Mental imagery content is associated with disease severity and specific brain functional connectivity changes in patients with Parkinson's disease.

Mental imagery is the mental re-creation of perceptual experiences, events and scenarios, and motor acts. In our previous study, we assessed whether motor imagery (MI) training combined with functional magnetic resonance imaging-based neurofeedback could improve the motor function of nondemented subjects with mild Parkinson's disease (PD) (N = 22). We used visual imagery (VI) (e.g., of scenes or events, but not of self-movements) training without neurofeedback for the control group (N = 22). Notably, both groups showed significant and comparable improvement in motor function after four weeks of daily imagery practice. In this study, we further examined the neural correlates of the motor enhancement as a result of the VI training by analyzing the self-reported VI content during daily practice and relating its quality to the functional connectivity characteristics of the same subjects. We demonstrated that the VI practice encompassed multisensory, spatial, affective, and executive processes all of which are also important for motor function in real life. Subjects with worse global disease severity also showed poorer quality of the VI content. Finally, the quality of the VI content showed significant positive correlations with the functional connectivity changes during the VI tasks in brain areas supporting visuospatial and sensorimotor processes. Our findings suggest that mental imagery training combining VI and MI may enhance motor function in patients with mild PD, and more broadly, underline the importance of incorporating self-reports of thoughts and experiences in neuroimaging studies that examine the brain mechanisms of complex cognitive processes especially in neuropsychiatric patient populations.

Neurofeedback-guided kinesthetic motor imagery training in Parkinson's disease: Randomized trial.

BACKGROUND: Parkinson's disease (PD) causes difficulty with maintaining the speed, size, and vigor of movements, especially when they are internally generated. We previously proposed that the insula is important in motivating intentional movement via its connections with the dorsomedial frontal cortex (dmFC). We demonstrated that subjects with PD can increase the right insula-dmFC functional connectivity using fMRI-based neurofeedback (NF) combined with kinesthetic motor imagery (MI). The current study is a randomized clinical trial testing whether NF-guided kinesthetic MI training can improve motor performance and increase task-based and resting-state right insula-dmFC functional connectivity in subjects with PD. METHODS: We assigned nondemented subjects with mild PD (Hoehn & Yahr stage ≤ 3) to the experimental kinesthetic MI with NF (MI-NF, n = 22) and active control visual imagery (VI, n = 22) groups. Only the MI-NF group received NF-guided MI training (10-12 runs). The NF signal was based on the right insula-dmFC functional connectivity strength. All subjects also practiced their respective imagery tasks at home daily for 4 weeks. Post-training changes in 1) task-based and resting-state right insula-dmFC functional connectivity were the primary imaging outcomes, and 2) MDS-UPDRS motor exam and motor function scores were the primary and secondary clinical outcomes, respectively. RESULTS: The MI-NF group was not significantly different from the VI group in any of the primary imaging or clinical outcome measures. The MI-NF group reported subjective improvement in kinesthetic body awareness. There was significant and comparable improvement only in motor function scores in both groups (secondary clinical outcome). This improvement correlated with NF regulation of the right insula-dmFC functional connectivity only in the MI-NF group. Both groups showed specific training effects in whole-brain functional connectivity with distinct neural circuits supporting kinesthetic motor and visual imagery (exploratory imaging outcome). CONCLUSIONS: The functional connectivity-based NF regulation was unsuccessful, however, both kinesthetic MI and VI practice improved motor function in our cohort with mild PD.

Distinct neural circuits are associated with subclinical neuropsychiatric symptoms in Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) can present with neuropsychiatric symptoms (here, anxiety, depression, and apathy) at any stage of the disease. We investigated the neural correlates of subclinical neuropsychiatric symptoms in relation to motor and cognitive symptoms in a high-functioning PD cohort. METHODS: Brain morphometry of the cognitively intact, early-stage (Hoehn & Yahr 2) PD group (n = 48) was compared to matched controls (n = 37). Whole-brain, pairwise, resting-state functional connectivity measures were correlated with neuropsychiatric symptom, motor exam, and global cognitive scores of the PD group. RESULTS: Factor analysis of highly collinear anxiety, depression, and apathy scores revealed a single principal component (i.e., composite neuropsychiatric symptom score) explaining 71.6% of variance. There was no collinearity between the neuropsychiatric, motor, and cognitive scores. Compared to controls, PD group showed only subcortical changes including amygdala and nucleus accumbens atrophy, and greater pallidal volume. Reduced functional connectivity in the limbic cortical-striatal circuits and increased functional connectivity between the cerebellum and occipito-temporal regions were associated with a more impaired neuropsychiatric profile. This functional connectivity pattern was distinct from those associated with motor deficits and global cognitive functioning. The individual components of the neuropsychiatric symptoms also exhibited unique connectivity patterns. LIMITATIONS: Patients were scanned in "on-medication" state only and a control group with similar neuropsychiatric symptoms was not included. CONCLUSION: Abnormal functional connectivity of distinct neural circuits is present even at the subclinical stage of neuropsychiatric symptoms in PD. Neuropsychiatric phenotyping is important and may facilitate early interventions to "reorganize" these circuits and delay/prevent clinical symptom onset.

Goal-directed behavior in individuals with mild Parkinson's disease: Role of self-efficacy and self-regulation.

INTRODUCTION: Deficits in goal-directed behavior are common in individuals with Parkinson's disease (PD) and have been ascribed to apathy. In addition to apathy, individuals' beliefs in their competence (self-efficacy) and capacity to regulate emotions, thoughts, and actions (self-regulation) are critical skills for goal-directed behavior. We investigated these skills and their relationship to motor and non-motor symptoms in individuals with PD. We also examined the neural correlates of these skills using functional magnetic resonance imaging (fMRI). METHODS: We enrolled 35 subjects with mild PD (Hoehn and Yahr stage ≤2.5) and used the new general self-efficacy (NGSES) and self-regulation scales (SRS). We correlated the scores on these scales with measures of cognition, anxiety, depression, apathy, fatigue, quality of life, and disease burden using stepwise regression analyses. We collected resting-state fMRI data in a 3-Tesla scanner and computed the pairwise functional connectivity among nodes of major networks. We correlated the connectivity maps with the NGSES and SRS scores. RESULTS: Our PD cohort demonstrated intact NGSES and SRS scores compared with respective population data. These scores showed significant negative correlation with apathy and disease burden. Stronger connectivity in the salience network and decoupling from the default mode network supported self-efficacy and self-regulation. CONCLUSIONS: Self-efficacy and self-regulation capacity seems preserved, but vulnerable to disease-related factors in individuals with mild PD. Educational programs cultivating this capacity could improve the coping skills of these individuals. Functional connectivity changes in salience and default mode networks may serve as neurobiological markers to demonstrate the effectiveness of such interventions.