Brain activation of patients with obsessive-compulsive disorder during neuropsychological and symptom provocation tasks before and after symptom improvement: a functional magnetic resonance imaging study.

BACKGROUND: Functional neuroimaging studies have implicated hyperactivity of the frontal cortex in obsessive-compulsive disorder (OCD); however, relationships between abnormal brain activity, clinical improvement, and neuropsychological function have not been clarified in OCD. To clarify the pathophysiology of this disorder, regional changes in brain function were examined during administration of cognitive and symptom provocation tasks in patients with OCD before and after treatment. METHODS: Ten outpatients with OCD participated in the study. Functional magnetic resonance imaging (fMRI) was performed before and after treatment. Stroop and symptom provocation tasks were administered during fMRI. Each patient was randomly allocated to receive either pharmacotherapy with fluvoxamine 200 mg/day (n = 4) or behavior therapy (n = 6) for 12 weeks. RESULTS: After 12-week treatment, mean (+/- SD) total score on the Yale-Brown Obsessive-Compulsive Scale decreased from 29.00 +/- 3.59 to 14.60 +/- 9.22, representing symptomatic improvement from moderate to mild. After symptom improvement, symptom provocation-related activation in the orbitofrontal, dorsolateral-prefrontal, and anterior cingulate cortices decreased. Conversely, Stroop task-related activation in the parietal cortex and cerebellum increased. CONCLUSIONS: After improvement of OCD with either fluvoxamine or behavioral therapy, hyperactivation of the frontal lobe related to a symptom-provocative state decreases, and posterior brain activity related to action-monitoring function increases.     

The relationship between regional cerebral blood flow and response to methylphenidate in children with attention-deficit hyperactivity disorder: comparison between non-responders to methylphenidate and responders

In a sample of children with attention-deficit hyperactivity disorder (ADHD), a voxel based investigation of regional cerebral blood flow (rCBF) during resting state was conducted to identify functional differences between non-responders to methylphenidate (MPH) and responders. Thirty-four children with ADHD were examined by technetium-99m-hexamethylporphylenamine oxime (HMPAO) SPECT. According to clinical response after 8 weeks of treatment with MPH, they were classified as non-responders to MPH and responders. Using SPM analysis, we compared the SPECT images of non-responders to MPH with those of responders. Non-responders to MPH had higher rCBF in the left anterior cingulate cortex, the left claustrum, the right anterior cingulate cortex, and the right putamen relative to responders. In addition, lower rCBF was found in the right superior parietal lobule in non-responders to MPH relative to responders. Further stepwise discriminant analysis revealed that 88.2% could be correctly classified as either non-responders to MPH or responders when considering the extracted rCBF values in the left anterior cingulate cortex, the left claustrum, and the right superior parietal lobule. The current findings suggest that non-responders to MPH may have different patterns of rCBF in brain regions, which have been known as a part of frontal-striatal circuitry and posterior attentional system, respectively.     

Decreased thalamic blood flow in obsessive-compulsive disorder patients responding to fluvoxamine

Functional imaging studies have pointed to a role of the orbitofrontal cortex (OFC), striatum and thalamus in the pathophysiology of obsessive-compulsive disorder (OCD). Effective treatment has been found to change brain activity within this circuitry. The aim of the present study was to explore possible differential effects of OCD responders and non-responders to drug treatment on the regional cerebral blood flow (rCBF). Measurements of rCBF were carried out in 15 out of 22 patients with OCD who completed an open-label trial with fluvoxamine. Patients were studied with 99mTc-HMPAO single photon emission computed tomography (SPECT) before and after 12 weeks of treatment. In addition, structural magnetic resonance imaging was obtained on all patients. Regions of interest comprised the OFC, caudate nucleus, putamen and thalamus. Seven patients responded to treatment. Levels of rCBF decreased significantly in the left caudate nucleus and the left and right putamen in both responders and non-responders to treatment. In responders, but not in non-responders, a significant decrease in rCBF was found in the right thalamus. Pre-treatment cerebellar and whole brain HMPAO uptake was significantly higher in responders to treatment compared with non-responders. We suggest that the thalamus plays a central role in the response to drug treatment.     

