Shared and distinct cortical morphometric alterations in five neuropsychiatric symptoms of Parkinson's disease.

Neuropsychiatric symptoms (including anxiety, depression, apathy, impulse-compulsive behaviors and hallucinations) are among the most common non-motor features of Parkinson's disease. Whether these symptoms should be considered as a direct consequence of the pathophysiologic mechanisms of Parkinson's disease is controversial. Morphometric similarity network analysis and epicenter mapping approach were performed on T1-weighted images of 505 patients with Parkinson's disease and 167 age- and sex-matched healthy participants from Parkinson's Progression Markers Initiative database to reveal the commonalities and specificities of distinct neuropsychiatric symptoms. Abnormal cortical co-alteration pattern in patients with neuropsychiatric symptoms was in somatomotor, vision and frontoparietal regions, with epicenters in somatomotor regions. Apathy, impulse-compulsive behaviors and hallucinations shares structural abnormalities in somatomotor and vision regions, with epicenters in somatomotor regions. In contrast, the cortical abnormalities and epicenters of anxiety and depression were prominent in the default mode network regions. By embedding each symptom within their co-alteration space, we observed a cluster composed of apathy, impulse-compulsive behaviors and hallucinations, while anxiety and depression remained separate. Our findings indicate different structural mechanisms underlie the occurrence and progression of different neuropsychiatric symptoms. Based upon these results, we propose that apathy, impulse-compulsive behaviors and hallucinations are directly related to damage of motor circuit, while anxiety and depression may be the combination effects of primary pathophysiology of Parkinson's disease and psychosocial causes.

Multimodal neuroimaging fusion unravel structural-functional-neurotransmitter change in Parkinson's disease with impulse control disorders.

BACKGROUND: Impulse control disorders (ICD) in Parkinson's disease (PD) is highly multifactorial in etiology and has intricate neural mechanisms. Our multimodal neuroimaging study aimed to investigate the specific patterns of structure-function-neurotransmitter interactions underlying ICD. METHODS: Thirty PD patients with ICD (PD-ICD), 30 without ICD (PD-NICD) and 32 healthy controls (HCs) were recruited. Gyrification and perivascular spaces (PVS) were computed to capture the alternations of cortical surface morphology and glymphatic function. Seed-based functional connectivity (FC) were performed to identify the corresponding functional changes. Further, JuSpace toolbox were employed for cross-modal correlations to evaluate whether the spatial patterns of functional alterations in ICD patients were associated with specific neurotransmitter system. RESULTS: Compared to PD-NICD, PD-ICD patients showed hypogyrification and enlarged PVS volume fraction in the left orbitofrontal gyrus (OFG), as well as decreased FC between interhemispheric OFG. The interhemispheric OFG connectivity reduction was associated with spatial distribution of µ-opioid pathway (r = -0.186, p = 0.029, false discovery rate corrected). ICD severity was positively associated with the PVS volume fraction of left OFG (r = 0.422, p = 0.032). Furthermore, gyrification index (LGI) and percent PVS (pPVS) in OFG and their combined indicator showed good performance in differentiating PD-ICD from PD-NICD. CONCLUSIONS: Our findings indicated that the co-altered structure-function-neurotransmitter interactions of OFG might be involved in the pathogenesis of ICD.

