Restoring Shank3 in the rostral brainstem of shank3ab−/− zebrafish autism models rescues sensory deficits

People with Phelan-McDermid Syndrome, caused by mutations in the SHANK3 gene, commonly exhibit reduced responses to sensory stimuli; yet the changes in brain-wide activity that link these symptoms to mutations in the shank3 gene remain unknown. Here we quantify movement in response to sudden darkness in larvae of two shank3 zebrafish mutant models and show that both models exhibit dampened responses to this stimulus. Using brain-wide activity mapping, we find that shank3−/− light-sensing brain regions show normal levels of activity while sensorimotor integration and motor regions are less active. Specifically restoring Shank3 function in a sensorimotor nucleus of the rostral brainstem enables the shank3−/− model to respond like wild-type. In sum, we find that reduced sensory responsiveness in shank3−/− models is associated with reduced activity in sensory processing brain regions and can be rescued by restoring Shank3 function in the rostral brainstem. These studies highlight the importance of Shank3 function in the rostral brainstem for integrating sensory inputs to generate behavioral adaptations to changing sensory stimuli.

The Brainstem-Informed Autism Framework: Early Life Neurobehavioral Markers

Autism spectrum disorders (ASD) have long-term implications on functioning at multiple levels. In this perspective, we offer a brainstem-informed autism framework (BIAF) that traces the protracted neurobehavioral manifestations of ASD to early life brainstem dysfunctions. Early life brainstem-mediated markers involving functions of autonomic/arousal regulation, sleep-wake homeostasis, and sensorimotor integration are delineated. Their possible contributions to the early identification of susceptible infants are discussed. We suggest that the BIAF expands our multidimensional understanding of ASD by focusing on the early involvement of brainstem systems. Importantly, we propose an integrated BIAF screener that brings about the prospect of a sensitive and reliable early life diagnostic scheme for weighing the risk for ASD. The BIAF screener could provide clinicians substantial gains in the future and may carve customized interventions long before the current DSM ASD phenotype is manifested using dyadic co-regulation of brainstem-informed autism markers.

Virally Encoded Connectivity Transgenic Overlay RNA sequencing (VECTORseq) defines projection neurons involved in sensorimotor integration

Behavior arises from concerted activity throughout the brain. Consequently, a major focus of modern neuroscience is defining the physiology and behavioral roles of projection neurons linking different brain areas. Single-cell RNA sequencing has facilitated these efforts by revealing molecular determinants of cellular physiology and markers that enable genetically targeted perturbations such as optogenetics, but existing methods for sequencing of defined projection populations are low-throughput, painstaking, and costly. We developed a straightforward, multiplexed approach, Virally Encoded Connectivity Transgenic Overlay RNA sequencing (VECTORseq). VECTORseq repurposes commercial retrogradely infecting viruses typically used to express functional transgenes, e.g., recombinases and fluorescent proteins, by treating viral transgene mRNA as barcodes within single-cell datasets. VECTORseq is compatible with different viral families, resolves multiple populations with different projection targets in one sequencing run, and identifies cortical and subcortical excitatory and inhibitory projection populations. Our study provides a roadmap for high-throughput identification of neuronal subtypes based on connectivity.

Does Long-Term Training in a Water Immersion Environment Change Interoception?

The aim of this study was to investigate individual interoception by comparing the responses of swimmers and baseball players when exposed to specific water environments, depending on training content and environment. Forty-eight healthy male university students were evaluated for their interoceptive response (accuracy, sensibility, and awareness) and heart rate following 25 min of water immersion (WI) at 35 °C. We assessed three conditions: pre-WI, during WI, and post-WI. The results indicated that interoceptive accuracy (IAcc) did not differ between groups because both swimming and baseball do not require emotional expression, as opposed to an activity such as dance. The heart rate was significantly decreased at post-WI compared to that at pre-WI. The IAcc of post-WI presented as higher than that of pre-WI. In addition, there was a significant negative correlation between the ratio of IAcc and that of HR among subjects. Moreover, the attention regulation subscale of the MAIA changed in the WI environment and the ratio of IAcc was negatively correlated with that of the not-distracting subscale of the MAIA. These results suggested that interoception did not differ among the athletes who had long-term training, which enabled them to acquire multi-modal sensorimotor integration, compared to that of non-athlete control participants. We conclude that interoception did not differ among athletes who had long-term training compared to that of non-athlete control participants.

Activation of sensorimotor integration processes with a brain-computer interface

A BCI-controlled hand exoskeleton activates neuroplasticity mechanisms, promoting motor learning. The contribution of perception to this phenomenon is understudied. The aim of this study was to assess the impact of sensorimotor integration on the effectiveness of neurorehabilitation based on the learning of a hand opening movement by stroke patients using BCI and to investigate the effect of ideomotor training on spasticity in the paretic hand. The study was conducted in 58 patients (median age: 63 (22; 83) years) with traumatic brain injury, ischemic (76%) or hemorrhagic (24%) stroke in the preceding 2 (1.0; 12.0) months. The patients received 15 (12; 21) ideomotor training sessions with a BMI-controlled hand exoskeleton. Hand function was assessed before and after rehabilitation on the Fugl–Meyer, ARAT, Frenchay, FIM, Rivermead, and Ashworth scales. An increase in muscle strength was observed in 40% of patients during flexion and extension of the radiocarpal joint and in 29% of patients during the abduction and adduction of the joint. Muscle strength simultaneously increased during the abduction and adduction of the radiocarpal joint (p < 0.004). Ideomotor training is ineffective for reducing spasticity because no statistically significant reduction in muscle tone was detected. Improved motor performance of the paretic hand was positively correlated with improvements in daily activities. Motor training of the paretic hand with a robotic orthosis activates kinesthetic receptors, restores sensation and improves fine motor skills through better sensorimotor integration.

Vestibular Stimulation May Drive Multisensory Processing: Principles for Targeted Sensorimotor Therapy (TSMT)

At birth, the vestibular system is fully mature, whilst higher order sensory processing is yet to develop in the full-term neonate. The current paper lays out a theoretical framework to account for the role vestibular stimulation may have driving multisensory and sensorimotor integration. Accordingly, vestibular stimulation, by activating the parieto-insular vestibular cortex, and/or the posterior parietal cortex may provide the cortical input for multisensory neurons in the superior colliculus that is needed for multisensory processing. Furthermore, we propose that motor development, by inducing change of reference frames, may shape the receptive field of multisensory neurons. This, by leading to lack of spatial contingency between formally contingent stimuli, may cause degradation of prior motor responses. Additionally, we offer a testable hypothesis explaining the beneficial effect of sensory integration therapies regarding attentional processes. Key concepts of a sensorimotor integration therapy (e.g., targeted sensorimotor therapy (TSMT)) are also put into a neurological context. TSMT utilizes specific tools and instruments. It is administered in 8-weeks long successive treatment regimens, each gradually increasing vestibular and postural stimulation, so sensory-motor integration is facilitated, and muscle strength is increased. Empirically TSMT is indicated for various diseases. Theoretical foundations of this sensorimotor therapy are discussed.