavioral activation

Vagus nerve stimulation (VNS) is used for management of a variety of neurological conditions, although the therapeutic mechanisms are not fully understood. Accumulating evidence suggests that VNS may modulate cortical state and plasticity through activation of broadly projecting neuromodulatory systems. Using a mouse model, we compared arousal-linked behaviors with dorsal cortical activity obtained with widefield and two-photon GCaMP6s calcium imaging and electrophysiological recordings. We observed robust and reliable cortical and behavioral dose-dependent activation in waking mice to VNS, including pupil dilation and, frequently, whisker movements and locomotion. Widefield calcium imaging and multiunit recording during VNS revealed that this observed increase in arousal state is coupled with a rapid and widespread increase in excitatory activity, including, but not limited to, activation of somatosensory, visual, motor, retrosplenial, and auditory cortical regions. Two-photon GCaMP6s calcium imaging of cholinergic and noradrenergic cortical axons revealed that VNS strongly activates these neuromodulatory systems. Importantly, VNS-evoked activation of neuromodulatory axons and excitatory neurons in the cortex persisted in mice under light anesthesia, in the absence of overt movement. Arousal state changes were abolished by vagus nerve transection, confirming that observed VNS effects were specific to nerve stimulation and triggered widespread activity above that which can be explained by motor activity. Taken together, our results support a model of VNS in which activation of subcortical structures leads to widespread activation of cortex and an increase in arousal state, at least partially due to the activation of cholinergic and noradrenergic modulatory pathways.

Hierarchical cortical gradients in somatosensory processing

Sensory information is processed in the visual cortex in distinct streams of different anatomical and functional properties. A comparable organizational principle has also been proposed to underlie auditory processing. This raises the question of whether a similar principle characterize the somatosensory domain. One property of a cortical stream is a hierarchical organization of the neuronal response properties along an anatomically distinct pathway. Indeed, several hierarchies between specific somatosensory cortical regions have been identified, primarily using electrophysiology, in non-human primates. However, it has been unclear how these local hierarchies are organized throughout the cortex. Here we used phase-encoded bilateral full-body light touch stimulation in healthy humans under functional MRI to study the large-scale organization of hierarchies in the somatosensory domain. We quantified two measures of hierarchy of BOLD responses, selectivity and laterality. We measured how selectivity and laterality change as we move away from the central sulcus within four gross anatomically-distinct regions. We found that both selectivity and laterality decrease in three directions: parietal, posteriorly along the parietal lobe, frontal, anteriorly along the frontal lobe and medial, inferiorly-anteriorly along the medial wall. The decline of selectivity and laterality along these directions provides evidence for hierarchical gradients. In view of the anatomical segregation of these three directions, the multiplicity of body representations in each region and the hierarchical gradients in our findings, we propose that as in the visual and auditory domains, these directions are streams of somatosensory information processing.

Gray matter alteration in heroin-dependent men: An atlas-based magnetic resonance imaging study

Previous imaging studies on heroin addiction have reported brain morphological alterations. However, the effects of heroin exposure on gray matter volume varied among different studies due to different factors such as substitution treatment or mandatory abstinence. Meanwhile, the relationship between gray matter and heroin use history remains unknown. Thirty-three male heroin-dependent (HD) individuals who are not under any substitution treatment or mandatory abstinence and 40 male healthy controls (HC) were included in this structural magnetic resonance imaging study. With an atlas-based approach, gray matter structures up to individual functional area were delineated, and the differences in their volumes between the HD and HC groups were analyzed. In addition, the relationship between gray matter volume and duration of heroin use was explored. The HD group demonstrated significantly lower cortical volume mainly in the prefrontal cortex and mesolimbic dopaminergic regions across different parcellation levels, whereas several visual and somatosensory cortical regions in the HD group had greater volume relative to the HC group at a more detailed parcellation level. The duration of heroin use was negatively correlated with the gray matter volume of prefrontal cortex. These findings suggest that heroin addiction be related to gray matter alteration and might be related to damage/maladaption of the inhibitory control, reward, visual, and somatosensory functions of the brain, although cognitive correlates are warranted in future study. In addition, the atlas-based morphology analysis is a potential tool to help researchers search biomarkers of heroin addiction.