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

BACKGROUND: Although apathy and impulse control disorders (ICDs) are considered to represent opposite extremes of a continuum of motivated behavior (i.e., hypo- and hyperdopaminergic behaviors), they may also co-occur in Parkinson's disease (PD). OBJECTIVES: We aimed to explore the co-occurrence of ICDs and apathy and its neural correlates analyzing gray matter (GM) changes in early untreated PD patients. Moreover, we aimed to investigate the possible longitudinal relationship between ICDs and apathy and their putative impact on cognition during the first five years of PD. METHODS: We used the Parkinson's Progression Markers Initiative (PPMI) database to identify the co-occurrence of apathy and ICDs in 423 early drug-naïve PD patients at baseline and at 5-year follow-up. Baseline MRI volumes and gray matter changes were analyzed between groups using voxel-based morphometry. Multi-level models assessed the longitudinal relationship (across five years) between apathy and ICDs and cognitive functioning. RESULTS: At baseline, co-occurrence of apathy and ICDs was observed in 23 patients (5.4%). This finding was related to anatomical GM reduction along the cortical regions involved in the limbic circuit and cognitive control systems. Longitudinal analyses indicated that apathy and ICDs were related to each other as well as to the combined use of levodopa and dopamine agonists. Worse apathetic and ICDs states were associated with poorer executive functions. CONCLUSIONS: Apathy and ICDs are joint non-exclusive neuropsychiatric disorders also in the early stages of PD and their co-occurrence was associated with GM decrease in several cortical regions of the limbic circuit and cognitive control systems.

Morphometric alterations of the mesocorticolimbic network in Parkinson's disease with impulse control disorders.

Impulse control disorders (ICDs) are a group of non-motor symptoms of Parkinson disease (PD) leading to significant psychosocial detrimental outcome. The mesocorticolimbic network plays a distinctive role in reward learning and executive decision making and has been suggested to be involved in ICDs in PD. To study morphometric changes of the mesocorticolimbic network in PD with ICD. A total of 18 patients of PD with ICD (PD + ICD), 19 patients of PD without ICD (PD - ICD) and 19 healthy controls (HC) were included in the study. ICDs were diagnosed using Questionnaire for Impulsive-Compulsive Disorders in PD-Rating Scale (QUIP-RS). MRI was done using a 3T scanner and assessment of cortical thickness and subcortical volumes were done using FreeSurfer. Brain regions known to be part of the mesocorticolimbic network were extracted and included for statistical analysis. There was no difference between PD + ICD and PD - ICD with regard to duration of illness or total dopaminergic medication. In comparison to HC, patients with PD + ICD demonstrated atrophy of the left frontal pole, and this atrophy neared significance in comparison to PD - ICD. The QUIP-RS had a negative correlation with left caudate volume in PD + ICD. The PD + ICD group showed distinct morphometric changes in regions involved in the mesocorticolimbic system which may contribute to the presence of ICD.

Functional correlates of response inhibition in impulse control disorders in Parkinson's disease.

Impulse control disorder is a prevalent side-effect of Parkinson's disease (PD) medication, with a strong negative impact on the quality of life of those affected. Although impulsivity has classically been associated with response inhibition deficits, previous evidence from PD patients with impulse control disorder (ICD) has not revealed behavioral dysfunction in response inhibition. In this study, 18 PD patients with ICD, 17 PD patients without this complication, and 15 healthy controls performed a version of the conditional Stop Signal Task during functional magnetic resonance imaging. Whole-brain contrasts, regions of interest, and functional connectivity analyses were conducted. Our aim was to investigate the neural underpinnings of two aspects of response inhibition: proactive inhibition, inhibition that has been prepared beforehand, and restrained inhibition, inhibition of an invalid inhibitory tendency. We observed that, in respect to the other two groups, PD patients with ICD exhibited hyperactivation of the stopping network bilaterally while performing proactive inhibition. When engaged in restrained inhibition, they showed hyperactivation of the left inferior frontal gyrus, an area linked to action monitoring. Restrained inhibition also resulted in changes to the functional co-activation between inhibitory regions and left inferior parietal cortex and right supramarginal gyrus. Our findings indicate that PD patients with ICD completed the inhibition task correctly, showing altered engagement of inhibitory and attentional areas. During proactive inhibition they showed bilateral hyperactivation of two inhibitory regions, while during restrained inhibition they showed additional involvement of attentional areas responsible for alerting and orienting.

Limbic hypoconnectivity in idiopathic REM sleep behaviour disorder with impulse control disorders.

