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Sensory over-responsivity is related to GABAergic inhibition in thalamocortical circuits.

ABSTRACT: Sensory over-responsivity (SOR), extreme sensitivity to or avoidance of sensory stimuli (e.g., scratchy fabrics, loud sounds), is a highly prevalent and impairing feature of neurodevelopmental disorders such as autism spectrum disorders (ASD), anxiety, and ADHD. Previous studies have found overactive brain responses and reduced modulation of thalamocortical connectivity in response to mildly aversive sensory stimulation in ASD. These findings suggest altered thalamic sensory gating which could be associated with an excitatory/inhibitory neurochemical imbalance, but such thalamic neurochemistry has never been examined in relation to SOR. Here we utilized magnetic resonance spectroscopy and resting-state functional magnetic resonance imaging to examine the relationship between thalamic and somatosensory cortex inhibitory (gamma-aminobutyric acid, GABA) and excitatory (glutamate) neurochemicals with the intrinsic functional connectivity of those regions in 35 ASD and 35 typically developing pediatric subjects. Although there were no diagnostic group differences in neurochemical concentrations in either region, within the ASD group, SOR severity correlated negatively with thalamic GABA (r?=?-0.48, p?

SUBMITTER: Wood ET

PROVIDER: S-EPMC7804323 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Sensory over-responsivity is related to GABAergic inhibition in thalamocortical circuits.

Wood Emily T ET Cummings Kaitlin K KK Jung Jiwon J Patterson Genevieve G Okada Nana N Guo Jia J O'Neill Joseph J Dapretto Mirella M Bookheimer Susan Y SY Green Shulamite A SA

Translational psychiatry 20210112 1

Sensory over-responsivity (SOR), extreme sensitivity to or avoidance of sensory stimuli (e.g., scratchy fabrics, loud sounds), is a highly prevalent and impairing feature of neurodevelopmental disorders such as autism spectrum disorders (ASD), anxiety, and ADHD. Previous studies have found overactive brain responses and reduced modulation of thalamocortical connectivity in response to mildly aversive sensory stimulation in ASD. These findings suggest altered thalamic sensory gating which could b ...[more]

PMID: 33436538

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Project description:Sensory over-responsivity, a subtype of sensory modulation disorder, is characterized by extreme negative reactions to normative sensory experiences. These over-reactions can interfere with daily activities and cause stress to children and their families. The etiology and developmental course of sensory over-responsivity is still largely unknown. We measured tactile and auditory over-responsivity in a population-based, typically developing sample of twins (N=978) at age two years via a caregiver report temperament questionnaire and again at age seven years via a sensory over-responsivity symptom inventory. Participating twins were treated as singletons although all analyses controlled for clustering within families. Children were divided into four trajectory groups based on risk status at both ages: low symptom (N=768), remitted (N=75), late-onset (N=112), and chronic (N=24). A subset of children who screened positive for SOR in toddlerhood (N = 102) took part in a pilot study focused on sensory over-responsivity at four years of age. Children in the chronic group had more severe symptoms of sensory sensitivity at age four years, including more motion sensitivity, than the other trajectory groups. Children in the chronic group had a younger gestational age and were more likely to be low birth-weight than the low symptom group. Differences between remitted and late-onset groups and the low-symptoms group were inconsistent across measures. Sensory over-responsivity was modestly correlated across ages (r = .22 for tactile over-responsivity and r = .11 for auditory over-responsivity), but symptoms were more stable among children born prematurely or who had more fearful and less soothable temperaments. A clear implication is that assessment over development may be necessary for a valid sensory processing disorder diagnosis, and a speculative implication is that sensory over-responsivity symptoms may be etiologically heterogeneous, with different causes of transient and stable symptoms.

Project description:Most sensory information destined for the neocortex is relayed through the thalamus, where considerable transformation occurs1,2. One means of transformation involves interactions between excitatory thalamocortical neurons that carry data to the cortex and inhibitory neurons of the thalamic reticular nucleus (TRN) that regulate the flow of those data3-6. Although the importance of the TRN has long been recognised7-9, understanding of its cell types, their organization and their functional properties has lagged behind that of the thalamocortical systems they control. Here we address this by investigating the somatosensory and visual circuits of the TRN in mice. In the somatosensory TRN we observed two groups of genetically defined neurons that are topographically segregated and physiologically distinct, and that connect reciprocally with independent thalamocortical nuclei through dynamically divergent synapses. Calbindin-expressing cells-located in the central core-connect with the ventral posterior nucleus, the primary somatosensory thalamocortical relay. By contrast, somatostatin-expressing cells-which reside along the surrounding edges of the TRN-synapse with the posterior medial thalamic nucleus, a higher-order structure that carries both top-down and bottom-up information10-12. The two TRN cell groups process their inputs in pathway-specific ways. Synapses from the ventral posterior nucleus to central TRN cells transmit rapid excitatory currents that depress deeply during repetitive activity, driving phasic spike output. Synapses from the posterior medial thalamic nucleus to edge TRN cells evoke slower, less depressing excitatory currents that drive more persistent spiking. Differences in the intrinsic physiology of TRN cell types, including state-dependent bursting, contribute to these output dynamics. The processing specializations of these two somatosensory TRN subcircuits therefore appear to be tuned to the signals they carry-a primary central subcircuit tuned to discrete sensory events, and a higher-order edge subcircuit tuned to temporally distributed signals integrated from multiple sources. The structure and function of visual TRN subcircuits closely resemble those of the somatosensory TRN. These results provide insights into how subnetworks of TRN neurons may differentially process distinct classes of thalamic information.

Project description:Individuals with autism spectrum disorder (ASD) are significantly more likely to experience sensory over-responsivity (SOR) compared to neurotypical controls. SOR in autism has been shown to be related to atypical functional connectivity in the salience network (SN), a brain network thought to help direct attention to the most relevant stimuli in one's environment. However, all studies to date which have examined the neurobiological basis of sensory processing in ASD have used primarily male samples so little is known about sex differences in the neural processing of sensory information. This study examined the relationship between SOR and resting-state functional connectivity in the SN for 37 males and 16 females with autism, ages 8-17 years. While there were no sex differences in parent-rated SOR symptoms, there were significant sex differences in how SOR related to SN connectivity. Relative to females with ASD, males with ASD showed a stronger association between SOR and increased connectivity between the salience and primary sensory networks, suggesting increased allocation to sensory information. Conversely, for females with ASD, SOR was more strongly related to increased connectivity between the SN and prefrontal cortex. Results suggest that the underlying mechanisms of SOR in ASD are sex specific, providing insight into the differences seen in the diagnosis rate and symptom profiles of males and females with ASD. LAY SUMMARY: Sensory over-responsivity (SOR) is common in autism. Most research on the neural basis of SOR has focused on males, so little is known about SOR or its neurobiology in females with autism spectrum disorder. Here despite no sex differences in SOR symptoms, we found sex differences in how SOR related to intrinsic connectivity in a salience detection network. Results show sex differences in the neural mechanisms underlying SOR and inform sex differences seen in diagnosis rates and symptom profiles in autism. Autism Res 2020, 13: 1489-1500. © 2020 International Society for Autism Research, Wiley Periodicals, Inc.

Dataset Information

Sensory over-responsivity is related to GABAergic inhibition in thalamocortical circuits.

Publications

Sensory over-responsivity is related to GABAergic inhibition in thalamocortical circuits.

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