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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

A framework for assessing dysfunctional activation and dACC-related network profiles of cortical, striatal, and thalamic networks in OCD. (A) The two panels depictive activation-based and seed-based approaches to identifying function and dysfunction. The equations represent basic linear model formalisms for each class of models. Note the convolution term (y0 × u) in the PPI based model that accounts for seed (y0 = dACC) modulation of targets in the task-oriented (u = working memory > rest) context. The regions of interest are schematically depicted on the mid-sagittal surface. The second figure schematically depicts the modulatory effects of the dACC assessed using psychophysiological interaction. (B) The factorial design space used for the study that assessed the effects of task-demand (1Back vs. 2Back) crossed with group.
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Figure 1: A framework for assessing dysfunctional activation and dACC-related network profiles of cortical, striatal, and thalamic networks in OCD. (A) The two panels depictive activation-based and seed-based approaches to identifying function and dysfunction. The equations represent basic linear model formalisms for each class of models. Note the convolution term (y0 × u) in the PPI based model that accounts for seed (y0 = dACC) modulation of targets in the task-oriented (u = working memory > rest) context. The regions of interest are schematically depicted on the mid-sagittal surface. The second figure schematically depicts the modulatory effects of the dACC assessed using psychophysiological interaction. (B) The factorial design space used for the study that assessed the effects of task-demand (1Back vs. 2Back) crossed with group.

Mentions: We had two principal aims in this study (summarized in Figure 1): (a) to investigate network profiles originating in the dACC in the task-active state using psychophysiological interaction (PPI) (Friston et al., 1997; O’Reilly et al., 2012), PPI is a simple framework within the general linear model for investigating contextual modulation of targets (e.g., regions within FSTC) by a seed (e.g., dACC) in a task-active context; (b) to investigate these profiles during parametrically manipulated verbal working memory, (Casey et al., 1995; Diwadkar et al., 2011, 2013), a domain that provides a rich window for investigating normal and dysfunctional activation and network profiles in the FSTC.


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)

A framework for assessing dysfunctional activation and dACC-related network profiles of cortical, striatal, and thalamic networks in OCD. (A) The two panels depictive activation-based and seed-based approaches to identifying function and dysfunction. The equations represent basic linear model formalisms for each class of models. Note the convolution term (y0 × u) in the PPI based model that accounts for seed (y0 = dACC) modulation of targets in the task-oriented (u = working memory > rest) context. The regions of interest are schematically depicted on the mid-sagittal surface. The second figure schematically depicts the modulatory effects of the dACC assessed using psychophysiological interaction. (B) The factorial design space used for the study that assessed the effects of task-demand (1Back vs. 2Back) crossed with group.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: A framework for assessing dysfunctional activation and dACC-related network profiles of cortical, striatal, and thalamic networks in OCD. (A) The two panels depictive activation-based and seed-based approaches to identifying function and dysfunction. The equations represent basic linear model formalisms for each class of models. Note the convolution term (y0 × u) in the PPI based model that accounts for seed (y0 = dACC) modulation of targets in the task-oriented (u = working memory > rest) context. The regions of interest are schematically depicted on the mid-sagittal surface. The second figure schematically depicts the modulatory effects of the dACC assessed using psychophysiological interaction. (B) The factorial design space used for the study that assessed the effects of task-demand (1Back vs. 2Back) crossed with group.
Mentions: We had two principal aims in this study (summarized in Figure 1): (a) to investigate network profiles originating in the dACC in the task-active state using psychophysiological interaction (PPI) (Friston et al., 1997; O’Reilly et al., 2012), PPI is a simple framework within the general linear model for investigating contextual modulation of targets (e.g., regions within FSTC) by a seed (e.g., dACC) in a task-active context; (b) to investigate these profiles during parametrically manipulated verbal working memory, (Casey et al., 1995; Diwadkar et al., 2011, 2013), a domain that provides a rich window for investigating normal and dysfunctional activation and network profiles in the FSTC.

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