Limits...
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

Within group changes in activation profiles as a function of load are depicted on identical ascending mosaics of axial views. The significant clusters (p < 0.05, cluster level) show significant increases in activation with increases in working memory related load. As seen, these increases are evident within both (A) healthy control and (B) OCD groups. These activation profiles establish within group effects of memory load across previously implicated load sensitive working memory related regions. These include dorsolateral prefrontal cortex (dPFC), the dorsal anterior cingulate (dACC), and the parietal cortex.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4362304&req=5

Figure 2: Within group changes in activation profiles as a function of load are depicted on identical ascending mosaics of axial views. The significant clusters (p < 0.05, cluster level) show significant increases in activation with increases in working memory related load. As seen, these increases are evident within both (A) healthy control and (B) OCD groups. These activation profiles establish within group effects of memory load across previously implicated load sensitive working memory related regions. These include dorsolateral prefrontal cortex (dPFC), the dorsal anterior cingulate (dACC), and the parietal cortex.

Mentions: Figure 2 depicts clusters (pc < 0.05) in FSTC showing increased within-group activation in response to increases in memory load (cluster relevant information in Table 2). In both groups, increased memory load results in increased recruitment of frontal and parietal regions, and the dACC. These results are unsurprising for the HC group. They are highly consistent with previous assessments of activation profiles in this circuit in HC (Braver et al., 1997; Cohen et al., 1997; Diwadkar et al., 2000), showing increased recruitment in brain circuits committed to implementing working memory related functions. The results in OCD are notable as they demonstrate that the memory effect exerts within-group effects consistent with HC. This is important evidence that FSTC in OCD is sensitive to load-related variations in working memory and that the overall implementation of the task generates load-related effects on activation profiles. Notable is an absence of load-related activation effects in the striatum or the thalamus, regions not typically implicated in core memory-related processing. The basal ganglia contribute to cortical-striatal processing loops that sub-serve complex processing, by supplementing prefrontal function (Hazy et al., 2006; Calzavara et al., 2007; Voytek and Knight, 2010). The thalamus forms cortical-thalamic processing units that integrate information from cortical and striatal loops to modulate complex behavior, but has generally not been sensitive to load-related variations in working memory (Haber and Calzavara, 2009).


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)

Within group changes in activation profiles as a function of load are depicted on identical ascending mosaics of axial views. The significant clusters (p < 0.05, cluster level) show significant increases in activation with increases in working memory related load. As seen, these increases are evident within both (A) healthy control and (B) OCD groups. These activation profiles establish within group effects of memory load across previously implicated load sensitive working memory related regions. These include dorsolateral prefrontal cortex (dPFC), the dorsal anterior cingulate (dACC), and the parietal cortex.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Within group changes in activation profiles as a function of load are depicted on identical ascending mosaics of axial views. The significant clusters (p < 0.05, cluster level) show significant increases in activation with increases in working memory related load. As seen, these increases are evident within both (A) healthy control and (B) OCD groups. These activation profiles establish within group effects of memory load across previously implicated load sensitive working memory related regions. These include dorsolateral prefrontal cortex (dPFC), the dorsal anterior cingulate (dACC), and the parietal cortex.
Mentions: Figure 2 depicts clusters (pc < 0.05) in FSTC showing increased within-group activation in response to increases in memory load (cluster relevant information in Table 2). In both groups, increased memory load results in increased recruitment of frontal and parietal regions, and the dACC. These results are unsurprising for the HC group. They are highly consistent with previous assessments of activation profiles in this circuit in HC (Braver et al., 1997; Cohen et al., 1997; Diwadkar et al., 2000), showing increased recruitment in brain circuits committed to implementing working memory related functions. The results in OCD are notable as they demonstrate that the memory effect exerts within-group effects consistent with HC. This is important evidence that FSTC in OCD is sensitive to load-related variations in working memory and that the overall implementation of the task generates load-related effects on activation profiles. Notable is an absence of load-related activation effects in the striatum or the thalamus, regions not typically implicated in core memory-related processing. The basal ganglia contribute to cortical-striatal processing loops that sub-serve complex processing, by supplementing prefrontal function (Hazy et al., 2006; Calzavara et al., 2007; Voytek and Knight, 2010). The thalamus forms cortical-thalamic processing units that integrate information from cortical and striatal loops to modulate complex behavior, but has generally not been sensitive to load-related variations in working memory (Haber and Calzavara, 2009).

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