A study of parallel implicit and explicit information processing in patients with obsessive-compulsive disorder

OBJECTIVE: This study examined implicit sequence learning in patients with obsessive-compulsive disorder (OCD) under dual-task conditions. Frontal-striatal networks support implicit learning and are implicated in the pathophysiology of OCD. Neuroimaging data suggest that during implicit learning, OCD patients use neural systems normally active during explicit learning to compensate for striatal dysfunction. METHOD: The authors examined implicit sequence learning in 25 OCD patients and 25 healthy comparison subjects using a dual-task paradigm, with subjects simultaneously engaged in an explicit memory task and an implicit learning task. They predicted that implicit learning in OCD subjects would be disrupted because concurrent explicit information-processing demands would prevent use of compensatory processes. RESULTS: OCD patients failed to show evidence of implicit learning and exhibited a significant deficit in comparison with healthy subjects. CONCLUSIONS: These results are consistent with the hypothesis that concurrent explicit and implicit information-processing demands interfere with implicit learning in OCD patients.     

Implicit sequence learning in obsessive-compulsive disorder: further support for the fronto-striatal dysfunction model.

BACKGROUND: Obsessive-compulsive disorder (OCD) is conceived as a disease that implicates dysfunctions in fronto-striatal brain systems. According to this model, performance deficits observed in patients with lesions in these brain areas are hypothesized to be present also in OCD patients. Implicit procedural learning, which refers to the acquisition of motor or nonmotor skills by practice, is one candidate function to test this prediction. METHODS: The serial reaction time task was used to assess implicit sequence learning of 33 patients with a diagnosis of OCD and 27 healthy control participants. In addition, explicit (i.e., conscious) knowledge of the sequence was determined. A subgroup of 24 patients was reassessed after intensive cognitive-behavioral psychotherapy. RESULTS: Implicit sequence learning was significantly reduced in the OCD group by 41%, while explicit learning and verbal abilities were unaffected. The deficit remained stable across time, although symptoms remitted substantially. Depressive symptoms did not account for the finding. Partial explicit knowledge of the sequence was not a predictor of the amount of implicit learning. CONCLUSIONS: Reduced implicit learning appears to be a dissociable trait of OCD patients. The results confirm previous findings and add supportive evidence for the fronto-striatal dysfunction model of OCD.     

Brain activation during implicit sequence learning in individuals with trichotillomania

Trichotillomania (TTM) may be related to obsessive-compulsive disorder (OCD) and other neuropsychiatric conditions characterized by cortico-striatal dysfunction. Functional imaging studies of OCD using an implicit learning task have found abnormalities in striatal and hippocampal activation. The current study investigated whether similar abnormalities occur in TTM. Functional MRI and the serial reaction time (SRT) task were used to assess striatal and hippocampal activation during implicit sequence learning in TTM and healthy control (HC) subjects. The results for 20 age- and education-matched participants (10 TTM, 10 HC) are reported. In comparison with HC participants, those with TTM exhibited no significant differences in implicit learning, or in activation within the striatum, hippocampus, or other brain regions. The current findings do not provide evidence for cortico-striatal dysfunction in TTM. Future studies directly comparing OCD and TTM subjects are warranted to confirm the specificity of abnormal striatal and hippocampal findings during implicit sequence learning in OCD.     

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.     

Functional magnetic resonance imaging evidence for a lack of striatal dysfunction during implicit sequence learning in individuals with animal phobia

OBJECTIVE: This study investigated the neural substrates of implicit sequence learning in subjects with and without small animal phobia, in a follow-up to analogous studies of obsessive-compulsive disorder (OCD). METHOD: Ten subjects with specific phobia and 10 healthy comparison subjects were studied by using a serial reaction time task paradigm and functional magnetic resonance imaging. RESULTS: A main effect of condition (implicit sequence learning versus random sequence) was observed across diagnostic groups in the right striatum, as well as in other regions. In the striatum, the a priori region of interest, there were no significant effects of diagnosis or the interaction of diagnosis and condition. CONCLUSIONS: Brain activation in the striatum of subjects with specific phobia does not significantly differ from that of normal comparison subjects during implicit sequence learning. This suggests different pathophysiological mechanisms for specific phobia in contrast to OCD, in which deficient striatal recruitment has been reproducibly found with this paradigm. This approach offers promise for demonstrating diagnostic specificity across different neuropsychiatric disorders based on the presence or absence of deficient striatal activation.     

Functional magnetic resonance imaging study of regional brain activation during implicit sequence learning in obsessive-compulsive disorder.

