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1.
Neuroscience ; 2020 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-32629155

RESUMO

Freezing of gait (FoG) is a brief, episodic absence or marked reduction of forward progression of the feet, despite the intention to walk, that is common in people with Parkinson's disease (PD). We hypothesized that not only motor, but higher level cognitive and attention areas may be impaired in freezers. In this study, we aimed to characterize differences in cortical and subcortical functional connectivity specific to FoG. We examined resting state neuroimaging and objective measures of FoG severity and gait from 103 individuals (28 PD+FoG, 36 PD-FoG and 39 healthy controls). Inertial sensors were used to quantify freezing severity and gait. Groups with and without FoG were matched on age, disease severity, cognitive status, and levodopa medication. MRI data was processed using surface-based registration. High-quality imaging data were used to characterize differences in connectivity specific to FoG using a pre-defined set of Regions of Interest and validated using whole-brain connectivity analysis. Associations between functional connectivity and objective measures of FoG were determined via predictive modeling using hold-out cross validation. We found that connectivity between the left globus pallidus and left somatosensory cortex and between two brain areas in the default and insular/vestibular networks exhibited significant differences specific to FoG and were also strong and significant predictors of FoG severity. Our findings suggest that the interplay among motor, default and vestibular areas of the left cortex are critical in the pathology of FoG.

2.
Hum Brain Mapp ; 2020 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-32198905

RESUMO

Alterations in regional subcortical brain volumes have been investigated as part of the efforts of an international consortium, ENIGMA, to identify reliable neural correlates of major depressive disorder (MDD). Given that subcortical structures are comprised of distinct subfields, we sought to build significantly from prior work by precisely mapping localized MDD-related differences in subcortical regions using shape analysis. In this meta-analysis of subcortical shape from the ENIGMA-MDD working group, we compared 1,781 patients with MDD and 2,953 healthy controls (CTL) on individual measures of shape metrics (thickness and surface area) on the surface of seven bilateral subcortical structures: nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen, and thalamus. Harmonized data processing and statistical analyses were conducted locally at each site, and findings were aggregated by meta-analysis. Relative to CTL, patients with adolescent-onset MDD (≤ 21 years) had lower thickness and surface area of the subiculum, cornu ammonis (CA) 1 of the hippocampus and basolateral amygdala (Cohen's d = -0.164 to -0.180). Relative to first-episode MDD, recurrent MDD patients had lower thickness and surface area in the CA1 of the hippocampus and the basolateral amygdala (Cohen's d = -0.173 to -0.184). Our results suggest that previously reported MDD-associated volumetric differences may be localized to specific subfields of these structures that have been shown to be sensitive to the effects of stress, with important implications for mapping treatments to patients based on specific neural targets and key clinical features.

3.
Am J Psychiatry ; 177(7): 589-600, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32046535

RESUMO

OBJECTIVE: 22q11.2 deletion syndrome (22q11DS) is among the strongest known genetic risk factors for schizophrenia. Previous studies have reported variable alterations in subcortical brain structures in 22q11DS. To better characterize subcortical alterations in 22q11DS, including modulating effects of clinical and genetic heterogeneity, the authors studied a large multicenter neuroimaging cohort from the ENIGMA 22q11.2 Deletion Syndrome Working Group. METHODS: Subcortical structures were measured using harmonized protocols for gross volume and subcortical shape morphometry in 533 individuals with 22q11DS and 330 matched healthy control subjects (age range, 6-56 years; 49% female). RESULTS: Compared with the control group, the 22q11DS group showed lower intracranial volume (ICV) and thalamus, putamen, hippocampus, and amygdala volumes and greater lateral ventricle, caudate, and accumbens volumes (Cohen's d values, -0.90 to 0.93). Shape analysis revealed complex differences in the 22q11DS group across all structures. The larger A-D deletion was associated with more extensive shape alterations compared with the smaller A-B deletion. Participants with 22q11DS with psychosis showed lower ICV and hippocampus, amygdala, and thalamus volumes (Cohen's d values, -0.91 to 0.53) compared with participants with 22q11DS without psychosis. Shape analysis revealed lower thickness and surface area across subregions of these structures. Compared with subcortical findings from other neuropsychiatric disorders studied by the ENIGMA consortium, significant convergence was observed between participants with 22q11DS with psychosis and participants with schizophrenia, bipolar disorder, major depressive disorder, and obsessive-compulsive disorder. CONCLUSIONS: In the largest neuroimaging study of 22q11DS to date, the authors found widespread alterations to subcortical brain structures, which were affected by deletion size and psychotic illness. Findings indicate significant overlap between 22q11DS-associated psychosis, idiopathic schizophrenia, and other severe neuropsychiatric illnesses.

4.
Cereb Cortex ; 29(12): 5217-5233, 2019 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-31271414

RESUMO

Secondhand smoke exposure is a major public health risk that is especially harmful to the developing brain, but it is unclear if early exposure affects brain structure during middle age and older adulthood. Here we analyzed brain MRI data from the UK Biobank in a population-based sample of individuals (ages 44-80) who were exposed (n = 2510) or unexposed (n = 6079) to smoking around birth. We used robust statistical models, including quantile regressions, to test the effect of perinatal smoke exposure (PSE) on cortical surface area (SA), thickness, and subcortical volumes. We hypothesized that PSE would be associated with cortical disruption in primary sensory areas compared to unexposed (PSE-) adults. After adjusting for multiple comparisons, SA was significantly lower in the pericalcarine (PCAL), inferior parietal (IPL), and regions of the temporal and frontal cortex of PSE+ adults; these abnormalities were associated with increased risk for several diseases, including circulatory and endocrine conditions. Sensitivity analyses conducted in a hold-out group of healthy participants (exposed, n = 109, unexposed, n = 315) replicated the effect of PSE on SA in the PCAL and IPL. Collectively our results show a negative, long term effect of PSE on sensory cortices that may increase risk for disease later in life.

5.
Artigo em Inglês | MEDLINE | ID: mdl-29201283

RESUMO

Human brain connectomics is a rapidly evolving area of research, using various methods to define connections or interactions between pairs of regions. Here we evaluate how the choice of (1) regions of interest, (2) definitions of a connection, and (3) normalization of connection weights to total brain connectivity and region size, affect our calculation of the structural connectome. Sex differences in the structural connectome have been established previously. We study how choices in reconstruction of the connectome affect our ability to classify subjects by sex using a support vector machine (SVM) classifier. The use of cluster-based regions led to higher accuracy in sex classification, compared to atlas-based regions. Sex classification was more accurate when based on finer cortical partitions and when using dilations of regions of interest prior to computing brain networks.

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