Sensory Processing Dysfunction Research Articles

Haptic and visuo-haptic impairments for object recognition in children with autism spectrum disorder: focus on the sensory and multisensory processing dysfunctions

Dysfunctions in sensory processing are widely described in individuals with autism spectrum disorder (ASD), although little is known about the developmental course and the impact of these difficulties on the learning processes during the preschool and school ages of ASD children. Specifically, as regards the interplay between visual and haptic information in ASD during developmental age, knowledge is very scarce and controversial. In this study, we investigated unimodal (visual and haptic) and cross-modal (visuo-haptic) processing skills aimed at object recognition through a behavioural paradigm already used in children with typical development (TD), with cerebral palsy and with peripheral visual impairments. Thirty-five children with ASD (age range: 5–11 years) and thirty-five age-matched and gender-matched typically developing peers were recruited. The procedure required participants to perform an object-recognition task relying on only the visual modality (black-and-white photographs), only the haptic modality (manipulation of real objects) and visuo-haptic transfer of these two types of information. Results are consistent with the idea that visuo-haptic transfer may be significantly worse in ASD children than in TD peers, leading to significant impairment in multisensory interactions for object recognition facilitation. Furthermore, ASD children tended to show a specific deficit in haptic information processing, while a similar trend of maturation of visual modality between the two groups is reported. This study adds to the current literature by suggesting that ASD differences in multisensory processes also regard visuo-haptic abilities necessary to identify and recognise objects of daily life.

Assessment of white matter microstructure integrity in subacute postconcussive vestibular dysfunction using NODDI

Abstract Vestibular symptoms, such as dizziness and balance impairment, are frequently reported following mild traumatic brain injury (mTBI) and are associated with a protracted recovery, yet the underlying neuroanatomical substrates remain unclear. The present study utilized advanced diffusion MRI (dMRI) techniques including both conventional diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) to investigate microstructural white matter integrity in individuals with postconcussive vestibular dysfunction (PCVD) within the subacute injury period (median of 35 days from injury; IQR of 23). Study participants included 23 individuals with subacute PCVD and 37 healthy control subjects who underwent imaging and comprehensive clinical vestibular testing. Between-group voxelwise analysis of differences in white matter revealed areas of higher intra-neurite volume fraction (VIn) and isotropic volume fraction (VIso) within PCVD subjects compared to controls, which involved overlapping regions within the left hemisphere of the brain. Affected areas of higher VIn and VIso included the superior longitudinal fasciculus (SLF) and superior and posterior corona radiata (SCR and PCR, respectively). We examined the relationship between clinical vestibular measures and diffusion metrics including DTI (fractional anisotropy [FA], mean diffusivity [MD], radial diffusivity [RD] and axial diffusivity [AD]) and NODDI (intraneurite volume fraction [VIn], isotropic volume fraction [VIso], dispersion anisotropy [DA], orientation dispersion indexTotal/Primary/Secondary [ODIT/P/S]) within 32 regions-of-interest. Clinical vestibular measures included self-reported measures, including the Dizziness Handicap Inventory, Visual Vertigo Analog Scale, and Vestibular/Ocular-Motor Screening, as well as objective vestibular testing using the sensory organization test. Significant correlations were found with clinical measures across all diffusion maps (except DA), within various regions of interest (ROIs), including SLF, SCR, and PCR. These results implicate several important association bundles that may potentiate sensory processing dysfunction related to PCVD. Whether these neuroanatomical differences found within the subacute phase of PCVD are in response to injury or represent preexisting structural variations that increase vulnerability to sensory processing dysfunction is unclear and remains an active area of study.

