Differential assessment of frontally-mediated behaviors between self- and informant-report in patients with obsessive-compulsive disorder following gamma ventral capsulotomy

Abstract

Obsessive-Compulsive Disorder (OCD) is a debilitating disorder causing marked distress and functional impairment. While advances in behavioral and pharmacotherapies have been effective for a majority of patients with OCD, 10-30% remain treatment refractory and severely impaired. For a subset of treatment-resistant individuals with the most severe and disabling (intractable) illness, gamma ventral capsulotomy (GVC) appears effective in reducing OCD symptoms and functional impairment. However, the effects of the ventral internal capsule lesion via GVC surgery on executive function in everyday life have been minimally investigated. Examining behavioral outcomes of GVC also provides a rare opportunity to probe the functional importance of the ventral prefrontal-subcortical connections of the internal capsule white matter tract in a relatively homogenous sample of patients with comparable white matter lesions. The present study investigated changes in frontally-mediated behaviors, measured by the Frontal Systems Behavior Scale (FrSBe), following GVC in 45 individuals with severe and otherwise intractable OCD, as rated by patients themselves and family members. Linear mixed effects models revealed a significant improvement in patient self-ratings on the FrSBe after surgery, while family ratings did not significantly change. Interestingly, improvement on the FrSBe for both self and family raters was significantly correlated with improvement in OCD symptomatology post-surgery, as measured by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). At the group level, we found no evidence of decline in frontally-mediated behaviors assessed by the FrSBe as a result of focal white matter disconnection via GVC. However, we cannot rule out the possibility that placebo effects or compromised patient self-awareness or insight contributed to the significant improvement in self ratings. Our measures may also have limited sensitivity to more selective impairments that could result from a small lesion to the ventral internal capsule. The present study demonstrates the need for detailed investigation of cognitive and behavioral changes as important factors when considering GVC as a viable treatment option for patients with refractory OCD.

Keywords: Executive function; Frontal lobe functions; Gamma ventral capsulotomy; Internal capsule lesion; Obsessive compulsive disorder; Ventromedial prefrontal cortex.

Figure 1.

T1-weighted magnetic resonance imaging acquired 12 months post-surgery showing double shot GVC bilateral lesions of the ventral portion of the internal capsule, visualized in the coronal (left) and axial (right) planes.

Figure 2.

Mean FrSBe scores at baseline and the first follow-up after surgery, for the 10 patients for whom within-subject comparisons were possible. Error bars represent standard errors of the mean across the 10 patients. One of the patients had too many missing items in the Apathy subscale, which also prevented calculation of a Total Score for that patient (n=9).

Figure 3.

Change in self-rated (left panel) and family-rated (right panel) FrSBe total scores over time for each patient. The 9 patients who had both self and family ratings pre- and post-surgery are represented with blue lines. For visualization purposes only, when multiple assessments were available within a time bin for a given patient, the assessments were averaged to yield a single score per patient per time bin. The mean and 95% confidence intervals are depicted in green.

Figure 4.

Correlation between self and family FrSBe ratings across all time points, r = 0.35, p = 0.03. Pre-surgical assessments are depicted with blue circles (Pearson’s r = 0.09, p = 0.71, n = 20), while post-surgery assessments are depicted with red circles (Pearson’s r = 0.51; p = 0.02, n = 33). Samples from the same patient over time are connected by colored lines.

Figure 5.

Correlation between Y-BOCS and FrSBe scores at (A) baseline, (B) <1.5 years after surgery, and (C) 1.5 - 5.5 years after surgery, for self (left column) and family (right column) ratings. When multiple assessments were performed within a time window, they were averaged to yield a single score per patient.

Figure 6.

Within- and across-patient correlation between Y-BOCS and FrSBe total scores for both self (top) and family (bottom) ratings. Filled-in circles represent scores at baseline, while empty circles represent post-surgery scores. The arrows show within-patient change over time.