INTRODUCTION: Current neuroimaging research has revealed several brain alterations in idiopathic REM sleep behaviour disorder (iRBD) that mirror and precede those reported in PD. However, none have specifically addressed the presence of changes across the reward system, and their role in the emergence of impulse control disorders (ICDs). We aimed to compare the volumetric and functional connectivity characteristics of the reward system in relation to the psychobehavioral profile of patients with iRBD versus healthy controls and PD patients. METHODS: Twenty patients with polysomnography confirmed iRBD along with 17 PD patients and 14 healthy controls (HC) underwent structural and functional resting-state brain MRI analysis. Participants completed the questionnaire for impulsive-compulsive disorders in PD (QUIP), the short UPPS-P impulsive behaviour scale, as well as neuropsychological testing of cognitive function. RESULTS: A higher percentage of iRBD patients reported hypersexuality, compared to HC and PD (p = 0.008). Whole-brain and striatal voxel-based morphometry analyses showed no significant clusters of reduced grey matter volume between groups. However, iRBD compared to HC demonstrated functional hypoconnectivity between the limbic striatum and temporo-occipital regions. Furthermore, the presence of ICDs correlated with hypoconnectivity between the limbic striatum and clusters located in cuneus, lingual and fusiform gyrus. CONCLUSION: Altered functional connectivity between the limbic striatum and posterior cortical regions was associated with increased hypersexuality in iRBD. It is possible that this change may ultimately predispose individuals to the emergence of ICDs when they receive dopaminergic medications, after transitioning to PD.

Incentive-driven decision-making networks in de novo and drug-treated Parkinson's disease patients with impulsive-compulsive behaviors: A systematic review of neuroimaging studies.

BACKGROUND: In Parkinson's disease (PD), impulsive-compulsive behaviors (ICBs) may develop as side-effect of dopaminergic medications. Abnormal incentive-driven decision-making, which is supported by the cognitive control and motivation interaction, may represent an ICBs signature. This systematic review explored whether structural and/or functional brain differences between PD patients with vs without ICBs encompass incentive-driven decision-making networks. METHODS: Structural and functional neuroimaging studies comparing PD patients with and without ICBs, either de novo or medicated, were included. RESULTS: Thirty articles were identified. No consistent evidence of structural alteration both in de novo and medicated PD patients were found. Differences in connectivity within the default mode, the salience and the central executive networks predate ICBs development and remain stable once ICBs are fully developed. Medicated PD patients with ICBs show increased metabolism and cerebral blood flow in orbitofrontal and cingulate cortices, ventral striatum, amygdala, insula, temporal and supramarginal gyri. Abnormal ventral striatum connectivity with anterior cingulate cortex and limbic structures was reported in PD patients with ICBs. DISCUSSION: Functional brain signatures of ICBs in PD encompass areas involved in cognitive control and motivational encoding networks of the incentive-driven decision-making. Functional alterations predating ICBs may be related to abnormal synaptic plasticity in these networks.

Higher Risk Taking and Impaired Probability Judgment in Behavioral Addiction.

BACKGROUND: Accumulating evidence suggests that deficits in decision-making and judgment may be involved in several psychiatric disorders, including addiction. Behavioral addiction is a conceptually new psychiatric condition, raising a debate of what criteria define behavioral addiction, and several impulse control disorders are equivalently considered as types of behavioral addiction. In this preliminary study with a relatively small sample size, we investigated how decision-making and judgment were compromised in behavioral addiction to further characterize this psychiatric condition. METHOD: Healthy control subjects (n = 31) and patients with kleptomania and paraphilia as behavioral addictions (n = 16) were recruited. A battery of questionnaires for assessments of cognitive biases and economic decision-making were conducted, as was a psychological test for the assessment of the jumping-to-conclusions bias, using functional near-infrared spectroscopy recordings of prefrontal cortical (PFC) activity. RESULTS: Although behavioral addicts exhibited stronger cognitive biases than controls in the questionnaire, the difference was primarily due to lower intelligence in the patients. Behavioral addicts also exhibited higher risk taking and worse performance in economic decision-making, indicating compromised probability judgment, along with diminished PFC activity in the right hemisphere. CONCLUSION: Our study suggests that behavioral addiction may involve impairments of probability judgment associated with attenuated PFC activity, which consequently leads to higher risk taking in decision-making.