Caudate volume differences among treatment responders,non-responders and controls in children with obsessive–compulsive disorder

Treatment response in obsessive–compulsive disorder (OCD) is heterogeneous and the neurobiological underpinnings of such variability are unknown. To investigate this issue, we looked for differences in brain structures possibly associated with treatment response in children with OCD. 29 children with OCD (7–17 years) and 28 age-matched controls underwent structural magnetic resonance imaging. Patients then received treatment with fluoxetine or group cognitive-behavioral therapy during 14 weeks, and were classified as treatment responders or non-responders. The caudate nucleus, thalamus and orbitofrontal cortex were selected a priori, according to previous evidence of their association with OCD and its treatment. Gray matter (GM) volume comparisons between responders, non-responders and controls were performed, controlling for total GM volume. 17 patients were classified as responders. Differences among responders, non-responders and controls were found in both caudate nuclei (both p-values = 0.041), but after Bonferroni correction for multiple comparisons, these findings were non-significant. However, after excluding the effect of an outlier, findings were significant for the right caudate (p = 0.004). Pairwise comparisons showed larger caudate GM volume in responders versus non-responders and controls, bilaterally. The right caudate accounted for 20.2% of the variance in Y-BOCS changes after treatment in a linear regression model, with a positive correlation (p = 0.016). We present a possible neural substrate for treatment response in pediatric OCD, which is in line with previous evidence regarding the caudate nucleus. Considering the limitations, further research is needed to replicate this finding and elucidate the heterogeneity of treatment response in children with OCD (National Clinical Trials Registration Number: NCT01148316).

     

Error-related hyperactivity of the anterior cingulate cortex in obsessive-compulsive disorder.

BACKGROUND: Hyperactivity of the anterior cingulate cortex (ACC) in patients with obsessive-compulsive disorder (OCD) has been shown to increase with symptom provocation and to normalize with treatment-induced symptom reduction. Although the functional significance of anterior cingulate involvement in OCD remains unknown, electrophysiological evidence has linked this region to error-processing abnormalities in patients with OCD. In this functional magnetic resonance imaging (fMRI) study, we sought to further localize error-processing differences within the ACC of OCD patients compared with healthy subjects. METHODS: Event-related fMRI data were collected for eight OCD patients and seven healthy subjects during the performance of a simple cognitive task designed to elicit errors but not OCD symptoms. RESULTS: Both OCD patients and healthy subjects demonstrated dorsal ACC activation during error commission. The OCD patients exhibited significantly greater error-related activation of the rostral ACC than comparison subjects. Activity in this region was positively correlated with symptom severity in the patients. CONCLUSIONS: Error-processing abnormalities within the rostral anterior cingulate occur in the absence of symptom expression in patients with OCD.     

Proton magnetic resonance spectroscopy reveals an abnormality in the anterior cingulate of a subgroup of obsessive-compulsive disorder patients

Numerous neuroimaging studies have suggested that obsessive-compulsive disorder (OCD) patients had a neurobiological abnormality in the frontal-subcortical circuits. On the other hand, there are distinct differences in the responses to pharmacological treatment among OCD patients. In the present study, we measured the concentration of N-acetyl aspartate (NAA), a putative marker of neuronal viability, with proton magnetic resonance spectroscopy (MRS) in OCD patients with different pharmacological responses. Participants comprised 20 patients and 26 healthy control subjects. OCD patients were divided into three groups according to the pharmacological response; responders to a selective serotonin reuptake inhibitor (SSRI) (group A: n=7), responders to SSRI with an atypical antipsychotic (group B: n=8) and non-responders to either SSRI or SSRI with an atypical antipsychotic (group C: n=5). Short echo proton MRS was used to measure NAA concentrations in the anterior cingulate, the left basal ganglia and the left prefrontal lobe of subjects. A significantly lower NAA concentration was observed only in group B compared with control subjects in the anterior cingulate. Our results suggest that a subgroup of OCD patients who respond to an SSRI with an atypical antipsychotic have distinct biological abnormalities in the anterior cingulate.     

