The Role of Attention in Somatosensory Processing: A Multi-trait, Multi-method Analysis

Sensory processing abnormalities in autism have largely been described by parent report. This study used a multi-method (parent-report and measurement), multi-trait (tactile sensitivity and attention) design to evaluate somatosensory processing in ASD. Results showed multiple significant within-method (e.g., parent report of different traits)/cross-trait (e.g., attention and tactile sensitivity) correlations, suggesting that parent-reported tactile sensory dysfunction and performance-based tactile sensitivity describe different behavioral phenomena. Additionally, both parent-reported tactile functioning and performance-based tactile sensitivity measures were significantly associated with measures of attention. Findings suggest that sensory (tactile) processing abnormalities in ASD are multifaceted, and may partially reflect a more global deficit in behavioral regulation (including attention). Challenges of relying solely on parent-report to describe sensory difficulties faced by children/families with ASD are also highlighted

GABA levels in left and right sensorimotor cortex correlate across individuals

Differences in -aminobutyric acid (GABA) levels measured with Magnetic Resonance Spectroscopy have been shown to correlate with behavioral performance over a number of tasks and cortical regions. These correlations appear to be regionally and functionally specific. In this study, we test the hypothesis that GABA levels will be correlated within individuals for functionally related regions—the left and right sensorimotor cortex. In addition, we investigate whether this is driven by bulk tissue composition. GABA measurements using edited MRS data were acquired from the left and right sensorimotor cortex in 24 participants. T1-weighted MR images were also acquired and segmented to determine the tissue composition of the voxel. GABA level is shown to correlate significantly between the left and right regions (r = 0.64, p < 0.03). Tissue composition is highly correlated between sides, but does not explain significant variance in the bilateral correlation. In conclusion, individual differences in GABA level, which have previously been described as functionally and regionally specific, are correlated between homologous sensorimotor regions. This correlation is not driven by bulk differences in voxel tissue composition

A Working Taxonomy for Describing the Sensory Differences of Autism

Background: Individuals on the autism spectrum have been long described to process sensory information differently than neurotypical individuals. While much effort has been leveraged towards characterizing and investigating the neurobiology underlying the sensory differences of autism, there has been a notable lack of consistency in the terms being used to describe the nature of those differences. Main body: We argue that inconsistent and interchangeable terminology-use when describing the sensory differences of autism has become problematic beyond mere pedantry and inconvenience. We begin by highlighting popular terms that are currently being used to describe the sensory differences of autism (e.g. sensitivity , reactivity and responsivity ) and discuss why poor nomenclature may hamper efforts towards understanding the aetiology of sensory differences in autism. We then provide a solution to poor terminology-use by proposing a hierarchical taxonomy for describing and referring to various sensory features. Conclusion: Inconsistent terminology-use when describing the sensory features of autism has stifled discussion and scientific understanding of the sensory differences of autism. The hierarchical taxonomy proposed was developed to help resolve lack of clarity when discussing the sensory differences of autism and to place future research targets at appropriate levels of analysis

Increased GABA concentrations in type 2 diabetes mellitus are related to lower cognitive functioning

Type 2 diabetes mellitus is associated with accelerated cognitive decline. The underlying pathophysiological mechanisms still remain to be elucidated although it is known that insulin signaling modulates neurotransmitter activity, including inhibitory γ-aminobutyric acid (GABA) and excitatory glutamate (Glu) receptors. Therefore, we examined whether levels of GABA and Glu are related to diabetes status and cognitive performance. Forty-one participants with type 2 diabetes and 39 participants without type 2 diabetes underwent detailed cognitive assessments and 3-Tesla proton MR spectroscopy. The associations of neurotransmitters with type 2 diabetes and cognitive performance were examined using multivariate regression analyses controlling for age, sex, education, BMI, and percentage gray/white matter ratio in spectroscopic voxel. Analysis revealed higher GABA+ levels in participants with type 2 diabetes, in participants with higher fasting blood glucose levels and in participants with higher HbA(1c) levels, and higher GABA+ levels in participants with both high HbA(1c) levels and less cognitive performance. To conclude, participants with type 2 diabetes have alterations in the GABAergic neurotransmitter system, which are related to lower cognitive functioning, and hint at the involvement of an underlying metabolic mechanism

Examining the Latent Structure and Correlates of Sensory Reactivity in Autism: A Multi-Site Integrative Data Analysis by the Autism Sensory Research Consortium