Measuring impulsivity in Parkinson's disease: a correlational and structural neuroimaging study using different tests.

BACKGROUND AND PURPOSE: Impulsivity is an aspect of personality and a major component of multiple neuropsychiatric conditions. In Parkinson's disease, it has been associated with the expression of impulse control disorders, a highly prevalent non-motor complication. Even though multiple tests of impulsivity have been used in this context, the impact of test choice has not been addressed. The aim was to evaluate whether different impulsivity measures in Parkinson's disease share substantial inter-scale and anatomical correlations or rather mirror different underlying phenomena. METHODS: In a consecutive sample of 89 Parkinson's disease patients without impulse control disorders, four common tests were evaluated assessing different aspects of impulsivity: impulsiveness trait, decisions under implicit risk with and without losses, and delay discounting. Correlations among test scores were analysed and each score was used as a regressor in a set of grey matter volume (GMV) voxel-based morphometry analyses to explore their brain structural correlates. RESULTS: No significant correlations were found between the different impulsivity tests. Furthermore, their structural brain correlates were divergent. Impulsiveness trait appeared to be associated with lower GMV in dorsal-lateral prefrontal cortices, implicit risk (with losses) with higher GMV in the left nucleus accumbens and lower left insular GMV, implicit risk (without losses) with higher GMV in the left lingual gyrus and lower GMV in the gyri recti and delay discounting with higher GMV in the left nucleus accumbens. CONCLUSIONS: In Parkinson's disease, different impulsivity measures reflect very dissimilar behavioural and brain structural correlates. Our results suggest that parkinsonian impulsivity is not a unitary phenomenon but rather a heterogeneous entity.

Non-motor symptoms and striatal dopamine transporter binding in early Parkinson's disease.

BACKGROUND: Non-motor symptoms (NMS) are common in Parkinson's disease (PD), but their relationships to nigrostriatal degeneration remain largely unexplored. METHODS: We evaluated 18 NMS scores covering 5 major domains in relation to concurrent and future dopamine transporter (DAT) imaging in 344 PD patients from the Parkinson's Progression and Markers Initiative (PPMI). We standardized NMS assessments into z-scores for side-by-side comparisons. Patients underwent sequential DaTSCAN imaging at enrollment and at months 12, 24, and 48. Specific binding ratios (SBR) were calculated using the occipital lobe reference region. We evaluated the association of striatal DAT binding at the four time points with each baseline NMS using mixed-effects regression models. RESULTS: Multiple baseline NMS were significantly associated with DAT binding at baseline and at follow-up scans. REM sleep behavior disorder (RBD) symptoms showed the strongest association - mean striatal SBR declined with increasing RBD symptom z-score (average of time-point-specific slopes per unit change in z-score: ßAVG = -0.083, SE = 0.017; p < 0.0001). In addition, striatal DAT binding was linearly associated with increasing baseline z-scores: positively for the memory (ßAVG=0.055, SE = 0.022; p = 0.01) and visuospatial (ßAVG=0.044, SE = 0.020; p = 0.03) cognitive domains, and negatively for total anxiety (ßAVG= -0.059, SE = 0.018; p = 0.001). Striatal DAT binding showed curvilinear associations with odor identification, verbal discrimination recognition, and autonomic dysfunction z-scores (p = 0.001, p = 0.0009, and p = 0.0002, respectively). Other NMS were not associated with DAT binding. CONCLUSIONS: Multiple NMS, RBD symptoms in particular, are associated with nigrostriatal dopaminergic changes in early PD.

Preservation of brain metabolism in recently diagnosed Parkinson's impulse control disorders.