Cerebral activation in children and adolescents with obsessive-compulsive disorder before and after treatment: a functional MRI study

BACKGROUND: Structural and functional fronto-striatal abnormalities are involved in the pathophysiology of obsessive-compulsive disorder (OCD). The aims of the present study were: (a) to investigate possible regional brain dysfunction in premotor cortico-striatal activity in drug-na?ve children and adolescents with OCD; (b) to correlate brain activation with severity of obsessive-compulsive symptomatology; and (c) to detect possible changes in brain activity after pharmacological treatment. METHOD: Twelve children and adolescents (age range 7-18 years; seven male, five female) with DSM-IV obsessive-compulsive disorder and twelve healthy subjects matched for age, sex and intellectual level were studied. Functional magnetic resonance imaging data were obtained during the performance of simple and complex sequences. RESULTS: Comparing the complex motor condition with the simple control condition, both patients and controls showed a pattern of cerebral activation involving the fronto-parietal cortex and basal ganglia. Compared with controls, OCD patients presented significantly higher brain activation bilaterally in the middle frontal gyrus. After 6 months of pharmacological treatment and with clear clinical improvement, activation in the left insula and left putamen decreased significantly. CONCLUSION: In a paediatric OCD sample that was treatment na?ve and without another psychiatric disorder we showed hyperactivation of the circuits that mediate symptomatic expression of OCD. The cerebral activation decreases after treatment and clinical improvement.     

强迫症与抑郁症的脑单光子发射计算机断层扫描对照研究

目的探讨强迫症、抑郁症局部脑血流量(rCBF)特点。方法应用单光子发射计算机断层扫描(SPECT)技术,对首发且未经治疗的39例强迫症患者、36例抑郁症患者和39名正常人于静息状态下行脑血流显像。以小脑皮质的放射性计数值为参考,对局部脑血流进行半定量分析。结果强迫症组两侧前额叶、前颞叶rCBF高于正常组(P<0.01);抑郁症组两侧前额叶、枕叶、扣带回及右前颞叶、右顶叶rCBF低于正常组(P<0.05);在两侧前额叶、前颞叶、顶叶、枕叶及右后额叶、扣带回,强迫症组rCBF高于抑郁症组(P<0.05)。结论强迫症组的前额叶及前颞叶呈高灌注改变,抑郁症组脑血流普遍低灌注,SPECT技术可望作为二者鉴别诊断的客观依据之一。     

HMPAO SPECT in Parkinson''s disease before and after levodopa: correlation with dopaminergic responsiveness.

Regional cerebral perfusion was evaluated by SPECT with technetium 99m hexamethylpropyleneamine oxime (99mTc HMPAO) as a tracer in 21 patients presenting with Parkinson's disease and in 11 normal controls. In the parkinsonian patients, scans were performed both off treatment, and after levodopa, and clinical dopaminergic responsiveness was evaluated. Uptake of HMPAO by the basal ganglia was significantly decreased in the parkinsonian subjects, compared with normal controls. This reduction was seen in both responders (n = 14) and non-responders (n = 7) to dopaminergic treatment. Uptake of HMPAO by the basal ganglia rose after treatment with levodopa, but the change was similar in both responders and non-responders. By contrast a striking difference in cortical HMPAO uptake was found between responders and non-responders, with significantly lower uptake in the medial temporal and posterior parietal cortex in the non-responders. This reduction was symmetrical. Basal ganglia perfusion assessed by this technique is unlikely to be of use in the diagnosis of Parkinson's disease that is responsive to dopaminergic treatment. The presence of extensive cortical involvement on a baseline scan correlates with a lack of dopaminergic responsiveness, however, and this may be useful diagnostically.     

