Sensorimotor Integration Research Articles

Human brain representations of internally generated outcomes of approximate calculation revealed by ultra-high-field brain imaging

Much of human culture’s advanced technology owes its existence to the ability to mentally manipulate quantities. Neuroscience has described the brain regions overall recruited by numerical tasks and the neuronal codes representing individual quantities during perceptual tasks. Nevertheless, it remains unknown how quantity representations are combined or transformed during mental computations and how specific quantities are coded in the brain when generated as the result of internal computations rather than evoked by a stimulus. Here, we imaged the brains of adult human subjects at 7 Tesla during an approximate calculation task designed to disentangle in- and outputs of the computation from the operation itself. While physically presented sample numerosities were distinguished in activity patterns along the dorsal visual pathway and within frontal and occipito-temporal regions, a representation of the internally generated result was most prominently detected in higher order regions such as angular gyrus and lateral prefrontal cortex. Behavioral precision in the task was related to cross-decoding performance between sample and result representations in medial IPS regions. This suggests the transformation of sample into result may be carried out within dorsal stream sensory-motor integration regions, and resulting outputs maintained for task purposes in higher-level regions in a format possibly detached from sensory-evoked inputs.

Muscle anatomy is reflected in the spatial organization of the spinal motoneuron pools

Neural circuits embed limb dynamics for motor control and sensorimotor integration. The somatotopic organization of motoneuron pools in the spinal cord may support these computations. Here, we tested if the spatial organization of motoneurons is related to the musculoskeletal anatomy. We created a 3D model of motoneuron locations within macaque spinal cord and compared the spatial distribution of motoneurons to the anatomical organization of the muscles they innervate. We demonstrated that the spatial distribution of motoneuron pools innervating the upper limb and the anatomical relationships between the muscles they innervate were similar between macaque and human species. Using comparative analysis, we found that the distances between motoneuron pools innervating synergistic muscles were the shortest, followed by those innervating antagonistic muscles. Such spatial organization can support the co-activation of synergistic muscles and reciprocal inhibition of antagonistic muscles. The spatial distribution of motoneurons may play an important role in embedding musculoskeletal dynamics.

The influence of psychoacoustic features on the formation of technical and emotionally expressive skills in piano teaching: integrative analysis in the context of sensorimotor integration and musical perception

The influence of psychoacoustic features on the formation of technical and emotionally expressive skills in piano teaching: integrative analysis in the context of sensorimotor integration and musical perception

A randomized controlled trial comparing different sites of high-velocity low amplitude thrust on sensorimotor integration parameters

Increasing evidence suggests that a high-velocity, low-amplitude (HVLA) thrust directed at a dysfunctional vertebral segment in people with subclinical spinal pain alters various neurophysiological measures, including somatosensory evoked potentials (SEPs). We hypothesized that an HVLA thrust applied to a clinician chosen vertebral segment based on clinical indicators of vertebral dysfunction, in short, segment considered as “relevant” would significantly reduce the N30 amplitude compared to an HVLA thrust applied to a predetermined vertebral segment not based on clinical indicators of vertebral dysfunction or segment considered as “non-relevant”. In this double-blinded, active-controlled, parallel-design study, 96 adults with recurrent mild neck pain, ache, or stiffness were randomly allocated to receiving a single thrust directed at either a segment considered as “relevant” or a segment considered as “non-relevant" in their upper cervical spine. SEPs of median nerve stimulation were recorded before and immediately after a single HVLA application delivered using an adjusting instrument (Activator). A linear mixed model was used to assess changes in the N30 amplitude. A significant interaction between the site of thrust delivery and session was found (F1,840 = 9.89, p < 0.002). Pairwise comparisons showed a significant immediate decrease in the N30 complex amplitude after the application of HVLA thrust to a segment considered “relevant” (− 16.76 ± 28.32%, p = 0.005). In contrast, no significant change was observed in the group that received HVLA thrust over a segment considered “non-relevant” (p = 0.757). Cervical HVLA thrust applied to the segment considered as “relevant” altered sensorimotor parameters, while cervical HVLA thrust over the segment considered as “non-relevant” did not. This finding supports the hypothesis that spinal site targeting of HVLA interventions is important when measuring neurophysiological responses. Further studies are needed to explore the potential clinical relevance of these findings.

