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Parkinson's disease (PD) is a neurodegenerative disorder causing postural control impairments. Postural control involves multiple domains, such as control of postural sway in stance, automatic postural responses (APRs) and anticipatory postural adjustments (APAs). We hypothesize that impairments in each postural domain is associated with resting-state functional connectivity (rsFC), accounted by predictive modeling and that cortical and cerebellar networks would predict postural control in people with PD (PwPD).To determine whether rsFC can predict three domains of postural control independently in PwPD and older adults (OA) based on predictive accuracy of models.The cohort consisted of 65 PwPD (67.7 +8.1 age) tested in their OFF-state and 42 OA (69.7 +8.2 age). Six body-worn, inertial sensors measured postural sway area while standing on foam, step length of APRs to a backward push-and-release perturbation, and magnitude of lateral APAs prior to voluntary gait initiation. Resting state-fMRI data was reported on 384 regions of interest that were grouped into 13 functional brain networks. Associations between rsFC and postural metrics were characterized using predictive modeling, with an independent training (n = 67) and validation (n = 40) dataset. Models were trained in the training sample and performance of the best model was validated in the independent test dataset.rsFC of different brain networks predicted each domain of postural control in PD: Frontoparietal and Ventral Attention rsFC for APAs; Cerebellar-Subcortical and Visual rsFC and Auditory and Cerebellar-Subcortical rsFC for APRs; Ventral Attention and Ventral Multimodal rsFC for postural sway. In OA, CinguloOpercular and Somatomotor rsFC predicted APAs.Our findings suggest that cortical networks predict postural control in PD and there is little overlap in brain network connectivities that predict different domains of postural control, given the rsFC methodology used. PwPD use different cortical networks for APAs compared to OA.

Background: Instrumented measures of balance and gait measure more specific balance and gait impairments than clinical rating scales. No prior studies have used objective balance/gait measures to examine associations with ventricular and brain volumes in people with Parkinson’s disease (PD). Objective: To test the hypothesis that larger ventricular and smaller cortical and subcortical volumes are associated with impaired balance and gait in people with PD. Methods: Regional volumes from structural brain images were included from 96 PD and 50 control subjects. Wearable inertial sensors quantified gait, anticipatory postural adjustments prior to step initiation (APAs), postural responses to a manual push, and standing postural sway on a foam surface. Multiple linear regression models assessed the relationship between brain volumes and balance/gait and their interactions in PD and controls, controlling for sex, age and corrected for multiple comparisons. Results: Smaller brainstem and subcortical gray matter volumes were associated with larger sway area in people with PD, but not healthy controls. In contrast, larger ventricle volume was associated with smaller APAs in healthy controls, but not in people with PD. A sub-analysis in PD showed significant interactions between freezers and non-freezers, in several subcortical areas with stride time variability, gait speed and step initiation. Conclusion: Our models indicate that smaller subcortical and brainstem volumes may be indicators of standing balance dysfunction in people with PD whereas enlarged ventricles may be related to step initiation difficulties in healthy aging. Also, multiple subcortical region atrophy may be associated with freezing of gait in PD.

We previously showed that both open-loop (beat of a metronome) and closed-loop (phase-dependent tactile feedback) cueing may be similarly effective in reducing Freezing of Gait (FoG), assessed with a quantitative FoG Index, while turning in place in the laboratory in a group of people with Parkinson's disease (PD). Despite the similar changes on the FoG Index, it is not known whether both cueing responses require attentional control, which would explain FoG Index improvement. The mechanisms underlying cueing responses are poorly understood. Here, we tested the hypothesis that the salience network would predict responsiveness (i.e., FoG Index improvement) to open-loop and closed-loop cueing in people with and without FoG of PD, as salience network contributes to tasks requiring attention to external stimuli in healthy adults. Thirteen people with PD with high-quality imaging data were analyzed to characterize relationships between resting-state MRI functional connectivity and responses to cues. The interaction of the salience network and retrosplenial-temporal networks was the best predictor of responsiveness to open-loop cueing, presenting the largest effect size (d = 1.16). The interaction between the salience network and subcortical as well as cingulo-parietal and subcortical networks were the strongest predictors of responsiveness to closed-loop cueing, presenting the largest effect sizes (d = 1.06 and d = 0.84, respectively). Salience network activity was a common predictor of responsiveness to both cueing, which suggests that auditory and proprioceptive stimuli during turning may require some level of cognitive and insular activity, anchored within the salience network, which explain FoG Index improvements in people with PD.

We previously showed that dual‐task cost (DTC) on gait speed in people with Parkinson's disease (PD) improved after 6 weeks of the Agility Boot Camp with Cognitive Challenge (ABC‐C) exercise program. Since deficits in dual‐task gait speed are associated with freezing of gait and gray matter atrophy, here we performed preplanned secondary analyses to answer two questions: (a) Do people with PD who are freezers present similar improvements compared to nonfreezers in DTC on gait speed with ABC‐C? (b) Can cortical thickness at baseline predict responsiveness to the ABC‐C? The DTC from 39 freezers and 43 nonfreezers who completed 6 weeks of ABC‐C were analyzed. A subset of 51 participants (21 freezers and 30 nonfreezers) with high quality imaging data were used to characterize relationships between baseline cortical thickness and delta (Δ) DTC on gait speed following ABC‐C. Freezers showed larger ΔDTC on gait speed than nonfreezers with ABC‐C program (p

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 individualswith 22q11DS and 330matched 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, 20.90 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, 20.91 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.

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 (ROIs) 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 (GP) 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.

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=2,510) or unexposed (n=6,079) 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 volume. 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.

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.