Male Urogenital System Mapped Onto the Sensory Cortex: Functional Magnetic Resonance Imaging Evidence

IntroductionThe projection of the human male urogenital system onto the paracentral lobule has not previously been mapped comprehensively. AimTo map specific urogenital structures onto the primary somatosensory cortex toward a better understanding of sexual response in men. MethodsUsing functional magnetic resonance imaging, we mapped primary somatosensory cortical responses to self-stimulation of the penis shaft, glans, testicles, scrotum, rectum, urethra, prostate, perineum, and nipple. We further compared neural response with erotic and prosaic touch of the penile shaft. Main Outcome MeasureWe identified the primary mapping site of urogenital structures on the paracentral lobule and identified networks involved in perceiving touch as erotic. ResultsWe mapped sites on the primary somatosensory cortex to which components of the urogenital structures project in men. Evidence is provided that penile cutaneous projection is different from deep penile projection. Similar to a prior report in women, we show that the nipple projects to the same somatosensory cortical region as the genitals. Evidence of differential representation of erotic and nonerotic genital self-stimulation is also provided, the former activating sensory networks other than the primary sensory cortex, indicating a role of “top-down” activity in erotic response. Clinical ImplicationsWe map primary sites of projection of urogenital structures to the primary somatosensory cortex and differentiate cortical sites of erotic from nonerotic genital self-stimulation. Strength & LimitationsTo our knowledge, this is the first comprehensive mapping onto the primary somatosensory cortex of the projection of the components of the urogenital system in men and the difference in cortical activation in response to erotic vs nonerotic self-stimulation. The nipple was found to project to the same cortical region as the genitals. Evidence is provided that superficial and deep penile stimulation project differentially to the cortex, suggesting that sensory innervation of the penis is provided by more than the (pudendal) dorsal nerve. ConclusionThis study reconciles prior apparently conflicting findings and offers a comprehensive mapping of male genital components to the paracentral lobule. We provide evidence of differential projection of light touch vs pressure applied to the penile shaft, suggesting differential innervation of its superficial, vs deep structure. Similar to the response in women, we found nipple projection to genital areas of the paracentral lobule. We also provide evidence of differential representation of erotic and nonerotic genital self-stimulation, the former activating sensory networks other than the primary sensory cortex, indicating a role of top-down activity in erotic response.Allen K, Wise N, Frangos E, et al. Male Urogenital System Mapped Onto the Sensory Cortex: Functional Magnetic Resonance Imaging Evidence. J Sex Med 2020;17:603–613.

Application of the Migraine Aura Complexity Score (MACS): Clinical and Neuroimaging Study.

Background: Manifestations of typical migraine aura can be numerous. Investigation of its pathophysiological mechanisms can be challenging if a stratification of phenotypes is not performed. In this context, the Migraine Aura Complexity Score (MACS), recently developed, may help. Here we aimed to categorize migraine patients into homogenous groups using MACS and to compare those groups with respect to patients' characteristics and neuroimaging findings.Methods: Participants who have a migraine with aura (MwA) were interviewed after each attack in order to obtain the characteristics of migraine aura. Thereafter, we scored the complexity of their auras by MACS. The MACS was used to categorize patients into three groups: MwA-S (with simple aura), MwA-MC (with moderately complex aura), and MwA-C (with complex aura). The patient characteristics and estimated cortical thickness of regions of interest, which are potentially linked to the symptoms that develop during the aura, were used to compare these groups.Results: In total, 338 MwA attacks were recorded in analyzed groups. Scotoma was the most frequently reported symptom in the groups, followed by somatosensory aura in the MwA-C group and zig-zag lines in the MwA-MC and MwA-S groups. Patients in the MwA-C and MwA-MC groups had a thicker cortex in the left primary visual cortex with respect to MwA-S group. In addition, patients in the MwA-C group had a thicker cortex in several visual and somatosensory cortical regions relative to the MwA-S group.Conclusions: Our results show that the newly developed MACS can be used for the stratification of MwA patients, herewith allowing the better investigation of changes in migraineurs' brains.