Neural extracellular matrix regulates visual sensory motor integration

Visual processing depends on sensitive and balanced synaptic neurotransmission. Extracellular matrix proteins in the environment of cells are key modulators in synaptogenesis and synaptic plasticity. In the present study, we provide evidence that the combined loss of the four extracellular matrix components, brevican, neurocan, tenascin-C, and tenascin-R, in quadruple knockout mice leads to severe retinal dysfunction and diminished visual motion processing invivo. Remarkably, impaired visual motion processing was accompanied by a developmental loss of cholinergic direction-selective starburst amacrine cells. Additionally, we noted imbalance of inhibitory and excitatory synaptic signaling in the quadruple knockout retina. Collectively, the study offers insights into the functional importance of four key extracellular matrix proteins for retinal function, visual motion processing, and synaptic signaling.

The conserved RNA-binding protein Imp is required for the specification and function of olfactory navigation circuitry in Drosophila

Complex behaviors depend on the precise developmental specification of neuronal circuits, but the relationship between genetic programs for neural development, circuit structure, and behavioral output is often unclear. The central complex (CX) is a conserved sensory-motor integration center in insects, which governs many higher-order behaviors and largely derives from a small number of type II neural stem cells (NSCs). Here, we show that Imp, a conserved IGF-II mRNA-binding protein expressed in type II NSCs, plays a role in specifying essential components of CX olfactory navigation circuitry. We show the following: (1) that multiple components of olfactory navigation circuitry arise from type II NSCs. (2) Manipulating Imp expression in type II NSCs alters the number and morphology of many of these circuit elements, with the most potent effects on neurons targeting the ventral layers of the fan-shaped body (FB). (3) Imp regulates the specification of Tachykinin-expressing ventral FB input neurons. (4) Imp is required in type II NSCs for establishing proper morphology of the CX neuropil structures. (5) Loss of Imp in type II NSCs abolishes upwind orientation to attractive odor while leaving locomotion and odor-evoked regulation of movement intact. Taken together, our findings establish that a temporally expressed gene can regulate the expression of a complex behavior by developmentally regulating the specification of multiple circuit components and provides a first step toward a developmental dissection of the CX and its roles in behavior.

Obstacle Avoidance in Healthy Adults and People with Multiple Sclerosis: Preliminary fNIRS Study.

This study examined how gait adaptation during predictable and non-predictable obstacle avoidance affects the sensorimotor network in both healthy controls (HC) and persons with multiple sclerosis (pwMS). We utilized fNIRS measurements of HbO2 and HHb to estimate cortical activations and connectivity networks, which were then analyzed using power spectral density (PSD) and partial directed coherence (PDC). The findings revealed distinct patterns of cortical activation and connectivity for each task condition in both groups. Healthy individuals displayed lower cortical activations in the bilateral motor cortex (MC) during non-predictable obstacle avoidance, indicating efficient neural processing. On the other hand, pwMS exhibited lower cortical activations across most brain areas during non-predictable tasks, suggesting potential limitations in neural resource allocation. When tasks were combined, pwMS demonstrated higher cortical activation across all recorded brain areas compared to HC, indicating a compensatory mechanism to maintain gait stability. Functional connectivity analysis revealed that pwMS recruited higher bilateral somatosensory association cortex (SAC) than HC, whereas healthy individuals engaged more bilateral premotor cortices (PMC). These findings suggest alterations in sensorimotor integration and motor planning in pwMS. Four machine learning models (KNN, SVM, DT, and DA) achieved high classification accuracies (92-99%) in differentiating between task conditions within each group. These results highlight the potential of integrating fNIRS-based cortical activation and connectivity measures with machine learning as biomarkers for MS-related impairments in cognitive-motor interaction. Such biomarkers could aid in predicting future mobility decline, fall risk, and disease progression.

Association between seated trunk control and cortical sensorimotor white matter brain changes in patients with chronic low back pain.

