Neural evidence for non-orofacial triggers in mild misophonia.

Misophonia, an extreme aversion to certain environmental sounds, is a highly prevalent yet understudied condition plaguing roughly 20% of the general population. Although neuroimaging research on misophonia is scant, recent work showing higher resting-state functional connectivity (rs-fMRI) between auditory cortex and orofacial motor cortex in misophonia vs. controls has led researchers to speculate that misophonia is caused by orofacial mirror neurons. Since orofacial motor cortex was defined using rs-fMRI, we attempted to theoretically replicate these findings using orofacial cortex defined by task-based fMRI instead. Further, given our recent work showing that a wide variety of sounds can be triggering (i.e., not just oral/nasal sounds), we investigated whether there is any neural evidence for misophonic aversion to non-orofacial stimuli. Sampling 19 adults with varying misophonia from the community, we collected resting state data and an fMRI task involving phoneme articulation and finger-tapping. We first defined "orofacial" cortex in each participant using rs-fMRI as done previously, producing what we call resting-state regions of interest (rsROIs). Additionally, we functionally defined regions (fROIs) representing "orofacial" or "finger" cortex using phoneme or finger-tapping activation from the fMRI task, respectively. To investigate the motor specificity of connectivity differences, we subdivided the rsROIs and fROIs into separate sensorimotor areas based on their overlap with two common atlases. We then calculated rs-fMRI between each rsROI/fROI and a priori non-sensorimotor ROIs. We found increased connectivity in mild misophonia between rsROIs and both auditory cortex and insula, theoretically replicating previous results, with differences extending across multiple sensorimotor regions. However, the orofacial task-based fROIs did not show this pattern, suggesting the "orofacial" cortex described previously was not capturing true orofacial cortex; in fact, using task-based fMRI evidence, we find no selectivity to orofacial action in these previously described "orofacial" regions. Instead, we observed higher connectivity between finger fROIs and insula in mild misophonia, demonstrating neural evidence for non-orofacial triggers. These results provide support for a neural representation of misophonia beyond merely an orofacial/motor origin, leading to important implications for the conceptualization and treatment of misophonia.

Thalamo-Prefrontal Connectivity Correlates With Early Command-Following After Severe Traumatic Brain Injury.

Recovery of consciousness after traumatic brain injury (TBI) is heterogeneous and difficult to predict. Structures such as the thalamus and prefrontal cortex are thought to be important in facilitating consciousness. We sought to investigate whether the integrity of thalamo-prefrontal circuits, assessed via diffusion tensor imaging (DTI), was associated with the return of goal-directed behavior after severe TBI. We classified a cohort of severe TBI patients (N = 25, 20 males) into Early and Late/Never outcome groups based on their ability to follow commands within 30 days post-injury. We assessed connectivity between whole thalamus, and mediodorsal thalamus (MD), to prefrontal cortex (PFC) subregions including dorsolateral PFC (dlPFC), medial PFC (mPFC), anterior cingulate (ACC), and orbitofrontal (OFC) cortices. We found that the integrity of thalamic projections to PFC subregions (L OFC, L and R ACC, and R mPFC) was significantly associated with Early command-following. This association persisted when the analysis was restricted to prefrontal-mediodorsal (MD) thalamus connectivity. In contrast, dlPFC connectivity to thalamus was not significantly associated with command-following. Using the integrity of thalamo-prefrontal connections, we created a linear regression model that demonstrated 72% accuracy in predicting command-following after a leave-one-out analysis. Together, these data support a role for thalamo-prefrontal connectivity in the return of goal-directed behavior following TBI.

Electrocorticography reveals thalamic control of cortical dynamics following traumatic brain injury.

The return of consciousness after traumatic brain injury (TBI) is associated with restoring complex cortical dynamics; however, it is unclear what interactions govern these complex dynamics. Here, we set out to uncover the mechanism underlying the return of consciousness by measuring local field potentials (LFP) using invasive electrophysiological recordings in patients recovering from TBI. We found that injury to the thalamus, and its efferent projections, on MRI were associated with repetitive and low complexity LFP signals from a highly structured phase space, resembling a low-dimensional ring attractor. But why do thalamic injuries in TBI patients result in a cortical attractor? We built a simplified thalamocortical model, which connotes that thalamic input facilitates the formation of cortical ensembles required for the return of cognitive function and the content of consciousness. These observations collectively support the view that thalamic input to the cortex enables rich cortical dynamics associated with consciousness.

