Roxana-Gabriela Mozolea

We used resting-state fMRI to assess whether there are sex differences in the functional connectivity of salt sensing brain regions during acute hypernatremia in young healthy adults. Despite having similar increases in serum sodium, thirst, systolic BP, and plasma AVP, functional connectivity between the SFO and OVLT increased with acute hypernatremia in men but decreased in women. This suggests there may be sex differences in salt sensing in brain regions that regulate sympathoexcitation and BP.

Despite the widespread use of older adults (OA) as controls in movement disorder studies, the specific effects of aging on the neural control of upper and lower limb movements remain unclear. While functional MRI paradigms focusing on hand movements are widely used to investigate age-related brain changes, research on lower limb movements is limited due to technical challenges in an MRI environment. This study addressed this gap by examining both upper and lower limb movements in healthy young adults (YA) vs. OA. Sixteen YA and 20 OA, matched for sex, dominant side, and cognitive status, performed pinch grip and ankle dorsiflexion tasks, each requiring 15% of their maximum voluntary contraction. While both groups achieved the target force and exhibited similar force variability and accuracy, OA displayed distinct differences in force control dynamics, with a slower rate of force increase in the hand task and a greater rate of force decrease in the foot task. Imaging results revealed that OA exhibited more widespread activation, extending beyond brain regions typically involved in movement execution. In the hand task, OA showed increased activity in premotor and visuo-motor integration regions, as well as in the cerebellar hemispheres. During the foot task, OA engaged the cerebellar hemispheres more than YA. Collectively, results suggest that OA may recruit additional brain regions to manage motor tasks, possibly to achieve similar performance. Future longitudinal studies that track changes over time could help clarify if declines in motor performance lead to corresponding changes in brain activation.

Background: While motor coordination problems are frequently reported among individuals with Parkinson’s disease (PD), the effects of the disease on the performance of multi-limb movements and the brain changes underlying impaired coordination are not well-documented.Objective: Functional magnetic resonance imaging (fMRI) was used to examine differences in brain activity during a task that involved the coordination of non-homologous limbs (i.e., ipsilateral hand and foot) in individuals with and without PD.Methods: Participants included 20 PD and 20 healthy control participants (HC). They were instructed to generate force in a coordinated manner by simultaneously contracting their ipsilateral hand and foot. PD were tested off their antiparkinsonian medication and on their more affected side, whereas the side in controls was randomized.Results: Although both groups were able to coordinate the two limbs to produce the expected level of force, PD had a slower rate of force production and relaxation compared to HC. Additionally, their globus pallidus and primary motor cortex were underactive, whereas their pre-supplementary motor area (pre-SMA) and lateral cerebellum were overactive relative to HC. Importantly, in PD, the fMRI activity within the pre-SMA correlated with the rate of force decrease.Conclusion: Multi-limb force control deficits in PD appear to be related to widespread underactivation within the basal ganglia-cortical loop. An overactivation of higher-level motor regions within the prefrontal cortex and lateral cerebellum may reflect increased cognitive control and performance monitoring that emerges during more complex motor tasks such as those that involve the coordination of multiple limbs.

Background: Research shows that individuals with Parkinson’s disease (PD) who have a postural instability and gait difficulties (PIGD) subtype have a faster disease progression compared to those with a tremor dominant (TD) subtype. Nevertheless, our understanding of the structural brain changes contributing to these clinical differences remains limited, primarily because many brain imaging techniques are only capable of detecting changes in the later stages of the disease.Objective: Free water (FW) has emerged as a robust progression marker in several studies, showing increased values in the posterior substantia nigra that predict symptom worsening. Here, we examined longitudinal FW changes in TD and PIGD across multiple brain regions.Methods: Participants were TD and PIGD enrolled in the Parkinson’s Progression Marker Initiative (PPMI) study who underwent diffusion MRI at baseline and 2 years later. FW changes were quantified for regions of interest (ROI) within the basal ganglia, thalamus, brainstem, and cerebellum.Results: Baseline FW in all ROIs did not differ between groups. Over 2 years, PIGD had a greater percentage increase in FW in the putamen, globus pallidus, and cerebellar lobule V. A logistic regression model incorporating percent change in motor scores and FW in these brain regions achieved 91.4% accuracy in discriminating TD and PIGD, surpassing models based solely on clinical measures (74.3%) or imaging (76.1%).Conclusion: The results further suggest the use of FW to study disease progression in PD and provide insight into the differential course of brain changes in early-stage PD subtypes.

Background: Much of our understanding of the deficits in force control in Parkinson’s disease (PD) relies on findings in the upper extremity. Currently, there is a paucity of data pertaining to the effect of PD on lower limb force control. Objective: The purpose of this study was to concurrently evaluate upper- and lower-limb force control in early-stage PD and a group of age- and gender-matched healthy controls. Methods: Twenty individuals with PD and twenty-one healthy older adults participated in this study. Participants performed two visually guided, submaximal (15% of maximum voluntary contractions) isometric force tasks: a pinch grip task and an ankle dorsiflexion task. PD were tested on their more affected side and after overnight withdrawal from antiparkinsonian medication. The tested side in controls was randomized. Differences in force control capacity were assessed by manipulating speed-based and variability-based task parameters. Results: Compared with controls, PD demonstrated slower rates of force development and force relaxation during the foot task, and a slower rate of relaxation during the hand task. Force variability was similar across groups but greater in the foot than in the hand in both PD and controls. Lower limb rate control deficits were greater in PD with more severe symptoms based on the Hoehn and Yahr stage. Conclusions: Together, these results provide quantitative evidence of an impaired capacity in PD to produce submaximal and rapid force across multiple effectors. Moreover, results suggest that force control deficits in the lower limb may become more severe with disease progression.