Trunk control involves integration of sensorimotor information in the brain. Individuals with chronic low back pain (cLBP) have impaired trunk control and show differences in brain structure and function in sensorimotor areas compared with healthy controls (HC). However, the relationship between brain structure and trunk control in this group is not well understood. This cross-sectional study aimed to compare seated trunk control and sensorimotor white matter (WM) structure in people with cLBP and HC and explore relationships between WM properties and trunk control in each group. Thirty-two people with cLBP and 35 HC were tested sitting on an unstable chair to isolate trunk control; performance was measured using the 95% confidence ellipse area (CEA95) of center-of-pressure tracing. A WM network between cortical sensorimotor regions of interest was derived using probabilistic tractography. WM microstructure and anatomical connectivity between cortical sensorimotor regions were assessed. A mixed-model ANOVA showed that people with cLBP had worse trunk control than HC (F = 12.96; p < .001; ηp2 = .091). There were no differences in WM microstructure or anatomical connectivity between groups (p = 0.564 to 0.940). In the cLBP group, WM microstructure was moderately correlated (|r| = .456 to .565; p ≤ .009) with trunk control. Additionally, the cLBP group demonstrated stronger relationships between anatomical connectivity and trunk control (|r| = .377 to .618 p < .034) compared to the HC group. Unique to the cLBP group, WM connectivity between right somatosensory and left motor areas highlights the importance of interhemispheric information exchange for trunk control. Parietal areas associated with attention and spatial reference frames were also relevant to trunk control. These findings suggest that people with cLBP adopt a more cortically driven sensorimotor integration strategy for trunk control. Future research should replicate these findings and identify interventions to effectively modulate this strategy.

Sensory integration research: priority scientific directions based on the analysis of Web of Science Core Collection resources

Background and Study Aim. Monitoring the condition of athletes is one of the leading tasks in sports science. Predicting success and skill growth is an integral part of monitoring. The fulfillment of this task requires the use of modern methods and the sensory integration analysis occupies an important place. The purpose of this article is to analyze publications on sensory integration and identify priority research areas in this field. Material and Methods. The bibliometric database Web of Science Core Collection (WoS) was analyzed. 388 sources that met the search criteria for 2013-2023 were selected for primary analysis. Bibliometric methods were used for processing the obtained information. The program VOSviewer 1.6.18 was used for keyword analysis and direct citation analysis with the construction of bibliometric maps, visualization of cluster density, and weight – citations. Results. The leading publication categories in WoS were Neurosciences, Sport Sciences, Psychology, Psychology Experimental, Physiology, Rehabilitation. The distribution of publications by years was fairly evenly. Most publications were related to Germany and the USA. The most frequent institutions were German Sport University Cologne, Universidade de Sao Paulo, Shanghai University of Sport, Institute National de la Sante et de la Recherche Medicale Inserm, University of Freiburg. The most cited authors were identified. The constructed bibliometric maps allowed us to identify the leading thematic areas of research and current research directions in the field. The two most important clusters were identified. The largest cluster reflects research on balance and posture and the use of special exercises for rehabilitation in different population groups. The second cluster includes the most significant keyword in the whole map – "sensorimotor integration". The works reflect studies of sensorimotor integration, the study of movement features, and coordination and control of movement at different levels. Conclusions. The conducted bibliometric analysis of publications confirms the relevance of sensorimotor integration. A stable interest in this problem has been determined. Research in this area has neurophysiological, sports-recreational, and medical-rehabilitation directions. Neurophysiological research is aimed at analyzing balance and equilibrium and the application of various tests and functional samples. The sport context studies sensory integration in different sports. Recreational publications have investigated sensory integration as a criterion of health. The therapeutic and rehabilitation focus explores the use of sensory integration as a criterion for treatment and rehabilitation. A characteristic feature is the intersection of these directions. There is a lack of studies devoted to sensory integration in sport dancing. There is a lack of studies aimed at studying the psychophysiological state. These types of research should be assessed as relevant.

Cell-Type Specific Connectivity of Whisker-Related Sensory and Motor Cortical Input to Dorsal Striatum.

