Cortical activity in Parkinson's disease during executive processing depends on striatal involvement

Abstract

Patients with idiopathic Parkinson's disease exhibit impairments in executive processes, including planning and set-shifting, even at the early stages of the disease. We have recently developed a new card-sorting task to study the specific role of the caudate nucleus in such executive processes and have shown, using functional magnetic resonance imaging (fMRI) in young healthy adults, that the caudate nucleus is specifically required when a set-shift must be planned. Here the same fMRI protocol was used to compare the patterns of activation in a group of early-stage Parkinson's disease patients (seven right-handed patients at Hoehn and Yahr stages 1 and 2; mean age 62 years, range 56-70) and matched control subjects. Increased cortical activation was observed in the patients compared with the control group in the condition not specifically requiring the caudate nucleus. On the other hand, decreased cortical activation was observed in the patient group in the condition significantly involving the caudate nucleus. This event-related fMRI study showed a pattern of cortical activation in Parkinson's disease characterized by either reduced or increased activation depending on whether the caudate nucleus was involved or not in the task. This activation pattern included not only the prefrontal regions but also posterior cortical areas in the parietal and prestriate cortex. These findings are not in agreement with the traditional model, which proposes that the nigrostriatal dopamine depletion results in decreased cortical activity. These observations provide further evidence in favour of the hypothesis that not only the nigrostriatal and but also the mesocortical dopaminergic substrate may play a significant role in the cognitive deficits observed in Parkinson's disease.

The Neural Circuitry of Executive Functions in Healthy Subjects and Parkinson's Disease

“…These findings suggested that both decreased and increased activation can occur in prefrontal areas during cognitive performance, and that the pattern of activity observed in a specific area of the PFC depended on its specific relationship with the striatum for the task at hand. Later, these observation where confirmed in another fMRI study in a similar group of PD patients using a different set-shifting task (that is, MCST) (Monchi et al, 2007) (Figure 8), in which a pattern of cortical activation was characterized by either reduced or increased activation depending on whether the caudate nucleus was involved or not in the task. This activation pattern included not only the prefrontal regions but also posterior cortical areas in the parietal and prestriate cortex.…”

“…Indeed, approximately 15-20% of the patients tend to develop severe cognitive impairments, and the risk of developing dementia is two to three times higher in PD patients than in aged-matched controls (Aarsland et al, 1996). The non-motor cognitive and behavioral disabilities include deficits of executive function, language, visuospatial/visuoconstructive abilities, memory, attention, skill learning, as well as behavioral changes such as depression, apathy, and impulse control disorders (Taylor and SaintCyr, 1995;Zgaljardic et al, 2004;Monchi et al, 2004;Owen, 2004;Monchi, 2007;Steeves et al, 2009). Although Roberts et al (1994) have shown that prefrontal DA depletion may cause marked working memory deficits in monkeys, cognitive disabilities in PD have also been associated with DA depletion within the caudate nucleus (Lewis et al, 2003;Carbon et al, 2004;Grahn et al, 2008).…”

Apathy in Parkinson's disease: clinical features, neural substrates, diagnosis, and treatment

“…This cognitive apathy might result from brain lesions aff ecting either the lateral (ie, dorsolateral and ventrolateral) prefrontal cortex or the caudate nucleus. 2 Several functional imaging studies 94,95 in patients with Parkinson's disease without dementia have supported this hypothesis, showing that these patients can present with abnormal activation at the level of the dorsolateral or ventrolateral prefrontal cortex and caudate nucleus during executive tasks. Results from glucose metabolism studies [96][97][98] with ¹⁸F-FDG PET in Parkinson's disease have shown that apathy severity is associated with metabolic activity in diff erent cognitive regions, including the inferior medial frontal gyrus, cingulate cortex, insula, cuneus, and tempo roparietal region.…”

Impaired planning in Parkinson's disease is reflected by reduced brain activation and connectivity

“…Imaging studies demonstrate that these CSTC loops and fronto‐parietal networks are impaired even in early stages of PD before executive impairment at the behavioural level is evident [Monchi et al, 2007; Trujillo et al, 2015]. In early‐stage PD, functional connectivity is impaired in both task‐related and resting‐state networks [Olde Dubbelink et al, 2014, 2013; Stoffers et al, 2008].…”