Developmental Alterations of Frontal-Striatal-Thalamic Connectivity in Obsessive-Compulsive Disorder

University of Michigan Medical School, MI, USA.
Journal of the American Academy of Child and Adolescent Psychiatry (Impact Factor: 7.26). 09/2011; 50(9):938-948.e3. DOI: 10.1016/j.jaac.2011.06.011
Source: PubMed


Pediatric obsessive-compulsive disorder is characterized by abnormalities of frontal-striatal-thalamic circuitry that appear near illness onset and persist over its course. Distinct frontal-striatal-thalamic loops through cortical centers for cognitive control (anterior cingulate cortex) and emotion processing (ventral medial frontal cortex) follow unique maturational trajectories, and altered connectivity within distinct loops may be differentially associated with OCD at specific stages of development.
Altered development of striatal and thalamic connectivity to medial frontal cortex was tested in 60 OCD patients compared with 61 healthy control subjects at child, adolescent, and adult stages of development, using resting-state functional connectivity MRI.
OCD in the youngest patients was associated with reduced connectivity of dorsal striatum and medial dorsal thalamus to rostral and dorsal anterior cingulate cortex, respectively. Increased connectivity of dorsal striatum to ventral medial frontal cortex was observed in patients at all developmental stages. In child patients, reduced connectivity between dorsal striatum and rostral anterior cingulate cortex correlated with OCD severity.
Frontal-striatal-thalamic loops involved in cognitive control are hypoconnected in young patients near illness onset, whereas loops implicated in emotion processing are hyperconnected throughout the illness.

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Available from: Emily R Stern
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    • "First, the strength of FC can be affected by resting-state conditions (i.e., eyes open (EO), EC, or EF) (Patriat et al., 2013; Yan et al., 2009). While three of the previous studies used EC resting-state data (Harrison et al., 2009, 2013; Sakai et al., 2011), Fitzgerald et al. (2011) and this study used EF resting-state data. Second, the spatial differences of seeds (e.g., seed size or location) can also influence the FC strength (Cole et al., 2010; Wang et al., 2009; Zalesky et al., 2010b). "
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    ABSTRACT: Compulsive behaviors in obsessive-compulsive disorder (OCD) may be related to deficits in reward processing mediated by corticostriatal circuitry, a brain network implicated in the pathophysiology of OCD. Performing compulsive actions can be perceived as a reward to OCD patients because it temporarily reduces the anxiety provoked by obsessions. Although most OCD literature provides evidence of altered regional activity in these corticostriatal circuits, very little is known about the connectivity between individual regions of the corticostriatal-limbic circuits, including the cognitive and affective neural circuitry associated with OCD. Thus, this study investigated the differences in functional connectivity (FC) patterns in this network during resting-state and incentive processing. Nineteen patients with OCD and 18 well-matched healthy controls were scanned during resting-state and a monetary incentive delay task (task state). FC was assessed using both voxel-wise and region-of-interest (ROI)-wise analyses. Voxel-wise FC analysis with the nucleus accumbens seed revealed that patients with OCD exhibited increased FC between the nucleus accumbens and the lateral orbitofrontal cortex during resting-state. Additionally, these patients showed decreased FC between the nucleus accumbens and limbic areas such as the amygdala during incentive processing. Exploratory ROI-wise FC analysis revealed that OCD patients demonstrated enhanced FC between the nucleus accumbens and the lateral orbitofrontal cortex and increased total connectivity of the lateral orbitofrontal cortex during resting-state. Additionally, patients showed alterations in FC between resting and task state. This study provides evidence that patients with OCD have altered FC in the corticostriatal-limbic network, particularly in striatal-amygdala and striatal-orbitofrontal circuitry, during incentive processing and resting-state. These findings also emphasize that functional connections in the network are modulated by affective/motivational states and further suggest that OCD patients may have abnormalities of such modulation in this network.
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    • "In brief, early onset OCD may be characterized by abnormal neuronal maturational processes . In fact, a recent study demonstrated that while adolescents and adults with OCD show increased frontostriatal brain metabolism as compared to matched healthy controls, young children with OCD showed decreased activity (Fitzgerald et al., 2011), a finding that has been repeatedly demonstrated in children with ADHD (Bush, Valera, & Seidman, 2005). Secondly, the instance of co-occurrence of ADHD and OCD appears to be very common in children with tic disorders (Mathews & Grados, 2011). "
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    • "Various disorders such as ADHD, Tourette's, OCD among other are known to involve the basal ganglia. In these disorders there is hyperkinetic movement and or behaviors that coincide with the particular loop that is affected, but in all cases the increase seems to be in the direct loop not the indirect loop (Middleton & Strick, 1994; Litvan et al., 1996; Litvan et al., 1998; Fitzgerald et al., 2011; Gonçalves, 2011; van den Heuvel et al., 2011). The principle question here is why these disorders would target an increase in this pathway in particular. "
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