Provocation of obsessive-compulsive symptoms: a quantitative voxel-based meta-analysis of functional neuroimaging studies

Objective

Recent functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) studies based on the symptom provocation paradigm have explored neural correlates of the cognitive and emotional processes associated with the emergence of obsessive–compulsive disorder (OCD) symptoms. Although most studies showed the involvement of cortico–subcortical loops originating in the orbitofrontal cortex and the anterior cingulate cortex, an increased activity within numerous other regions of the brain has inconsistently been reported across studies. To provide a quantitative estimation of the cerebral activation patterns related to the performance of the symptom provocation task by OCD patients, we conducted a voxel-based meta-analysis.

Methods

We searched the PubMed and MEDLINE databases for studies that used fMRI and PET and that were based on the symptom provocation paradigm. We entered data into a paradigm-driven activation likelihood estimation meta-analysis.

Results

We found significant likelihoods of activation in cortical and subcortical regions of the orbitofrontal and anterior cingulate loops. The left dorsal frontoparietal network, including the dorsolateral prefrontal cortex and precuneus, and the left superior temporal gyrus also demonstrated significant likelihoods of activation.

Conclusion

Consistent results across functional neuroimaging studies suggest that the orbitofrontal and anterior cingulate cortices are involved in the mediation of obsessive–compulsive symptoms. Based on recent literature, we suggest that activations within the dorsal frontoparietal network might be related to patients'' efforts to resist the obsessive processes induced by the provocation task. Further research should elucidate the specific neural correlates of the various cognitive and emotional functions altered in OCD.Medical subject headings: obsessive-compulsive disorder, magnetic resonance imaging, positron-emission tomography     

Clinical features of patients with obsessive-compulsive disorder showing different pharmacological responses]

BACKGROUND: Although selective serotonin reuptake inhibitors (SSRIs) are the mainstay of pharmacological treatment for obsessive-compulsive disorder (OCD), some OCD patients do not show improvement. Sometimes, the addition of a low-dose atypical antipsychotic, such as risperidone, or olanzapine, to ongoing SSRI treatment has been shown to be effective. However, there are patients who still show no response after trials with this augmentation therapy. In the present study, we examined the clinical features of OCD patients who showed different responses to pharmacological treatment. SUBJECTS AND METHOD: Fifty OCD patients were divided into three groups according to their pharmacological responses: responders to SSRI (group A: n= 25), responders to SSRI with an atypical antipsychotic (group B: n= 15), and non-responders to both SSRI and SSRI with an atypical antipsychotic (group C: n= 10). We examined the clinical features such as age, sex, age of onset, duration of illness, types of obsessive-compulsive symptoms, severity, improvement after treatment, insight into disease, depression, comorbidity, involving family members in compulsive or ritualistic behavior, and the level of social adaptation of each OCD group. RESULTS: Twenty five patients showed a good response to SSRI monotherapy, 15 showed a response to antipsychotic augmentation, and 10 were non-responders to both SSRI and SSRI with an atypical antipsychotic. Significantly lower insight levels were observed only in group B and higher depressive levels in group C. OCD patients who were refractory to SSRI monotherapy showed comorbidity at a significantly higher frequency. OCD patients in group A showed significantly greater improvement, and group B showed inferior social adaptation after treatment. There were no significant differences in age, sex, age of onset, duration of illness, severity, involving family members in compulsive or ritualistic behavior, and social adaptation before treatment in the three OCD groups. CONCLUSION: There were differences in the clinical features of OCD patients who showed different responses to pharmacological treatment. Our results suggest that OCD is clinically and biologically heterogeneous. It may be important to divide OCD patients into subgroups for future studies.     

Rapid effects of brief intensive cognitive-behavioral therapy on brain glucose metabolism in obsessive-compulsive disorder

