Motor network dynamic resting state fMRI connectivity of neurotypical children in regions affected by cerebral palsy.

Background: Normative childhood motor network resting-state fMRI effective connectivity is undefined, yet necessary for translatable dynamic resting-state-network-informed evaluation in pediatric cerebral palsy. Methods: Cross-spectral dynamic causal modeling of resting-state-fMRI was investigated in 50 neurotypically developing 5- to 13-year-old children. Fully connected six-node network models per hemisphere included primary motor cortex, striatum, subthalamic nucleus, globus pallidus internus, thalamus, and contralateral cerebellum. Parametric Empirical Bayes with exhaustive Bayesian model reduction and Bayesian modeling averaging informed the model; Purdue Pegboard Test scores of hand motor behavior were the covariate at the group level to determine the effective-connectivity-functional behavior relationship. Results: Although both hemispheres exhibited similar effective connectivity of motor cortico-basal ganglia-cerebellar networks, magnitudes were slightly greater on the right, except for left-sided connections of the striatum which were more numerous and of opposite polarity. Inter-nodal motor network effective connectivity remained consistent and robust across subjects. Age had a greater impact on connections to the contralateral cerebellum, bilaterally. Motor behavior, however, affected different connections in each hemisphere, exerting a more prominent effect on the left modulatory connections to the subthalamic nucleus, contralateral cerebellum, primary motor cortex, and thalamus. Discussion: This study revealed a consistent pattern of directed resting-state effective connectivity in healthy children aged 5-13 years within the motor network, encompassing cortical, subcortical, and cerebellar regions, correlated with motor skill proficiency. Both hemispheres exhibited similar effective connectivity within motor cortico-basal ganglia-cerebellar networks reflecting inter-nodal signal direction predicted by other modalities, mainly differing from task-dependent studies due to network differences at rest. Notably, age-related changes were more pronounced in connections to the contralateral cerebellum. Conversely, motor behavior distinctly impacted connections in each hemisphere, emphasizing its role in modulating left sided connections to the subthalamic nucleus, contralateral cerebellum, primary motor cortex, and thalamus. Motor network effective connectivity was correlated with motor behavior, validating its physiological significance. This study is the first to evaluate a normative effective connectivity model for the pediatric motor network using resting-state functional MRI correlating with behavior and serves as a foundation for identifying abnormal findings and optimizing targeted interventions like deep brain stimulation, potentially influencing future therapeutic approaches for children with movement disorders.

Association of Sinonasal Inflammation With Functional Brain Connectivity.

Importance: In recent years, there have been several meaningful advances in the understanding of the cognitive effects of chronic rhinosinusitis. However, an investigation exploring the potential link between the underlying inflammatory disease and higher-order neural processing has not yet been performed. Objective: To describe the association of sinonasal inflammation with functional brain connectivity (Fc), which may underlie chronic rhinosinusitis-related cognitive changes. Design, Setting, and Participants: This is a case-control study using the Human Connectome Project (Washington University-University of Minnesota Consortium of the Human Connectome Project 1200 release), an open-access and publicly available data set that includes demographic, imaging, and behavioral data for 1206 healthy adults aged 22 to 35 years. Twenty-two participants demonstrated sinonasal inflammation (Lund-Mackay score [LMS] ≥ 10) and were compared with age-matched and sex-matched healthy controls (LMS = 0). These participants were further stratified into moderate (LMS < 14, n = 13) and severe (LMS ≥ 14, n = 9) inflammation groups. Participants were screened and excluded if they had a history of psychiatric disorder and/or neurological or genetic diseases. Participants with diabetes or cardiovascular disease were also excluded, as these conditions may affect neuroimaging quality. The data were accessed between October 2019 and August 2020. Data analysis was performed between May 2020 and August 2020. Main Outcomes and Measures: The primary outcome was the difference in resting state Fc within and between the default mode, frontoparietal, salience, and dorsal attention brain networks. Secondary outcomes included assessments of cognitive function using the National Institutes of Health Toolbox Cognition Battery. Results: A total of 22 patients with chronic rhinosinusitis and 22 healthy controls (2 [5%] were aged 22-25 years, 26 [59%] were aged 26-30 years, and 16 [36%] were aged 31-35 years; 30 [68%] were men) were included in the analysis. Participants with sinonasal inflammation showed decreased Fc within the frontoparietal network, in a region involving bilateral frontal medial cortices. This region demonstrated increased Fc to 2 nodes within the default-mode network and decreased Fc to 1 node within the salience network. The magnitude of these differences increased with inflammation severity (dose dependent). There were no significant associations seen on cognitive testing. Conclusions and Relevance: In this case-control study, participants with sinonasal inflammation showed decreased brain connectivity within a major functional hub with a central role in modulating cognition. This region also shows increased connectivity to areas that are activated during introspective and self-referential processing and decreased connectivity to areas involved in detection and response to stimuli. Future prospective studies are warranted to determine the applicability of these findings to a clinical chronic rhinosinusitis population.

