A circuit‐based approach to modulate hypersexuality in Parkinson's disease

Abstract

Aim: Impulse-control disorder is a common neuropsychiatric complication in Parkinson's disease (PD) under dopamine replacement therapy. Prior studies tested the balance between enhanced desire towards reward and cognitive control deficits, hypothesized to be biased towards the former in impulse control disorders. We provide evidence for this hypothesis by measuring behavioral and neural patterns behind the influence of sexual desire over response inhibition and tools towards functional restoration using repetitive transcranial stimulation in patients with hypersexuality as predominant impulsive disorder. Methods:The effect of sexual cues on inhibition was measured with a novel erotic stop-signal task under on and off dopaminergic medication. Task-related functional and anatomical connectivity models were estimated in 16 hypersexual and 17 nonhypersexual patients with PD as well as in 17 healthy controls. Additionally, excitatory neuromodulation using intermittent theta-burst stimulation (sham-controlled) was applied over the pre-supplementary motor area in 20 additional hypersexual patients with PD aiming to improve response inhibition.Results: Compared with their nonhypersexual peers, patients with hypersexuality recruited caudate, pre-supplementary motor area, ventral tegmental area, and anterior cingulate cortex while on medication. Reduced connectivity was found between pre-supplementary motor area and caudate nucleus in hypersexual compared with nonhypersexual patients (while medicated), a result paralleled by compensatory enhanced anatomical connectivity. Furthermore, stimulation over the pre-supplementary motor area improved response inhibition in hypersexual patients with PD when exposed to sexual cues. Conclusion:This study, therefore, has identified a specific fronto-striatal and mesolimbic circuitry underlying uncontrolled sexual responses in medicated patients with PD where cortical neuromodulation halts its expression.

Anatomical correlates of apathy and impulsivity co-occurrence in early Parkinson’s disease

“…In contrast, the underlying changes mediating impulsive-like behavior can be attributed to anatomical reductions in cognitive control areas found in the current study, including the medial prefrontal cortex and pre-SMA. Indeed, abnormal activity of the dorsal medial PFC and pre-SMA areas has been reported in PD + ICD [ 29 ], associated with abnormal control in PD + ICD due to its role in executive control and response inhibition [ 30 ]. An alternative non-exclusive view would entail that the reduced GM density in the pre-SMA participate in the co-occurrence of dysfunctional changes in various behavioral roles mediated via limbic structures [ 31 ].…”

Aberrant brain topological organization and granger causality connectivity in Parkinson’s disease with impulse control disorders

“…Our findings could provide compelling evidence for further comprehending the neurophysiological mechanism of ICD and might provide candidate brain targets for non-invasive neuromodulation. As the recent clinical trial reported, excitatory neuromodulation over the pre-supplementary motor area was successfully applied to improve response inhibition in PD-ICD patients (Mata-Marin et al, 2022). Some limitations must be mentioned.…”