Cortical thickness and functional connectivity changes in Chinese chess experts.

BACKGROUND: Repeated practice to acquire expertise could result in the structural and functional changes in relevant brain circuits as a result of long-term potentiation, neurogenesis, glial genesis, and remodeling. PURPOSE: The goal of this study is to use surface-based morphology (SBM) to study cortical thickness differences in Chinese chess experts and novices, and to use regions of cortical thickness differences as seeds to guide a resting state connectivity analysis of the same population. METHODS: A raw public dataset from Huaxi MR Research Center consisting of 29 Chinese chess experts and 29 novices was used in this study, with both T1-weighted and resting state functional MRI. Surface based morphometry was performed on the T1 images with the Freesurfur pipeline, with a vertex significance threshold of p<0.05 and a cluster false discovery rate of α < 0.05. Regions with significant differences were used in a seed-based comparison of resting state functional connectivity carried out with Statistical Parameter Mapping (SPM) and the Connectivity Toolbox (CONN). Regions of connectivity differences within groups were computed with a voxel significance threshold of p<0.05 and a cluster false discovery rate of α < 0.01. RESULTS: Ten regions of the cortex of Chinese chess experts were found to be thinner than chess novices, including regions involved in visual processing, attention, working and episodic memory, and mental imagery, as well as several regions in the prefrontal cortex. There were no regions where experts' cortices were thicker than novices. Three of the thinner regions exhibited increased functional connectivity to distant brain regions in chess experts. CONCLUSIONS: Brain regions that are structurally affected by chess training are associated with processes that would likely have a high utility in chess expertise. Using a hierarchical control model, we hypothesize that the functional changes linked with some of these structural changes are related to the professionally trained chess players' ability to perceive and use contextual information, visuospatial perception, and outcome prediction in the domain of chess, all contributing to their exceptional performance.

Anatomical brain MRI study of pediatric cancer survivors treated with chemotherapy: Correlation with behavioral measures.

The negative impacts of chemotherapy on pediatric patients treated with chemotherapy during the formative years of brain development are understudied compared to adult chemotherapy cancer patients. This work investigated the morphometry, cortical thickness, and subcortical volumes using MRI and their correlations with behavioral measures in pediatric oncology survivors treated with chemotherapy. Chemotherapy-treated childhood cancer survivors (N = 15, 15.12 ± 5.98 years old) diagnosed with a non-central nervous system malignancy and healthy age-matched controls (N = 15, 15.13 ± 4.21 years old) were studied. MRI was acquired at 3 Tesla. Behavioral Rating Inventory of Executive Functioning (BRIEF) Parental Rating, Purdue Pegboard manual dexterity and n-back working memory measures were administered. Structural MRI scans at 3 Tesla were acquired. Voxel-based morphometry, cortical thickness and subcortical volumes were analyzed and correlated with behavioral scores. Parametric statistics with a p < .05 and adjusted for multiple comparison corrections were performed. Patients exhibited significantly smaller gray-matter volumes in the left globus pallidum, bilateral thalami, left caudate and left nucleus accumbens (p < .05) and thinner cortex in the right parahippocampal gyrus (p < .05) compared to controls. BRIEF scores were similar to normative values. Purdue Pegboard revealed manual dexterity deficits compared to normative values, and the n-back task showed working-memory deficits in patients compared to controls. Left thalamus volume positively correlated with dexterity performance (p = .029). The number of correct answers positively correlated and the number of incorrect answers negatively correlated with total-brain and white-matter volume (p < .05), but not gray-matter volume (p > .05). Our results support the hypothesis that the neurotoxicity of systemic chemotherapy has widespread negative effects on brain development in pediatric oncology patients with relatively mild cognitive deficits. MRI identified neuroanatomical changes have the potential to provide neural correlates of the sequelae associated with pediatric chemotherapy.

Functional, anatomical and diffusion tensor MRI study of radiology expertise.