BACKGROUND: Differences in responding to sensory stimuli, including sensory hyperreactivity (HYPER), hyporeactivity (HYPO), and sensory seeking (SEEK) have been observed in autistic individuals across sensory modalities, but few studies have examined the structure of these supra-modal traits in the autistic population. METHODS: Leveraging a combined sample of 3868 autistic youth drawn from 12 distinct data sources (ages 3-18 years and representing the full range of cognitive ability), the current study used modern psychometric and meta-analytic techniques to interrogate the latent structure and correlates of caregiver-reported HYPER, HYPO, and SEEK within and across sensory modalities. Bifactor statistical indices were used to both evaluate the strength of a general response pattern factor for each supra-modal construct and determine the added value of modality-specific response pattern scores (e.g., Visual HYPER). Bayesian random-effects integrative data analysis models were used to examine the clinical and demographic correlates of all interpretable HYPER, HYPO, and SEEK (sub)constructs. RESULTS: All modality-specific HYPER subconstructs could be reliably and validly measured, whereas certain modality-specific HYPO and SEEK subconstructs were psychometrically inadequate when measured using existing items. Bifactor analyses supported the validity of a supra-modal HYPER construct (ω LIMITATIONS: Conclusions may not be generalizable beyond the specific pool of items used in the current study, which was limited to caregiver report of observable behaviors and excluded multisensory items that reflect many real-world sensory experiences. CONCLUSION: Of the three sensory response patterns, only HYPER demonstrated sufficient evidence for valid interpretation at the supra-modal level, whereas supra-modal HYPO/SEEK constructs demonstrated substantial psychometric limitations. For clinicians and researchers seeking to characterize sensory reactivity in autism, modality-specific response pattern scores may represent viable alternatives that overcome many of these limitations

Frequency drift in MR spectroscopy at 3T

Purpose: Heating of gradient coils and passive shim components is a common cause of instability in the B-0 field, especially when gradient intensive sequences are used. The aim of the study was to set a benchmark for typical drift encountered during MR spectroscopy (MRS) to assess the need for real-time field-frequency locking on MRI scanners by comparing field drift data from a large number of sites.Method: A standardized protocol was developed for 80 participating sites using 99 3T MR scanners from 3 major vendors. Phantom water signals were acquired before and after an EPI sequence. The protocol consisted of: minimal preparatory imaging; a short pre-fMRI PRESS; a ten-minute fMRI acquisition; and a long post-fMRI PRESS acquisition. Both pre- and post-fMRI PRESS were non-water suppressed. Real-time frequency stabilization/adjustment was switched off when appropriate. Sixty scanners repeated the protocol for a second dataset. In addition, a three-hour post-fMRI MRS acquisition was performed at one site to observe change of gradient temperature and drift rate. Spectral analysis was performed using MATLAB. Frequency drift in pre-fMRI PRESS data were compared with the first 5:20 minutes and the full 30:00 minutes of data after fMRI. Median (interquartile range) drifts were measured and showed in violin plot. Paired t-tests were performed to compare frequency drift pre- and post-fMRI. A simulated in vivo spectrum was generated using FID-A to visualize the effect of the observed frequency drifts. The simulated spectrum was convolved with the frequency trace for the most extreme cases. Impacts of frequency drifts on NAA and GABA were also simulated as a function of linear drift. Data from the repeated protocol were compared with the corresponding first dataset using Pearson's and intraclass correlation coefficients (ICC).Results: Of the data collected from 99 scanners, 4 were excluded due to various reasons. Thus, data from 95 scanners were ultimately analyzed. For the first 5:20 min (64 transients), median (interquartile range) drift was 0.44 (1.29) Hz before fMRI and 0.83 (1.29) Hz after. This increased to 3.15 (4.02) Hz for the full 30 min (360 transients) run. Average drift rates were 0.29 Hz/min before fMRI and 0.43 Hz/min after. Paired t-tests indicated that drift increased after fMRI, as expected (p &lt; 0.05). Simulated spectra convolved with the frequency drift showed that the intensity of the NAA singlet was reduced by up to 26%, 44 % and 18% for GE, Philips and Siemens scanners after fMRI, respectively. ICCs indicated good agreement between datasets acquired on separate days. The single site long acquisition showed drift rate was reduced to 0.03 Hz/min approximately three hours after fMRI.Discussion: This study analyzed frequency drift data from 95 3T MRI scanners. Median levels of drift were relatively low (5-min average under 1 Hz), but the most extreme cases suffered from higher levels of drift. The extent of drift varied across scanners which both linear and nonlinear drifts were observed.</p

Induced and Evoked Properties of Vibrotactile Adaptation in the Primary Somatosensory Cortex