Transcutaneous cervical vagus nerve stimulation improves sensory performance in humans: a randomized controlled crossover pilot study

Accurate senses depend on high-fidelity encoding by sensory receptors and error-free processing in the brain. Progress has been made towards restoring damaged sensory receptors. However, methods for on-demand treatment of impaired central sensory processing are scarce. Prior invasive studies demonstrated that continuous vagus nerve stimulation (VNS) in rodents can activate the locus coeruleus-norepinephrine system to rapidly improve central sensory processing. Here, we investigated whether transcutaneous VNS improves sensory performance in humans. We conducted three sham-controlled experiments, each with 12 neurotypical adults, that measured the effects of transcutaneous VNS on metrics of auditory and visual performance, and heart rate variability (HRV). Continuous stimulation was delivered to cervical (tcVNS) or auricular (taVNS) branches of the vagus nerve while participants performed psychophysics tasks or passively viewed a display. Relative to sham stimulation, tcVNS improved auditory performance by 37% (p = 0.00052) and visual performance by 23% (p = 0.038). Participants with lower performance during sham conditions experienced larger tcVNS-evoked improvements (p = 0.0040). Lastly, tcVNS increased HRV during passive viewing, corroborating vagal engagement. No evidence for an effect of taVNS was observed. These findings validate the effectiveness of tcVNS in humans and position it as a method for on-demand interventions of impairments associated with central sensory processing dysfunction.

Gray matter correlates of attention-deficit hyperactivity disorder in boys versus girls with sensory processing dysfunction

Abstract Neuroimaging shows volumetric alterations of gray matter in attention-deficit hyperactivity disorder (ADHD); however, results are conflicting. This may be due to heterogeneous phenotypic sampling and limited sensitivity of volumetric analysis. Creating more homogenous cohorts and investigating gray matter microstructure may yield meaningful biomarkers for scientific and clinical applications. Children with sensory processing dysfunction (SPD) have differences in white matter microstructure, but not gray matter volumetric differences. Approximately 40% of SPD children meet research criteria for ADHD. We apply deep learning segmentation of MRI to measure gray matter volume (GMV) and density (GMD) in SPD children with (SPD+ADHD) and without co-morbid ADHD (SPD-ADHD). We hypothesize GMV and GMD are linked to ADHD but with sex-specific regional patterns. We find boys with SPD+ADHD have widespread reduction of GMD in neocortex, limbic cortex, and cerebellum versus boys with SPD-ADHD. The greatest differences are in sensory cortex with less involvement of prefrontal regions associated with attention networks and impulse control. In contrast, changes of ADHD in girls with SPD are in brainstem nuclei responsible for dopaminergic, noradrenergic, and serotonergic neurotransmission. Hence, neural correlates of ADHD in SPD are sexually dimorphic. In boys, ADHD may result from downstream effects of abnormal sensory cortical development.

White matter microstructure of children with sensory over-responsivity is associated with affective behavior.

Sensory processing dysfunction (SPD) is linked to altered white matter (WM) microstructure in school-age children. Sensory over-responsivity (SOR), a form of SPD, affects at least 2.5% of all children and has substantial deleterious impact on learning and mental health. However, SOR has not been well studied using microstructural imaging such as diffusion MRI (dMRI). Since SOR involves hypersensitivity to external stimuli, we test the hypothesis that children with SOR require compensatory neuroplasticity in the form of superior WM microstructural integrity to protect against internalizing behavior, leaving those with impaired WM microstructure vulnerable to somatization and depression. Children ages 8-12years old with neurodevelopmental concerns were assessed for SOR using a comprehensive structured clinical evaluation, the Sensory Processing 3 Dimensions Assessment, and underwent 3 Tesla MRI with multishell multiband dMRI. Tract-based spatial statistics was used to measure diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) metrics from global WM and nineteen selected WM tracts. Correlations of DTI and NODDI measures with measures of somatization and emotional disturbance from the Behavioral Assessment System for Children, 3rd edition (BASC-3), were computed in the SOR group and in matched children with neurodevelopmental concerns but not SOR. Global WM fractional anisotropy (FA) is negatively correlated with somatization and with emotional disturbance in the SOR group but not the non-SOR group. Also observed in children with SOR are positive correlations of radial diffusivity (RD) and free water fraction (FISO) with somatization and, in most cases, emotional disturbance. These effects are significant in boys with SOR, whereas the study is underpowered for girls. The most affected white matter are medial lemniscus and internal capsule sensory tracts, although effects of SOR are observed in many cerebral, cerebellar, and brainstem tracts. White matter microstructure is related to affective behavior in children with SOR.