BACKGROUND: Impulse control disorders (ICD) are a common and disrupting complication of Parkinson's disease (PD) treatment. Although their relationship with dopaminergic activity is well studied, their brain metabolic correlates are mostly unknown. METHODS: In this work we studied brain metabolism using brain 18F-FDG-PET. We performed a case-control study nested within a cohort of PD patients free of ICD at baseline to compare ICD patients right after ICD diagnosis and prior to any treatment modification with matched ICD-free patients. We also compared both PD groups with healthy controls. RESULTS: When compared with ICD-free PD patients, PD patients with recently diagnosed ICD showed higher glucose metabolism in widespread areas comprising prefrontal cortices, both amygdalae and default mode network hubs (p < 0.05, corrected). When compared to healthy controls, they did not show hypermetabolism, and the only hypometabolic region was the right caudate. In turn, ICD-free patients showed diffuse hypometabolism when compared to healthy controls. CONCLUSION: Our results suggest brain metabolism is more preserved in PD patients with ICD than patients without ICD. This metabolic preservation could be related to ICD development.

Impulse control under emotion processing: an fMRI investigation in borderline personality disorder compared to non-patients and cluster-C personality disorder patients.

Impulsivity is a characteristic syndromal and neurobehavioral feature of borderline personality disorder (BPD). Research suggests an important interaction between high negative emotions and low behavioral inhibition in BPD. However, knowledge about the generalizability across stimulus categories and diagnosis specificity is limited. We investigated neural correlates of hypothesized impaired response inhibition of BPD patients to negative, positive and erotic stimuli, by comparing them to non-patients and cluster-C personality disorder patients. During fMRI scanning, 53 BPD patients, 34 non-patients and 20 cluster-C personality disorder patients completed an affective go/no-go task, including social pictures. BPD patients showed more omission errors than non-patients, independent of the stimulus category. Furthermore, BPD patients showed higher activity in the inferior parietal lobule and frontal eye fields when inhibiting negative versus neutral stimuli. Activity of the inferior parietal lobule correlated positively with the BPD checklist subscale impulsivity. When inhibiting emotional stimuli, BPD patients showed an altered brain activity in the inferior parietal lobe and frontal eye fields, whereas previously shown dysfunctional prefrontal activity was not replicated. BPD patients showed a general responsivity across stimulus categories in the frontal eye fields, whereas effects in the inferior parietal lobe were specific for negative stimuli. Results of diagnosis specificity support a dimensional rather than a categorical differentiation between BPD and cluster-C patients during inhibition of social emotional stimuli. Supported by behavioral results, BPD patients showed no deficiencies in emotionally modulated response inhibition per se but the present findings rather hint at attentional difficulties for emotional information.

Unmasking neurobiological commonalities between addictive disorders and impulse control disorders in Parkinson's disease.

Changes in reward circuitry have been studied extensively in substance and behavioural addictions. However, comparatively little is known about the neurobiology underlying impulse control disorders (ICDs) in Parkinson's disease, which show roughly similar risk factors and behavioural presentations to both stimulant and behavioural addictions. ICDs occur in a subset of susceptible patients with Parkinson's disease (PD) following intake of dopamine replacement therapy (DRT). These behavioural disorders often have debilitating effects on a patient's quality of life and increase caregiver burden. This comprehensive review examined findings of 40 neuroimaging studies of ICDs in PD to determine (a) whether there are putative neurobiological commonalities between traditional substance and behavioural addictions and DRT-induced ICD in PD and (b) opportunities for future studies to advance current neurobiological understanding of the phenomenon. Results revealed that strikingly similar (a) deficits in dopaminergic receptor expression, (b) connectivity changes in corticostriatal circuitry and (c) neural responses to cue exposure are observed in both ICDs in PD and addictive disorders. These findings point to the value of adopting a transdiagnostic approach when studying addicted populations and pave the way for demystifying this peculiar, often-devastating phenomenon in PD that has so far proven extremely difficult to treat and predict with any precision.

Neural bases of impulse control disorders in Parkinson's disease: A systematic review and an ALE meta-analysis.

