Dystonia is a hyperkinetic movement disorder, characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements, postures, or both. Executive dysfunction is ...a feature of cognitive function in idiopathic and DYT1 dystonia. Psychiatric morbidity is increased in dystonia, and depression, anxiety, obsessive compulsive disorders are the most common disorders. Sleep problems and pain are also frequently experienced. Evidence suggest that mood and anxiety disorders are intrinsic to the neurobiology of dystonia, but also that psychiatric co-morbidity can be secondary to pain experience and the psychosocial functioning and quality of life of the patients. Medical treatment of dystonia with botulinum toxin injections into affected muscles or with deep brain stimulation surgery improves the symptoms as well as mood and the quality of the patients and does not produce any adverse effects on cognitive function.
Executive dysfunction can be present from the early stages of Parkinson's disease (PD). It is characterized by deficits in internal control of attention, set shifting, planning, inhibitory control, ...dual task performance, and on a range of decision‐making and social cognition tasks. Treatment with dopaminergic medication has variable effects on executive deficits, improving some, leaving some unchanged, and worsening others. In this review, we start by defining the specific nature of executive dysfunction in PD and describe suitable neuropsychological tests. We then discuss how executive deficits relate to pathology in specific territories of the basal ganglia, consider the impact of dopaminergic treatment on executive function (EF) in this context, and review the changes in EFs with disease progression. In later sections, we summarize correlates of executive dysfunction in PD with motor performance (e.g., postural instability, freezing of gait) and a variety of psychiatric (e.g., depression, apathy) and other clinical symptoms, and finally discuss the implications of these for the patients’ daily life.
Recently, it has been proposed that similar to goal-directed and habitual action mediated by the fronto-striatal circuits, the fronto-striato-subthalamic-pallidal-thalamo-cortical network may also ...mediate goal-directed and habitual (automatic) inhibition in both the motor and non-motor domains. Within this framework, some of the clinical manifestations of Parkinson's disease, dystonia, Tourette syndrome and obsessive–compulsive disorder can be considered to represent an imbalance between goal-directed and habitual action and inhibition. It is possible that surgical interventions targeting the basal ganglia nuclei, such as deep brain stimulation of the subthalamic nucleus or the internal segment of the globus pallidus, improve these disorders by restoring a functional balance between facilitation and inhibition in the fronto-striatal networks. These proposals require investigation in future studies.
This article is part of the themed issue ‘Movement suppression: brain mechanisms for stopping and stillness’.
Classically, the basal ganglia have been considered to have a role in producing habitual and goal-directed behaviours. In this article, we review recent evidence that expands this role, indicating ...that the basal ganglia are also involved in neural and behavioural inhibition in the motor and non-motor domains. We then distinguish between goal-directed and habitual (also known as automatic) inhibition mediated by fronto-striato-subthalamic-pallido-thalamo-cortical networks. We also suggest that imbalance between goal-directed and habitual action and inhibition contributes to some manifestations of Parkinson's disease, Tourette syndrome and obsessive-compulsive disorder. Finally, we propose that basal ganglia surgery improves these disorders by restoring a functional balance between facilitation and inhibition.
Inhibition of inappropriate, habitual or prepotent responses is an essential component of executive control and a cornerstone of self-control. Via the hyperdirect pathway, the subthalamic nucleus ...(STN) receives inputs from frontal areas involved in inhibition and executive control. Evidence is reviewed from our own work and the literature suggesting that in Parkinson's disease (PD), deep brain stimulation (DBS) of the STN has an impact on executive control during attention-demanding tasks or in situations of conflict when habitual or prepotent responses have to be inhibited. These results support a role for the STN in an inter-related set of processes: switching from automatic to controlled processing, inhibitory and executive control, adjusting response thresholds and influencing speed-accuracy trade-offs. Such STN DBS-induced deficits in inhibitory and executive control may contribute to some of the psychiatric problems experienced by a proportion of operated cases after STN DBS surgery in PD. However, as no direct evidence for such a link is currently available, there is a need to provide direct evidence for such a link between STN DBS-induced deficits in inhibitory and executive control and post-surgical psychiatric complications experienced by operated patients.