Interhemispheric connectivity dynamics of brain activity indused by cortical spreading depolarization in rats

Growing experimental and clinical evidence indicates the crucial role of network dysfunction in neurological disorders’ pathogenesis, including migraine, one of the most prevalent chronic brain diseases. Episodic headache attacks, frequently unilateral, accompanied by an aura, are associated with migraine. Migraine aura is a neurological condition characterized by the temporary development of unilateral sensory, motor, and/or speech disturbances. The symptoms are thought to indicate transient cerebral dysfunction in the cerebral cortex resulting from cortical spreading depolarization (SD), a wave of strong cellular depolarization that gradually spreads through the cortex at a rate of 3–5 mm/min. Electrophysiologically, the cortical SD wave is revealed by a high-amplitude slow negative shift in the extracellular potential and temporary suppression of the electrical activity of the cortex (EEG depression). The change in extracellular potential is associated with strong neuroglial depolarization and disruption of local ion homeostasis, which lasts for 1–2 min in healthy neuronal tissue. The SD results in a momentary suppression of the spontaneous electrical activity within the cortex, which is preceded by a brief excitation of the neurons. The neurological symptoms of the aura suggest a unilateral impairment of interhemispheric interactions during the early phase of a migraine attack. Our study investigated the effect of unilateral SD (a probable pathophysiological mechanism of migraine aura) on interhemispheric functional communication in freely behaving rats using local field potentials of the visual and motor cortex. Two methods were used to examine connectivity: mutual information function, computed using the method proposed in [1], and phase synchronization, calculated through the method [2], for four frequency bands: delta (1–4 Hz), theta (4–10 Hz), beta (10–25 Hz), and gamma (25–50 Hz). This was done by performing calculations on non-overlapping twenty-second intervals. Functional connectivity evolution was analyzed using local field potential records collected from homotopic points of the motor and visual cortex of two hemispheres in freely moving rats after inducing a single unilateral cortical SD in the somatosensory cortex. Cortical SD caused a significant wide-band decline (3–4 times) in interhemispheric functional connectivity in both the visual and motor cortex areas. Following the depolarization wave, the functional decoupling of the hemispheres began and progressively intensified, concluding by 5 min after the induction of the cortical SD wave. The network impairment displayed region- and frequency-specific features, with greater prominence observed in the visual cortex than in the motor cortex. The decline in functional connectivity was concurrent with abnormal animal behavior and aberrant activity in the ipsilateral cortex that appeared after the SD wave had ended. The study indicated that unilateral SD leads to a reversible decline in the functional interhemispheric connectivity in the awake animal cortex. Given the crucial role of synchronizing cortical oscillations for processing sensory information and integrating sensorimotor functions, the intracortical functional interactions disruption resulting from a unilateral SD wave, which we discovered in our present study, could contribute to the neuropathological mechanisms of migraine aura and sensory processing dysfunction during a migraine attack.

Teachers' and Parents' Assessment of Challenges in Children Exhibiting Sensory Seeking Behavior and Possible Effects of the Use of Ball Vests: A Pre-Post Study.

Children with dysfunction in sensory processing (DSP) may experience challenges, which might affect their participation in activities and potentially also their further development. This study examined the challenges of children with DSP who exhibit sensory seeking behavior, the differences in these challenges between boys and girls, and the possible effects of their use of ball vests. The challenges of 70 pupils (aged 6-12 years) exhibiting sensory seeking behavior were assessed by their parents (n = 66) and teachers (n = 60) by surveys containing items from the 'Strengths and Difficulties Questionnaire' (SDQ) and the 'Five to Fifteen' (FTF) questionnaire. Differences in the SDQ/FTF scores between boys and girls were explored using chi-square analysis. The potential effects of the ball vest were assessed using a study-specific follow-up survey. Linear mixed model regression analysis was used to examine associations between the extent of use of the vest and the assessed effects. The pupils were assessed for challenges that interfered with their learning (62%), forming friendships (51.7%), and the classroom environment (56.9%). After three weeks, the parents found that some pupils had improved regarding attention (39%), body perception (34%), and hyperactivity and impulsivity (33%). The teachers reported that 30% of the pupils had improved their coping skills in learning.

