Penfield revisited?

While motor-system abnormalities are the defining features of PD, cognitive and neuropsychiatric symptoms are of major importance.1,2⇓ Disturbances in mood and motivation, such as depression, apathy, anxiety, impulsivity, and mood lability, are particularly common. These behavior changes can be seen early in the course of PD and may antedate motor dysfunction, providing empirical evidence for an “organic” rather than reactive etiology. Postmortem and in vivo biochemical as well as neuroimaging studies lend support to this hypothesis, with mesolimbic dopamine and serotonin abnormalities and fronto-limbic dysfunction demonstrated in affected patient subgroups.3 Neuropsychiatric symptoms can also begin later in the illness suggesting that additional factors, acting in concert with ongoing neurodegenerative changes, are important in their etiology. These factors include progressive and fluctuating motor symptoms, medication side effects, premorbid personality traits, psychosocial stressors, and the presence of medical, neurologic, and psychiatric comorbidity.4 It is not yet clear how these factors interact or which are most critical, a fact underscored by the absence of neurobehavioral signs in many patients with seemingly comparable disease features and risk factors. Nonetheless, most neuropsychiatric syndromes are usually attributed to selective dysfunction of specific prefrontal and limbic cortical-striatal-thalamic pathways.5 This conceptual approach directly parallels strategies used to delineate physiologic and biochemic abnormalities mediating motor symptoms.6 Classic lesion-deficit studies support such links, with onset of depression, mania, …