Brief intensive cognitive-behavioral therapy (CBT) using exposure and response prevention significantly improves obsessive-compulsive disorder (OCD) symptoms in as little as 4 weeks. However, it has been thought that much longer treatment was needed to produce the changes in brain function seen in neuroimaging studies of OCD. We sought to elucidate the brain mediation of response to brief intensive CBT for OCD and determine whether this treatment could induce functional brain changes previously seen after longer trials of pharmacotherapy or standard CBT. [(18)F]-fluorodeoxyglucose positron emission tomography brain scans were obtained on 10 OCD patients before and after 4 weeks of intensive individual CBT. Twelve normal controls were scanned twice, several weeks apart, without treatment. Regional glucose metabolic changes were compared between groups. OCD symptoms, depression, anxiety and overall functioning improved robustly with treatment. Significant changes in normalized regional glucose metabolism were seen after brief intensive CBT (P=0.04). Compared to controls, OCD patients showed significant bilateral decreases in normalized thalamic metabolism with intensive CBT but had a significant increase in right dorsal anterior cingulate cortex activity that correlated strongly with the degree of improvement in OCD symptoms (P=0.02). The rapid response of OCD to intensive CBT is mediated by a distinct pattern of changes in regional brain function. Reduction of thalamic activity may be a final common pathway for improvement in OCD, but response to intensive CBT may require activation of dorsal anterior cingulate cortex, a region involved in reappraisal and suppression of negative emotions.     

Neurobiological model of obsessive–compulsive disorder: Evidence from recent neuropsychological and neuroimaging findings

Obsessive–compulsive disorder (OCD) was previously considered refractory to most types of therapeutic intervention. There is now, however, ample evidence that selective serotonin reuptake inhibitors and behavior therapy are highly effective methods for treatment of OCD. Furthermore, recent neurobiological studies of OCD have found a close correlation between clinical symptoms, cognitive function, and brain function. A large number of previous neuroimaging studies using positron emission tomography, single‐photon emission computed tomography or functional magnetic resonance imaging (fMRI) have identified abnormally high activities throughout the frontal cortex and subcortical structures in patients with OCD. Most studies reported excessive activation of these areas during symptom provocation. Furthermore, these hyperactivities were decreased after successful treatment using either selective serotonin reuptake inhibitors or behavioral therapy. Based on these findings, an orbitofronto‐striatal model has been postulated as an abnormal neural circuit that mediates symptomatic expression of OCD. On the other hand, previous neuropsychological studies of OCD have reported cognitive dysfunction in executive function, attention, nonverbal memory, and visuospatial skills. Moreover, recent fMRI studies have revealed a correlation between neuropsychological dysfunction and clinical symptoms in OCD by using neuropsychological tasks during fMRI. The evidence from fMRI studies suggests that broader regions, including dorsolateral prefrontal and posterior regions, might be involved in the pathophysiology of OCD. Further, we should consider that OCD is heterogeneous and might have several different neural systems related to clinical factors, such as symptom dimensions. This review outlines recent neuropsychological and neuroimaging studies of OCD. We will also describe several neurobiological models that have been developed recently. Advanced findings in these fields will update the conventional biological model of OCD.     

Functional brain imaging in obsessive-compulsive disorder secondary to neurological lesions

Obsessive-compulsive disorder (OCD) may result from a range of neurological lesions in frontal and basal ganglia areas. However, relatively few studies have explored functional brain imaging in acquired OCD. METHODS: Charts of patients presenting to our Neuropsychiatry Unit where obsessive-compulsive symptoms appeared secondary to neurological lesions were reviewed. Demographic information and clinical diagnoses were collated, and brain SPECT scans reviewed. Six patients with various neurological conditions presented with OCD. All demonstrated decreased blood flow in the temporal lobes as well as cortical perfusion abnormalities in the frontal lobes (focal areas of decreased perfusion in one patient, focal areas of increased perfusion in two, and a combination of focal increased and decreased frontal perfusion in three cases). Abnormal blood flow may be seen in a number of different brain regions in acquired OCD. It is unclear whether these changes reflect primary neurological lesions or secondary changes to compensate for such damage. However, increased frontal blood flow in OCD may be hypothesized to reflect a compensatory mechanism.     