BACKGROUND: Repeated practice to acquire expertise could result in the structural and functional changes in relevant brain circuits as a result of long-term potentiation, neurogenesis, glial genesis, and remodeling. PURPOSE: The goal of this study is to use task fMRI to study the brain of expert radiologists performing a diagnosis task where a series of medical images were presented during fMRI acquisition for 12s and participants were asked to choose a diagnosis. Structural and diffusion-tensor MRI were also acquired. METHODS: Radiologists (N = 12, 11M, 38.2±10.3 years old) and non-radiologists (N = 17, 15M, 30.6±5.5 years old) were recruited with informed consent. Medical images were presented for 12 s and three multiple choices were displayed and the participants were asked to choose a diagnosis. fMRI, structural and diffusion-tensor MRI were acquired. fMRI analysis used FSL to determine differences in fMRI responses between groups. Voxel-wise analysis was performed to determine if subcortical volume, cortical thickness and fractional anisotropy differed between groups. Correction for multiple comparisons used false discovery rate. RESULTS: Radiologists showed overall lower task-related brain activation than non-radiologists. Radiologists showed significantly lower activation in the left lateral occipital cortex, left superior parietal lobule, occipital pole, right superior frontal and precentral gyri, lingual gyrus, and the left intraparietal sulcus (p<0.05). There were no significant differences between groups in cortical thickness, subcortical volume and fractional anisotropy (p>0.05). CONCLUSIONS: Radiologists and non-radiologists had no significant difference in structural metrics. However, in diagnosis tasks, radiologists showed markedly lower task-related brain activations overall as well as a number of high-order visual and non-visual brain regions than non-radiologists. Some brain circuits appear to be uniquely associated with differential-diagnosis paradigm expertise that are not involved in simpler object-recognition cases. Improved understanding of the brain circuitry involved in acquisition of expertise might be used to design optimal training paradigms.

Neural correlates of working memory function in pediatric cancer survivors treated with chemotherapy: an fMRI study.

The goal of this study is to investigate the neural correlates of working memory function associated with chemotherapy in pediatric cancer survivors using event-related functional MRI (fMRI) analysis. Fifteen pediatric cancer survivors treated with chemotherapy and 15 healthy controls were studied. Blood oxygenation level dependent (BOLD) fMRI was acquired. A visual n-back task was used to test working memory function during the fMRI scan. Responses were recorded via an MRI compatible button box for analysis. fMRI scans were analyzed using statistical parametric mapping software. All statistics were corrected for multiple comparisons by false discovery rate, with p < 0.05 as significance. Patients however gave more incorrect responses (p < 0.05), more no responses (p < 0.05), and longer response times (p < 0.05) compared with healthy controls. Correct responses generated significantly lower BOLD responses in the posterior cingulate for pediatric cancer survivors compared with controls (p < 0.05). Incorrect responses generated significantly greater BOLD responses in the angular gyrus in survivors (p < 0.05), and no response trials generated greater BOLD responses within the superior parietal lobule (p < 0.05) compared with controls. Working memory impairment appears to be due to an inability to manipulate information and to retrieve information from memory. The ability to delineate the affected neural circuits associated with chemotherapy-induced cognitive impairment could inform treatment strategies, identify patients at high risk of developing cognitive deficits, and pre-emptively tailor behavioral enrichment to overcome specific cognitive deficits.

Characterization of gray-matter multiple sclerosis lesions using double inversion recovery, diffusion, contrast-enhanced, and volumetric MRI.