The neural mechanisms of mindfulness-based pain relief: a functional magnetic resonance imaging-based review and primer.

The advent of neuroimaging methodologies, such as functional magnetic resonance imaging (fMRI), has significantly advanced our understanding of the neurophysiological processes supporting a wide spectrum of mind–body approaches to treat pain. A promising self-regulatory practice, mindfulness meditation, reliably alleviates experimentally induced and clinical pain. Yet, the neural mechanisms supporting mindfulness-based pain relief remain poorly characterized. The present review delineates evidence from a spectrum of fMRI studies showing that the neural mechanisms supporting mindfulness-induced pain attenuation differ across varying levels of meditative experience. After brief mindfulness-based mental training (ie, less than 10 hours of practice), mindfulness-based pain relief is associated with higher order (orbitofrontal cortex and rostral anterior cingulate cortex) regulation of low-level nociceptive neural targets (thalamus and primary somatosensory cortex), suggesting an engagement of unique, reappraisal mechanisms. By contrast, mindfulness-based pain relief after extensive training (greater than 1000 hours of practice) is associated with deactivation of prefrontal and greater activation of somatosensory cortical regions, demonstrating an ability to reduce appraisals of arising sensory events. We also describe recent findings showing that higher levels of dispositional mindfulness, in meditation-naïve individuals, are associated with lower pain and greater deactivation of the posterior cingulate cortex, a neural mechanism implicated in self-referential processes. A brief fMRI primer is presented describing appropriate steps and considerations to conduct studies combining mindfulness, pain, and fMRI. We postulate that the identification of the active analgesic neural substrates involved in mindfulness can be used to inform the development and optimization of behavioral therapies to specifically target pain, an important consideration for the ongoing opioid and chronic pain epidemic.

An Activation Likelihood Estimate Meta-analysis of Thalamocortical Dysconnectivity in Psychosis

BackgroundThalamocortical dysconnectivity is hypothesized to underlie the pathophysiology of psychotic disorders, including schizophrenia and bipolar disorder, and individuals at clinical high risk. Numerous studies have examined connectivity networks seeding from the thalamus during rest, revealing a pattern of thalamo-fronto-cerebellar hypoconnectivity and thalamosensory hyperconnectivity. However, given variability in these networks, as well as their relationships with clinical and cognitive symptoms, thalamocortical connectivity’s status as a biomarker and treatment target for psychotic disorders remains unclear. MethodsA literature search was performed to identify thalamic seed-based connectivity studies conducted in patients with psychotic disorders. Activation likelihood estimate analysis examined the reported coordinates for hypoconnectivity (healthy control participants > patients with psychosis) and hyperconnectivity (patients with psychosis > healthy control participants). The relationship between hypoconnectivity and hyperconnectivity, as well as their relationships with clinical and cognitive measures, was meta-analyzed. ResultsEach activation likelihood estimate included 20 experiments (from 17 publications). Thalamocortical hypoconnectivity was observed in middle frontal, cingulate, and thalamic regions, while hyperconnectivity was observed in motor, somatosensory, temporal, occipital, and insular cortical regions. Meta-analysis of the studies reporting correlations between hypo- and hyperconnectivity showed a strong negative relationship. Meta-analysis of studies reporting correlations between hyperconnectivity and symptoms showed small but significant positive relationships. ConclusionsActivation likelihood estimates of thalamocortical hypoconnectivity revealed a network of prefrontal and thalamic regions, while hyperconnections identified sensory areas. The strong negative relationship between these thalamocortical deflections suggests that they arrive from a common mechanism and may account for aspects of psychosis. These findings identify reliable thalamocortical networks that may guide future studies and serve as crucial treatment targets for psychotic disorders.