Effectiveness of a Sensory Play Activity Program with Parent Engagement for Children with Autism Spectrum Disorder: A Randomized Control Trial

Background: According to DSM-5, sensory processing problems are among diagnostic criteria in children with autism spectrum disorder (ASD). Various studies have shown that play, as the main occupation of children, can be helpful in performing sensory interventions. Solving sensory problems is one of the most common demands of families with children with ASD. Children's families play a key role in the implementation of occupational therapeutic interventions. Objectives: This randomized clinical trial investigated the effectiveness of sensory play activities performed by parents at home on the sensory patterns of children with ASD. Methods: Fifty-one children with ASD, aged 3 to 6 years, were divided into the intervention and control groups. All participants attended 16 sessions of in-person individualized sensory integration therapy (SIT) in a clinic for 8 weeks. In the intervention group, children received 8 sessions of a sensory play activity intervention performed by parents at home. Data collection instruments included the Gilliam Autism Rating Scale-2 and the sensory profile 2. Parametric (independent and paired t-test) and non-parametric (Mann-Whitney and Wilcoxon tests) were used for statistical analysis to compare between-group and within-group mean differences. Results: The results showed that although all four sensory processing patterns improved significantly in both groups (P < 0.05) (i.e., the within-group effect), children in the intervention group showed significant improvements in three sensory patterns, including sensory avoiding, sensory sensitivity, and sensory registration (P< 0.01). There was no significant difference in the mean score of the sensory seeking pattern between the 2 groups (P > 0.05). Conclusions: Sensory integration therapy improved dysfunctional sensory processing patterns in ASD children, an effect that was enhanced by the simultaneous implementation of sensory play interventions.

Sensory-Based Interventions in School-Based Occupational Therapy: A Scoping Review

ABSTRACT Education is a primary childhood occupation. Dysfunction in sensory processing can make it challenging for children to succeed in school. School-based occupational therapy (SBOT) services address these differences through sensory-based interventions. Limited research exists to support the use of sensory-based interventions in school-based settings. The purpose of this study is to summarize existing research supporting the use of sensory-based interventions in SBOT and to identify gaps in the literature. A scoping review methodological framework was used to search seven databases. Descriptive numerical summary and qualitative thematic analysis were used to summarize and report the results. Nineteen articles met the inclusion criteria for this study. Quantitative results describe variations in diagnoses, outcomes, and intervention types. Major qualitative themes include the impact of sensory-based interventions on classroom participation and engagement, and the efficacy of treatment methods used in SBOT. Gaps in the literature include the long-term effects and specificity of sensory-based interventions. There are many factors that may influence the effectiveness of interventions. Individualized OT services are needed to consider the intricacies of the child-environment interaction. Additional research is needed to support the efficacy of sensory-based interventions in SBOT.

Neurite orientation dispersion and density imaging of white matter microstructure in sensory processing dysfunction with versus without comorbid ADHD.

Sensory Processing Dysfunction (SPD) is common yet understudied, affecting up to one in six children with 40% experiencing co-occurring challenges with attention. The neural architecture of SPD with Attention Deficit and Hyperactivity Disorder (ADHD) (SPD+ADHD) versus SPD without ADHD (SPD-ADHD) has yet to be explored in diffusion tensor imaging (DTI) and Neurite Orientation Dispersion and Density Imaging (NODDI) has yet to be examined. The present study computed DTI and NODDI biophysical model parameter maps of one hundred children with SPD. Global, regional and voxel-level white matter tract measures were analyzed and compared between SPD+ADHD and SPD-ADHD groups. SPD+ADHD children had global WM Fractional Anisotropy (FA) and Neurite Density Index (NDI) that trended lower than SPD-ADHD children, primarily in boys only. Data-driven voxelwise and WM tract-based analysis revealed statistically significant decreases of NDI in boys with SPD+ADHD compared to those with SPD-ADHD, primarily in projection tracts of the internal capsule and commissural fibers of the splenium of the corpus callosum. We conclude that WM microstructure is more delayed/disrupted in boys with SPD+ADHD compared to SPD-ADHD, with NODDI showing a larger effect than DTI. This may represent the combined WM pathology of SPD and ADHD, or it may result from a greater degree of SPD WM pathology causing the development of ADHD.