Parkinson's disease (PD) is characterized by a range of motor symptoms. Besides the cardinal symptoms (akinesia and bradykinesia, tremor and rigidity), PD patients show additional motor deficits, ...including: gait disturbance, impaired handwriting, grip force and speech deficits, among others. Some of these motor symptoms (e.g., deficits of gait, speech, and handwriting) have similar clinical profiles, neural substrates, and respond similarly to dopaminergic medication and deep brain stimulation (DBS). Here, we provide an extensive review of the clinical characteristics and neural substrates of each of these motor symptoms, to highlight precisely how PD and its medical and surgical treatments impact motor symptoms. In conclusion, we offer a unified framework for understanding the range of motor symptoms in PD. We argue that various motor symptoms in PD reflect dysfunction of neural structures responsible for action selection, motor sequencing, and coordination and execution of movement.
Summary A dopaminergic deficiency in patients with Parkinson's disease (PD) causes abnormalities of movement, behaviour, learning, and emotions. The main motor features (ie, tremor, rigidity, and ...akinesia) are associated with a deficiency of dopamine in the posterior putamen and the motor circuit. Hypokinesia and bradykinesia might have a dual anatomo-functional basis: hypokinesia mediated by brainstem mechanisms and bradykinesia by cortical mechanisms. The classic pathophysiological model for PD (ie, hyperactivity in the globus pallidus pars interna and substantia nigra pars reticulata) does not explain rigidity and tremor, which might be caused by changes in primary motor cortex activity. Executive functions (ie, planning and problem solving) are also impaired in early PD, but are usually not clinically noticed. These impairments are associated with dopamine deficiency in the caudate nucleus and with dysfunction of the associative and other non-motor circuits. Apathy, anxiety, and depression are the main psychiatric manifestations in untreated PD, which might be caused by ventral striatum dopaminergic deficit and depletion of serotonin and norepinephrine. In this Review we discuss the motor, cognitive, and psychiatric manifestations associated with the dopaminergic deficiency in the early phase of the parkinsonian state and the different circuits implicated, and we propose distinct mechanisms to explain the wide clinical range of PD symptoms at the time of diagnosis.
Firstly, to identify subthalamic region stimulation clusters that predict maximum improvement in rigidity, bradykinesia and tremor, or emergence of side-effects; and secondly, to map-out the cortical ...fingerprint, mediated by the hyperdirect pathways which predict maximum efficacy.
High angular resolution diffusion imaging in twenty patients with advanced Parkinson's disease was acquired prior to bilateral subthalamic nucleus deep brain stimulation. All contacts were screened one-year from surgery for efficacy and side-effects at different amplitudes. Voxel-based statistical analysis of volumes of tissue activated models was used to identify significant treatment clusters. Probabilistic tractography was employed to identify cortical connectivity patterns associated with treatment efficacy.
All patients responded well to treatment (46% mean improvement off medication UPDRS-III p < 0.0001) without significant adverse events. Cluster corresponding to maximum improvement in tremor was in the posterior, superior and lateral portion of the nucleus. Clusters corresponding to improvement in bradykinesia and rigidity were nearer the superior border in a further medial and posterior location. The rigidity cluster extended beyond the superior border to the area of the zona incerta and Forel-H2 field. When the clusters where averaged, the coordinates of the area with maximum overall efficacy was X = −10(−9.5), Y = −13(-1) and Z = −7(−3) in MNI(AC-PC) space. Cortical connectivity to primary motor area was predictive of higher improvement in tremor; whilst that to supplementary motor area was predictive of improvement in bradykinesia and rigidity; and connectivity to prefrontal cortex was predictive of improvement in rigidity.
These findings support the presence of overlapping stimulation sites within the subthalamic nucleus and its superior border, with different cortical connectivity patterns, associated with maximum improvement in tremor, rigidity and bradykinesia.
•Optimal DBS tissue activation areas are identified in the subthalamic nucleus.•Stimulation in the supero-lateral subthalamic nucleus is most effective.•Connectivity pattern predicts improvement in cardinal symptoms in Parkinson's.
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