Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Apathy is a complex, behavioural disorder associated with reduced spontaneous initiation of actions. Although present in mild forms in some healthy people, it is a pathological state in conditions such as Alzheimer's and Parkinson's disease where it can have profoundly devastating effects. Understanding the mechanisms underlying apathy is therefore of urgent concern but this has proven difficult because widespread brain changes in neurodegenerative diseases make interpretation difficult and there is no good animal model. Here we present a very rare case with profound apathy following bilateral, focal lesions of the basal ganglia, with globus pallidus regions that connect with orbitofrontal (OFC) and ventromedial prefrontal cortex (VMPFC) particularly affected. Using two measures of oculomotor decision-making we show that apathy in this individual was associated with reward insensitivity. However, reward sensitivity could be established partially with levodopa and more effectively with a dopamine receptor agonist. Concomitantly, there was an improvement in the patient's clinical state, with reduced apathy, greater motivation and increased social interactions. These findings provide a model system to study a key neuropsychiatric disorder. They demonstrate that reward insensitivity associated with basal ganglia dysfunction might be an important component of apathy that can be reversed by dopaminergic modulation.
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PMID:Dopamine reverses reward insensitivity in apathy following globus pallidus lesions. 2272 58

Patients with Parkinson disease (PD) often experience nonmotor symptoms including cognitive deficits, depression, and anxiety. Cognitive and affective processes are thought to be mediated by prefrontal cortico-basal ganglia circuitry. However, the topography and neurophysiology of prefrontal cortical activity during complex tasks are not well characterized. We used high-resolution electrocorticography in pFC of patients with PD and essential tremor, during implantation of deep brain stimulator leads in the awake state, to understand disease-specific changes in prefrontal activity during an emotional face processing task. We found that patients with PD had less task-related theta-alpha power and greater task-related gamma power in the dorsolateral pFC, inferior frontal cortex, and lateral OFC. These findings support a model of prefrontal neurophysiological changes in the dopamine-depleted state, in which focal areas of hyperactivity in prefrontal cortical regions may compensate for impaired long-range interactions mediated by low-frequency rhythms. These distinct neurophysiological changes suggest that nonmotor circuits undergo characteristic changes in PD.
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PMID:Altered Prefrontal Theta and Gamma Activity during an Emotional Face Processing Task in Parkinson Disease. 3132 65