BACKGROUND: Corticostriatal circuitry has been implicated in the pathophysiology of obsessive-compulsive disorder (OCD). The serial reaction time (SRT) task, a paradigm that tests implicit sequence learning, has been used with imaging to probe striatal function. Initial studies have indicated that OCD patients exhibit deficient striatal activation and aberrant hippocampal recruitment compared with healthy control (HC) subjects. Here, we used the SRT and functional magnetic resonance imaging (fMRI) to replicate prior results in a larger sample and to test for relationships between regional activation and OCD symptom dimensions. METHODS: Using SPM99, fMRI-SRT data from 12 OCD and 12 matched HC subjects were analyzed. Symptom dimensions followed a four-factor model scored on a 0- to 10-point scale. RESULTS: For the implicit learning versus random contrast, group by condition interactions revealed aberrant recruitment within the hippocampus as well as orbitofrontal cortex (OCD > HC) but no striatal group differences. However, an inverse correlation was found between striatal activation and specific symptom factors. CONCLUSIONS: These results replicate previous smaller studies showing aberrant hippocampal recruitment in OCD during SRT performance. Although findings of deficient striatal activation in OCD were not replicated, correlation results suggest that this inconsistency may be attributable to differences among OCD symptom dimensions.     

Selective cognitive deficits in obsessive-compulsive disorder compared to panic disorder with agoraphobia

OBJECTIVE: Visual-spatial and executive functions deficits have been reported in obsessive-compulsive disorder (OCD). We investigated their specificity comparing cognitive function in OCD, panic disorder with agoraphobia (PD/A) and controls by a comprehensive neuropsychological battery. METHOD: Fifty-five subjects (25 OCD, 15 PD/A, 15 controls) without current depressive episode underwent structured clinical interview for DSM-IV, Yale-Brown Obsessive Compulsive Scale, Hamilton Anxiety Rating Scale, Hamilton Depression Rating Scale. Neuropsychological battery assessed: executive functions, visual discrimination, spatial memory and learning, verbal memory, general intellectual functioning. RESULTS: OCD showed controlled fluency, visual-spatial construction, learning and memory deficits; PD/A spatial learning impairment. OCD was discriminated from PD/A and controls by three tests scores, predicting group membership for 76.4% of the cases. CONCLUSION: Visual-constructive and controlled fluency deficits seem specific in OCD, while the spatial learning deficit, shared with PD patients, may not be disorder-specific, but anxiety-related. Results support the proposed ventral frontal-striatal circuit involvement in OCD.     

Anterior limb lesions in bilateral internal capsules and memory function in patients with refractory obsessive-compulsive disorder

BACKGROUND: Previous studies have shown that lesions in the anterior limb of the internal capsule contribute to obsessive-compulsive symptoms in patients with refractory obsessive-compulsive disorder (OCD). However, few reports have addressed the effects of lesions in the anterior limb of the internal capsule on cognition, learning, and memory functions in patients with refractory OCD.OBJECTIVE: To investigate the degree of damage to memory tasks in refractory OCD patients following lesions to the anterior limb of the internal capsule. DESIGN, TIME AND SETTING: A case-controlled, observational study was performed at the Department of Functional Neurosurgery, Ruijin Hospital, Shanghai Jiao-Tong University, China from May 2007 to March 2008. PARTICIPANTS: A total of 10 refractory OCD patients were admitted to the Department of Functional Neurosurgery, Ruijin Hospital, Shanghai Jiao-Tong University, China from May 2007 to March 2008 and were recruited for this study. The OCD patients were of equal gender, with an average age of (25.1 ± 9.6) years. An additional 10 healthy volunteers were enrolled from a community of Shanghai City as controls; they were of equal gender and aged (25.1 ± 8.6) years. METHODS: A total of 10 refractory OCD patients were subjected to lesions in the anterior limbs of the bilateral internal capsules. Wechsler Memory Scale-Chinese Revision (WMS-CR, as a task of explicit memory) and the Nissen Version (serial reaction time task) software (SRTT, as a task of implicit memory) were applied to determine memory functions and learning performance in pre- and post-operative OCD patients and controls. MAIN OUTCOME MEASURES: WMS scores, reaction time in SRTT, and Yale-Brown obsessive compulsive scale scores were measured in pre- and post-operative OCD patients and controls. RESULTS: Compared to controls, the pre-operative OCD patients exhibited reduced memory task scores (P = 0.005), whereas scores for reciting numbers of backwards digits were greater (P = 0.000). Figure recall and associative memory were less in OCD patients at 1 week following surgery than in the pre-operative OCD patients (P = 0.042, P = 0.002, respectively). Reaction time in implicit SRTT was significantly longer in pre-operative OCD patients compared with controls and post-operative OCD patients (P = 0.01, P = 0.03, respectively). These results suggested ameliorated SRTT following neurosurgery. Yale-Brown Obsessive Compulsive Scale results revealed significantly improved OCD following lesions in the internal capsule (P = 0.04). Some post-operative OCD patients suffered from deficits in short-term memory and implicit memory. CONCLUSION: Lesions in anterior limbs of bilateral internal capsules improve obsessive- compulsive symptoms and implicit memory in OCD patients, but result in aggravated short-term memory deficits.     

