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Dysfunctional Activation and Brain Network Profiles in Youth with Obsessive-Compulsive Disorder: A Focus on the Dorsal Anterior Cingulate during Working Memory.

Diwadkar VA, Burgess A, Hong E, Rix C, Arnold PD, Hanna GL, Rosenberg DR - Front Hum Neurosci (2015)

Bottom Line: This in turn may be predictive of many of the cognitive and behavioral deficits associated with complex behavioral phenotypes.Our results indicate that OCD is characterized by significantly increased dACC modulation of cortical, striatal, and thalamic targets during working memory, and that this aberrant increase in OCD patients is maintained regardless of working memory demand.The results constitute compelling evidence of dysfunctional brain network interactions in OCD and suggest that these interactions may be related to a combination of network inefficiencies and dACC hyper-activity that has been associated with the phenotype.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry and Behavioral Neurosciences, Brain Imaging Research Division, Wayne State University School of Medicine , Detroit, MI , USA.

ABSTRACT
Brain network dysfunction is emerging as a central biomarker of interest in psychiatry, in large part, because psychiatric conditions are increasingly seen as disconnection syndromes. Understanding dysfunctional brain network profiles in task-active states provides important information on network engagement in an experimental context. This in turn may be predictive of many of the cognitive and behavioral deficits associated with complex behavioral phenotypes. Here we investigated brain network profiles in youth with obsessive-compulsive disorder (OCD), contrasting them with a group of age-comparable controls. Network interactions were assessed during simple working memory: in particular, we focused on the modulation by the dorsal anterior cingulate cortex (dACC) of cortical, striatal, and thalamic regions. The focus on the dACC was motivated by its hypothesized role in the pathophysiology of OCD. However, its task-active network signatures have not been investigated before. Network interactions were modeled using psychophysiological interaction, a simple directional model of seed to target brain interactions. Our results indicate that OCD is characterized by significantly increased dACC modulation of cortical, striatal, and thalamic targets during working memory, and that this aberrant increase in OCD patients is maintained regardless of working memory demand. The results constitute compelling evidence of dysfunctional brain network interactions in OCD and suggest that these interactions may be related to a combination of network inefficiencies and dACC hyper-activity that has been associated with the phenotype.

No MeSH data available.


Related in: MedlinePlus

Dysfunctional activation profiles in OCD (relative to controls) are depicted for both (A) the 1Back level of memory and (B) the 2Back level of memory load. Increased activation in OCD (p < 0.05, cluster level) is depicted on identical ascending mosaics of axial views. These activation profiles indicate increased activation in dorsolateral prefrontal cortex (dPFC), the dorsal anterior cingulate (dACC), and the parietal cortex in OCD. Notably the degree of dysfunctional activation in OCD scales as a function of memory load. We speculate that the parametric demands as expressed in dysfunctional activation profiles load disproportionately in OCD participants. As will be seen, brain network profiles in OCD do not strictly follow activation patterns, evidence that signatures of network interactions may complement psychopathology revealed in activation models.
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Figure 3: Dysfunctional activation profiles in OCD (relative to controls) are depicted for both (A) the 1Back level of memory and (B) the 2Back level of memory load. Increased activation in OCD (p < 0.05, cluster level) is depicted on identical ascending mosaics of axial views. These activation profiles indicate increased activation in dorsolateral prefrontal cortex (dPFC), the dorsal anterior cingulate (dACC), and the parietal cortex in OCD. Notably the degree of dysfunctional activation in OCD scales as a function of memory load. We speculate that the parametric demands as expressed in dysfunctional activation profiles load disproportionately in OCD participants. As will be seen, brain network profiles in OCD do not strictly follow activation patterns, evidence that signatures of network interactions may complement psychopathology revealed in activation models.

Mentions: Figure 3 depicts clusters (pc < 0.05) in FSTC showing increased activation in OCD (relative to HC) at each level of memory load (cluster relevant information in Table 3). Several effects are evident. Dysfunctional activation profiles are observed in the frontal and parietal cortices and in the dACC at both levels of load. Absent is evidence of dysfunctional activation profiles in the striatum or the thalamus. Moreover, dysfunction in activation profiles scales as a function of memory load: Increased memory demand leads to increased activation in cortical regions. These analyses are consistent with previous studies in FSTC in OCD participants in other behavioral domains such as conflict monitoring that are closely associated with behavioral phenotypes in the illness (Huyser et al., 2011). As one of our study aims was to assess whether hyper-activation in FSTC constitutes a domain-general property of brain regions in OCD, these analyses extend the findings beyond the domain of conflict processing and suggest that multiple tasks engaging FSTC are sensitive for detecting activation-related dysfunction.


