The modulatory effect of self-paced and cued motor execution on subthalamic beta-bursts in Parkinson's disease: Evidence from deep brain recordings in humans

Deep brain stimulation (DBS) electrodes provide an unparalleled window to record and investigate neuronal activity right at the core of pathological brain circuits. In Parkinson's disease (PD), basal ganglia beta-oscillatory activity (13-35 Hz) seems to play an outstanding role. Conventional DBS, which globally suppresses beta-activity, does not meet the requirements of a targeted treatment approach given the intricate interplay of physiological and pathological effects of beta-frequencies. Here, we wanted to characterise the local field potential (LFP) in the subthalamic nucleus (STN) in terms of beta-burst prevalence, amplitude and length between movement and rest as well as during self-paced as compared to goal-directed motor control. Our electrophysiological recordings from externalised DBS-electrodes in nine patients with PD showed a marked decrease in beta-burst durations and prevalence during movement as compared to rest as well as shorter and less frequent beta-bursts during cued as compared to self-paced movements. These results underline the importance of beta-burst modulation in movement generation and are in line with the clinical observation that cued motor control is better preserved than self-paced movements. Furthermore, our findings motivate the use of adaptive DBS based on beta-bursts, which selectively trim longer beta-bursts, as it is more suitable and efficient over a range of motor behaviours than conventional DBS

Goal-directed and habitual control in the basal ganglia: implications for Parkinson's disease

Progressive loss of the ascending dopaminergic projection in the basal ganglia is a fundamental pathological feature of Parkinson's disease. Studies in animals and humans have identified spatially segregated functional territories in the basal ganglia for the control of goal-directed and habitual actions. In patients with Parkinson's disease the loss of dopamine is predominantly in the posterior putamen, a region of the basal ganglia associated with the control of habitual behaviour. These patients may therefore be forced into a progressive reliance on the goal-directed mode of action control that is mediated by comparatively preserved processing in the rostromedial striatum. Thus, many of their behavioural difficulties may reflect a loss of normal automatic control owing to distorting output signals from habitual control circuits, which impede the expression of goal-directed action. © 2010 Macmillan Publishers Limited. All rights reserved

Daily Habits in Parkinson's Disease: Validation of the Daily Habit Scale

Objective: The objective of the study was to validate a new scale for assessing habitual behavior—the Daily Habit Scale in patients with Parkinson's disease. Background: Parkinson's disease patients are impaired in habit learning and skill acquisition. Despite repeated practice, they have difficulty developing habitual responses. Methods: One hundred seventy-nine patients (Median (Mdn) = 69 [64–76], 65 females) participated in the study. Corrected item-to-total correlations were calculated to assess the item-convergent and item discriminant validity. Confirmatory factor analysis and assessment of internal consistency were also carried out. Concurrent validity in respect to measures of anxiety and depression, apathy, impulsivity, personality, multidimensional health locus of control, and health-related quality of life was also calculated. To determine the test–retest reliability of the scale, 30 patients (Mdn = 69 [66–73], 9 females) completed a second copy of the scale 6 months after the first. Results: Twenty-nine items (76%) and 9 items (24%) of the 38-item scale, respectively, showed a very good and good convergent validity. All the items discriminated between their own factor and the other factors. The comparative fit index of 0.932 indicated an acceptable model fit of the data, whereas the root mean square error of approximation of 0.06 moderate model fit. The scale had a good internal consistency (Cronbach α = 0.792), and a moderate test–retest reliability (0.57). Females had higher scores on two factors compared to men (Factor 3: household activities and Factor 8: sleep-related activities). Conclusions: The Daily Habit Scale is a reliable and valid tool to measure daily habits in Parkinson's disease

High on Habits

The neural circuits involved in learning and executing goal-directed actions, which are governed by action-outcome contingencies and sensitive to changes in the expected value of the outcome, have been shown to be different from those mediating habits, which are less dependent on action-outcome relations and changes in outcome value. Extended training, different reinforcement schedules, and substances of abuse have been shown to induce a shift from goal-directed performance to habitual performance. This shift can be beneficial in everyday life, but can also lead to loss of voluntary control and compulsive behavior, namely during drug seeking in addiction. Although the brain circuits underlying habit formation are becoming clearer, the molecular mechanisms underlying habit formation are still not understood. Here, we review a recent study where Hilario et al. (2007) established behavioral procedures to investigate habit formation in mice in order to investigate the molecular mechanisms underlying habit formation. Using those procedures, and a combination of genetic and pharmacological tools, the authors showed that endocannabinoid signaling is critical for habit formation