Implicit and explicit memory in patients with obsessive-compulsive disorder: an event-related potential study

The implicit and explicit memory in patients with obsessive-compulsive disorder (OCD) was investigated using the event-related potential (ERP). For the assessment of implicit memory, a lexical decision task was administered. Among a total of 320 words and 140 non-words, 200 words were repeated, while the remaining 120 words and the 140 non-words were not repeated. For explicit memory, a continuous recognition task was administered, in which 280 words were repeated and 100 were not repeated. On the recognition task, both the controls and OCD patients showed more positivity to the old words than to the new words during the 200-600 ms period post-stimulus. Both groups showed faster response time to the old words than to the new words. On the lexical decision task, the controls showed the old/new effect during the 200-500 ms period post-stimulus, while the OCD patients did not. However, OCD patient showed faster response time to the old words than to the new words, although OCD patients showed prolonged response times to the old words compared to the controls. These results indicate that OCD patients have preserved explicit and implicit memory. The absence of old/new effect on ERP in OCD patients was discussed in terms of dysfunction of frontostriatal system, which plays an important role in both OCD and implicit memory.     

The role of the basal ganglia and its cortical connections in sequence learning: Evidence from implicit and explicit sequence learning in Parkinson's disease

Implicit (unconscious/incidental) and explicit (conscious/intentional) learning are considered to have distinct neural substrates. It is proposed that implicit learning is mediated by the basal ganglia (BG), while explicit learning has been linked to the medial temporal lobes (MTL). To test such a dissociation we investigated implicit and explicit sequence learning in Parkinson's disease (PD), a disorder characterized by striatal dysfunction. We studied both implicit and explicit learning of a 12-item sequence of target locations in 13 PD patients and 15 age-matched controls. In the implicit sequence learning task all participants completed 10 blocks of a probabilistic serial reaction time (SRT) task in which they were exposed to the sequence without explicit knowledge of it. Participants also completed between 1 and 10 blocks of an explicit sequence learning task in which the sequence was learned deliberately by trial-and-error. Both implicit and explicit sequence learning were significantly impaired in PD patients compared to controls. The results indicate that, in addition to playing a role in implicit sequence learning, the BG and its frontal projections are also involved in explicit sequence learning.     

Shape deformity of the corpus striatum in obsessive-compulsive disorder

Volumetric changes of striatal structures based on magnetic resonance imaging (MRI) have been inconsistent in patients with obsessive-compulsive disorder (OCD) due to methodological limitations. The purpose of this study was to investigate shape deformities of the corpus striatum in patients with OCD. We performed 3-D shape deformation analysis of the caudate nucleus, the putamen, and the globus pallidus in 36 patients with OCD and 36 healthy normal subjects. Shape analysis showed deformity of the striatal structures, especially the caudate nucleus. Outward deformities in the superior, anterior portion of the bilateral caudate were observed in patients with OCD. In addition, an outward deformity in the inferior, lateral portion of the left putamen was also detected. These results suggest that patients with OCD have shape deformities of the corpus striatum, especially the caudate nucleus, compared with healthy normal subjects, and that shape analysis may provide an important complement to volumetric MRI studies in investigating the pathophysiology of OCD.     

Comorbid major depression in obsessive-compulsive disorder patients

Although major depressive disorder (MDD) has been consistently considered the most frequent complication of obsessive-compulsive disorder (OCD), little is known about the clinical characteristics of patients with both disorders. This study assessed 815 Brazilian OCD patients using a comprehensive psychiatric evaluation. Clinical and demographic variables, including OCD symptom dimensions, were compared among OCD patients with and without MDD. Our findings showed that prevalence rates of current MDD (32%) and lifetime MDD (67.5%) were similar for both sexes in this study. In addition, patients with comorbid MDD had higher severity scores of OCD symptoms. There was no preferential association of MDD with any particular OCD symptom dimension. This study supports the notion that depressed OCD patients present more severe general psychopathology.     