Olanzapine augmentation of fluvoxamine-refractory obsessive-compulsive disorder (OCD): a 12-week open trial

A few studies have tried antipsychotic augmentation in obsessive-compulsive disorder (OCD) patients who are non-responders to selective serotonin reuptake inhibitors. The aim of this study was to investigate the efficacy and tolerability of olanzapine addition to fluvoxamine-refractory OCD patients and to assess if a comorbid chronic tic disorder or a concomitant schizotypal personality disorder was associated with response. Twenty-three OCD non-responders to a 6-month, open-label trial with fluvoxamine (300 mg/day) entered a 3-month open-label trial of augmentation with olanzapine (5 mg/day). OC symptom change was measured with the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and the Clinical Global Impression (CGI) scale. Differences between responders and non-responders were assessed with regard to age, sex, duration of illness, baseline Y-BOCS score, and comorbidity with chronic tic disorders or schizotypal personality disorder. A significant decrease of mean Y-BOCS score between pre- and post-treatment (26. 8+/-3.0 vs. 18.9+/-5.9) was found at endpoint. Ten patients (43.5%) were rated as responders. The most common side effects were mild to moderate weight gain and sedation. In our sample, three patients (13. 04%) had a chronic motor tic disorder, and four (17.39%) had a codiagnosis of schizotypal personality disorder. Concomitant schizotypal personality disorder was the only factor significantly associated with response. It appears that augmentation of olanzapine in fluvoxamine-refractory OCD may be effective in a large number of patients, including those with comorbid schizotypal personality disorder.     

Autonomic responses and neural-cardiac coupling during individually tailored symptom provocation in obsessive-compulsive disorder

Elevated anxiety in obsessive-compulsive disorder (OCD) has been linked to cortico-limbic hyperactivation, whereas hyperarousal of the autonomous nerve system (ANS) has inconsistently been found. We investigate ANS functioning during symptom provocation with individually tailored OCD-relevant pictures in 14 unmedicated patients and 14 controls and link it to activation in brain areas involved in ANS regulation. In addition to OCD-triggers, aversive and neutral control stimuli were included. Both groups showed increased skin conductance and heart rate changes to aversive control stimuli, whereas only patients demonstrated augmented skin conductance responses to OCD-triggers. Overall ANS hyperarousal in patients relative to controls was found at trend level. Activity in limbic and paralimbic areas in OCD patients was increased to both generally aversive and OCD-relevant stimuli, whereas dorsolateral prefrontal cortex (DLPFC) hyperactivation, covarying with cardiac responses in patients but not in controls, was present for disorder-relevant triggers only. Despite the small study group, these preliminary findings suggest ANS hyperactivity during OCD symptom provocation that could reflect arousal to the perceived threatening value of OCD-triggers and might mediate elevated anxiety.     

Differential cerebral metabolic changes with paroxetine treatment of obsessive-compulsive disorder vs major depression

BACKGROUND: Serotonin reuptake inhibitors (SRIs) effectively treat both major depressive disorder (MDD) and obsessive-compulsive disorder (OCD). We compared and contrasted the functional neuroanatomical effects of SRIs in OCD and MDD as these 2 disorders occurred separately and concurrently by measuring pretreatment to posttreatment cerebral glucose metabolic changes in OCD vs MDD vs concurrent OCD + MDD. METHODS: We obtained [(18)F]fluorodeoxyglucose positron emission tomography (PET) brain scans on 25 subjects with OCD, 25 with MDD, and 16 with concurrent OCD + MDD before and after 8 to 12 weeks of treatment with paroxetine hydrochloride. Controls (n = 16) were scanned 10 to 12 weeks apart without treatment. Treatment response was defined as a more than 25% decline in OCD symptom severity, a more than 50% decline in MDD severity, and "much improved" clinical global impression. RESULTS: Although all patient groups received the same paroxetine dose for the same duration, regional metabolic changes differed significantly among diagnostic groups. Subjects with OCD alone showed significant metabolic decreases in the right caudate nucleus, right ventrolateral prefrontal cortex (VLPFC), bilateral orbitofrontal cortex, and thalamus that were not seen in any other group. Both the MDD and concurrent OCD + MDD groups showed metabolic decreases in the left VLPFC and increases in the right striatum. Treatment response was associated with a decrease in striatal metabolism in nondepressed OCD patients but with an increase in striatal activity in patients with OCD + MDD. CONCLUSIONS: Brain metabolic responses to SRIs are both disorder-specific and response-specific. They vary according to the underlying pathophysiology of the patient and the degree of symptomatic improvement.     