Assessment of Visual Perception in Children with Autism Spectrum Disorder

Autism spectrum disease (ASD) is a nervous disorder. In this disease children have sensory processing dysfunction and they unable to communicate, interact, and showed repetition in behaviours. The present study was designed to determine visual impairment frequency in children with autism spectrum disorder (ASD). A descriptive study was performed in Paediatrics Department of Children's Hospital and The Institute of Child Health, Lahore. Data was collected in six months and 52 patients of both gender were considered. A total of 40 boys and 12 girls of 3-8 years old children were included. A structured Questionnaire based on visual perception was designed to determine the visual sensory processing issues in children with an autism spectrum disorder. The findings showed a strong difficulties in the visual sense particularly in differentiation among the colours and eye tracking in autism children. It was concluded that sense of sight highly affected in the patients of autism spectrum disorder.

Hemispheric lateralization of white matter microstructure in children and its potential role in sensory processing dysfunction.

Diffusion tensor imaging (DTI) studies have demonstrated white matter microstructural differences between the left and right hemispheres of the brain. However, the basis of these hemispheric asymmetries is not yet understood in terms of the biophysical properties of white matter microstructure, especially in children. There are reports of altered hemispheric white matter lateralization in ASD; however, this has not been studied in other related neurodevelopmental disorders such as sensory processing disorder (SPD). Firstly, we postulate that biophysical compartment modeling of diffusion MRI (dMRI), such as Neurite Orientation Dispersion and Density Imaging (NODDI), can elucidate the hemispheric microstructural asymmetries observed from DTI in children with neurodevelopmental concerns. Secondly, we hypothesize that sensory over-responsivity (SOR), a common type of SPD, will show altered hemispheric lateralization relative to children without SOR. Eighty-seven children (29 females, 58 males), ages 8-12 years, presenting at a community-based neurodevelopmental clinic were enrolled, 48 with SOR and 39 without. Participants were evaluated using the Sensory Processing 3 Dimensions (SP3D). Whole brain 3 T multi-shell multiband dMRI (b = 0, 1,000, 2,500 s/mm2) was performed. Tract Based Spatial Statistics were used to extract DTI and NODDI metrics from 20 bilateral tracts of the Johns Hopkins University White-Matter Tractography Atlas and the lateralization Index (LI) was calculated for each left-right tract pair. With DTI metrics, 12 of 20 tracts were left lateralized for fractional anisotropy and 17/20 tracts were right lateralized for axial diffusivity. These hemispheric asymmetries could be explained by NODDI metrics, including neurite density index (18/20 tracts left lateralized), orientation dispersion index (15/20 tracts left lateralized) and free water fraction (16/20 tracts lateralized). Children with SOR served as a test case of the utility of studying LI in neurodevelopmental disorders. Our data demonstrated increased lateralization in several tracts for both DTI and NODDI metrics in children with SOR, which were distinct for males versus females, when compared to children without SOR. Biophysical properties from NODDI can explain the hemispheric lateralization of white matter microstructure in children. As a patient-specific ratio, the lateralization index can eliminate scanner-related and inter-individual sources of variability and thus potentially serve as a clinically useful imaging biomarker for neurodevelopmental disorders.

Characterization of Fragile X Mental Retardation Protein expression in human nociceptors and their axonal projections to the spinal dorsal horn.

Fragile X Mental Retardation Protein (FMRP) regulates activity-dependent RNA localization and local translation to modulate synaptic plasticity throughout the central nervous system. Mutations in the FMR1 gene that hinder or ablate FMRP function cause Fragile X Syndrome (FXS), a disorder associated with sensory processing dysfunction. FXS premutations are associated with increased FMRP expression and neurological impairments including sex dimorphic presentations of chronic pain. In mice, FMRP ablation causes dysregulated dorsal root ganglion (DRG) neuron excitability and synaptic vesicle exocytosis, spinal circuit activity, and decreased translation-dependent nociceptive sensitization. Activity-dependent, local translation is a key mechanism for enhancing primary nociceptor excitability that promotes pain in animals and humans. These works indicate that FMRP likely regulates nociception and pain at the level of the primary nociceptor or spinal cord. Therefore, we sought to better understand FMRP expression in the human DRG and spinal cord using immunostaining in organ donor tissues. We find that FMRP is highly expressed in DRG and spinal neuron subsets with substantia gelatinosa exhibiting the most abundant immunoreactivity in spinal synaptic fields. Here, it is expressed in nociceptor axons. FMRP puncta colocalized with Nav1.7 and TRPV1 receptor signals suggesting a pool of axoplasmic FMRP localizes to plasma membrane-associated loci in these branches. Interestingly, FMRP puncta exhibited notable colocalization with calcitonin gene-related peptide (CGRP) immunoreactivity selectively in female spinal cord. Our results support a regulatory role for FMRP in human nociceptor axons of the dorsal horn and implicate it in the sex dimorphic actions of CGRP signaling in nociceptive sensitization and chronic pain.

