Impulsivity Relates to Relative Preservation of Mesolimbic Connectivity in Patients with Parkinson Disease

Sparks, Hiro; Riskin-Jones, Hannah; Price, Chester W.; DiCesare, Jasmine A T; Bari, Ausaf; Hashoush, Nadia G.; Pouratian, Nader

doi:10.1016/j.nicl.2020.102259

Cited by 5 publications

(7 citation statements)

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“…Ultimately, opposite correlations between patients were seen between the pre-SMA-caudate tract and SSRT, which altogether suggests a dual neurobiological problem (local and descending pre-SMA connectivity) in the cognitive control network 91,92 . Thus, reductions in top-down control rely upon paradoxical increases of white matter integrity, a possible neural compensatory response previously reported in Parkinson’s disease and ICD 72,93,94 .…”

Section: Discussionmentioning

confidence: 67%

A circuit-based approach to repair hypersexuality in Parkinson’s disease

Mata-Marín

Pineda-Pardo

Michiels

et al. 2022

Preprint

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One common neuropsychiatric complication in patients with Parkinson's disease treated with dopamine replacement therapy is impulse control disorders. A proportion of patients under dopamine agonist exhibit excessive desire towards appetitive cues accompanied by lost control over behaviour in forms of pathological gambling, hypersexuality or binge eating. The balance between enhanced desire towards sexual cues and cognitive control changes has been hypothesized to be biased toward the former in individuals with hypersexuality and impulse control disorders. Yet, some studies report no behavioural differences in cognitive control differences between impulsive patients and general Parkinson's disease, suggesting possible functional changes along the mesocorticolimbic cortico-subcortical circuitry. Here, we provide evidence for this hypothesis by comparing the neurobiological substrate of sexual disturbance over response inhibition associated to medication states in Parkinson's disease patients with a specific subtype of impulse control disorders (i.e., hypersexuality). We assessed the impact of sexual cues on response inhibition using a novel erotic stop signal task inside an fMRI. A total of 50 participants were included divided in 16 hypersexual and 17 non-hypersexual Parkinson's disease patients and 17 healthy controls. Task-related activations, functional and anatomical connectivity models were performed. Additionally, a separate sample of 20 hypersexual Parkinson's disease patients received excitatory neuromodulation (sham-controlled) over the pre-supplementary motor area (based on fMRI group-based results) aiming to improve response inhibition when exposed to sexual cues. Compared with their non-hypersexual peers, medication perturbed 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 modelling 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 compared to non-hypersexual Parkinson's disease patients (while medicated). 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 when exposed to sexual cues in hypersexual Parkinson's disease. 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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Section: Discussionmentioning

confidence: 67%

A circuit-based approach to repair hypersexuality in Parkinson’s disease

Mata-Marín

Pineda-Pardo

Michiels

et al. 2022

Preprint

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“…Ultimately, opposite correlations between patients were seen between the pre–SMA‐caudate tract and SSRT (positive for patients with PD − HS while negative for patients with PD + HS), which overall suggests a dual neurobiological problem (local and descending pre‐SMA connectivity) in the inhibitory network 62,63 . Thus, reductions in top‐down control rely on paradoxical increases of white matter integrity, a possible neural compensatory response previously reported in patients with PD and ICD 40,64,65 …”

Section: Discussionmentioning

confidence: 86%

“…62,63 Thus, reductions in top-down control rely on paradoxical increases of white matter integrity, a possible neural compensatory response previously reported in patients with PD and ICD. 40,64,65 The neurobiological changes in pre-SMA to caudate connectivity in our PD + HS sample may be explained by experience-dependent plasticity. 61 Previous evidence indicates how repeated behaviors lead to experience-dependent tract changes after daily training of executive function 66 or after repeated alcohol consumption.…”

Section: Dysfunctional Circuitry In Hypersexuality: Functional and An...mentioning

confidence: 92%

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

Mata-Marín

Pineda‐Pardo

Michiels

et al. 2023

Psychiatry Clin Neurosci

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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.

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“…Consistent with our results, the preservation of connectivity between the substantia nigra and limbic network targets has been reported in PD patients with ICBs. 18 D3 agonist-induced hyperdopaminergic stimulation might revitalize the reward system in PD-ICBs but might not activate the reward system in PD-nICBs because of degeneration.…”

Section: Hyperdopaminergic Stimulation Of the Relatively Preserved Re...mentioning

confidence: 98%

“…17 Additionally, a study investigating structural connectivity revealed the relative preservation of the connection between the substantial nigra and the mesolimbic system. 18 However, there have been no detailed assessments of white matter microstructures in PD patients with ICBs; thus, the precise white matter alterations associated with ICB in PD remain unclear. On the basis of these findings, we evaluated white matter microstructures using advanced DW-MRI and myelin imaging techniques to elucidate the pathological white matter pathways of ICBs in PD.…”

Section: Introductionmentioning

confidence: 99%

White matter microstructures in Parkinson's disease with and without impulse control behaviors

Takeshige‐Amano

Hatano

Kamagata

et al. 2022

Ann Clin Transl Neurol

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Background: Impulse control behaviors (ICBs) in Parkinson's disease (PD) are thought to be caused by an overdose of dopaminergic therapy in the relatively spared ventral striatum, or by hypersensitivity of this region to dopamine. Alterations in brain networks are now also thought to contribute to the development of ICBs. Objective: To comprehensively assess white matter microstructures in PD patients with ICBs using advanced diffusion MRI and magnetization transfer saturation (MT-sat) imaging. Methods: This study included 19 PD patients with ICBs (PD-ICBs), 18 PD patients without ICBs (PD-nICBs), and 20 healthy controls (HCs). Indices of diffusion tensor imaging (DTI), diffusion kurtosis imaging, neurite orientation dispersion and density imaging, and MT-sat imaging were evaluated using tract-based spatial statistics (TBSS), regions of interest (ROIs), and tract-specific analysis (TSA). Results: Compared with HCs, PD-nICBs had significant alterations in many major white matter tracts in most parameters. In contrast, PD-ICBs had only partial changes in several parameters. Compared with PD-ICBs, TBSS, ROI, and TSA analyses revealed that PD-nICBs had lower axial kurtosis, myelin volume fraction, and orientation dispersion index in the uncinate fasciculus and external capsule, as well as in the retrolenticular part of the internal capsule. These are components of the reward system and the visual and emotional perception areas, respectively. Interpretation: Myelin and axonal changes in fibers related to the reward system and visual emotional recognition might be more prominent in PD-nICBs than in PD-ICBs.

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Impulsivity Relates to Relative Preservation of Mesolimbic Connectivity in Patients with Parkinson Disease

Cited by 5 publications

References 0 publications

A circuit-based approach to repair hypersexuality in Parkinson’s disease

A circuit-based approach to repair hypersexuality in Parkinson’s disease

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

White matter microstructures in Parkinson's disease with and without impulse control behaviors

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