Prolonged exposure to afferent stimulation (“adaptation”) can cause profound short-term changes in the responsiveness of cortical sensory neurons. While several models have been proposed that link adaptation to single-neuron dynamics, including GABAergic inhibition, the process is currently imperfectly understood at the whole-brain level in humans. Here, we used magnetoencephalography (MEG) to examine the neurophysiological correlates of adaptation within SI in humans. In one condition, a 25 Hz adapting stimulus (5 s) was followed by a 1 s 25 Hz probe (“same”), and in a second condition, the adapting stimulus was followed by a 1 s 180 Hz probe (“different”). We hypothesized that changes in the mu-beta activity band (reflecting GABAergic processing) would be modulated differently between the “same” and “different” probe stimuli. We show that the primary somatosensory (SI) mu-beta response to the “same” probe is significantly reduced (p=0.014) compared to the adapting stimulus, whereas the mu-beta response to the “different” probe is not (p=n.s.). This reduction may reflect sharpening of the spatiotemporal pattern of activity after adaptation. The stimulus onset mu-beta response did not differ between a 25 Hz adapting stimulus and a 180 Hz probe, suggesting that the mu-beta response is independent of stimulus frequency. Furthermore, we show a sustained evoked and induced desynchronization for the duration of the adapting stimulus, consistent with invasive studies. Our findings are important in understanding the neurophysiology underlying short-term and stimulus-induced plasticity in the human brain and shows that the brain response to tactile stimulation is altered after only brief stimulation

Age-dependent, lasting effects of methylphenidate on the GABAergic system of ADHD patients

Stimulants are the main pharmacological treatment for patients with attention-deficit/hyperactivity disorder (ADHD). Their current prescription rates are rising, both in children, adolescents and adults. Related to the impulse control phenotype, both preclinical and clinical studies have demonstrated lower.-amino butyric acid (GABA) levels in prefrontal brain regions in ADHD. Whereas stimulant treatment increases GABA levels, preclinical studies have suggested that stimulant treatment effects may be age-dependent. As the long-term consequences of stimulant use in ADHD children and adolescents have so far been poorly studied, we used magnetic resonance spectroscopy to assess GABA+ and glutamate + glutamine (Glx) levels in the medial prefrontal cortex (mPFC) of adult ADHD patients, both before and after an oral methylphenidate (MPH) challenge. Three groups were studied: 1) ADHD patients who were first treated with stimulants before 16 years of age, i. e. during periods of ongoing brain development (early-stimulant-treated, EST); 2) patients first treated with stimulants in adulthood (i. e.> 23 years) (late-stimulant-treated, LST), and 3) stimulant-treatmentnaive (STN) ADHD patients. Reduced basal GABA+ levels were found in EST compared to LST patients (p = 0.04), while after an MPH challenge, only the EST patients showed significant increases in GABA+ (p = 0.01). For Glx, no differences were found at baseline, nor after an MPH challenge. First stimulant exposure at a young age is thus associated with lower baseline levels of GABA+ and increased responsivity in adulthood. This effect could not be found in patients that started treatment at an adult age. Hence, while adult stimulant treatment seems to exert no major effects on GABA+ levels in the mPFC, MPH may induce long-lasting alterations in the adult mPFC GABAergic system when treatment was started at a young ag

GABA Concentrations in the Anterior Cingulate Cortex Are Associated with Fear Network Function and Fear Recovery in Humans

Relapse of fear after successful treatment is a common phenomenon in patients with anxiety disorders. Animal research suggests that the inhibitory neurotransmitter γ-aminobutyric acid (GABA) plays a key role in the maintenance of extinguished fear. Here, we combined magnetic resonance spectroscopy and functional magnetic resonance imaging to investigate the role of GABA in fear recovery in 70 healthy male participants. We associated baseline GABA levels in the dorsal anterior cingulate cortex (dACC) to indices of fear recovery as defined by changes in skin conductance responses (SCRs), blood oxygen level dependent responses, and functional connectivity from fear extinction to fear retrieval. The results showed that high GABA levels were associated with increased SCRs, enhanced activation of the right amygdala, and reduced amygdala-ventromedial prefrontal cortex connectivity during fear recovery. Follow-up analyses exclusively for the extinction phase showed that high GABA levels were associated with reduced amygdala activation and enhanced amygdala-ventromedial prefrontal cortex connectivity, despite the absence of correlations between GABA and physiological responses. Follow-up analyses for the retrieval phase did not show any significant associations with GABA. Together, the association between GABA and increases in SCRs from extinction to retrieval, without associations during both phases separately, suggests that dACC GABA primarily inhibits the consolidation of fear extinction. In addition, the opposite effects of GABA on amygdala activity and connectivity during fear extinction compared to fear recovery suggest that dACC GABA may initially facilitate extinction learning