Objective: To define the neural circuitry underlying hypersexuality in Parkinson’s disease and to provide novel therapeutic options by employing neuromodulatory techniques.

Background: The balance between cognitive control and enhanced desire towards sexual cues has been hypothesized to be biased toward the latter in individuals with Parkinson’s disease and impulse control disorders, suggesting possible neurocognitive and connectivity changes along the mesocorticolimbic circuitry. Here, we provide evidence for this hypothesis by comparing the neurobiological substrate of sexual cues disturbance over cognitive control associated to a medication-induced hyperdopaminergic state in hypersexual Parkinson´s disease, a specific subtype of impulse control disorders.

Method: We assessed the impact of sexual cues on response inhibition using a novel erotic stop signal task inside an fMRI. 50 participants were included (16 hypersexual; 17 non-hypersexual patients with Parkinson’s disease; 17 controls). Task-related activations, functional and anatomical connectivity models were performed. Additionally, 20 extra hypersexual Parkinson’s disease patients received excitatory neuromodulation with transcranial magnetic stimulation (sham-controlled) over the pre-supplementary motor area aiming to improve response inhibition.

Results: Compared with their non-hypersexual peers, medication altered response inhibition upon presentation of sexual cues in patients with hypersexuality, recruiting a network involving caudate, pre-supplementary motor area, ventral tegmental area, and anterior cingulate cortex. Dynamic causal modeling revealed distinct best models to account for cortico-subcortical interactions with reduced task-related inputs in pre-supplementary motor area and descending connectivity to caudate in hypersexual Parkinson’s disease patients. This was sustained by enhanced fractional anisotropy and reduced mean diffusivity in the pre-supplementary motor area-caudate pathway. Importantly, stimulation over the pre-supplementary motor area improved response inhibition in hypersexual Parkinson’s disease.

Conclusion: We identified a specific fronto-striatal and mesolimbic circuitry underlying uncontrolled sexual behaviours in Parkinson’s disease induced by medication, with recovery options by applying neuromodulation.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/defining-and-restoring-the-underlying-neural-circuitry-of-hypersexuality-in-parkinsons-disease/