It remains unknown whether migraine headache has a progressive component in its pathophysiology. Quantitative MRI may provide valuable insight into abnormal changes in the migraine interictum and assist in identifying disrupted brain networks. We carried out a data-driven study of structural integrity and functional connectivity of the resting brain in migraine without aura. MRI scanning was performed in 36 patients suffering from episodic migraine without aura and 33 age-matched healthy subjects. Voxel-wise analysis of regional brain volume was performed by registration of the T1-weighted MRI scans into a common study brain template using the tensor-based morphometry (TBM) method. Changes in functional synchronicity of the brain networks were assessed using probabilistic independent component analysis (ICA). TBM revealed that migraine is associated with reduced volume of the medial prefrontal cortex (mPFC). Among 375 functional brain networks, resting-state connectivity was decreased between two components spanning the visual cortex, posterior insula, and parietal somatosensory cortex. Our study reveals structural and functional alterations of the brain in the migraine interictum that may stem from underlying disease risk factors and the “silent” aura phenomenon. Longitudinal studies will be needed to investigate whether interictal brain changes are progressive and associated with clinical disease trajectories.

Background Attention‐deficit hyperactivity disorder (ADHD) is associated with white matter (WM) microstructure. Our objective was to investigate how WM microstructure is longitudinally related to symptom remission in adolescents and young adults with ADHD. Methods We obtained diffusion‐weighted imaging (DWI) data from 99 participants at two time‐points (mean age baseline: 16.91 years, mean age follow‐up: 20.57 years). We used voxel‐wise Tract‐Based Spatial Statistics (TBSS) with permutation‐based inference to investigate associations of inattention (IA) and hyperactivity‐impulsivity (HI) symptom change with fractional anisotropy (FA) at baseline, follow‐up, and change between time‐points. Results Remission of combined HI and IA symptoms was significantly associated with reduced FA at follow‐up in the left superior longitudinal fasciculus and the left corticospinal tract (CST; PFWE = 0.038 and PFWE = 0.044, respectively), mainly driven by an association between HI remission and follow‐up CST FA (PFWE = 0.049). There was no significant association of combined symptom decrease with FA at baseline or with changes in FA between the two assessments. Conclusions In this longitudinal DWI study of ADHD using dimensional symptom scores, we show that greater symptom decrease is associated with lower follow‐up FA in specific WM tracts. Altered FA thus may appear to follow, rather than precede, changes in symptom remission. Our findings indicate divergent WM developmental trajectories between individuals with persistent and remittent ADHD, and support the role of prefrontal and sensorimotor tracts in the remission of ADHD.

Molecular mechanisms underlying Alzheimer's disease (AD) are difficult to investigate, partly because diagnosis lags behind the insidious pathological processes. Therefore, identifying AD neuroimaging markers and their genetic modifiers may help study early mechanisms of neurodegeneration. We aimed to identify brain regions of the highest vulnerability to AD using a data‐driven search in the AD Neuroimaging Initiative (ADNI, n = 1,100 subjects), and further explored genetic variants affecting this critical brain trait using both ADNI and the younger UK Biobank cohort ( n = 8,428 subjects). Tensor‐Based Morphometry (TBM) and Independent Component Analysis (ICA) identified the limbic system and its interconnecting white‐matter as the most AD‐vulnerable brain feature. Whole‐genome analysis revealed a common variant in SHARPIN that was associated with this imaging feature (rs34173062, p = 2.1 × 10 −10 ). This genetic association was validated in the UK Biobank, where it was correlated with entorhinal cortical thickness bilaterally ( p = .002 left and p = 8.6 × 10 −4 right), and with parental history of AD ( p = 2.3 × 10 −6 ). Our findings suggest that neuroanatomical variation in the limbic system and AD risk are associated with a novel variant in SHARPIN. The role of this postsynaptic density gene product in β1‐integrin adhesion is in line with the amyloid precursor protein (APP) intracellular signaling pathway and the recent genome‐wide evidence.

Aging, the greatest risk factor for Alzheimer's disease (AD), may lead to the accumulation of somatic mutations in neurons. We investigated whether somatic mutations, specifically in longer genes, are implicated in AD etiology. First, we modeled the theoretical likelihood of genes being affected by aging‐induced somatic mutations, dependent on their length. We then tested this model and found that long genes are indeed more affected by somatic mutations and that their expression is more frequently reduced in AD brains. Furthermore, using gene‐set enrichment analysis, we investigated the potential consequences of such long gene disruption. We found that long genes are involved in synaptic adhesion and other synaptic pathways that are predicted to be inhibited in the brains of AD patients. Taken together, our findings indicate that long gene–dependent synaptic impairment may contribute to AD pathogenesis.