fMRI of neuronal activation with symptom provocation in unmedicated patients with obsessive compulsive disorder

BACKGROUND: Previous studies suggest that a neural circuit involving over-activation of cortical, paralimbic, limbic, and striatal structures may underlie OCD symptomatology, but results may have been limited by medication use in those studies. To address this, we examined the effects of symptom induction on fMRI neural activation in medication-free patients with OCD. METHODS: Seven outpatients with OCD were exposed to individually tailored provocative and innocuous stimuli during fMRI scans. Self-ratings of OCD symptoms were performed prior to each scan and after exposure to stimuli. Images were analyzed as composite data sets and individually. RESULTS: Stimulus presentation was associated with significant increases in OCD self-ratings. Significant activation was demonstrated in several regions of the frontal cortex (orbitofrontal, superior frontal, and the dorsolateral prefrontal); the anterior, medial and lateral temporal cortex; and the right anterior cingulate. Right superior frontal activation inversely correlated with baseline compulsion symptomatology and left orbitofrontal cortical activation was inversely associated with changes in OCD self-ratings following provocative stimuli. CONCLUSIONS: These results in unmedicated patients are consistent with those from previous studies with medicated patients and suggest that OCD symptomatology is mediated by multiple brain regions including the anterior cingulate as well as frontal and temporal brain regions.     

Increased error-related brain activity in pediatric obsessive-compulsive disorder before and after treatment

OBJECTIVE: The error-related negativity is a negative deflection in the event-related potential maximal approximately 50 msec after the commission of errors. The error-related negativity is generated in the anterior cingulate cortex, and both anterior cingulate cortex hyperactivity and increased error-related brain activity have been reported in adults with obsessive-compulsive disorder (OCD). However, no study to date, to the authors' knowledge, has examined error-related brain activity in pediatric patients with OCD, and no study has examined error-related brain activity in OCD both before and after treatment. METHOD: The error-related negativity was measured in 18 treatment-seeking pediatric patients with OCD and 18 age-matched comparison subjects. Of these patients, 10 returned for a second testing session after cognitive behavior therapy; 13 comparison children participated a second time after a comparable interval. RESULTS: In the pretreatment group, the error-related negativity was reliably larger in pediatric patients with OCD in relation to comparison subjects. This difference was also evident after treatment. There was no relationship between error-related negativity and symptom severity or changes in symptom severity. CONCLUSIONS: Consistent with studies in adult patients, increased error-related brain activity is evident in pediatric patients with OCD. Furthermore, increased error-related brain activity does not appear to change as a function of symptom reduction after therapy. These results suggest that an increased error-related negativity may be a trait-like marker for psychopathology and might be a useful endophenotype.     

Proton magnetic resonance spectroscopy reveals an abnormality in the anterior cingulate of a subgroup of obsessive–compulsive disorder patients

Numerous neuroimaging studies have suggested that obsessive–compulsive disorder (OCD) patients had a neurobiological abnormality in the frontal-subcortical circuits. On the other hand, there are distinct differences in the responses to pharmacological treatment among OCD patients. In the present study, we measured the concentration of N-acetyl aspartate (NAA), a putative marker of neuronal viability, with proton magnetic resonance spectroscopy (MRS) in OCD patients with different pharmacological responses. Participants comprised 20 patients and 26 healthy control subjects. OCD patients were divided into three groups according to the pharmacological response; responders to a selective serotonin reuptake inhibitor (SSRI) (group A: n = 7), responders to SSRI with an atypical antipsychotic (group B: n = 8) and non-responders to either SSRI or SSRI with an atypical antipsychotic (group C: n = 5). Short echo proton MRS was used to measure NAA concentrations in the anterior cingulate, the left basal ganglia and the left prefrontal lobe of subjects. A significantly lower NAA concentration was observed only in group B compared with control subjects in the anterior cingulate. Our results suggest that a subgroup of OCD patients who respond to an SSRI with an atypical antipsychotic have distinct biological abnormalities in the anterior cingulate.