Gender specific neural correlates of emotion and cognition

Evidence suggests that regions within the anterior cingulate cortex (ACC) are sensitive both to emotional and cognitive task demands. This experiment asked whether emotional and cognitive demands are processed separately by ventral and dorsal regions within the ACC, respectively. Results revealed significant individual variability between changes in anxiety and response times with practice during performance of a verb generation task. Correlational analyses of the functional magnetic resonance imaging (fMRI) data were inconclusive. However, exploratory analyses suggest that while the ventral and dorsal subdivisions of the medial prefrontal cortex, which encompasses the ACC, make specialized contributions to the processing of emotion and cognition, respectively, the two subdivisions also appear to interact. These analyses also suggest that there could be a difference in how women and men balance the competing demands of emotion and cognition that might be related to differences in self-concept and neural activity in the default mode network

Sleep disturbances in Wolfram syndrome

BACKGROUND: Wolfram syndrome is a rare disorder associated with diabetes mellitus, diabetes insipidus, optic nerve atrophy, hearing and vision loss, and neurodegeneration. Sleep complaints are common but have not been studied with objective measures. Our goal was to assess rates of sleep apnea and objective and self-reported measures of sleep quality, and to determine the relationship of sleep pathology to other clinical variables in Wolfram syndrome patients. METHODS: Genetically confirmed Wolfram syndrome patients were evaluated at the 2015 and 2016 Washington University Wolfram Syndrome Research Clinics. Patients wore an actigraphy device and a type III ambulatory sleep study device and completed the Epworth Sleepiness Scale (ESS), the Pittsburgh Sleep Quality Index (PSQI) and/or the Pediatric Sleep Questionnaire (PSQ). PSQI and PSQ questionnaire data were compared to a previously collected group of controls. Patients were characterized clinically with the Wolfram Unified Rating Scale (WURS) and a subset underwent magnetic resonance imaging (MRI) for brain volume measurements. RESULTS: Twenty-one patients were evaluated ranging from age 8.9-29.7 years. Five of 17 (29%) adult patients fit the criteria for obstructive sleep apnea (OSA; apnea-hypopnea index [AHI] ≥ 5) and all 4 of 4 (100%) children aged 12 years or younger fit the criteria for obstructive sleep apnea (AHI\u27s ≥ 1). Higher AHI was related to greater disease severity (higher WURS Physical scores). Higher mixed apnea scores were related to lower brainstem and cerebellar volumes. Patients\u27 scores on the PSQ were higher than those of controls, indicating greater severity of childhood obstructive sleep-related breathing disorders. CONCLUSIONS: Wolfram syndrome patients had a high rate of OSA. Further study would be needed to assess how these symptoms change over time. Addressing sleep disorders in Wolfram syndrome patients would likely improve their overall health and quality of life

Acute changes in mood induced by subthalamic deep brain stimulation in Parkinson disease are modulated by psychiatric diagnosis

BACKGROUND: Deep brain stimulation of the subthalamic nucleus (STN DBS) reduces Parkinson disease (PD) motor symptoms but has unexplained, variable effects on mood. OBJECTIVE: The study tested the hypothesis that pre-existing mood and/or anxiety disorders or increased symptom severity negatively affects mood response to STN DBS. METHODS: Thirty-eight PD participants with bilateral STN DBS and on PD medications were interviewed with Structured Clinical Interview for DSM-IV-TR Axis I Disorders (SCID) and completed Beck Depression Inventory (BDI) and Spielberger State Anxiety Inventory (SSAI) self-reports. Subsequently, during OFF and optimal ON (clinical settings) STN DBS conditions and while off PD medications, motor function was assessed with the United Parkinson Disease Rating Scale (UPDRS, part III), and participants rated their mood with Visual Analogue Scales (VAS), and again completed SSAI. VAS mood variables included anxiety, apathy, valence and emotional arousal. RESULTS: STN DBS improved UPDRS scores and mood. Unexpectedly, PD participants diagnosed with current anxiety or mood disorders experienced greater STN DBS-induced improvement in mood than those diagnosed with remitted disorders or who were deemed as having never met threshold criteria for diagnosis. BDI and SSAI scores did not modulate mood response to STN DBS, indicating that clinical categorical diagnosis better differentiates mood response to STN DBS than self-rated symptom severity. SCID diagnosis, BDI and SSAI scores did not modulate motor response to STN DBS. CONCLUSIONS: PD participants diagnosed with current mood or anxiety disorders are more sensitive to STN DBS-induced effects on mood, possibly indicating altered basal ganglia circuitry in this group

Plasma neurofilament light chain levels are elevated in children and young adults with Wolfram syndrome