Impulse control disorders (ICD) occur in some patients affected by Parkinson's disease (PD). Previous studies revealed an involvement of basal ganglia in ICD, but recent morphological, molecular and functional imaging studies showed that alterations of some extrastriatal regions contribute to development of ICD in PD, with mixed results. To identify the brain regions underlying ICD in PD, a systematic review of morphometric and functional studies was performed, complemented by an ALE meta-analysis of functional studies. The review of structural studies revealed no significant changes in any cortical and subcortical region in patients with ICD. The review of functional studies revealed increased activity in the Ventral Striatum and OrbitoFrontal Cortex and decreased activity in Anterior Cingulate Cortex (ACC). Clusters of hyperactivation in ventral striatum and of hypoactivation in ACC were confirmed by ALE meta-analysis. In conclusion, the present study strongly supported that ICD in PD are related to a dysfunction of limbic divisions of the striatum and of the prefrontal cortex and provided a neurofunctional basis for devising potential therapeutic interventions.

Nigrostriatal dopamine transporter availability, and its metabolic and clinical correlates in Parkinson's disease patients with impulse control disorders.

PURPOSE: Previous studies in patients with Parkinson's disease (PD) and impulse control disorders (ICDs) have produced heterogeneous results regarding striatal dopamine transporter (DaT) binding and activity in the mesocorticolimbic network. Our aim here was to study the relationship between striatal DaT availability and cortical metabolism, as well as motor, behavioural and cognitive features of PD patients with ICD. METHODS: In a group of PD patients with ICD (PD-ICD, n = 16) and 16 matched PD patients without ICD (PD-noICD, n = 16), DaT single-photon emission computed tomography (SPECT) imaging (DaTSCAN) was used to study DaT availability in predefined striatal volumes of interest (VOIs): putamen, caudate nucleus and ventral striatum (VS). In addition, the specific association of striatal DaT binding with cortical limbic and associative metabolic activity was evaluated by 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in PD-ICD patients and investigated using statistical parametric mapping (SPM8). Finally, associations between DaT availability and motor, behavioural and cognitive features were assessed. RESULTS: PD-ICD patients had a significantly lower DaT density in the VS than PD-noICD patients, which was inversely associated with ICD severity. Lower DaT availability in the VS was associated with lower FDG uptake in several cortical areas belonging to the limbic and associative circuits, and in other regions involved in reward and inhibition processes (p < 0.0001 uncorrected; k > 50 voxels). No significant results were observed using a higher conservative threshold (p < 0.05; FDR corrected). PD-ICD patients also displayed impairment in interference and attentional Stroop Task execution, and more anxiety, all associated with reduced DaT availability in the VS and caudate nucleus. CONCLUSIONS: ICDs in PD patients are related to reduced DaT binding in the VS, which accounts for dysfunction in a complex cortico-subcortical network that involves areas of the mesolimbic and mesocortical systems, being associated with reward evaluation, salience attribution and inhibitory control processes.

Functional imaging studies of Impulse Control Disorders in Parkinson's disease need a stronger neurocognitive footing.

Impulse control disorders (ICDs) in Parkinson's disease (PD) are associated with dopaminergic dysfunction and treatment, but have no satisfactory therapeutic solution. While studies assessing the neurofunctional bases of ICDs are important for advancing our understanding and management of ICDs, they remain sparse and inconsistent. Based on a systematic analysis of the neuroimaging literature, the present review pinpoints various abnormalities beyond the mesocorticolimbic circuit that supports reward processing, suggesting possible dysfunction at the sensorimotor, executive and affective levels. We advocate that: 1) Future studies should use more sophisticated psychological models and behavioral designs that take into account the potentially multifaceted aspect of ICDs; this would allow a more accurate assessment of the underlying neurocognitive processes, which are not all dependent on the dopaminergic system. 2) Future neuroimaging studies should rely more strongly on task-based, event-related analyses to disentangle the various mechanisms that can be dysfunctional in ICDs. We believe these guidelines constitute a prerequisite towards distinguishing causes, correlates and individual susceptibility factors of PD patients with ICDs.