Approach and avoidance learning in obsessive-compulsive disorder

Background: Current neurobiological models of obsessive–compulsive disorder (OCD) propose a dysfunction of cortico‐striato‐thalamo‐cortical circuits that leads to enhanced activity in frontal and striatal brain regions. In accordance with that, OCD patients show alterations in learning and flexible adaptation to changing task requirements. The purpose of this study was to examine feedback‐based learning and to investigate whether learning from positive and negative feedback is differentially altered in OCD. Methods: In this study, 18 OCD patients and 18 healthy comparison subjects conducted a probabilistic selection task. The task consisted of an acquisition and a test phase and allowed disentangling the extent of learning based on positive and negative feedback. Results: Groups did not differ during probabilistic feedback learning in the acquisition phase. In the test phase, OCD patients showed a negative learning bias in contrast to comparison subjects who showed a positive learning bias. Patients were better at avoiding stimuli that were initially associated with negative outcomes than at approaching stimuli that were associated with positive feedbacks. This interaction was also found for reaction times in that patients were faster in avoiding negative and slower in approaching positive stimuli. Conclusion: Enhanced avoidance learning was found in OCD patients that points to exaggerated anticipation and avoidance of aversive outcomes. Further studies are required to investigate whether neurobiological mechanisms, such as dopaminergic signaling or outcome processing, in the orbitofrontal cortex relate to enhanced negative learning in OCD. Depression and Anxiety, 2011. © 2010 Wiley‐Liss, Inc.     

Impairment of incidental memory for frequency in patients with obsessive-compulsive disorder.

The aim of our study was to investigate whether patients with obsessive-compulsive disorder (OCD) have impaired incidental memory for frequency. Fifty-four subjects (27 OCD patients and 27 matched control subjects) performed a task assessing estimation of occurrence of previously heard words. Performance on this task was compared with other intentional verbal memory tasks (recognition, recall and learning of common words). We also correlated memory for frequency with frontal lobe tests (Wisconsin Card Sorting Test, Trail Making Tests A and B, and verbal fluency). Performance on incidental learning of frequency was significantly worse in the OCD group than in control subjects. Other verbal memory measures did not show significant differences. Performance in the frequency task correlated with verbal fluency. Although intentional verbal memories are normal in OCD patients, incidental memory for frequency is impaired, suggesting that prefrontal systems are involved in OCD.     

Everyday memory functioning in obsessive- compulsive disorder.

Memory performance in obsessive-compulsive disorder (OCD) is discussed as a pathogenetic risk factor for the emergence of OCD, particularly checking compulsions. At present, however, findings are mixed and little is known about memory performance in tasks relevant to everyday functioning in patients with OCD. For the present study, memory performance was assessed in 31 patients diagnosed with OCD and 33 healthy controls with the Rivermead Behavioural Memory Test (RBMT), which covers a wide range of verbal and nonverbal memory components as well as prospective memory. OCD patients performed comparably to healthy controls on the memory task for verbal, nonverbal, and prospective memory (p > .1). According to norm values, memory performance was unimpaired in most OCD patients. The present findings further challenge a broad account of the "memory deficit" hypothesis of OCD and compulsive checking, respectively.     

The role of the striatum in processing language rules: evidence from word perception in Huntington's disease

On the assumption that linguistic faculties reflect both lexical storage in the temporal cortex and combinatorial rules in the striatal circuits, several authors have shown that striatal-damaged patients are impaired with conjugation rules while retaining lexical knowledge of irregular verbs [Teichmann, M., Dupoux, E., Kouider, S., Brugières, P., Boissé, M. F., Baudic, S., Cesaro, P., Peschanski, M., & Bachoud-Lévi, A. C. (2005). The role of the striatum in rule application. The model of Huntington's disease at early stage. Brain, 128, 1155-1167; Ullman, M. T., Corkin, S., Coppola, M., Hickok, G., Growdon, J. H., Koroshetz, W. J., & Pinker, S. (1997). A neural dissociation within language: Evidence that the mental dictionary is part of declarative memory, and that grammatical rules are processed by the procedural system. Journal of Cognitive Neuroscience, 9, 266-276]. Yet, such impairment was documented only with explicit conjugation tasks in the production domain. Little is known about whether it generalizes to other language modalities such as perception and whether it refers to implicit language processing or rather to intentional rule operations through executive functions. We investigated these issues by assessing perceptive processing of conjugated verb forms in a model of striatal dysfunction, namely, in Huntington's Disease (HD) at early stages. Rule application and lexical processes were evaluated in an explicit task (acceptability judgments on verb and nonword forms) and in an implicit task (lexical decision on frequency-manipulated verb forms). HD patients were also assessed in executive functions, and striatal atrophy was evaluated with magnetic resonance imaging (bicaudate ratio). Results from both tasks showed that HD patients were selectively impaired for rule application but lexical abilities were spared. Bicaudate ratios correlated with rule scores on both tasks, whereas executive parameters only correlated with scores on the explicit task. We argue that the striatum has a core function in linguistic rule application generalizing to perceptive aspects of morphological operations and pertaining to implicit language processes. In addition, we suggest that the striatum may enclose computational circuits that underpin explicit manipulation of regularities.     