Visual temporal discrimination is impaired in patients with migraine without aura.

Dysfunctional sensory processing is described in migraine. This study aimed to evaluate visual perception in patients with migraine without aura using the visual temporal discrimination (VTD) test. A total of 45 participants were enrolled in this prospective exploratory study. In all, 15 patients had migraine without aura and 15 healthy volunteers were analyzed in the study. The VTD threshold (VTDT) was measured using light-emitting diode lights to perceive two separate visual stimuli as clearly distinct. VTD was tested during the attack and the interictal period. The disease duration, attack side, visual analog scale for pain, accompanying symptoms, and allodynia were recorded during the attack. The VTDT of each visual field in both attack (mean [SD] 102.3[38.4]ms for the right visual field and 106.3[52.2]ms for the left) and the interictal periods (mean [SD] 75.2[27.9]ms for the right and 78.2[27.9]ms for the left) were significantly higher than in the control group (mean [SD] 45.3[9.9]ms for the right and 48.2[11.9]ms for the left) (p < 0.001, p < 0.001, p=0.003, p < 0.001, respectively). The ipsilateral threshold during the attack was significantly prolonged compared to the interictal period (mean [SD] 143.8[53.8] vs. 78[19.6]ms, p=0.025) and the contralateral threshold during the attack (mean [SD] 143.8[53.8] vs. 71.9[14.1]ms, p=0.025). The ipsilateral threshold was significantly correlated with the visual analog score (r=0.894, p < 0.001) and frequency of the attacks (r=0.696, p=0.004), but not correlated with photophobia. The VTDTs are prolonged both ictally and interictally in patients with migraine without aura attacks. Ipsilateral threshold prolongation is more pronounced during lateralized migraine attacks. The results suggest dysfunctional visual perception is not limited to the migraine attack period, and a defective sensory processing/modulation in the visual pathways may involve the superior colliculus.

Sensory Processing Dysfunction and Genito-Pelvic Pain/Penetration Disorder: Women share their experiences of participating in a sensory-based home programme

INTRODUCTION: Sensory processing dysfunction (SPD) has only recently been described in women with genito-pelvic pain/penetration disorder (GPPPD). However, female sexual pain is a virtually unknown area of practice for occupational therapists providing intervention for adults with SPD AIM: To describe the experiences of women with GPPPD with identified sensory processing dysfunction (SPD) who followed a sensory-based home programme METHODS: Purposive, non-probability sampling was used to recruit participants for the qualitative arm of the study after they presented with SPD in the quantitative part of the study. Semi-structured individual interviews were used to gather information and sufficient information power was reached after five participants were interviewed. Data were analysed descriptively using inductive thematic and saliency analyses RESULTS: Two themes were identified. Theme one: Changes experienced after participating in a sensory-based home programme, reflected increased insight into SPD (allowing participants to identify sensory triggers) and intra-personal changes (increased tolerance of sensory stimuli, feelings of control and I can breathe again). Theme two: Coping strategies employed by women with SPD and GPPPD, included sensory seeking, changes to home and work environments, positive reinterpretation/growth, acceptance, and socio-emotional support (you're not the only one. There are plenty of us out there CONCLUSION: A sensory-based home programme, catering to specific sensory profiles is beneficial as a non-invasive occupational therapy intervention approach (based on sensory integrative therapy) for women with both SPD and GPPPD Implications for occupational therapy: • SPD in the context of sexual pain is an emergent field in occupational therapy, thus occupational therapists need to expand service-delivery to this population and other practitioners such as gynaecologists must be alerted to occupational therapy as a non-invasive, and non-pharmaceutical intervention option for patients. • Contribute to the knowledgebase of sensory integration in the adult population. • Improve the occupational therapist's role in sexuality. • Emphasize the importance of insight as part of a treatment programme.

