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.

Self-control problems in Intermittent Explosive Disorder: Presentation of an explanatory approach.

BACKGROUND AND OBJECTIVES: Intermittent Explosive Disorder (IED) is an impulsive aggression disorder with self-control problems. However, the mechanisms underpinning the self-control problems in IED have not been clearly investigated. Therefore, this study examined the nature of self-control problems and their types, including cognitive inhibition, behavioral inhibition, and emotional interference in IED. METHODS: Participants included three groups: IED (n = 54), psychiatric control (n = 59), and healthy control (n = 62). They were first screened with SCL-90-R, and then they were clinically interviewed. They all did computerized neurocognitive tasks, including Color-Word Stroop Task, Emotional Stroop Task, Go-NoGo Task, and Stop-Signal Task. RESULTS: MANOVA analyses showed that the IED group had poorer performance in cognitive inhibition, response inhibition, and increased emotional interference than the two psychiatric and healthy control groups. They performed much worse than the other two groups, particularly in action cancellation (Stop-Signal Task), and showed increasingly emotional interference. LIMITATIONS: The brain reaction of individuals while doing the tasks was not examined, and some variables were not measured. Also, it is unclear how the emotional eruption interferes with cognitive content and behavioral inhibition. CONCLUSIONS: These findings indicate that self-control problems in IED can be due to deficient cognitive, emotional, and behavioral inhibitions, each appearing sequentially during a step-by-step process and facilitating the onset of IED signs and symptoms. Such a distinguished understanding of the role of neurocognitive mechanisms can lead to the development of accurate explanatory approaches and increase the effectiveness of treatment.

Tai Chi Chuan evidence related to impulsivity and impulse related disorders: A scoping review.

BACKGROUND: The purpose of this study was to review the evidence for the potential of Tai Chi Chuan (TCC) as a model of meditative movement in benefiting people with impulsivity related disorders and provide guidance for future research. METHODS: A scoping review of the literature was conducted in five databases. Eligibility criteria were original articles reporting TCC based interventions or included TCC techniques and provided any assessment on impulsivity or related measures, impulse control disorders, or other psychiatric disorders related to impulsivity (e.g., addictive disorders, ADHD, and other conduct disorders). Twenty-eight out of 304 studies initially retrieved were reviewed. The reports concentrated mostly on neurodegenerative conditions, cognitive decline, and substance use disorders (SUD). RESULTS: TCC had several positive effects in cognitive domains resulting in improvements in memory, executive functions, inhibitory control, attention, and verbal fluency. These improvements in memory, executive function, including inhibitory control and attention, and verbal fluency were associated with changes in the brain plasticity, resting activity, and other neurobiological markers. CONCLUSION: Albeit no study was found on the use of TCC in impulse control disorders or impulse related conditions, other than SUD, the findings suggest that considering the behavioral impact of TCC, especially the improvement of executive functions, it could be a valuable therapeutic tool for approaching impulse control related disorders.

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.

Brunner syndrome associated MAOA mutations result in NMDAR hyperfunction and increased network activity in human dopaminergic neurons.

Monoamine neurotransmitter abundance affects motor control, emotion, and cognitive function and is regulated by monoamine oxidases. Among these, Monoamine oxidase A (MAOA) catalyzes the degradation of dopamine, norepinephrine, and serotonin into their inactive metabolites. Loss-of-function mutations in the X-linked MAOA gene have been associated with Brunner syndrome, which is characterized by various forms of impulsivity, maladaptive externalizing behavior, and mild intellectual disability. Impaired MAOA activity in individuals with Brunner syndrome results in bioamine aberration, but it is currently unknown how this affects neuronal function, specifically in dopaminergic (DA) neurons. Here we generated human induced pluripotent stem cell (hiPSC)-derived DA neurons from three individuals with Brunner syndrome carrying different mutations and characterized neuronal properties at the single cell and neuronal network level in vitro. DA neurons of Brunner syndrome patients showed reduced synaptic density but exhibited hyperactive network activity. Intrinsic functional properties and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-mediated synaptic transmission were not affected in DA neurons of individuals with Brunner syndrome. Instead, we show that the neuronal network hyperactivity is mediated by upregulation of the GRIN2A and GRIN2B subunits of the N-methyl-d-aspartate receptor (NMDAR), resulting in increased NMDAR-mediated currents. By correcting a MAOA missense mutation with CRISPR/Cas9 genome editing we normalized GRIN2A and GRIN2B expression, NMDAR function and neuronal population activity to control levels. Our data suggest that MAOA mutations in Brunner syndrome increase the activity of dopaminergic neurons through upregulation of NMDAR function, which may contribute to the etiology of Brunner syndrome associated phenotypes.