Ghrelin and leptin levels in patients with obsessive-compulsive disorder

To examine the importance of ghrelin and leptin in the pathogenesis of obsessive-compulsive disorder (OCD), we measured serum ghrelin and leptin levels, lipid profile and body mass index (BMI) in 43 patients with OCD and 20 healthy controls. The patients were divided into two subgroups according to whether DSM-IV OCD was accompanied with major depressive disorder (MDD) (OCD+MDD) or not (OCD-MDD). There was no statistically significant difference in ghrelin and leptin levels between groups. The OCD+MDD group had a trend of higher ghrelin levels and lower leptin levels than the OCD-MDD and control groups. There was a negative correlation between change in serum ghrelin and leptin levels only in the OCD+MDD group. Neither ghrelin nor leptin showed any correlation with severity of MDD and OCD. In conclusion, our results suggest that OCD is not associated with leptin or ghrelin levels. More comprehensive and detailed studies are needed to decipher the exact role of ghrelin and leptin in OCD.     

Patients with Parkinson's disease learn to control complex systems via procedural as well as non-procedural learning

The striatum is considered to mediate some forms of procedural learning. Complex dynamic control (CDC) tasks involve an individual having to make a series of sequential decisions to achieve a specific outcome (e.g. learning to operate and control a car), and they involve procedural learning. The aim of this study was to test the hypothesis that patients with Parkinson's disease who have striatal dysfunction, are impaired on CDC tasks only when learning involves procedural learning. 26 patients with Parkinson's disease (PD) and 26 age-matched controls performed two CDC tasks, one in which training was observation-based (non-procedural), and a second in which training was action-based (procedural). Both groups were able to control the system to a specific criterion equally well, regardless of the training condition. However, when reporting their knowledge of the underlying structure of the system, both groups showed poorer accuracy when learning took place through observation-based compared with action-based training. Moreover, the controls' accuracy in reporting the underlying structure of the systems was superior to that of PD patients. The findings suggest that the striatal dysfunction in Parkinson's disease is not associated with impairment of procedural learning, regardless of whether the task involved procedural learning or not. It is possible that the learning and performance on CDC tasks are mediated by perceptual priming mechanisms in the neocortex.     

Comorbidity in obsessive-compulsive disorder: focus on depression

The authors investigated the comorbidity between obsessive-compulsive disorder (OCD) and other psychiatric disorders in a group of 154 outpatients. The influence of an associate major depressive disorder (MDD) on the outcome of treatment with clomipramine was examined in a subgroup of 52 patients. The results showed that MDD was the most frequent disorder associated with OCD (almost 20% of the patients), followed by generalized anxiety and panic disorder. The co-presence of depression delayed the effect of clomipramine.     

Dissociation of decisions in ambiguous and risky situations in obsessive–compulsive disorder

Patients with obsessive–compulsive disorder (OCD) often show deficits in everyday decision-making, a phenomenon which is leading to a growing research interest in neuropsychological aspects of decision-making in OCD. Previous investigations of OCD patients demonstrated deficits in the Iowa Gambling Task (IGT), a decision-making task with implicit rules. Results were interpreted as reflecting orbitofrontal cortex dysfunctions observed in OCD. The aim of the present study is to investigate OCD patients' performance on the Game of Dice Task (GDT), a decision-making task with explicit and stable rules. For this purpose, 23 patients with OCD and 22 healthy comparison subjects were examined with the GDT and the IGT as well as with tests of executive functioning. While patients performed worse than comparison subjects on the IGT, they were unimpaired on the GDT and executive functioning tasks. Results further emphasize dysfunctions of the orbitofrontal cortex, but indicate intact functioning of the dorsolateral prefrontal cortex in patients with OCD.