Imaging behavioural complications of Parkinson's disease.

In addition to motor symptoms, behavioural complications are commonly found in patients with Parkinson's disease (PD). Behavioural complications, including depression, anxiety, apathy, impulse control disorder and psychosis, together have a large impact on PD patient's quality of life. Many neuroimaging studies using PET, SPECT and MRI techniques have been conducted to study the underlying neural mechanisms of PD pathogenesis and pathophysiology in relation to its behavioural complications. This review will survey these PET, SPECT and MRI studies to describe the current understanding of the neuro-chemical, functional and structural changes associated with behavioural complications in PD patients.

Molecular Imaging of Opioid System in Idiopathic Parkinson's Disease.

Opioid receptors are localized throughout peripheral and central nervous system and interact with endogenous opioid peptides and drugs including heroin, synthetic opioids, and pain relievers (codeine, morphine). If several opioid PET tracers exist for preclinical studies, only a few have been used in human. Some tracers are selective for one subtype of opioid receptors (e.g., [11C]CAF (carfentanil) for µ receptor) while others are not ([11C]DPN (diprenorphine)). As shown by imaging studies, the opioid system is involved in pain processing, but also in addiction, neuropsychiatric manifestations (harm avoidance, sadness, novelty seeking behavior), feeding and food disorders and, finally, movement disorders and levodopa-induced dyskinesias. However, no imaging study has analyzed the potential dysfunction of opioid system in pain manifestations in Parkinson's disease. In addition, the involvement of opioid system in impulse control disorders and neuropsychiatric manifestations has never been studied in Parkinson's disease. Thus, there is an urgent need to understand the impact of opioid system dysfunctions in Parkinson's disease.

Molecular Imaging of Addictive Behavior in Idiopathic Parkinson's Disease.

Parkinson's disease (PD) is commonly associated with motor symptoms, however cognitive and neurobehavioral complications are increasingly recognized and contribute to long-term disability. Dopamine replacement therapy is effective for motor symptoms, but can also lead to motor side-effects and addictive behavior such as impulse control disorders. Molecular imaging is advancing our knowledge of the mechanisms involved in the development of behavioral addictions. This chapter will discuss potential risk factors and associations with the development of addictive behavior in PD including the role of dopaminergic medication and genetic predisposition. We further will describe the common neurobiology and similarities of addictive behavior in PD to addiction, particularly the neuroanatomy of reward processing and its alteration in substance and behavioral addictions. Finally, we will discuss molecular imaging approaches which are helping to delineate the structure as well as the dynamic interactions between different components involving neurotransmitters, transporters, and receptors.

Imaging studies of kleptomania in a middle-aged woman with obsessive-compulsive disorder: a case report.

A 57-year-old woman who had been arrested for shoplifting visited our hospital. She was diagnosed with kleptomania. She had previously been diagnosed with CREST (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia) syndrome and obsessive-compulsive disorder. Cranial magnetic resonance imaging showed mild atrophy of the bilateral dorsolateral prefrontal cortices, left hippocampus, and occipital cortex, as well as diffuse mild T2 hyperintensity in the deep and subcortical white matter, including the frontal region. During a single-photon emission computed tomography scan, significant hyperperfusion was observed in the right ventral striatum, including the nucleus accumbens, ventral thalamus, and right ventrolateral prefrontal areas. Patchy hypoperfusion was found in the bilateral posterior cingulate, parietal, and occipital regions. The patient's neurocognitive function was normal, except for slight impairment of her executive function. Her symptoms and neuroimaging findings were not suggestive of a specific neurocognitive disorder. Hyperactivity of the right ventral striatum may contribute to both obsessive-compulsive disorder and kleptomania. Although frontotemporal lobar degeneration is a major neurocognitive disorder related to illegal behaviours, CREST syndrome-induced white matter microstructural damage in the orbitofrontal lobe could have caused our patient's kleptomania.