Hypersexuality in neurological diseases: do we see only the tip of the iceberg?

The purpose of this commentary is to investigate the pathophysiological mechanisms underlying hypersexuality and its manifestation in neurological diseases through a meta-analysis. Studies were identified by searching on PubMed, Web of Science and Cochrane databases. All results of each database between 2014 and 2020 were evaluated for possible inclusion. After an accurate revision of complete manuscripts, forty articles satisfied the inclusion/exclusion criteria. Data from our meta-analysis indicated hypersexuality to be a frequent sexual disorder in patients with neurological disorders, especially neurodegenerative ones. Hypersexuality could negatively affect a patient's management and outcomes. This commentary discusses studies that are often incomplete for evaluation measures or sample selection. In our opinion, it is necessary to consider hypersexuality with particular attention, so more extensive sample studies are needed to find the most appropriate treatment to improve the quality of life for both the patient and the caregiver.

Changing Gears - DBS For Dopaminergic Desensitization in Parkinson's Disease?

In Parkinson's disease, both motor and neuropsychiatric complications unfold as a consequence of both incremental striatal dopaminergic denervation and intensifying long-term dopaminergic treatment. Together, this leads to 'dopaminergic sensitization' steadily increasing motor and behavioral responses to dopaminergic medication that result in the detrimental sequalae of long-term dopaminergic treatment. We review the clinical presentations of 'dopaminergic sensitization', including rebound off and dyskinesia in the motor domain, and neuropsychiatric fluctuations and behavioral addictions with impulse control disorders and dopamine dysregulation syndrome in the neuropsychiatric domain. We summarize state-of-the-art deep brain stimulation, and show that STN-DBS allows dopaminergic medication to be tapered, thus supporting dopaminergic desensitization. In this framework, we develop our integrated debatable viewpoint of "changing gears", that is we suggest rethinking earlier use of subthalamic nucleus deep brain stimulation, when the first clinical signs of dopaminergic motor or neuropsychiatric complications emerge over the steadily progressive disease course. In this sense, subthalamic deep brain stimulation may help reduce longitudinal motor and neuropsychiatric symptom expression - importantly, not by neuroprotection but by supporting dopaminergic desensitization through postoperative medication reduction. Therefore, we suggest considering STN-DBS early enough before patients encounter potentially irreversible psychosocial consequences of dopaminergic complications, but importantly not before a patient shows first clinical signs of dopaminergic complications. We propose to consider neuropsychiatric dopaminergic complications as a new inclusion criterion in addition to established motor criteria, but this concept will require validation in future clinical trials. ANN NEUROL 2021;90:699-710.

Attentional dysfunction and the punding spectrum in Parkinson's disease.

BACKGROUND: Punding is a complication of Parkinson's disease (PD) treatment and stimulant abuse that features excessive preoccupation with repetitive and/or aimless behaviors. We hypothesized that cognitive impairment and functional limitations influence how punding behaviors manifest in PD. METHODS: We extracted data on punding, hobbyism, and cognition from the Parkinson's Progression Marker Initiative (PPMI). Punding and hobbyism were measured with the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease (QUIP) scale. We determined how cognition predicted punding and hobbyism behaviors-adjusting for levodopa dose, Hoehn & Yahr stage, disease duration, and age-using generalized estimating equation (GEE) logistic regression. Activities of daily living (ADL) and motor impairment were measured with the MDS-UPDRS scale. RESULTS: In GEE logistic regression models, punding was selectively associated with lower scores on the Letter Number Sequencing test (LNS), the primary attention test in PPMI (Odds ratio: 0.87 (95% CI: 0.79-0.96); p = 0.022). This was corroborated by a subscale-analysis of Montreal Cognitive Assessment (MoCA) scores, as only the attention subscale was significantly associated with punding (OR: 0.59 (0.45-0.77); p < 0.001). Baseline impairment in LNS (Hazard ratio: 2.52 (1.22-5.20); p = 0.012) and MoCA attention (HR: 2.68 (1.32-5.42); p = 0.006) predicted earlier punding in Cox regression. In turn, ADL dysfunction predicted punding (OR: 1.55 (1.20-2.00); p < 0.001), but not hobbyism. CONCLUSION: Attentional dysfunction is a domain-specific cognitive biomarker of punding risk in PD. Further, attentional capacity and functional impairment may determine the complexity of perseverative behaviors on the continuum from rudimentary punding to semi-purposeful hobbyism.