The anterior dorsolateral striatum (DLS) is heavily innervated by convergent excitatory projections from the primary motor (M1) and sensory cortex (S1) and considered an important site of sensorimotor integration. M1 and S1 corticostriatal synapses have functional differences in their connection strength with striatal spiny projection neurons (SPNs) and fast-spiking interneurons (FSIs) in the DLS and, as a result, exert distinct influences on sensory-guided behaviors. In the present study, we tested whether M1 and S1 inputs exhibit differences in the subcellular anatomical distribution of striatal neurons. We injected adeno-associated viral vectors encoding spaghetti monster fluorescent proteins (sm.FPs) into M1 and S1 in male and female mice and used confocal microscopy to generate 3D reconstructions of corticostriatal inputs to single identified SPNs and FSIs obtained through ex vivo patch clamp electrophysiology. We found that M1 and S1 dually innervate SPNs and FSIs; however, there is a consistent bias towards the M1 input in SPNs that is not found in FSIs. In addition, M1 and S1 inputs were distributed similarly across the proximal, medial, and distal regions of SPN and FSI dendrites. Notably, closely localized M1 and S1 clusters of inputs were more prevalent in SPNs than FSIs, suggesting that cortical inputs are integrated through cell-type specific mechanisms. Our results suggest that the stronger functional connectivity from M1 to SPNs compared to S1, as previously observed, is due to a higher quantity of synaptic inputs. Our results have implications for how sensorimotor integration is performed in the striatum through cell-specific differences in corticostriatal connections.

Action-specific feature processing in the human cortex: An fMRI study

Sensorimotor integration involves feedforward and reentrant processing of sensory input. Grasp-related motor activity precedes and is thought to influence visual object processing. Yet, while the importance of reentrant feedback is well established in perception, the top-down modulations for action and the neural circuits involved in this process have received less attention. Do action-specific intentions influence the processing of visual information in the human cortex? Using a cue-separation fMRI paradigm, we found that action-specific instruction processing (manual alignment vs. grasp) became apparent only after the visual presentation of oriented stimuli, and occurred as early as in the primary visual cortex and extended to the dorsal visual stream, motor and premotor areas. Further, dorsal stream area aIPS, known to be involved in object manipulation, and the primary visual cortex showed task-related functional connectivity with frontal, parietal and temporal areas, consistent with the idea that reentrant feedback from dorsal and ventral visual stream areas modifies visual inputs to prepare for action. Importantly, both the task-dependent modulations and connections were linked specifically to the object presentation phase of the task, suggesting a role in processing the action goal. Our results show that intended manual actions have an early, pervasive, and differential influence on the cortical processing of vision.

Elovanoids and Precursor Free Fatty Acid 34:6 Confer Robust Neuroprotection after Experimental Traumatic Brain Injury

One-third of the close to 70 million people suffering from traumatic brain injury (TBI) have an increased risk for developing chronic cognitive impairments, including Alzheimer’s-like Dementia (AD). We studied neuroprotection by Elovanoid-34:6 (ELV-N34) and its precursor free-fatty- acid-34:6 (FFA34:6) following TBI in male Sprague-Dawley rats using fluid percussion injury (FPI) or controlled cortical impact (CCI) models. At 1 and 24 hours post-surgery, rats were intranasally administered saline, ELV-N34, or FFA34:6 (only in the CCI model). Rats underwent composite neurological testing to assess sensorimotor integration. On day 14, FPI animals were sacrificed, and MRI and diffuse tensor imaging (DTI) were performed to assess lesion size and white matter connectivity. On day 3, CCI animals were used for multi-omic analysis using 10x Chromium, Illumina Sequencing, and Seurat v4.0.1. Total neurological scores for animals administered ELV-N34 and FFA34:6 were lower than controls, and scores for FFA34:6 treated rats were lower than those of ELV34:6 treated rats (p&lt;0.05). MRI and DTI showed smaller lesions and preserved white matter connectivity in the ELV34:6 group. Single cell analysis with ELV-N34 treatment revealed downregulation of Spp1, Fos, and Gfap genes and upregulation of Trem2 and Pld5 genes. FFA34:6 treatment revealed downregulation of inflammatory genes Spp1, Ccl2, and Vim. These changing gene cluster patterns are implicated in neurodegenerative diseases. We demonstrated that ELV-N34 and FFA34:6 convey behavioral, structural, and genetic neuroprotective bioactivity in experimental TBI.

Reversible deactivation of motor cortex reveals that areas in parietal cortex are differentially dependent on motor cortex for the generation of movement.

