Inhibitory framing in hypersexual patients with Parkinson's disease. An fMRI pilot study.

Hypersexuality in medicated patients with PD is caused by an increased influence of motivational drive areas and a decreased influence of inhibitory control areas due to dopaminergic medication. In this pilot study, we test a newly developed paradigm investigating the influence of dopaminergic medication on brain activation elicited by sexual pictures with and without inhibitory contextual framing. Twenty PD patients with and without hypersexuality were examined with fMRI either OFF or ON standardized dopaminergic medication. The paradigm consisted of a priming phase where either a neutral context or an inhibitory context was presented. This priming phase was either followed by a sexual or a neutral target. Sexual, compared to neutral pictures resulted in a BOLD activation of various brain regions implicated in sexual processing. Hypersexual PD patients showed increased activity compared to PD controls in these regions. There was no relevant effect of medication between the two groups. The inhibitory context elicited less activation in inhibition-related areas in hypersexual PD, but had no influence on the perception of sexual cues. The paradigm partially worked: reactivity of motivational brain areas to sexual cues was increased in hypersexual PD and inhibitory contextual framing lead to decreased activation of inhibitory control areas in PD. We could not find a medication effect and the length of the inhibitory stimulus was not optimal to suppress reactivity to sexual cues. Our data provide new insights into the mechanisms of hypersexuality and warrant a replication with a greater cohort and an optimized stimulus length in the future.

Discounting Behavior in Problem Gambling.

Problem gamblers discount delayed rewards more rapidly than do non-gambling controls. Understanding this impulsivity is important for developing treatment options. In this article, we seek to make two contributions: First, we ask which of the currently debated economic models of intertemporal choice (exponential versus hyperbolic versus quasi-hyperbolic) provides the best description of gamblers' discounting behavior. Second, we ask how problem gamblers differ from habitual gamblers and non-gambling controls within the most favored parametrization. Our analysis reveals that the quasi-hyperbolic discounting model is strongly favored over the other two parametrizations. Within the quasi-hyperbolic discounting model, problem gamblers have both a significantly stronger present bias and a smaller long-run discount factor, which suggests that gamblers' impulsivity has two distinct sources.

Oscillatory brain activity associated with skin conductance responses in the context of risk.

Understanding the neural correlates of risk-sensitive skin conductance responses can provide insights into their connection to emotional and cognitive processes. To provide insights into this connection, we studied the cortical correlates of risk-sensitive skin conductance peaks using electroencephalography. Fluctuations in skin conductance responses were elicited while participants played a threat-of-shock card game. Precise temporal information about skin conductance peaks was obtained by applying continuous decomposition analysis on raw electrodermal signals. Shortly preceding skin conductance peaks, we observed a decrease in oscillatory power in the frequency range between 3 and 17 Hz in occipitotemporal cortical areas. Atlas-based analysis indicated the left lingual gyrus as the source of the power decrease. The oscillatory power averaged across 3-17 Hz showed a significant negative relationship with the skin conductance peak amplitude. Our findings indicate a possible interaction between attention and threat perception.NEW & NOTEWORTHY We studied neural oscillations associated with risk-sensitive skin conductance responses. Going beyond previous studies, we applied methods with high-temporal resolution to account for the temporal properties of the sympathetic activity. Preceding skin conductance peaks, we observed decreased occipital cortex oscillatory power and a relationship between the oscillatory power decrease and the skin conductance peak amplitude. Our study suggests an interaction between attention and emotion such as threat perception reflected in skin conductance responses.

Alexithymia-an independent risk factor for impulsive-compulsive disorders in Parkinson's disease.

Impulsive-compulsive disorders (ICDs) are frequent side effects of dopaminergic medication in Parkinson's disease (PD). Alexithymia, a personality trait characterized by difficulties identifying and describing feelings and an externally oriented thinking style, has been linked to various impulse-control problems in the general population. In PD, the prevalence of alexithymia is approximately twice as high as in the general population. However, whether alexithymia is associated with ICDs in PD is currently unknown. We examined the relationship between self-reported ICDs and alexithymia in a sample of 91 PD patients (89 on dopaminergic medication). Additional self-report measures assessed impulsivity, depression, anxiety, behavioral inhibition/approach, and emotion-regulation strategies. We observed that alexithymia, and particularly difficulty identifying feelings and difficulty describing feelings, was significantly correlated with ICDs, even when controlling for impulsivity, anxiety, and depression. In addition, a group analysis revealed that PD patients with clinical and moderate levels of alexithymia had significantly more ICDs than non-alexithymic patients, suggesting that even moderately high alexithymia levels increase the risk for ICDs in PD. Our results identify alexithymia as an independent risk factor for ICDs in PD. Thus, the inclusion of alexithymia in the neuropsychiatric assessment of patients with PD may help identify patients at risk for ICDs.