Neural Representations of the Voice Tremor Spectrum.

OBJECTIVES: Voice tremor is a common movement disorder that manifests as involuntary oscillations of laryngeal muscles, leading to rhythmic alterations in voice pitch and loudness. Differential diagnosis of essential tremor of voice (ETv) is often challenging and includes dystonic tremor of voice (DTv), which is characterized by irregular, isometric contractions of laryngeal muscles during dystonic activity. Although clinical characteristics of voice tremor are well described, the pathophysiology underlying its heterogeneous phenomenology remains limited. METHODS: We used a multimodal approach of functional magnetic resonance imaging for assessment of brain activity during symptomatic speech production, high-resolution magnetic resonance imaging for the examination of cortical thickness and gray matter volume, and diffusion-weighted imaging for evaluation of white matter integrity to identify disorder-specific neural alterations and their relationships with the symptomatology of ETv and DTv. RESULTS: We found a broad overlap between cortical alterations in ETv and DTv, involving sensorimotor regions responsible for the integration of multisensory information during speech production, such as primary sensorimotor, inferior/superior parietal, and inferior temporal cortices. In addition, ETv and DTv showed unique patterns of abnormalities in regions controlling speech motor preparation, which were localized in the cerebellum in ETv and the premotor cortex, insula, and superior temporal gyrus in DTv. Neural alterations in superior parietal and inferior temporal cortices were correlated with ETv severity, whereas changes in the left premotor cortex were associated with DTv severity. CONCLUSIONS: Our findings point to the pathophysiological spectrum underlying ETv and DTv and favor a more heterogeneous rather than dichotomous diagnostic classification of these voice tremor disorders. © 2020 International Parkinson and Movement Disorder Society.

Sexual Dimorphism Within Brain Regions Controlling Speech Production.

Neural processing of speech production has been traditionally attributed to the left hemisphere. However, it remains unclear if there are structural bases for speech functional lateralization and if these may be partially explained by sexual dimorphism of cortical morphology. We used a combination of high-resolution MRI and speech-production functional MRI to examine cortical thickness of brain regions involved in speech control in healthy males and females. We identified greater cortical thickness of the left Heschl's gyrus in females compared to males. Additionally, rightward asymmetry of the supramarginal gyrus and leftward asymmetry of the precentral gyrus were found within both male and female groups. Sexual dimorphism of the Heschl's gyrus may underlie known differences in auditory processing for speech production between males and females, whereas findings of asymmetries within cortical areas involved in speech motor execution and planning may contribute to the hemispheric localization of functional activity and connectivity of these regions within the speech production network. Our findings highlight the importance of consideration of sex as a biological variable in studies on neural correlates of speech control.

The extrinsic risk and its association with neural alterations in spasmodic dysphonia.

INTRODUCTION: Spasmodic dysphonia (SD) is an isolated focal dystonia characterized by laryngeal spasms during voluntary voice production. Environmental factors have been assumed to play a role in SD pathophysiology; however, the exact extrinsic risk factors and their association with neural alterations remain unknown. METHODS: A total of 186 SD patients and 85 healthy controls completed a structured 177-question survey, consisting of questions on general biographical information, medical history, symptomatology of dystonia. Data were imputed in a stepwise regression model to identify extrinsic risk factors for SD. In addition, functional MRI data from a subset of this cohort were analyzed to determine brain activation abnormalities associated with the SD extrinsic risk. RESULTS: We found that (1) recurrent upper respiratory infections, gastroesophageal reflux, and neck trauma, all of which influence sensory feedback from the larynx, represent extrinsic risk factors, likely triggering the manifestation of SD symptoms, and (2) neural alterations in the regions necessary for sensorimotor preparation and integration are influenced by an extrinsic risk in susceptible individuals. CONCLUSIONS: These findings provide evidence for the extrinsic risk in SD development and demonstrate the link with alterations in the sensorimotor preparatory network that collectively contribute to the multifactorial pathophysiology of SD.