PURPOSE: To investigate gray-matter (GM) lesions in relapsing-remitting multiple sclerosis (MS) using double-inversion recovery (DIR) MRI, determine GM lesions prevalence, spatial distribution and characterize their contrast-enhancement, diffusion characteristics and compare them to white-matter (WM) lesions. This is the first study, to our knowledge, to investigate GM MS lesions using double-inversion recovery MRI, to determine GM lesion prevalence and location, and characterize contrast-enhancement and diffusion characteristics, compared to WM lesion characteristics in the same patients. We also correlated GM lesion counts, volume and apparent diffusion coefficient (ADC) with total brain, WM, and GM volumes, as well as 25-foot walk test as a clinical disability. MATERIALS AND METHODS: This retrospective study included 44 relapsing-remitting MS patients (12M/32F, 41 ± 13 years) and 24 age-matched healthy controls (14M/10F, 36 ± 13 years). Lesions were segmented based on DIR and grouped into GM, subcortical WM, and periventricular WM lesions. ADC was tabulated for contrast-enhancing and non-enhancing lesions. Unpaired two sample t-tests were used for comparison between groups. Linear regression was used to evaluate the relationship between number of GM lesions, number of total lesions, total GM lesion volume, and total WM lesion volume with brain volumes and clinical data. RESULTS: GM MS lesions were present in the majority (86.4%, 38/44) of RRMS patients based on DIR, suggesting GM damage plays an important role in MS pathogenesis. The majority of the GM lesions were located in the frontal lobe. The percentage of lesions in GM that were contrast-enhanced was similar to those in WM, suggesting that blood-brain barrier integrity is likely affected similarly in GM and WM. Contrast-enhanced GM lesions showed higher ADC. GM lesion count and volume were correlated with global and regional brain atrophy, and with more severe disability group. CONCLUSION: This study characterized GM MS lesions using double-inversion recovery, contrast-enhanced and diffusion MRI. Understanding GM lesion pathophysiology using MRI in vivo, may prove useful for improving targeted therapy and monitoring disease progression.

Resting-state functional connectivity networks associated with fatigue in multiple sclerosis with early age onset.

BACKGROUND: Fatigue is one of the most commonly experienced symptoms in multiple sclerosis (MS). The neural correlates of fatigue in MS, in general and specifically in early onset, remain poorly understood. This study employed resting-state fMRI (rsfMRI) to investigate the functional connectivity of fatigue in MS patients with early age onset. METHODS: Twenty-seven relapsing-remitting MS patients (20 ± 7yo at the age of diagnosis and 26.0 ±â€¯5.5yo at the time of study) were recruited and 22 patients were studied. Structural and rsfMRI sequences were performed on a 3-Tesla Seimens MRI scanner. Seed-based analysis was performed using CONN Functional Connectivity Toolbox for Statistic Parametric Mapping. The Fatigue Severity Scale (FSS) and the Modified Fatigue Impact scale (MFIS) as well as EDSS, Beck Depression Inventory, and symptomatology were measured. Non-fatigued (N = 12) and fatigued patients (N = 10) were separated based on FSS scores, with a score of 5 or greater being classified as fatigued. Group differences in rsfMRI between non-fatigued and fatigued patients were analyzed. Correlations between these functional connectivity differences and behavioral fatigue scores were also analyzed. RESULTS: Ages, disease duration, lesion load, lesion volume, and neurologic disability were not significantly different between non-fatigued and fatigued patients (p > 0.05). Fatigued patients showed significantly stronger connectivity between the right thalamus and right precentral gyrus (T = 4.58, p = 0.015), and a trending increase in connectivity between the left hippocampus and left precentral gyrus (T = 7.55, p = 0.051). Patients with fatigue showed significantly reduced connectivity between the right thalamus and left parietal operculum (T= -4.28, p = 0.0002), left thalamus and right superior frontal gyrus (T=-5.54, p = 0.046), and between the left insula and posterior cingulate (T=-9.4, p = 0.003). The connectivity between the left insula and posterior cingulate was significantly correlated with the cognitive score of MFIS (R2 = -0.471, p = 0.027) and FSS (R2 = -0.719, p = 0.0001). The connectivity between the right thalamus and left parietal operculum was significantly correlated with MFIS cognitive scores (R2 = -0.431, p = 0.045) and with FSS scores (R2 = 0.402, p = 0.006). Correlations remained significant after accounting for depression scores. CONCLUSIONS: rsfMRI identified Alterations in two distinct connections (the connectivity between insula and posterior cingulate gyrus and between the right thalamus and right precentral gyrus) that differed between fatigued and non-fatigued patients, as well as correlated with cognitive fatigue severity. These findings suggest that disruption of sensorimotor, high-order motor, and non-motor executive function likely contributes to the neural mechanism of fatigue in MS. Knowledge of the neural mechanisms of underlying MS fatigue could inform more effective treatment strategies.