Non-motor symptom burden in patients with Parkinson's disease with impulse control disorders and compulsive behaviours: results from the COPPADIS cohort.

The study was aimed at analysing the frequency of impulse control disorders (ICDs) and compulsive behaviours (CBs) in patients with Parkinson's disease (PD) and in control subjects (CS) as well as the relationship between ICDs/CBs and motor, nonmotor features and dopaminergic treatment in PD patients. Data came from COPPADIS-2015, an observational, descriptive, nationwide (Spain) study. We used the validated Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) for ICD/CB screening. The association between demographic data and ICDs/CBs was analyzed in both groups. In PD, this relationship was evaluated using clinical features and treatment-related data. As result, 613 PD patients (mean age 62.47 ± 9.09 years, 59.87% men) and 179 CS (mean age 60.84 ± 8.33 years, 47.48% men) were included. ICDs and CBs were more frequent in PD (ICDs 12.7% vs. 1.6%, p < 0.001; CBs 7.18% vs. 1.67%, p = 0.01). PD patients had more frequent previous ICDs history, premorbid impulsive personality and antidepressant treatment (p < 0.05) compared with CS. In PD, patients with ICDs/CBs presented younger age at disease onset, more frequent history of previous ICDs and premorbid personality (p < 0.05), as well as higher comorbidity with nonmotor symptoms, including depression and poor quality of life. Treatment with dopamine agonists increased the risk of ICDs/CBs, being dose dependent (p < 0.05). As conclusions, ICDs and CBs were more frequent in patients with PD than in CS. More nonmotor symptoms were present in patients with PD who had ICDs/CBs compared with those without. Dopamine agonists have a prominent effect on ICDs/CBs, which could be influenced by dose.

Co-occurrence of apathy and impulse control disorders in Parkinson disease.

OBJECTIVE: To empirically test whether apathy and impulse control disorders (ICDs) represent independent, opposite ends of a motivational spectrum. METHODS: In this single-center, cross-sectional study, we obtained retrospective demographics and clinical data for 887 patients with idiopathic Parkinson disease (PD) seen at a tertiary care center. Mood and motivation disturbances were classified using recommended cutoff scores from self-reported measures of apathy, ICD, anxiety, and depression. RESULTS: Prevalence rates included 29.0% of patients with PD with depression, 40.7% with anxiety, 41.3% with apathy, 27.6% with ICDs, and 17.0% with both apathy and ICD. The majority (61.6%) of people reporting clinically significant ICDs also reported clinically significant apathy, and more than a third of patients with apathy (41.3%) also reported elevated ICD. Anxiety and depression were highest in patients with both apathy and ≥1 ICDs. Dopamine agonist use was higher in people with only ICD compared to people with only apathy. Mood significantly interacted with demographic variables to predict motivational disturbances. CONCLUSIONS: Motivational disturbances are common comorbid conditions in patients with PD. In addition, these complex behavioral syndromes interact with mood in clinically important ways that may influence the design of future clinical trials and the development of novel therapies. This study challenges the concept of apathy and ICD in PD as opposite ends of a spectrum.

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.

Augmentation in restless legs syndrome: an eye tracking study on emotion processing.

