Dopamine modulates default mode network deactivation in elderly individuals during the Tower of London task
ABSTRACT Task-induced deactivation is frequently reported in the ventro-medial prefrontal cortex (vmPFC) and posterior cingulate cortex (PCC), regions considered to belong to the default mode network. To investigate the effect of dopamine on task-induced deactivation, we used positron emission tomography to measure cerebral blood flow during performance of the Tower of London task before and after administration of the dopamine receptor agonist apomorphine in six healthy volunteers (49-66 years old) and six Parkinson disease patients (52-69 years old). Although task-induced deactivation was observed in the vmPFC and PCC in both groups and in both conditions, an inverse correlation between activation and problem complexity was observed in the vmPFC only in the apomorphine condition.
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- "Thus there is evidence that dopamine improves DMN function and connectivity, though not all reports agree. Nagano- Saito and colleagues  found no difference in PD or control subjects in MPF or PCC connectivity before versus after the administration of the dopamine receptor agonist apomorphine. Thus our findings, that DMN connectivity is reduced in PD subjects on dopamine replacement therapy may represent dysfunction over and above the effects of dopamine replacement, making it relevant to the bulk of the PD population. "
ABSTRACT: Background: Parkinson's disease (PD) can result in cognitive impairment. Executive dysfunction often appears early, followed by more widespread deficits later in the course of the disease. Disruption of parallel basal ganglia thalamo-cortical loops that subserve motor and cognitive function has been described in PD. However, there is emerging evidence that the default mode network, a cortical network that is active at rest with reduced activation during task performance, may also play a role in disease related cognitive decline. Objective: To determine the relative contribution of the executive control and default mode networks to parkinsonian executive dysfunction in medicated non-demented patients. Methods: We used BOLD fMRI to measure resting state functional connectivity in the executive control and default mode (DM) networks, and examined switching, processing speed, working memory/attention and motor performance in 14 medicated non-demented PD participants and 20 controls. Results: Performance on neuropsychological measures was similar across groups. Functional connectivity was not different across disease conditions in the executive control network. DMN functional connectivity was decreased in the PD group, specifically between posterior cingulate, medial prefrontal, and inferior parietal nodes. Greater DMN functional connectivity was associated with faster processing speed in the PD group. Conclusions: The continuous relationship between DMN disconnection and executive task performance indicates a possible biological contributor to parkinsonian cognitive deficits. The dynamics of executive control network change may be different than that of the DMN, suggesting less sensitivity to early cognitive deficits.03/2014; 4(3). DOI:10.3233/JPD-130341
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- "The meta-analysis that explored consistent, task-induced deactivations across a large number of neuroimaging studies from different task domains demonstrated involvement of ACC/DMPFC and PCC/precuneus, VMPFC and TPJ bilaterally (Figure 3). These results are in line with findings from our own previous investigation of task-induced deactivations, but also other analyses, which have repeatedly demonstrated that these brain regions exhibit task-related decreases in neural activity during tasks which require engagement with external stimuli , , , . "
ABSTRACT: Previous research suggests overlap between brain regions that show task-induced deactivations and those activated during the performance of social-cognitive tasks. Here, we present results of quantitative meta-analyses of neuroimaging studies, which confirm a statistical convergence in the neural correlates of social and resting state cognition. Based on the idea that both social and unconstrained cognition might be characterized by introspective processes, which are also thought to be highly relevant for emotional experiences, a third meta-analysis was performed investigating studies on emotional processing. By using conjunction analyses across all three sets of studies, we can demonstrate significant overlap of task-related signal change in dorso-medial prefrontal and medial parietal cortex, brain regions that have, indeed, recently been linked to introspective abilities. Our findings, therefore, provide evidence for the existence of a core neural network, which shows task-related signal change during socio-emotional tasks and during resting states.PLoS ONE 02/2012; 7(2):e30920. DOI:10.1371/journal.pone.0030920 · 3.23 Impact Factor
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- "Administration of a dopamine agonist increased activity in prefrontal regions in PD patients and was associated with improved performance. In PD patients, administration of apomorphine during performance of the TOL revealed greater deactivation of ventro-medial prefrontal cortex, a region belonging to the default network, as a function of task complexity . Finally, Jubault and colleagues  found that treatment with dopaminergic therapy had no effect on brain activity in regions implicated in planning a set shift (i.e., caudate nucleus, ventrolateral, posterior, and dorsolaterlal prefrontal cortex) in PD patients but increased activity in the premotor cortex, essentially normalizing the pattern observed for set-shift execution. "
ABSTRACT: Cognitive abnormalities are a feature of Parkinson's disease (PD). Unlike motor symptoms that are clearly improved by dopaminergic therapy, the effect of dopamine replacement on cognition seems paradoxical. Some cognitive functions are improved whereas others are unaltered or even hindered. Our aim was to understand the effect of dopamine replacement therapy on various aspects of cognition. Whereas dorsal striatum receives dopamine input from the substantia nigra (SN), ventral striatum is innervated by dopamine-producing cells in the ventral tegmental area (VTA). In PD, degeneration of SN is substantially greater than cell loss in VTA and hence dopamine-deficiency is significantly greater in dorsal compared to ventral striatum. We suggest that dopamine supplementation improves functions mediated by dorsal striatum and impairs, or heightens to a pathological degree, operations ascribed to ventral striatum. We consider the extant literature in light of this principle. We also survey the effect of dopamine replacement on functional neuroimaging in PD relating the findings to this framework. This paper highlights the fact that currently, titration of therapy in PD is geared to optimizing dorsal striatum-mediated motor symptoms, at the expense of ventral striatum operations. Increased awareness of contrasting effects of dopamine replacement on dorsal versus ventral striatum functions will lead clinicians to survey a broader range of symptoms in determining optimal therapy, taking into account both those aspects of cognition that will be helped versus those that will be hindered by dopaminergic treatment.03/2011; 2011(8414):572743. DOI:10.4061/2011/572743