BACKGROUND: Functional movement disorders, a common cause of neurological disabilities, can occur with heterogeneous motor manifestations including functional weakness. However, the underlying mechanisms related to brain function and connectivity are unknown. OBJECTIVE: To identify brain connectivity alterations related to functional weakness we assessed network centrality changes in a group of patients with heterogeneous motor manifestations using task-free functional MRI in combination with different network centrality approaches. METHODS: Task-free functional MRI was performed in 48 patients with heterogeneous motor manifestations including 28 patients showing functional weakness and 65 age- and sex-matched healthy controls. Functional connectivity differences were assessed using different network centrality approaches, i.e. global correlation, eigenvector centrality, and intrinsic connectivity. Motor symptom severity was assessed using The Simplified Functional Movement Disorders Rating Scale and correlated with network centrality. RESULTS: Comparing patients with and without functional weakness showed significant network centrality differences in the left temporoparietal junction and precuneus. Patients with functional weakness showed increased centrality in the same anatomical regions when comparing functional weakness with healthy controls. Moreover, in the same regions, patients with functional weakness showed a positive correlation between motor symptom severity and network centrality. This correlation was shown to be specific to functional weakness with an interaction analysis, confirming a significant difference between patients with and without functional weakness. CONCLUSIONS: We identified the temporoparietal junction and precuneus as key regions involved in brain connectivity alterations related to functional weakness. We propose that both regions may be promising targets for phenotype-specific non-invasive brain stimulation.

• Klíčová slova
• Brain connectivity, Functional connectivity, Functional magnetic resonance imaging, Functional movement disorders, Functional weakness, Motor conversion disorder, Precuneus, Temporoparietal junction,
• MeSH
• konverzní poruchy * MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mapování mozku MeSH
• mozek * diagnostické zobrazování   MeSH
• temenní lalok MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Levodopa is the first-line treatment for Parkinson's disease, although the precise mechanisms mediating its efficacy remain elusive. We aimed to elucidate treatment effects of levodopa on brain activity during the execution of fine movements and to compare them with deep brain stimulation of the subthalamic nuclei. We studied 32 patients with Parkinson's disease using functional MRI during the execution of finger-tapping task, alternating epochs of movement and rest. The task was performed after withdrawal and administration of a single levodopa dose. A subgroup of patients (n = 18) repeated the experiment after electrode implantation with stimulator on and off. Investigating levodopa treatment, we found a significant interaction between both factors of treatment state (off, on) and experimental task (finger tapping, rest) in bilateral putamen, but not in other motor regions. Specifically, during the off state of levodopa medication, activity in the putamen at rest was higher than during tapping. This represents an aberrant activity pattern probably indicating the derangement of basal ganglia network activity due to the lack of dopaminergic input. Levodopa medication reverted this pattern, so that putaminal activity during finger tapping was higher than during rest, as previously described in healthy controls. Within-group comparison with deep brain stimulation underlines the specificity of our findings with levodopa treatment. Indeed, a significant interaction was observed between treatment approach (levodopa, deep brain stimulation) and treatment state (off, on) in bilateral putamen. Our functional MRI study compared for the first time the differential effects of levodopa treatment and deep brain stimulation on brain motor activity. We showed modulatory effects of levodopa on brain activity of the putamen during finger movement execution, which were not observed with deep brain stimulation.

• Klíčová slova
• Parkinson’s disease, deep brain stimulation, dopaminergic treatment, functional magnetic resonance imaging, levodopa,
• Publikační typ
• časopisecké články MeSH