Primates are characterized by specializations for manual manipulation, including expansion of posterior parietal cortex (PPC) and, in Catarrhines, evolution of a dexterous hand and opposable thumb. Previous studies examined functional interactions between motor cortex and PPC in New World monkeys and galagos, by inactivating M1 and evoking movements from PPC. These studies found that portions of PPC depend on M1 to generate movements. We now add a species that more closely resembles humans in hand morphology and PPC: macaques. Inactivating portions of M1 resulted in all evoked movements being reduced (28%) or completely abolished (72%) at the PPC sites tested (in areas 5L, PF, and PFG). Anterior parietal area 2 was similarly affected (26% reduced and 74% abolished) and area 1 was the least affected (12% no effect, 54% reduced, and 34% abolished). Unlike previous studies in New World monkeys and galagos, interactions between both nonanalogous (heterotopic) and analogous (homotopic) M1 and parietal movement domains were commonly found in most areas. These experiments demonstrate that there may be two parallel networks involved in motor control: a posterior parietal network dependent on M1 and a network that includes area 1 that is relatively independent of M1. Furthermore, it appears that the relative size and number of cortical fields in parietal cortex in different species correlates with homotopic and heterotopic effect prevalence. These functional differences in macaques could contribute to more numerous and varied muscle synergies across major muscle groups, supporting the expansion of the primate manual behavioral repertoire observed in Old World monkeys.NEW & NOTEWORTHY Motor cortex and anterior and posterior parietal cortex form a sensorimotor integration network. We tested the extent to which parietal areas could initiate movements independent of M1. Our findings support the contention that, although areas 2, 5L, PF, and PFG are highly dependent on M1 to produce movement, area 1 may constitute a parallel corticospinal pathway that can function somewhat independently of M1. A similar functional architecture may underlie dexterous tool use in humans.

Precise sensorimotor control impacts reproductive fitness of C. elegans in 3D environments.

The ability of animals to sense and navigate towards relevant cues in complex and elaborate habitats is paramount for their survival and reproductive success. The nematode Caenorhabditis elegans uses a simple and elegant sensorimotor program to track odors in its environments. Whether this allows the worm to effectively navigate a complex environment and increase its evolutionary success has not been tested yet. We designed an assay to test whether C. elegans can track odors in a complex 3D environment. We then used a previously established 3D cultivation system to test whether defect in tracking odors to find food in a complex environment affected their brood size. We found that wild-type worms can accurately migrate toward a variety of odors in 3D. However, mutants of the muscarinic acetylcholine receptor GAR-3 which have a sensorimotor integration defect that results in a subtle navigational defect steering towards attractive odors, display decreased chemotaxis to the odor butanone not seen in the traditional 2D assay. We also show that the decreased ability to locate appetitive stimuli in 3D leads to reduced brood size not observed in the standard 2D culture conditions. Our study shows that mutations in genes previously overlooked in 2D conditions can have a significant impact in the natural habitat, and highlights the importance of considering the evolutionary selective pressures that have shaped the behavior, as well as the underlying genes and neural circuits.

Interareal Synaptic Inputs Underlying Whisking-Related Activity in the Primary Somatosensory Barrel Cortex.

Body movements influence brain-wide neuronal activities. In the sensory cortex, thalamocortical bottom-up inputs and motor-sensory top-down inputs are thought to affect the dynamics of membrane potentials (Vm ) of neurons and change their processing of sensory information during movements. However, direct perturbation of the axons projecting to the sensory cortex from other remote areas during movements has remained unassessed, and therefore the interareal circuits generating motor-related signals in sensory cortices remain unclear. Using a Gi/o -coupled opsin, eOPN3, we here inhibited interareal signals incoming to the whisker primary somatosensory barrel cortex (wS1) of awake male mice and tested their effects on whisking-related changes in neuronal activities in wS1. Spontaneous whisking in air induced the changes in spike rates of a subset of wS1 neurons, which were accompanied by depolarization and substantial reduction of slow-wave oscillatory fluctuations of Vm Despite an extensive innervation, inhibition of inputs from the whisker primary motor cortex (wM1) to wS1 did not alter the spike rates and Vm dynamics of wS1 neurons during whisking. In contrast, inhibition of axons from the whisker-related thalamus (wTLM) and the whisker secondary somatosensory cortex (wS2) to wS1 largely attenuated the whisking-related supra- and sub-threshold Vm dynamics of wS1 neurons. Notably, silencing inputs from wTLM markedly decreased the modulation depth of whisking phase-tuned neurons in wS1, while inhibiting wS2 inputs did not impact the whisking variable tuning of wS1 neurons. Thus, sensorimotor integration in wS1 during spontaneous whisking is predominantly facilitated by direct synaptic inputs from wTLM and wS2 rather than from wM1.

