Dopamine overdose hypothesis: Evidence and clinical implications
TLDR
This review considers the evidence that has accumulated in the areas of reversal learning, motor sequence learning, and other cognitive tasks and considers the purported inverted‐U shaped relationship between dopamine levels and performance.Abstract:
About a half a century has passed since dopamine was identified as a neurotransmitter, and it has been several decades since it was established that people with Parkinson's disease receive motor symptom relief from oral levodopa. Despite the evidence that levodopa can reduce motor symptoms, there has been a developing body of literature that dopaminergic therapy can improve cognitive functions in some patients but make them worse in others. Over the past two decades, several laboratories have shown that dopaminergic medications can impair the action of intact neural structures and impair the behaviors associated with these structures. In this review, we consider the evidence that has accumulated in the areas of reversal learning, motor sequence learning, and other cognitive tasks. The purported inverted-U shaped relationship between dopamine levels and performance is complex and includes many contributory factors. The regional striatal topography of nigrostriatal denervation is a critical factor, as supported by multimodal neuroimaging studies. A patient's individual genotype will determine the relative baseline position on this inverted-U curve. Dopaminergic pharmacotherapy and individual gene polymorphisms can affect the mesolimbic and prefrontal cortical dopaminergic functions in a comparable, inverted-U dose-response relationship. Depending on these factors, a patient can respond positively or negatively to levodopa when performing reversal learning and motor sequence learning tasks. These tasks may continue to be relevant as our society moves to increased technological demands of a digital world that requires newly learned motor sequences and adaptive behaviors to manage daily life activities.read more
Citations
More filters
Journal ArticleDOI
The neurobiological basis of cognitive impairment in Parkinson's disease.
TL;DR: Critical assessment of animal models shows that chronic low‐dose MPTP treatment in primates recapitulates PD‐MCI over time, enhancing the current biological concept of PD‐ MCI as having enhanced dopamine deficiency in frontostriatal pathways as well as involvement of other neurotransmitter systems.
Journal ArticleDOI
Motor symptoms in Parkinson's disease: A unified framework.
Ahmed A. Moustafa,Ahmed A. Moustafa,Srinivasa Chakravarthy,Joseph R. Phillips,Ankur Gupta,Szabolcs Kéri,Bertalan Polner,Michael J. Frank,Marjan Jahanshahi +8 more
TL;DR: It is argued that various motor symptoms in PD reflect dysfunction of neural structures responsible for action selection, motor sequencing, and coordination and execution of movement.
Journal ArticleDOI
The highs and lows of beta activity in cortico-basal ganglia loops
TL;DR: The hypothesis is developed that the degree of synchronization in this frequency band is a critical factor in gating computation across a population of neurons, with increases in beta band synchrony entailing a loss of information‐coding space and hence computational capacity.
Journal ArticleDOI
Cognitive Contributions to Freezing of Gait in Parkinson Disease: Implications for Physical Rehabilitation
TL;DR: A novel theoretical framework is proposed for exercise interventions that jointly address both the specific cognitive and mobility challenges of people with PD who freeze.
Journal ArticleDOI
Motor Learning Deficits in Parkinson's Disease (PD) and Their Effect on Training Response in Gait and Balance: A Narrative Review
TL;DR: The effect of PD on motor learning and the effect of motor learning deficits on response to physical therapy and training programs are evaluated, focusing specifically on features related to PIGD.
References
More filters
Journal Article
Evidence for the existence of monoamine-containing neurons in the central nervous system. i. demonstration of monoamines in the cell bodies of brain stem neurons.
Dahlstroem A,Fuxe K +1 more
Journal ArticleDOI
Book reviewHandbook of Chemical Neuroanatomy: Methods in Chemical Neuroanatomy. Edited by A. Bjorklund and T. Hokfelt. Elsevier, Amsterdam, 1983. Cloth bound, 548 pp. UK £140. (Volume 1 in the series).
Journal ArticleDOI
Ageing and parkinson's disease: substantia nigra regional selectivity
Julian Fearnley,Andrew J. Lees +1 more
TL;DR: It is suggested that age-related attrition of pigmented nigral cells is not an important factor in the pathogenesis of Parkinson's disease and the regional selectivity of PD is relatively specific.
Journal ArticleDOI
Uneven pattern of dopamine loss in the striatum of patients with idiopathic Parkinson's disease. Pathophysiologic and clinical implications.
TL;DR: It is proposed that the motor deficits that are a constant and characteristic feature of idiopathic Parkinson's disease are for the most part a consequence of dopamine loss in the putamen, and that the dopamine-related caudate deficits are less marked or restricted to discrete functions only.
Journal ArticleDOI
A Neostriatal Habit Learning System in Humans
TL;DR: This double dissociation shows that the limbic-diencephalic regions damaged in amnesia and the neostriatum damaged in Parkinson's disease support separate and parallel learning systems.