Neurological Abnormalities
OCD has been linked with various neurological abnormalities and numerous studies have been directed toward the identification of the specific brain regions implicated in OCD.
Hollander et al (1990) conducted a study designed to detect neurological soft signs, which are signs of central nervous system dysfunction that are determined by an abnormal performance on motor and sensory tests, when no other visible neurological signs are present (Hollander et al,1990). This study analyzed numerous tests of coordination, sensory and visuospatial ability. The results showed that, compared with a group of normal control subjects, the subjects with OCD showed significantly more soft signs. For example, there were increases in the number of abnormalities for fine motor coordination, involuntary movements and visuospatial findings among subjects with OCD, but there were no differences reported in sensory abilities. Furthermore, the presence of depression and severity of compulsions did not correlate with soft signs; however, there was a significant positive correlation between the severity of obsessions and the total number of soft signs. This finding in particular supports the belief that soft signs may be an indication of obsessionality and not of psychiatric illness in general (Hollander et al,1990). There was also a non-significant increase in left-sided findings, which cannot be extended in support of theories of laterality in OCD, but "may suggest a right hemispheric dysfunction in a subgroup of patients with OCD" (Hollander et al,1990,30). The results also revealed that subjects with OCD presented more involuntary movements and an abnormality of mirror movements which does suggest a basal ganglia dysfunction (Hollander et al,1990). The authors hypothesize that structural abnormalities at various levels in the brain could result in a dysregulation of the serotonergic system because serotonergic pathways ascend from brain stem nuclei and pass through the median forebrain bundle, eventually spreading to the cortical and motor systems (Hollander et al,1990).
Another study (Laplane et al,1989) investigated the role of the basal ganglia in OC symptoms by conducting tests on patients with bilateral basal ganglia lesions which were caused by various forms of trauma; such as, wasp stings and carbon monoxide poisoning. All patients exhibited inertia and loss of drive which are signs of a frontal lobe-like syndrome, but several patients also exhibited stereotyped activities. The brain damage was observed by CT scans and MRI and it was found that lesions were restricted to the lentiform nuclei and especially affected the pallidum. PET scans in 7 of 8 patients showed dysfunction in the prefrontal cortex as a result of the damage to the lentiform nuclei. These observations suggest the importance of circuits which link the prefrontal cortex with particular areas of the neostriatum, one of which is the pallidum (Laplane et al,1989). The authors hypothesize that these lentiform nuclei lesions have affected "association circuits linking some compartments of the basal gnaglia and the prefrontal cortex" (Laplane et al,1989,700). It is believed that information from the basal ganglia is transmitted to specific regions of the frontal lobe. The motor circuit is the most well known of these and is directed to the supplementary motor area, but it is the association circuits which are probably involved with the subjects in this study (Laplane et al,1989). Specifically, the authors propose a dorsolateral prefrontal circuit through which neostriatal input is directed to the dorsolateral head of the caudate nucleus and is then projected to the globus pallidus and rostral areas of the substantia nigra (Laplane et al,1989). Another association circuit, which includes a sector of the caudate nucleus and a part of the pallidal segment, ends in the lateral orbitofrontal cortex (Laplane et al,1989). Although no conclusive theories about OCD can be drawn from this data, researchers believe that these circuits may be responsible for steretyped motor activities (Laplane et al,1989). Previous research on nonhuman primates has shown that bilateral lesions of the lateral orbitofrontal cortex or parts of the caudate nuclei result in difficulty in the ability to make changes in behavioural sets (Laplane et al,1989). Consequently, the data from this study supports the hypothesis that basal ganglia dysfunction is present in OCD and the authors suggest that the lentiform nuclei lesions could be responsible for the behavioural abnormalities which accompany this disorder (Laplane et al,1989).
Another study (Baxter et all,1988) evaluated cerebral function by measuring cerebral glucose metabolic rates in particular brain regions. Previous studies have found metabolic abnormalities in the orbitofrontal region, caudate nucleus and prefrontal gyri (Swedo et al,1992). In this study, non-depressed obsessive-compulsives were compared with a control group of normal subjects. The results showed that the subjects with OCD had elevated metabolic rates in the entire cerebral hemispheres, the head of the caudate nuclei, the orbital gyri and the orbital gyri relative to the ipsilateral hemisphere (the orbital-hemisphere ratio) compared with the control group. The increased activity in the orbital cortex of OCD subjects supports the hypothesis that OCD does involve abnormalities in the neurological activity of the caudate nuclei and orbital regions (Baxter et al,1988). Moreover, because this study used non-depressed subjects, these abnormalities are not confounded by the changes that may occur in the neurological activity of depressed individuals; however, the effects of anxiety or tension cannot be excluded.
Another method of analyzing brain activity is by measuring regional cerebral blood flow (rCBF). One study by Rubin, Villanueva-Meyer, Ananth, Trajmar and Mena (1992) used Tc-HMPAO to assess rCBF. Tc-HMPAO is a lipophilic molecule that can cross the blood-brain barrier and is converted to a hydrophilic form that becomes trapped within the brain. The amount of Tc-HMPAO that is trapped is determined by blood flow, membrane permeability, uptake into cells and the rate of conversion into hydrophilic form (Rubin, Villanueva-Meyer, Ananth, Trajmar & Mena,1992). The results showed no difference in cortical or basal ganglia rCBF between patients with OCD and matched control subjects, but patients with OCD did show increased uptake in the high dorsal parietal cortex bilaterally. There was also evidence of reduced uptake in the head of the caudate nucleus bilaterally. Later analysis demonstrated a positive correlation between rCBF and the severity of OCD symptoms and a small positive correlation between the duration of OCD and uptake. This data also supports the hypothesis that OCD involves abnormal neurological activity in different regions, including the orbitofrontal cortex and the caudate nucleus.