Wolfram syndrome is a rare disease caused by pathogenic variants in th

Neuroimaging evidence of deficient axon myelination in Wolfram syndrome

Wolfram syndrome is a rare autosomal recessive genetic disease characterized by insulin dependent diabetes and vision, hearing and brain abnormalities which generally emerge in childhood. Mutations in the WFS1 gene predispose cells to endoplasmic reticulum stress-mediated apoptosis and may induce myelin degradation in neuronal cell models. However, in vivo evidence of this phenomenon in humans is lacking. White matter microstructure and regional volumes were measured using magnetic resonance imaging in children and young adults with Wolfram syndrome (n = 21) and healthy and diabetic controls (n = 50). Wolfram patients had lower fractional anisotropy and higher radial diffusivity in major white matter tracts and lower volume in the basilar (ventral) pons, cerebellar white matter and visual cortex. Correlations were found between key brain findings and overall neurological symptoms. This pattern of findings suggests that reduction in myelin is a primary neuropathological feature of Wolfram syndrome. Endoplasmic reticulum stress-related dysfunction in Wolfram syndrome may interact with the development of myelin or promote degeneration of myelin during the progression of the disease. These measures may provide objective indices of Wolfram syndrome pathophysiology that will be useful in unraveling the underlying mechanisms and in testing the impact of treatments on the brain

Evidence for altered neurodevelopment and neurodegeneration in Wolfram syndrome using longitudinal morphometry

Abstract Wolfram syndrome is a rare disease caused by mutations in the WFS1 gene leading to symptoms in early to mid-childhood. Brain structural abnormalities are present even in young children, but it is not known when these abnormalities arise. Such information is critical in determining optimal outcome measures for clinical trials and in understanding the aberrant neurobiological processes in Wolfram syndrome. Using voxel-wise and regional longitudinal analyses, we compared brain volumes in Wolfram patients (n = 29; ages 5–25 at baseline; mean follow-up = 3.6 years), to age and sex-equivalent controls (n = 52; ages 6–26 at baseline; mean follow-up = 2.0 years). Between groups, white and gray matter volumes were affected differentially during development. Controls had uniformly increasing volume in white matter, whereas the Wolfram group had stable (optic radiations) or decreasing (brainstem, ventral pons) white matter volumes. In gray matter, controls had stable (thalamus, cerebellar cortex) or decreasing volumes (cortex), whereas the Wolfram group had decreased volume in thalamus and cerebellar cortex. These patterns suggest that there may be early, stalled white matter development in Wolfram syndrome, with additional degenerative processes in both white and gray matter. Ideally, animal models could be used to identify the underlying mechanisms and develop specific interventions

Early brain vulnerability in Wolfram syndrome.

Wolfram Syndrome (WFS) is a rare autosomal recessive disease characterized by insulin-dependent diabetes mellitus, optic nerve atrophy, diabetes insipidus, deafness, and neurological dysfunction leading to death in mid-adulthood. WFS is caused by mutations in the WFS1 gene, which lead to endoplasmic reticulum (ER) stress-mediated cell death. Case studies have found widespread brain atrophy in late stage WFS. However, it is not known when in the disease course these brain abnormalities arise, and whether there is differential vulnerability across brain regions and tissue classes. To address this limitation, we quantified regional brain abnormalities across multiple imaging modalities in a cohort of young patients in relatively early stages of WFS. Children and young adults with WFS were evaluated with neurological, cognitive and structural magnetic resonance imaging measures. Compared to normative data, the WFS group had intact cognition, significant anxiety and depression, and gait abnormalities. Compared to healthy and type 1 diabetic control groups, the WFS group had smaller intracranial volume and preferentially affected gray matter volume and white matter microstructural integrity in the brainstem, cerebellum and optic radiations. Abnormalities were detected in even the youngest patients with mildest symptoms, and some measures did not follow the typical age-dependent developmental trajectory. These results establish that WFS is associated with smaller intracranial volume with specific abnormalities in the brainstem and cerebellum, even at the earliest stage of clinical symptoms. This pattern of abnormalities suggests that WFS has a pronounced impact on early brain development in addition to later neurodegenerative effects, representing a significant new insight into the WFS disease process. Longitudinal studies will be critical for confirming and expanding our understanding of the impact of ER stress dysregulation on brain development

Mean (±SD) age and gender distribution and clinical variables for control groups and WFS group for DTI scans.

<p>Abbreviation. HC: healthy controls; T1C: diabetic controls; WFS: Wolfram Syndrome group; SD: standard deviation.</p><p>There were no differences between groups for age (p = .24) or gender (p = .28) but there was a significant. difference in duration of diabetes between T1C and WFS (p = .001).</p