Speech motor adaptation during synchronous and metronome-timed speech.

Sensorimotor integration during speech has been investigated by altering the sound of a speaker's voice in real time; in response, the speaker learns to change their production of speech sounds in order to compensate (adaptation). This line of research has however been predominantly limited to very simple speaking contexts, typically involving (a) repetitive production of single words and (b) production of speech while alone, without the usual exposure to other voices. This study investigated adaptation to a real-time perturbation of the first and second formants during production of sentences either in synchrony with a prerecorded voice (synchronous speech group) or alone (solo speech group). Experiment 1 (n = 30) found no significant difference in the average magnitude of compensatory formant changes between the groups; however, synchronous speech resulted in increased between-individual variability in such formant changes. Participants also showed acoustic-phonetic convergence to the voice they were synchronizing with prior to introduction of the feedback alteration. Furthermore, the extent to which the changes required for convergence agreed with those required for adaptation was positively correlated with the magnitude of subsequent adaptation. Experiment 2 tested an additional group with a metronome-timed speech task (n = 15) and found a similar pattern of increased between-participant variability in formant changes. These findings demonstrate that speech motor adaptation can be measured robustly at the group level during performance of more complex speaking tasks; however, further work is needed to resolve whether self-voice adaptation and other-voice convergence reflect additive or interactive effects during sensorimotor control of speech. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Contributed Session III: Active vision shapes ocular dominance.

Ocular dominance is a basic visual property that shows short-term plasticity in adult humans, where 2h of monocular deprivation leads to a homeostatic shift of ocular dominance in favour of the deprived eye. Using an altered reality setting, we found that this homeostatic plasticity can be triggered without depriving one eye of visual input, but merely perturbing the temporal correspondence between voluntary actions and vision in one eye. Participants wore a VR set; its monocular screens were connected with cameras monitoring the front space, which participants used to perform a complex visuomotor task. During a 60 minute period, the input to the dominant eye was delayed by 333 ms, making it useless for visuomotor coordination. Following this, ocular dominance (quantified by binocular rivalry) was systematically shifted in favour of the delayed eye, a similar effect as that produced by monocular contrast-deprivation. The shift was only observed when participants actively engaged in the visuomotor task, not when they passively watched a confederate perform the same task. We interpret these results in the light of parallel fMRI experiments where monocular deprivation is associated with a global system reconfiguration that pivots around a key area for sensorimotor integration, the Pulvinar. Based on our findings, we suggest that active vision is foundational to weighting sensory information, even at the level of simple visual processes as those setting ocular dominance.

Embodied strategies for public speaking anxiety: evaluation of the Corp-Oral program

BackgroundPublic speaking is an indispensable skill that can profoundly influence success in both professional and personal spheres. Regrettably, managing anxiety during a speech poses a significant challenge for many of the population. This research assessed the impacts of a Corp-Oral program, designed to manage public speaking anxiety in university students, based on, body awareness, embodied message techniques, simulation, embodied visualization, body transformation, and gesture enhancement.MethodsThirty-six students (61% women; Mage = 20.22, SD = 1.23 years) were randomly assigned to either an experimental group (n = 18), which underwent the Corp-Oral program, or a control group (n = 18). Self-perceived anxiety, heart rate, and electroencephalography were measured in a pre-test and a post-test.ResultsThe study reveals that the Corp-Oral program significantly (p &amp;lt; 0.005) reduced both physiological responses (heart rate) and self-reported measures of anxiety. The alteration was more noticeable in self-reported anxiety measures (a decrease of 33.217%) than in heart rate (a decrease of 4.659%). During the speech, the experimental group exhibited increased cortical activation in areas related to emotional regulation, consciousness, sensorimotor integration, and movement control. A significant increase in frontal alpha asymmetry was observed for the experimental group in the post-test, but there were no significant variations in the theta/beta ratio.ConclusionThese findings underline the benefit of managing public speaking anxiety not merely by reducing it but by channeling it through embodied strategies. These strategies could lead to greater action awareness that would cushion the physiological effect of the anxiety response and help generate a better self-perception of the anxiety state.

