Development of human visual cortical function: A scoping review of task- and naturalistic-fMRI studies through the interactive specialization and maturational frameworks.

Overarching theories such as the interactive specialization and maturational frameworks have been proposed to describe human functional brain development. However, these frameworks have not yet been systematically examined across the fMRI literature. Visual processing is one of the most well-studied fields in neuroimaging, and research in this area has recently expanded to include naturalistic paradigms that facilitate study in younger age ranges, allowing for an in-depth critical appraisal of these frameworks across childhood. To this end, we conducted a scoping review of 94 developmental visual fMRI studies, including both traditional experimental task and naturalistic studies, across multiple sub-domains (early visual processing, category-specific higher order processing, naturalistic visual processing). We found that across domains, many studies reported progressive development, but few studies describe regressive or emergent changes necessary to fit the maturational or interactive specialization frameworks. Our findings suggest a need for the expansion of developmental frameworks and clearer reporting of both progressive and regressive changes, along with well-powered, longitudinal studies.

Identification of a mosaic MTOR variant in purified neuronal DNA in a patient with focal cortical dysplasia using a novel depth electrode harvesting technique.

OBJECTIVE: Recent studies have identified brain somatic variants as a cause of focal epilepsy. These studies relied on resected tissue from epilepsy surgery, which is not available in most patients. The use of trace tissue adherent to depth electrodes used for stereo electroencephalography (EEG) has been proposed as an alternative but is hampered by the low cell quality and contamination by nonbrain cells. Here, we use our improved depth electrode harvesting technique that purifies neuronal nuclei to achieve molecular diagnosis in a patient with focal cortical dysplasia (FCD). METHODS: Depth electrode tips were collected, pooled by brain region and seizure onset zone, and nuclei were isolated and sorted using fluorescence-activated nuclei sorting (FANS). Somatic DNA was amplified from neuronal and astrocyte nuclei using primary template amplification followed by exome sequencing of neuronal DNA from the affected pool, unaffected pool, and saliva. The identified variant was validated using droplet digital polymerase chain reaction (PCR). RESULTS: An 11-year-old male with drug-resistant genetic-structural epilepsy due to left anterior insula FCD had seizures from age 3 years. Stereo EEG confirmed seizure onset in the left anterior insula. The two anterior insula electrodes were combined as the affected pool and three frontal electrodes as the unaffected pool. FANS isolated 140 neuronal nuclei from the affected and 245 neuronal nuclei from the unaffected pool. A novel somatic missense MTOR variant (p.Leu489Met, CADD score 23.7) was identified in the affected neuronal sample. Droplet digital PCR confirmed a mosaic gradient (variant allele frequency = .78% in affected neuronal sample; variant was absent in all other samples). SIGNIFICANCE: Our findings confirm that harvesting neuronal DNA from depth electrodes followed by molecular analysis to identify brain somatic variants is feasible. Our novel method represents a significant improvement compared to the previous method by focusing the analysis on high-quality cells of the cell type of interest.

Detecting Apathy in Individuals with Parkinson's Disease: A Systematic Review.

BACKGROUND: Individuals experiencing apathy in Parkinson's disease (PD) have a lack of emotion and motivation. Apathy often overlaps with comorbidities such as depression, and is sometimes difficult to detect. OBJECTIVE: To examine diagnostic accuracy of apathy-screening tools compared with a gold standard (clinician diagnosis) among adult outpatients with PD. METHODS: A systematic review was conducted. Six research databases were searched to May 23, 2018. Diagnostic accuracy measures, including sensitivity and specificity were gathered. RESULTS: 1,007 full-text articles were reviewed with seven full-text articles included. The gold standard was considered a clinician diagnosis as apathy is not defined in the DSM/ICD. Diagnostic accuracy measures were reported for the Lille Apathy Rating Scale (LARS) both informant- and observer-rated, Unified Parkinson's Disease Rating Scale (UPDRS), Apathy Scale (AS), Apathy Evaluation Scale (AES), Non-Motor Symptoms Questionnaire (NMS-Q), and Dimensional Apathy Scale (DAS). The AES had the best reported sensitivity and specificity values, both 90%. The AS had the highest reported specificity at 100%, with 66% sensitivity. Pooled prevalence of apathy was 29.1% (95% CI 21.5%-36.6%). CONCLUSIONS: While 18 screening tools exist to screen for apathy in PD, only six have been validated against clinician diagnosis. The AES had the highest reported sensitivity and specificity and is a brief, easy to use tool. The AS was designed specifically for use in PD populations and has the highest reported specificity. Future research should focus on the development of an accepted gold standard, to further understand accuracy measures of all available apathy screening tools.