Finally, a study (Swedo et al,1992) was conducted to assess the neurological changes that occur following drug treatment. The cerebral glucose metabolism of subjects was measured before treatment and again after at least one year of drug therapy. Previous research has demonstrated that prefrontal and orbitofrontal hypermetabolism were correlated with symptom severity (Swedo et al,1992). Earlier studies also suggested that a poor response to pharmacotherapy could be predicted by hypermetabolism in the orbitalfrontal cortex and the anterior cingulate (Swedo et al,1992). Because past studies have shown contradictory evidence regarding the metabolic changes that occur with drug therapy the researchers in this study hypothesized that the "changes in cerebral glucose metabolism in OCD might vary by region and clinical status" (Swedo et al,1992,690). PET scans of the prefrontal and orbitofrontal regions, anterior cingulate gyrus, and caudate nucleus were compared at pretreatment and after drug treatment. The PET scan results were also compared with measures of the severity of OCD, anxiety and depression, and clinical improvement of symptoms. The results of the post-treatment PET scans revealed a significant positive correlation between ratings of OCD severity and right prefrontal normalized metabolism. Among the patients still receiving drug treatment, there was a positive correlation between ratings of OCD severity and normalized right prefrontal metabolism; and a negative correlation between OCD severity and normalized metabolism of the left caudate. All subjects showed a significant decrease in glucose metabolism in the right and left orbitofrontal regions compared with baseline measures. The patients who had shown a positive response to drug therapy experienced a larger decrease in metabolism of the left orbitofrontal region than nonresponders. A decrease in the right orbitofrontal metabolism was correlated with 2 measures of OCD symptom improvement for those receiving drug therapy and there was a trend toward a correlation between decreased metabolism in this region and improvement in symptoms of anxiety. The decrease in the right orbitofrontal metabolism was also positively correlated with CMI plasma levels; however, decreases in this region were observed in the majority of patients and no differences in the improvement status of these patients were found. The baseline hypermetabolism of this region has also been correlated with poor short-term response to CMI (Swedo et al,1992); therefore, the authors suggest that the hypermetabolism is dependent on the state of OCD and that decreases will occur when the symptoms are alleviated regardless of whether the improvement is achieved spontaneously or with medication (Swedo et al,1992). The association of CMI plasma level and orbitofrontal metabolism may suggest that the site of action for this drug is in the orbitofrontal region. The nonresponders in this study also demonstrated higher rates of pretreatment glucose metabolism in the right orbitofrontal and right anterior cingulate than responders, which further implicates the involvement of this region in OCD (Swedo et al,1992). Finally, the authors note that there is inconsistent evidence regarding abnormalities in the orbitofrontal regions (Swedo et al,1992). For example, a recent study reported that fluoxetine and behaviour therapy had no significant effect on orbitofrontal metabolism, but "successful treatment with either modality decreased (normalized) caudate nuclei hypermetabolism" (Swedo et al,1992,693). Reconciliation of these inconsistencies is necessary for the development of a theory explaining the pathology of OCD. One view proposes that the differences in neurological activity are caused by the distinct effects of the various SSRIs, in this case CMI and fluoxetine, on dopaminergic pathways (Swedo et al,1992). Alternatively, differences in the length of time between treatment and neuroimaging scans could be depicting different stages of neurological activity produced by the treatments. It is possible that the effects on the caudate nuclei occur earlier in treatment and gradually decrease when the orbital regions, and more conscious mechanisms, become involved (Swedo et al,1992). The authors conclude that if the caudate and orbitofrontal regions were considered as part of a basl-ganglia-thalamocortical circuit, then the present data would appear to be consistent with previous results (Swedo et al,1992).
In conclusion, the evidence of abnormal metabolic activity in regions of the basal ganglia and the frontal lobe in patients with OCD is supported by studies addressing a variety of areas. The improvement in symptoms after psychosurgery also suggests that an abnormality in the connections between the limbic system and the frontal cortex is probably a factor in OCD. The pharmacotherapy studies provide evidence of serotonergic dysfunction; however, the negative correlation between the selectivity and potency of SSRIs and antiobsessive response implies that other neurotransmitter systems, such as, the noradrenergic or dopaminergic pathways, may be involved in OCD as well. Specifically, the role of the dopaminergic system is probably important because of its prominence in basal ganglia functioning. Finally, the occurrence of OC symptoms in disorders which affect the basal ganglia and in patients with brain damage to this region provides corroboration of basal ganglia dysfunction in OCD. Although a comprehensive theory explaining the pathology of OCD is still forthcoming, the data from physiological studies suggests that OCD is a neurological disease with an underlying biological cause. Consequently, future research should continue to focus on identifying the specific pathways involved in this disorder and developing effective treatments to correct these abnormalitites.
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