The onset of OCD following focal brain lesions can provide valuable clues regarding the anatomical bases of OCD. In principle, simply because a lesion in a given brain region can produce OCD, that does not necessarily imply that all or even some cases of non-lesion-related OCD involve impairments in that region. Nevertheless, if lesion studies highlight the same general circuits that have been implicated in anatomical and functional imaging studies of OCD, the case for a causal role for those circuits in the pathogenesis of OCD becomes stronger.
Multiple reports describe cases of OCD following lesions confined to the basal ganglia (Carmin, Wiegartz, Yunus, & Gillock, 2002
; Chacko, Corbin, & Harper, 2000
; Laplane et al., 1989
; Lopez-Rodriguez, Gunay, & Glaser, 1997
; Rodrigo Escalona, Adair, Roberts, & Graeber, 1997
; Weilburg et al., 1989
; Weiss & Jenike, 2000
); two describe cases following lesions confined to the OFC (K. W. Kim & Lee, 2002
; Ogai, Iyo, Mori, & Takei, 2005
); a few describe cases following lesions involving broader expanses of frontal cortex (Swoboda & Jenike, 1995
; Ward, 1988
; Weiss & Jenike, 2000
); and a few others describe cases following more widespread lesions, which nonetheless also involve the frontal lobes (typically including the OFC) or the basal ganglia (Berthier, Kulisevsky, Gironell, & Lopez, 2001
; Gamazo-Garran, Soutullo, & Ortuno, 2002
; Max et al., 1995
). In addition, two case reports describe improvements in pre-existing OCD after hemorrhage in the basal ganglia (Fujii, Otsuka, Suzuki, Endo, & Yamadori, 2005
; Yaryura-Tobias & Neziroglu, 2003
The consistency of the brain areas involved in these case reports and those implicated in anatomical and functional imaging studies of patients with OCD suggests a causal role for the frontal cortices – in particular, the OFC – and the basal ganglia in the pathogenesis of OCD. Some caution is warranted when interpreting the findings of case reports, however, for three main reasons. First, the number of subjects involved is relatively small, even when considering the findings of all available case reports. Second, the stress associated with having a brain lesion could, by itself, aggravate or even precipitate some cases of OCD. In fact, greater psychosocial adversity is associated with the development of obsessive-compulsive symptoms following traumatic brain injury (Grados et al., 2008
). Third, the possibility of reporting bias cannot be excluded, given that several of the cases mentioned above were reported after theories of the involvement of the OFC and respective loops through the basal ganglia had appeared in the literature, and clinicians may have been more willing to report cases consistent with that theoretical framework. To the extent that childhood- and adult-onset OCD may have differing etiologies, these cases may also bear mostly on adult-onset illness, as the vast majority of them involve adults (often older adults).
A large, prospective study assessed new-onset obsessive-compulsive symptoms in 80 children and adolescents (ages 6–18) following severe traumatic brain injury (Grados et al., 2008
). This study reported a high prevalence of new-onset obsessions or compulsions one year after injury, with 21 out of the 80 subjects reporting obsessions or compulsions at that time but not before the lesion. Conversely, 5 subjects who had obsessions or compulsions before the lesion no longer had them one year after the lesion. Medial prefrontal and temporal lobe lesions were associated with new-onset obsessions, but this effect disappeared when obsessions and compulsions were considered conjointly. OFC lesions seemed to be associated with fewer symptoms, suggesting that anatomical integrity of the OFC is required for the onset of OCD. This is consistent with neurosurgical treatments for OCD that disrupt the OFC or its connections, but contrasts with the case reports that have implicated lesions of the OFC in the onset of OCD (K. W. Kim & Lee, 2002
; Ogai et al., 2005
). A possible explanation for this discrepancy is that lesions to certain subregions of the OFC may cause OCD, whereas lesions to other subregions may prevent its expression.
This study suffered from three important limitations. First, it used an ROI approach that examined only the areas that have traditionally been implicated in OCD (OFC, medial prefrontal cortex, basal ganglia, and thalamus), plus the temporal lobe. Second, symptoms were assessed one year after injury, and their onset or disappearance could, at least in some cases, be due simply to the passing of time. The non-inclusion of a group of matched non-injured controls in the study precludes any inferences regarding the extent to which the changes in symptoms were caused by the injury. Third, scanning and symptom assessment occurred 9 months apart. In addition, the focus of the study was on obsessive-compulsive symptoms, not full-blown OCD. In fact, only 2 out of the 80 children had new-onset OCD following the lesion.
In summary, several reports describe cases of OCD following lesions of the basal ganglia or frontal cortex (with an emphasis on the OFC); two reports describe cases of improvement in OCD after lesions of the basal ganglia. A larger, prospective study (Grados et al., 2008
) also suggests a role for the OFC in obsessive-compulsive symptoms following brain injury, although in that study lesions to the OFC were inversely related to symptom severity. The same study also reported an association between lesions to the medial prefrontal cortex (which included the ACC) and obsessions. All of these findings are consistent with the hypothesis that the pathogenesis of OCD involves CBGTC loops, in particular the loops involving the OFC and possibly the ACC.
Despite the convergence of findings from lesion studies with those from anatomical and functional imaging studies, the correct way to conceptualize the relation of lesion findings with functional imaging findings remains elusive. For example, we have seen above that the OFC is often hyperactive in (non-lesion-related) OCD. Do we interpret this as evidence that activity of the OFC is somehow causally related to the symptoms of OCD, and therefore expect a lesion of the OFC to improve symptoms, given that a lesioned OFC would not be active? Or do we interpret the imaging data as evidence that the OFC is working in overdrive to try to inhibit or control the expression of OCD symptoms, and therefore expect a lesion of the OFC to worsen the symptoms? Or do we interpret the hyperactivity in OFC not as a sign of heightened function but rather of dysfunction in that region, and therefore expect that lesions of the OFC might produce OCD, by making the OFC dysfunctional? Different versions of all of these hypotheses can be found, implicitly or explicitly, in the literature. Existing lesion studies do not, however, help us discriminate between these alternatives, given that lesions of the OFC have been associated with both increases and decreases in OCD symptoms. More research is needed to address these questions.
Another question, raised specifically by findings of the prospective study described above (Grados et al., 2008
), is whether the temporal lobe may also be involved in the pathogenesis of OCD. In support of this possibility, temporal lobe epilepsy has been associated with OCD and obsessive-compulsive symptoms (Kroll & Drummond, 1993
; Monaco et al., 2005
). In addition, several studies have reported anatomical abnormalities in the superior temporal gyrus in patients with OCD (Choi et al., 2006
; J. J. Kim et al., 2001
; Shin et al., 2007
; Yoo et al., 2008
). One possibility, which we have already discussed, is that the temporal lobe – in particular the superior temporal gyrus – is involved in OCD via its connections with the regions of the striatum that are part of the OFC/ACC CBGTC loops (Alexander et al., 1986
). However, additional research is needed to test this hypothesis.