Increased Prevalence of Sensory Processing Issues in Pediatric Gastrointestinal Patient Population.

Background Sensory processing dysfunction in children has been linked to attention-deficit/hyperactivity disorder, autism, feeding disorders, and functional abdominal pain. However, little is known about sensory processing in the broader pediatric gastroenterology population. Objective To characterize frequency and type of sensory processing dysfunction seen in pediatric gastroenterology compared to a general pediatric population. Methods The Short Sensory Profile 2 was administered to the parents of children ranging 3-14 years, being seen in a pediatric gastrointestinal (GI) subspecialty clinic or general pediatric clinic. Short Sensory Profile 2 scores from age- and gender-matched groups were compared with nonparametric statistics. Results Sensory processing dysfunction was increased in children seen in the GI clinic compared to children in the general pediatric clinic. Short Sensory Profile 2 quadrant analysis revealed greatest differences in avoiding, primarily in young females of the GI population. Conclusion Children presenting to a pediatric GI clinic demonstrate greater sensory processing dysfunction compared to children in a general pediatric practice.

The brain-body disconnect: A somatic sensory basis for trauma-related disorders.

Although the manifestation of trauma in the body is a phenomenon well-endorsed by clinicians and traumatized individuals, the neurobiological underpinnings of this manifestation remain unclear. The notion of somatic sensory processing, which encompasses vestibular and somatosensory processing and relates to the sensory systems concerned with how the physical body exists in and relates to physical space, is introduced as a major contributor to overall regulatory, social-emotional, and self-referential functioning. From a phylogenetically and ontogenetically informed perspective, trauma-related symptomology is conceptualized to be grounded in brainstem-level somatic sensory processing dysfunction and its cascading influences on physiological arousal modulation, affect regulation, and higher-order capacities. Lastly, we introduce a novel hierarchical model bridging somatic sensory processes with limbic and neocortical mechanisms regulating an individual's emotional experience and sense of a relational, agentive self. This model provides a working framework for the neurobiologically informed assessment and treatment of trauma-related conditions from a somatic sensory processing perspective.

Multisensory integration and white matter pathology: Contributions to cognitive dysfunction.

The ability to simultaneously process and integrate multiple sensory stimuli is paramount to effective daily function and essential for normal cognition. Multisensory management depends critically on the interplay between bottom-up and top-down processing of sensory information, with white matter (WM) tracts acting as the conduit between cortical and subcortical gray matter (GM) regions. White matter tracts and GM structures operate in concert to manage both multisensory signals and cognition. Altered sensory processing leads to difficulties in reweighting and modulating multisensory input during various routine environmental challenges, and thus contributes to cognitive dysfunction. To examine the specific role of WM in altered sensory processing and cognitive dysfunction, this review focuses on two neurologic disorders with diffuse WM pathology, multiple sclerosis and mild traumatic brain injury, in which persistently altered sensory processing and cognitive impairment are common. In these disorders, cognitive dysfunction in association with altered sensory processing may develop initially from slowed signaling in WM tracts and, in some cases, GM pathology secondary to WM disruption, but also because of interference with cognitive function by the added burden of managing concurrent multimodal primary sensory signals. These insights promise to inform research in the neuroimaging, clinical assessment, and treatment of WM disorders, and the investigation of WM-behavior relationships.