Neurophysiological explorations across the spectrum of psychosis, autism, and depression, during wakefulness and sleep: protocol of a prospective case–control transdiagnostic multimodal study (DEMETER)

BackgroundQuantitative electroencephalography (EEG) analysis offers the opportunity to study high-level cognitive processes across psychiatric disorders. In particular, EEG microstates translate the temporal dynamics of neuronal networks throughout the brain. Their alteration may reflect transdiagnostic anomalies in neurophysiological functions that are impaired in mood, psychosis, and autism spectrum disorders, such as sensorimotor integration, speech, sleep, and sense of self. The main questions this study aims to answer are as follows: 1) Are EEG microstate anomalies associated with clinical and functional prognosis, both in resting conditions and during sleep, across psychiatric disorders? 2) Are EEG microstate anomalies associated with differences in sensorimotor integration, speech, sense of self, and sleep? 3) Can the dynamic of EEG microstates be modulated by a non-drug intervention such as light hypnosis?MethodsThis prospective cohort will include a population of adolescents and young adults, aged 15 to 30 years old, with ultra-high-risk of psychosis (UHR), first-episode psychosis (FEP), schizophrenia (SCZ), autism spectrum disorder (ASD), and major depressive disorder (MDD), as well as healthy controls (CTRL) (N = 21 × 6), who will be assessed at baseline and after one year of follow-up. Participants will undergo deep phenotyping based on psychopathology, neuropsychological assessments, 64-channel EEG recordings, and biological sampling at the two timepoints. At baseline, the EEG recording will also be coupled to a sensorimotor task and a recording of the characteristics of their speech (prosody and turn-taking), a one-night polysomnography, a self-reference effect task in virtual reality (only in UHR, FEP, and CTRL). An interventional ancillary study will involve only healthy controls, in order to assess whether light hypnosis can modify the EEG microstate architecture in a direction opposite to what is seen in disease.DiscussionThis transdiagnostic longitudinal case–control study will provide a multimodal neurophysiological assessment of clinical dimensions (sensorimotor integration, speech, sleep, and sense of self) that are disrupted across mood, psychosis, and autism spectrum disorders. It will further test the relevance of EEG microstates as dimensional functional biomarkers.Trial registrationClinicalTrials.gov Identifier NCT06045897.

Whisker kinematics in the cerebellum.

The whisker system is widely used as a model system for understanding sensorimotor integration. Purkinje cells in the crus regions of the cerebellum have been reported to linearly encode whisker midpoint, but it is unknown whether the paramedian and simplex lobules as well as their target neurons in the cerebellar nuclei also encode whisker kinematics and if so which ones. Elucidating how these kinematics are represented throughout the cerebellar hemisphere is essential for understanding how the cerebellum coordinates multiple sensorimotor modalities. Exploring the cerebellar hemisphere of mice using optogenetic stimulation, we found that whisker movements can be elicited by stimulation of Purkinje cells in not only crus1 and crus2, but also in the paramedian lobule and lobule simplex; activation of cells in the medial paramedian lobule had on average the shortest latency, whereas that of cells in lobule simplex elicited similar kinematics as those in crus1 and crus2. During spontaneous whisking behaviour, simple spike activity correlated in general better with velocity than position of the whiskers, but it varied between protraction and retraction as well as per lobule. The cerebellar nuclei neurons targeted by the Purkinje cells showed similar activity patterns characterized by a wide variety of kinematic signals, yet with a dominance for velocity. Taken together, our data indicate that whisker movements are much more prominently and diversely represented in the cerebellar cortex and nuclei than assumed, highlighting the rich repertoire of cerebellar control in the kinematics of movements that can be engaged during coordination. KEY POINTS: Excitation of Purkinje cells throughout the cerebellar hemispheres induces whisker movement, with the shortest latency and longest duration within the paramedian lobe. Purkinje cells have differential encoding for the fast and slow components of whisking. Purkinje cells encode not only the position but also the velocity of whiskers. Purkinje cells with high sensitivity for whisker velocity are preferentially located in the medial part of lobule simplex, crus1 and lateral paramedian. In the downstream cerebellar nuclei, neurons with high sensitivity for whisker velocity are located at the intersection between the medial and interposed nucleus.