8 research outputs found
Genetic Variation of a DRD2 Co-expression Network is Associated with Changes in Prefrontal Function After D2 Receptors Stimulation
Dopamine D2 receptors (D2Rs) contribute to the inverted U-shaped relationship between dopamine signaling and prefrontal
function. Genetic networks from post-mortem human brain revealed 84 partner genes co-expressed with DRD2. Moreover,
eight functional single nucleotide polymorphisms combined into a polygenic co-expression index (PCI) predicted coexpression
of this DRD2 network and were associated with prefrontal function in humans. Here, we investigated the nonlinear
association of the PCI with behavioral and Working Memory (WM) related brain response to pharmacological D2Rs
stimulation. Fifty healthy volunteers took part in a double-blind, placebo-controlled, functional MRI (fMRI) study with
bromocriptine and performed the N-Back task. The PCI by drug interaction was significant on both WM behavioral scores (P
= 0.046) and related prefrontal activity (all corrected P < 0.05) using a polynomial PCI model. Non-linear responses under
placebo were reversed by bromocriptine administration. fMRI results on placebo were replicated in an independent sample
of 50 participants who did not receive drug administration (P = 0.034). These results match earlier evidence in non-human
primates and confirm the physiological relevance of this DRD2 co-expression network. Results show that in healthy
subjects, different alleles evaluated as an ensemble are associated with non-linear prefrontal responses. Therefore, brain
response to a dopaminergic drug may depend on a complex system of allelic patterns associated with DRD2 co-expression
BROMOCRIPTINE CHALLENGE AFFECTS WORKING MEMORY PROCESSING IN HUMANS DEPENDING ON DRD2-RELATED GENES
Prefrontal Activity and Connectivity with the Basal Ganglia during Performance of Complex Cognitive Tasks Is Associated with Apathy in Healthy Subjects.
Convergent evidence indicates that apathy affects cognitive behavior in different neurological and psychiatric conditions. Studies of clinical populations have also suggested the primary involvement of the prefrontal cortex and the basal ganglia in apathy. These brain regions are interconnected at both the structural and functional levels and are deeply involved in cognitive processes, such as working memory and attention. However, it is unclear how apathy modulates brain processing during cognition and whether such a modulation occurs in healthy young subjects. To address this issue, we investigated the link between apathy and prefrontal and basal ganglia function in healthy young individuals. We hypothesized that apathy may be related to sub-optimal activity and connectivity in these brain regions.Three hundred eleven healthy subjects completed an apathy assessment using the Starkstein's Apathy Scale and underwent fMRI during working memory and attentional performance tasks. Using an ROI approach, we investigated the association of apathy with activity and connectivity in the DLPFC and the basal ganglia.Apathy scores correlated positively with prefrontal activity and negatively with prefrontal-basal ganglia connectivity during both working memory and attention tasks. Furthermore, prefrontal activity was inversely related to attentional behavior.These results suggest that in healthy young subjects, apathy is a trait associated with inefficient cognitive-related prefrontal activity, i.e., it increases the need for prefrontal resources to process cognitive stimuli. Furthermore, apathy may alter the functional relationship between the prefrontal cortex and the basal ganglia during cognition
Auto-regulation of Th1 responses through carboxypeptidase M-generated C5a-desArg
<p>Rendered image of the brain depicting the dorsolateral prefrontal clusters whose activity correlated positively with apathy scores during (a) working memory and (b) attentional control tasks. See the text for statistics.</p
Demographic data and Apathy Scale (AS) data for the whole sample (All) and for the subsamples performing the working memory (N-Back) and attentional control (VAC) tasks.
<p>Demographic data and Apathy Scale (AS) data for the whole sample (All) and for the subsamples performing the working memory (N-Back) and attentional control (VAC) tasks.</p
Behavioral data for the subsamples performing the working memory (N-Back) and attentional control (VAC) tasks.
<p>Behavioral data for the subsamples performing the working memory (N-Back) and attentional control (VAC) tasks.</p
Prefrontal Activity and Connectivity with the Basal Ganglia during Performance of Complex Cognitive Tasks Is Associated with Apathy in Healthy Subjects
Objective Convergent evidence indicates that apathy affects cognitive behavior in different neurological
and psychiatric conditions. Studies of clinical populations have also suggested the primary
involvement of the prefrontal cortex and the basal ganglia in apathy. These brain regions are
interconnected at both the structural and functional levels and are deeply involved in cognitive
processes, such as working memory and attention. However, it is unclear how apathy modulates
brain processing during cognition and whether such a modulation occurs in healthy
young subjects. To address this issue, we investigated the link between apathy and prefrontal
and basal ganglia function in healthy young individuals. We hypothesized that apathy may be
related to sub-optimal activity and connectivity in these brain regions. Methods
Three hundred eleven healthy subjects completed an apathy assessment using the Starkstein's
Apathy Scale and underwent fMRI during working memory and attentional performance
tasks. Using an ROI approach, we investigated the association of apathy with
activity and connectivity in the DLPFC and the basal ganglia.Results
Apathy scores correlated positively with prefrontal activity and negatively with prefrontalbasal
ganglia connectivity during both working memory and attention tasks. Furthermore,
prefrontal activity was inversely related to attentional behavior. Conclusions
These results suggest that in healthy young subjects, apathy is a trait associated with inefficient
cognitive-related prefrontal activity, i.e., it increases the need for prefrontal resources
to process cognitive stimuli. Furthermore, apathy may alter the functional relationship
between the prefrontal cortex and the basal ganglia during cognition