Quantitative electroencephalography parameters as neurophysiological biomarkers of schizophrenia-related deficits: A Phase II substudy of patients treated with iclepertin (BI 425809)

Patients with schizophrenia experience cognitive impairment related to neural network dysfunction and deficits in sensory processing. These deficits are thought to be caused by N-methyl-D-aspartate receptor hypofunction and can be assessed in patient populations using electroencephalography (EEG). This substudy from a Phase II, randomized, double-blind, placebo-controlled, parallel-group study investigating the safety and efficacy of the novel glycine transporter-1 inhibitor, iclepertin (BI 425809), assessed the potential of EEG parameters as clinically relevant biomarkers of schizophrenia and response to iclepertin treatment. Eligible patients were randomized to once-daily add-on iclepertin (2, 5, 10, or 25 mg), or placebo (1:1:1:1:2 ratio) for 12 weeks. EEG data were recorded from a subgroup of patients (n = 79) at baseline and end of treatment (EoT). EEG parameters of interest were mismatch negativity (MMN), auditory steady-state response (ASSR), and resting state gamma power, and their correlations with clinical assessments. At baseline, MMN and ASSR exhibited consistent correlations with clinical assessments, indicating their potential value as neurophysiological biomarkers of schizophrenia-related deficits. ASSR measures were positively correlated to the MATRICS Consensus Cognitive Battery overall and neurocognitive composite scores; MMN amplitude was positively correlated with Positive and Negative Syndrome Scale scores. However, correlations between change from baseline (CfB) at EoT in clinical assessments, and baseline or CfB at EoT for EEG parameters were modest and inconsistent between dose groups, which might indicate low potential of these EEG parameters as predictive and treatment response biomarkers. Further methodological refinement is needed to establish EEG parameters as useful drug development tools for schizophrenia.

Enhanced Feedback Inhibition Due to Increased Recruitment of Somatostatin-Expressing Interneurons and Enhanced Cortical Recurrent Excitation in a Genetic Mouse Model of Migraine.

Migraine is a complex brain disorder, characterized by attacks of unilateral headache and global dysfunction in multisensory information processing, whose underlying cellular and circuit mechanisms remain unknown. The finding of enhanced excitatory, but unaltered inhibitory, neurotransmission at cortical synapses between pyramidal cells (PCs) and fast-spiking interneurons (FS INs) in mouse models of familial hemiplegic migraine (FHM) suggested the hypothesis that dysregulation of the excitatory-inhibitory (E/I) balance in specific circuits is a key pathogenic mechanism. Here, we investigated the cortical layer 2/3 (L2/3) feedback inhibition microcircuit involving somatostatin-expressing (SOM) INs in FHM1 mice of both sexes carrying a gain-of-function mutation in CaV2.1. Unitary inhibitory neurotransmission at SOM IN-PC synapses was unaltered while excitatory neurotransmission at both PC-SOM IN and PC-PC synapses was enhanced, because of increased probability of glutamate release, in FHM1 mice. Short-term synaptic depression was enhanced at PC-PC synapses while short-term synaptic facilitation was unaltered at PC-SOM IN synapses during 25-Hz repetitive activity. The frequency-dependent disynaptic inhibition (FDDI) mediated by SOM INs was enhanced, lasted longer and required shorter high-frequency bursts to be initiated in FHM1 mice. These findings, together with previous evidence of enhanced disynaptic feedforward inhibition by FS INs, suggest that the increased inhibition may effectively counteract the increased recurrent excitation in FHM1 mice and may even prevail in certain conditions. Considering the involvement of SOM INs in γ oscillations, surround suppression and context-dependent sensory perception, the facilitated recruitment of SOM INs, together with the enhanced recurrent excitation, may contribute to dysfunctional sensory processing in FHM1 and possibly migraine.SIGNIFICANCE STATEMENT Migraine is a complex brain disorder, characterized by attacks of unilateral headache and global dysfunction in multisensory information processing, whose underlying cellular and circuit mechanisms remain unknown, although dysregulation of the excitatory-inhibitory (E/I) balance in specific circuits could be a key pathogenic mechanism. Here, we provide insights into these mechanisms by investigating the cortical feedback inhibition microcircuit involving somatostatin-expressing interneurons (SOM INs) in a mouse model of a rare monogenic migraine. Despite unaltered inhibitory synaptic transmission, the disynaptic feedback inhibition mediated by SOM INs was enhanced in the migraine model because of enhanced recruitment of the INs. Recurrent cortical excitation was also enhanced. These alterations may contribute to context-dependent sensory processing dysfunctions in migraine.