The functional anatomy of impulse control disorders.

Impulsive-compulsive disorders such as pathological gambling, hypersexuality, compulsive eating, and shopping are side effects of the dopaminergic therapy for Parkinson's disease. With a lower prevalence, these disorders also appear in the general population. Research in the last few years has discovered that these pathological behaviors share features similar to those of substance use disorders (SUD), which has led to the term "behavioral addictions". As in SUDs, the behaviors are marked by a compulsive drive toward and impaired control over the behavior. Furthermore, animal and medication studies, research in the Parkinson's disease population, and neuroimaging findings indicate a common neurobiology of addictive behaviors. Changes associated with addictions are mainly seen in the dopaminergic system of a mesocorticolimbic circuit, the so-called reward system. Here we outline neurobiological findings regarding behavioral addictions with a focus on dopaminergic systems, relate them to SUD theories, and try to build a tentative concept integrating genetics, neuroimaging, and behavioral results.

Unlucky punches: the vulnerability-stress model for the development of impulse control disorders in Parkinson's disease.

Impulse-control disorders are commonly observed during dopamine-replacement therapy in Parkinson's disease, but the majority of patients seems "immune" to this side effect. Epidemiological evidence suggests that a major risk factor may be a specific difference in the layout of the dopaminergic-reinforcement system, of which the ventral striatum is a central player. A series of imaging studies of the dopaminergic system point toward a presynaptic reduction of dopamine-reuptake transporter density and dopamine synthesis capacity. Here, we review current evidence for a vulnerability-stress model in which a relative reduction of dopaminergic projections to the ventral striatum and concomitant sensitization of postsynaptic neurons represent a predisposing (hypodopaminergic) vulnerability. Stress (hyperdopaminergic) is delivered when dopamine replacement therapy leads to a relative overdosing of the already-sensitized ventral striatum. These alterations are consistent with consecutive changes in reinforcement mechanisms, which stimulate learning from reward and impede learning from punishment, thereby fostering the development of impulse-control disorders. This vulnerability-stress model might also provide important insights into the development of addictions in the non-Parkinsonian population.

It's all about gains: Risk preferences in problem gambling.

Problem gambling is a serious socioeconomic problem involving high individual and social costs. In this article, we study risk preferences of problem gamblers including their risk attitudes in the gain and loss domains, their weighting of probabilities, and their degree of loss aversion. Our findings indicate that problem gamblers are systematically more risk taking and less sensitive toward changes in probabilities in the gain domain only. Neither their risk attitudes in the loss domain nor their degree of loss aversion are significantly different from the controls. Additional evidence for a similar degree of sensitivity toward negative outcomes is gained from skin conductance data-a psychophysiological marker for emotional arousal-in a threat-of-shock task. (PsycINFO Database Record

Validation of the questionnaire for impulsive-compulsive disorders in Parkinson's disease (QUIP) and the QUIP-rating scale in a German speaking sample.

Impulsive-compulsive disorders are frequent in patients with Parkinson's disease (PD). Recently, a screening questionnaire and rating scale were developed for these disorders: the questionnaire for impulsive-compulsive disorders (QUIP) and QUIP-rating scale (QUIP-RS). We assessed the validity of these instruments in the German language in order to reevaluate the benefit and to obtain German screening tools in clinical practice. A convenience sample of 156 patients was assessed in Kiel and Vienna. The patients filled out the QUIP-current, the QUIP-anytime and the QUIP-RS. We validated the questionnaires against a gold standard diagnosis via receiver operating characteristic curves and determined optimal cut-off scores for the instruments. Excluding walkabout, which was not shown to be valid, sensitivities ranged from 60-92 % for the QUIP-current, 68-91 % for the QUIP-anytime, and 73-100 % for the QUIP-RS. Specificities were >71 % for QUIP-current, >69 % for QUIP-anytime and >62 % for QUIP-RS. With its very good sensitivities, the QUIP-RS is a valid instrument to assess impulsive-compulsive disorders and makes an early detection of behavioral disorders in PD possible. The QUIP-anytime was also shown to be a valid screening instrument. Both are expected to prove useful in scientific and clinical practice.