Dysfunctional Activation and Brain Network Profiles in Youth with Obsessive-Compulsive Disorder: A Focus on the Dorsal Anterior Cingulate during Working Memory.

Diwadkar VA, Burgess A, Hong E, Rix C, Arnold PD, Hanna GL, Rosenberg DR - Front Hum Neurosci (2015)

Dysfunctional activation profiles in OCD (relative to controls) are depicted for both (A) the 1Back level of memory and (B) the 2Back level of memory load. Increased activation in OCD (p < 0.05, cluster level) is depicted on identical ascending mosaics of axial views. These activation profiles indicate increased activation in dorsolateral prefrontal cortex (dPFC), the dorsal anterior cingulate (dACC), and the parietal cortex in OCD. Notably the degree of dysfunctional activation in OCD scales as a function of memory load. We speculate that the parametric demands as expressed in dysfunctional activation profiles load disproportionately in OCD participants. As will be seen, brain network profiles in OCD do not strictly follow activation patterns, evidence that signatures of network interactions may complement psychopathology revealed in activation models.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4362304&req=5

Figure 3: Dysfunctional activation profiles in OCD (relative to controls) are depicted for both (A) the 1Back level of memory and (B) the 2Back level of memory load. Increased activation in OCD (p < 0.05, cluster level) is depicted on identical ascending mosaics of axial views. These activation profiles indicate increased activation in dorsolateral prefrontal cortex (dPFC), the dorsal anterior cingulate (dACC), and the parietal cortex in OCD. Notably the degree of dysfunctional activation in OCD scales as a function of memory load. We speculate that the parametric demands as expressed in dysfunctional activation profiles load disproportionately in OCD participants. As will be seen, brain network profiles in OCD do not strictly follow activation patterns, evidence that signatures of network interactions may complement psychopathology revealed in activation models.
Mentions: Figure 3 depicts clusters (pc < 0.05) in FSTC showing increased activation in OCD (relative to HC) at each level of memory load (cluster relevant information in Table 3). Several effects are evident. Dysfunctional activation profiles are observed in the frontal and parietal cortices and in the dACC at both levels of load. Absent is evidence of dysfunctional activation profiles in the striatum or the thalamus. Moreover, dysfunction in activation profiles scales as a function of memory load: Increased memory demand leads to increased activation in cortical regions. These analyses are consistent with previous studies in FSTC in OCD participants in other behavioral domains such as conflict monitoring that are closely associated with behavioral phenotypes in the illness (Huyser et al., 2011). As one of our study aims was to assess whether hyper-activation in FSTC constitutes a domain-general property of brain regions in OCD, these analyses extend the findings beyond the domain of conflict processing and suggest that multiple tasks engaging FSTC are sensitive for detecting activation-related dysfunction.

Bottom Line: This in turn may be predictive of many of the cognitive and behavioral deficits associated with complex behavioral phenotypes.Our results indicate that OCD is characterized by significantly increased dACC modulation of cortical, striatal, and thalamic targets during working memory, and that this aberrant increase in OCD patients is maintained regardless of working memory demand.The results constitute compelling evidence of dysfunctional brain network interactions in OCD and suggest that these interactions may be related to a combination of network inefficiencies and dACC hyper-activity that has been associated with the phenotype.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry and Behavioral Neurosciences, Brain Imaging Research Division, Wayne State University School of Medicine , Detroit, MI , USA.

ABSTRACT
Brain network dysfunction is emerging as a central biomarker of interest in psychiatry, in large part, because psychiatric conditions are increasingly seen as disconnection syndromes. Understanding dysfunctional brain network profiles in task-active states provides important information on network engagement in an experimental context. This in turn may be predictive of many of the cognitive and behavioral deficits associated with complex behavioral phenotypes. Here we investigated brain network profiles in youth with obsessive-compulsive disorder (OCD), contrasting them with a group of age-comparable controls. Network interactions were assessed during simple working memory: in particular, we focused on the modulation by the dorsal anterior cingulate cortex (dACC) of cortical, striatal, and thalamic regions. The focus on the dACC was motivated by its hypothesized role in the pathophysiology of OCD. However, its task-active network signatures have not been investigated before. Network interactions were modeled using psychophysiological interaction, a simple directional model of seed to target brain interactions. Our results indicate that OCD is characterized by significantly increased dACC modulation of cortical, striatal, and thalamic targets during working memory, and that this aberrant increase in OCD patients is maintained regardless of working memory demand. The results constitute compelling evidence of dysfunctional brain network interactions in OCD and suggest that these interactions may be related to a combination of network inefficiencies and dACC hyper-activity that has been associated with the phenotype.

No MeSH data available.


Related in: MedlinePlus