Patients with Parkinson disease (PD) demonstrate deficits in executive tasks that include planning and set shifting.^1,2 However, the underlying disease-related mechanism is not completely understood. Using functional imaging, neuronal substrates of those deficits were mainly found in the frontostriatal circuitry. Depending on the involvement of the dorsal caudate nucleus (NC), both hypoactivity and hyperactivity of prefrontal areas have been reported in unmedicated patients with PD when compared with controls.^3-5

Visual hallucinations (VHs) are abnormal perceptions in the absence of an adequate visual stimulus. Complex well-formed VHs have been described in several pathologic conditions, including peduncular hallucinosis, schizophrenia, cortical Lewy body dementia, and Parkinson disease (PD). A potential common substrate for complex VHs in all of these conditions is suppression of normal inhibitory cortical inputs over the visual association cortex, leading to complex VHs as a “release phenomenon.”¹ However, the neural mechanisms underlying VHs remain unclear. Although dopamine may have a role,² indirect evidence indicates that serotonin may also contribute to the pathogenesis of complex VHs, probably via involvement of the serotonin 2 receptor. In fact, hallucinogenic lysergic acid diethylamide acts via serotonin 2A receptors,³ and atypical antipsychotics (eg, clozapine and quetiapine fumarate) that effectively reduce VHs, as well as dopamine receptor antagonists, are serotonin 2A and 2C receptor antagonists.⁴ In PD, this antipsychotic effect on VHs occurs at low dosages (approximately 10-fold less than in schizophrenia); at such dosages, there is high occupancy of serotonin 2A receptors and low occupancy of dopamine receptors.⁵ Together, these observations suggest that serotonin 2A receptors may be involved in VHs in PD; however, the pathogenesis underlying these phenomena and the potential action site of serotonin 2A ligands in reducing such symptoms is unknown to date. Therefore, the specific objective of this pilot study was to measure for the first time in vivo changes in serotonin 2A receptor binding using the selective serotonin 2A receptor ligand setoperone F 18⁶ during positron emission tomography (PET) among age-matched nondemented patients having PD with well-formed VHs vs patients having PD without VHs.

Objective: Some patients with Parkinson disease (PD) develop pathological gambling when treated with dopamine agonists (DAs). However, little is known about DA-induced changes in neuronal networks that may underpin this drug-induced change in behavior in vulnerable individuals. In this case-control study, we aimed to investigate DA-induced changes in brain activity that may differentiate patients with PD with DA-induced pathological gambling (gamblers) from patients with PD without such a history (controls). Methods: Following overnight withdrawal of antiparkinsonian medication, patients were studied with H₂¹⁵O PET before and after administration of DA (3 mg apomorphine) to measure changes in regional cerebral blood flow as an index of regional brain activity during a card selection game with probabilistic feedback. Results: We observed that the direction of DA-related activity change in brain areas that are implicated in impulse control and response inhibition (lateral orbitofrontal cortex, rostral cingulate zone, amygdala, external pallidum) distinguished gamblers from controls. DA significantly increased activity in these areas in controls, while gamblers showed a significant DA-induced reduction of activity. Conclusions: We propose that in vulnerable patients with PD, DAs produce an abnormal neuronal pattern that resembles those found in nonparkinsonian pathological gambling and drug addiction. DA-induced disruption of inhibitory key functions—outcome monitoring (rostral cingulate zone), acquisition and retention of negative action-outcome associations (amygdala and lateral orbitofrontal cortex)—together with restricted access of those areas to executive control (external pallidum)—may well explain loss of impulse control and response inhibition in vulnerable patients with PD, thereby fostering the development of pathological gambling.