OBJECTIVE: To assess emotional processing and alexithymia in patients with restless legs syndrome (RLS) with augmentation versus those who never had augmentation. METHODS: We recruited 26 patients who had a history of augmentation (AUG), either current or past, 27 RLS patients treated with dopamine agonists who never had augmentation (RLS controls), and 21 healthy controls (HC). All participants were screened for impulse control disorders (ICDs). Alexithymia was assessed by means of the Toronto Alexithymia Scale - 20 (TAS-20). Facial emotion recognition was tested through an eye-tracking task. Furthermore, all participants performed neuropsychological tests assessing global cognitive status, impulsivity, anxiety, and depression. RESULTS: ICD symptoms occurred more frequently in AUG patients than in RLS controls (P = 0.047). Patients with AUG scored higher on the TAS-20 (P = 0.007) and the attentional subdomain of an impulsivity scale (BIS-11; P = 0.015) compared to HC. Patients with AUG also performed worse on the facial emotion recognition task relative to RLS controls (P = 0.009) and HC (P = 0.003). We found a group difference for the time to first fixation and the fixation count in the mouth region (P = 0.019 and P = 0.021, respectively). There were no other differences in the eye tracking examination. INTERPRETATION: This study showed evidence of poorer emotional processing in patients who had augmentation compared to RLS patients without augmentation and healthy controls. The altered exploration pattern of faces and the higher alexithymia scores suggest abnormalities in emotion processing in patients with augmentation.

Buying-shopping disorder, emotion dysregulation, coping and materialism: a comparative approach with gambling patients and young people and adolescents.

OBJECTIVE: The comorbidity between gambling disorder (GD) and buying-shopping disorder (BSD) has led to explore the core features that could be interacting between them. The main aim of this study was to examine the differences in both conditions considering emotion dysregulation, coping and materialism, as well as the relationship between these variables and their interaction with age and sex. METHODS: A community sample (n = 281 adolescents) and a sample of individuals with GD (n = 31) was compared. Both samples were split into a group with BSD and a group without it. RESULTS: The prevalence of participants who met the criteria for BSD was higher in the GD sample than in the community sample; the GD sample also presented higher values in the psychological variables studied. In the community sample group, positive associations were found between BSD severity and materialism and emotion dysregulation levels. In the GD sample, BSD severity was higher for participants who reported higher levels in materialism and lower scores in coping strategies. Variables impacted BSD severity differently according to sex and age covariates. CONCLUSIONS: The results of the interaction of the variables could be useful to design prevention and treatment approaches addressed to specific groups of age and sex. KEY POINTS Buying-shopping disorder (BSD) has been compared in clinical and community samples. The clinical sample was constituted by Gambling disorder (GD) patients. The variables emotion dysregulation, coping and materialism have been considered. Variables impacted BSD severity differently according to sex and age covariates.

Impulsive and compulsive behaviors in Parkinson's disease: Impact on quality of and satisfaction with life, and caregiver burden.

INTRODUCTION: To disentangle the association between impulsive and compulsive behaviors (ICBs), health-related quality of life (HRQOL), satisfaction with life (SwL), and caregiver distress in dyads of people with Parkinson's disease (PwP) and caregivers. METHODS: Data used in this study were obtained from the ongoing Norwegian ParkWest study, a population-based longitudinal cohort study of the incidence, neurobiology and prognosis of PD in Western Norway. One hundred and one dyads of PwP free of dementia and their caregivers were included 5 years after PD diagnosis and inclusion in the ParkWest study. Standardized clinical rating scales were used to evaluate ICBs, HRQOL, SwL and caregiver distress. RESULTS: Of 101 PwP-caregiver dyads, self-reported ICBs were seen in 33% of PwP and only caregiver-reported ICBs in 12% of PwP. PwP-reported ICBs were associated with poorer HRQOL and SwL, whereas ICBs reported by caregivers only were associated with increased caregiver distress, but not poorer HRQOL or SwL in PwP. CONCLUSIONS: ICBs have adverse effects on HRQOL, SwL and caregiver distress. These findings underpin the need for proper identification and management of ICBs in PwP.

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.

Occurrence and clinical characteristics of Compulsive Sexual Behavior Disorder (CSBD): A cluster analysis in two independent community samples.