Whole brain vascular imaging in a mouse model of Alzheimer’s disease with two-photon microscopy

Given known correlations between vascular health and cognitive impairment, the development of tools to image microvasculature in the whole brain could help investigate these correlations. We explore the feasibility of using an automated serial two-photon microscope to image fluorescent gelatin-filled whole rodent brains in three-dimensions (3-D) with the goal of carrying group studies. Vascular density (VD) was computed using automatic segmentation combined with coregistration techniques to build a group-level vascular metric in the whole brain. Focusing on the medial prefrontal cortex, cerebral cortex, the olfactory bulb, and the hippocampal formation, we compared the VD of three age groups (2-, 4.5-, and 8-months-old), for both wild type mice and a transgenic model (APP/PS1) with pathology resembling Alzheimer's disease (AD). We report a general loss of VD caused by the aging process with a small VD increase in the diseased animals in the somatomotor and somatosensory cortical regions and the olfactory bulb, partly supported by MRI perfusion data. This study supports previous observations that AD transgenic mice show a higher VD in specific regions compared with WT mice during the early and late stages of the disease (4.5 to 8 months), extending results to whole brain mapping.

Cortical projections to the superior colliculus in grey squirrels (Sciurus carolinensis).

The superior colliculus is an important midbrain structure involved with integrating information from varying sensory modalities and sending motor signals to produce orienting movements towards environmental stimuli. Because of this role, the superior colliculus receives a multitude of sensory inputs from a wide variety of subcortical and cortical structures. Proportionately, the superior colliculus of grey squirrels is among the largest in size of all studied mammals, suggesting the importance of this structure in the behavioural characteristics of grey squirrels. Yet, our understanding of the connections of the superior colliculus in grey squirrels is lacking, especially with respect to possible cortical influences. In this study, we placed anatomical tracer injections within the medial aspect of the superior colliculus of five grey squirrels (Sciurus carolinensis) and analysed the areal distribution of corticotectal projecting cells in flattened cortex. V1 projections to the superior colliculus were studied in two additional animals. Our results indicate that the superior colliculus receives cortical projections from visual, higher order somatosensory, and higher order auditory regions, as well as limbic, retrosplenial and anterior cingulate cortex. Few, if any, corticotectal projections originate from primary motor, primary somatosensory or parietal cortical regions. This distribution of inputs is similar to the distribution of inputs described in other rodents such as rats and mice, yet the lack of inputs from primary somatosensory and motor cortex is features of corticotectal inputs more similar to those observed in tree shrews and primates, possibly reflecting a behavioural shift from somatosensory (vibrissae) to visual navigation.

Timing of cortical activation during spontaneous swallowing.

Saliva accumulation in the oropharynx generates an automatic pattern of swallowing in the brainstem in animals. Previous fMRI studies have found that spontaneous saliva and water swallows in humans evoked activation following swallow onset in both precentral motor and postcentral somatosensory cortical regions. Using event-related averaging of continuous functional near infrared spectroscopy (fNIRS), we examined cortical hemodynamic responses (HDR) from 5s before to 35s after spontaneous reflexive saliva swallow onset in the lateral postcentral somatosensory and precentral motor regions in both hemispheres in healthy volunteers. Three HDR changes from baseline were detected. First, the onset of HDR occurred 2s before swallow onset in the left postcentral somatosensory area and 0.67s before swallow onset in the right postcentral somatosensory area. Second, an early HDR peak amplitude occurred 3-4s after swallow onset in all four regions. Z scores relative to baseline pre-swallow cortical activity levels averaged 20 and 22.7s in the right and left somatosensory regions and 10 and 15.8s in left and right motor areas, respectively. Finally, a late HDR peak occurring between 22 and 23s after swallow onset in the somatosensory regions and 17-19s in the motor areas likely resulted from esophageal peristalsis. Overall, cortical activation timing relative to swallow onsets showed activation began before the pharyngeal phase of swallowing in the somatosensory areas. This indicates that somatosensory triggering of swallowing occurs not only in the brainstem but also in the cortex for reflexive saliva swallowing in awake humans.