Striatal Dopamine and the Interface between Motivation and Cognition

Brain dopamine has long been known to be implicated in the domains of appetitive motivation and cognition. Recent work indicates that dopamine also plays a role in the interaction between appetitive motivation and cognition. Here we review this work. Animal work has revealed an arrangement of spiraling connections between the midbrain and the striatum that subserves a mechanism by which dopamine can direct information flow from ventromedial to more dorsal regions in the striatum. In line with current knowledge about dopamine's effects on cognition, we hypothesize that these striato-nigro-striatal connections provide the basis for functionally specific effects of appetitive motivation on cognition. One implication of this hypothesis is that appetitive motivation can induce cognitive improvement or impairment depending on task demands

Contributions of the striatum to learning, motivation, and performance: an associative account

It has long been recognized that the striatum is composed of distinct functional sub-units that are part of multiple cortico-striatal-thalamic circuits. Contemporary research has focused on the contribution of striatal sub-regions to three main phenomena: learning of associations between stimuli, actions and rewards; selection between competing response alternatives; and motivational modulation of motor behavior. Recent proposals have argued for a functional division of the striatum along these lines, attributing, for example, learning to one region and performance to another. Here, we consider empirical data from human and animal studies, as well as theoretical notions from both the psychological and computational literatures, and conclude that striatal sub-regions instead differ most clearly in terms of the associations being encoded in each region

Role Of The Dorsal Striatum In Learning and Decision Making

The striatum, the input region of the basal ganglia, has been shown to mediate many cognitive functions. The striatum itself can be functionally segregated into dorsal (DS) and ventral striatum (VS). For more than 60 years, DS has been reported to mediate stimulus-response learning, though evidence has been accruing pointing to a role in decision making. These literatures have been growing independently and an aim of this thesis was to bridge these two bodies of knowledge. We directly investigated the role of DS in stimulus-response learning versus decision making using functional magnetic resonance imaging (fMRI) in patients with Parkinson’s disease (Chapter 2) and obsessive compulsive disorder (Chapter 3). In Chapter 4, the role of DS in stimulus-response habit learning was tested in healthy individuals using fMRI. In three separate experiments (Chapters 2-4), all of the results strongly support the notion that DS mediates decision making and not learning. DS is implicated in many disorders ranging from Parkinson’s disease, obsessive compulsive disorder and addiction, and clarifying the role of DS in cognitive function is paramount for understanding substrates of disease and developing treatments

THE RELATIVE CONTRIBUTION OF GOAL-DIRECTED AND HABIT SYSTEMS TO PSYCHIATRIC DISORDERS

Psychiatric disorders may be caused by underlying imbalances between goal-directed and habit systems in the brain. Numerous studies have aimed to establish whether this is because of a goal-directed system deficit, enhanced habit system, or both. This transdiagnostic approach to studying psychiatric disorders is increasingly popular. Maladaptive habitual behaviour is present in many disorders. It is the principal observation in disorders of compulsivity and is also present in other psychiatric disorders that are not primarily characterised by compulsive behaviour. The psychopathology that causes these disorders might be similar and could be targeted with specific treatment. Traditional categorical classification systems of psychiatric disorders do not reflect similarities in neurobiological dysfunction. The comorbidity and overlap between psychiatric disorders means that a dimensional classifications system based on underlying brain system dysfunction might be more appropriate. In this paper, the neural and neuromodulatory systems that contribute to goal-directed and habit systems are discussed. Account is taken of model-based and model-free computational learning mechanisms that are thought to give rise to goal-directed and habitual control respectively. Different psychiatric disorders that have a deficit in goal-directed behaviour or habit systems are then explored to see if there are similarities in the underlying neural systems despite differences in clinical presentation. It concludes that the relative contribution of goal-directed and habit systems in psychiatric disorders is not evenly distributed. Similar dysfunction of these systems might cause different psychiatric disorders. This neurobiological finding might influence classification systems and research into potential treatments