BACKGROUND AND AIMS: Compulsive Sexual Behavior Disorder (CSBD) is characterized by a persistent failure to control intense and recurrent sexual impulses, urges, and/or thoughts, resulting in repetitive sexual behavior that causes a marked impairment in important areas of functioning. Despite its recent inclusion in the forthcoming ICD-11, concerns regarding its assessment, diagnosis, prevalence or clinical characteristics remain. The purpose of this study was to identify participants displaying CSBD through a novel data-driven approach in two independent samples and outline their sociodemographic, sexual, and clinical profile. METHODS: Sample 1 included 1,581 university students (females = 56.9%; Mage = 20.58) whereas sample 2 comprised 1,318 community members (females = 43.6%; Mage = 32.37). First, we developed a new composite index to assess the whole range of CSBD symptoms based on three previously validated scales. Based on this new composite index, we subsequently identified individuals with CSBD through a cluster analytic approach. RESULTS: The estimated occurrence of CSBD was 10.12% in sample 1 and 7.81% in sample 2. Participants with CSBD were mostly heterosexual males, younger than respondents without CSBD, reported higher levels of sexual sensation seeking and erotophilia, an increased offline and especially online sexual activity, more depressive and anxious symptoms, and poorer self-esteem. CONCLUSIONS: This research provides further evidence on the occurrence of CSBD based on an alternative data-driven approach, as well as a detailed and nuanced description of the sociodemographic, sexual, and clinical profile of adults with this condition. Clinical implications derived from these findings are discussed in detail.

The structural connectivity of subthalamic deep brain stimulation correlates with impulsivity in Parkinson's disease.

Subthalamic deep brain stimulation (STN-DBS) for Parkinson's disease treats motor symptoms and improves quality of life, but can be complicated by adverse neuropsychiatric side-effects, including impulsivity. Several clinically important questions remain unclear: can 'at-risk' patients be identified prior to DBS; do neuropsychiatric symptoms relate to the distribution of the stimulation field; and which brain networks are responsible for the evolution of these symptoms? Using a comprehensive neuropsychiatric battery and a virtual casino to assess impulsive behaviour in a naturalistic fashion, 55 patients with Parkinson's disease (19 females, mean age 62, mean Hoehn and Yahr stage 2.6) were assessed prior to STN-DBS and 3 months postoperatively. Reward evaluation and response inhibition networks were reconstructed with probabilistic tractography using the participant-specific subthalamic volume of activated tissue as a seed. We found that greater connectivity of the stimulation site with these frontostriatal networks was related to greater postoperative impulsiveness and disinhibition as assessed by the neuropsychiatric instruments. Larger bet sizes in the virtual casino postoperatively were associated with greater connectivity of the stimulation site with right and left orbitofrontal cortex, right ventromedial prefrontal cortex and left ventral striatum. For all assessments, the baseline connectivity of reward evaluation and response inhibition networks prior to STN-DBS was not associated with postoperative impulsivity; rather, these relationships were only observed when the stimulation field was incorporated. This suggests that the site and distribution of stimulation is a more important determinant of postoperative neuropsychiatric outcomes than preoperative brain structure and that stimulation acts to mediate impulsivity through differential recruitment of frontostriatal networks. Notably, a distinction could be made amongst participants with clinically-significant, harmful changes in mood and behaviour attributable to DBS, based upon an analysis of connectivity and its relationship with gambling behaviour. Additional analyses suggested that this distinction may be mediated by the differential involvement of fibres connecting ventromedial subthalamic nucleus and orbitofrontal cortex. These findings identify a mechanistic substrate of neuropsychiatric impairment after STN-DBS and suggest that tractography could be used to predict the incidence of adverse neuropsychiatric effects. Clinically, these results highlight the importance of accurate electrode placement and careful stimulation titration in the prevention of neuropsychiatric side-effects after STN-DBS.

Developing an understanding of skin picking in people with Prader-Willi syndrome: A structured literature review and re-analysis of existing data.

A search of the PubMed and Web of Science databases for articles on skin picking in PWS was undertaken identifying case studies; trials of specific treatments; and descriptions of when skin picking occurs, what sites are chosen, and what initiates and sustains this behaviour. Published papers have also considered how skin picking might link to the PWS genotype and whether it is best considered to be part of the repetitive and ritualistic behaviours characteristic of the syndrome. To answer specific questions raised as a result of the review additional analysis was undertaken using data from our earlier population-based study of PWS. We consider this behaviour of skin picking using the framework of the Research Domains Criteria that is cross diagnostic and focuses on the identification of specific neurobiological, psychological and cognitive processes. PWS illustrates the likely interplay between different processes that first initiate and then maintain such behaviour. Treatment development depends on better understanding these mechanisms and their relative contribution to the behaviour.