Functional MRI correlates of visuospatial planning in out-patient depression and anxiety.

OBJECTIVE: Major depressive disorder (MDD) has been associated with executive dysfunction and related abnormal prefrontal activity, whereas the status of executive function (EF) in frequently co-occurring anxiety disorders and in comorbid depression-anxiety is unclear. We aimed to study functional MRI correlates of (visuospatial) planning in MDD and anxiety disorders and to test for the effects of their comorbidity. METHOD: Functional MRI was employed during performance of a parametric Tower of London task in out-patients with MDD (n = 65), MDD with comorbid anxiety (n = 82) or anxiety disorders without MDD (n = 64), and controls (n = 63). RESULTS: Moderately/severely depressed patients with MDD showed increased left dorsolateral prefrontal activity as a function of task load, together with subtle slowing during task execution. In mildly depressed and remitted MDD patients, in anxiety patients, and in patients with comorbid depression-anxiety, task performance was normal and no activation differences were observed. Medication use and regional brain volume were not associated with altered visuospatial planning. CONCLUSION: Prefrontal hyperactivation during high planning demands is not a trait characteristic, but a state characteristic of MDD without comorbid anxiety, occurring independent of SSRI use. Disturbances in planning or the related activation are probably not a feature of anxiety disorders with or without comorbid MDD, supporting the current distinction between anxiety disorders and depression.

Differential frontal-striatal and paralimbic activity during reversal learning in major depressive disorder and obsessive-compulsive disorder.

BACKGROUND: Several lines of research suggest a disturbance of reversal learning (reward and punishment processing, and affective switching) in patients with major depressive disorder (MDD). Obsessive-compulsive disorder (OCD) is also characterized by abnormal reversal learning, and is often co-morbid with MDD. However, neurobiological distinctions between the disorders are unclear. Functional neuroimaging (activation) studies comparing MDD and OCD directly are lacking. METHOD: Twenty non-medicated OCD-free patients with MDD, 20 non-medicated MDD-free patients with OCD, and 27 healthy controls performed a self-paced reversal learning task in an event-related design during functional magnetic resonance imaging (fMRI). RESULTS: Compared with healthy controls, both MDD and OCD patients displayed prolonged mean reaction times (RTs) but normal accuracy. In MDD subjects, mean RTs were correlated with disease severity. Imaging results showed MDD-specific hyperactivity in the anterior insula during punishment processing and in the putamen during reward processing. Moreover, blood oxygen level-dependent (BOLD) responses in the dorsolateral prefrontal cortex (DLPFC) and the anterior PFC during affective switching showed a linear decrease across controls, MDD and OCD. Finally, the OCD group showed blunted responsiveness of the orbitofrontal (OFC)-striatal loop during reward, and in the OFC and anterior insula during affective switching. CONCLUSIONS: This study shows frontal-striatal and (para)limbic functional abnormalities during reversal learning in MDD, in the context of generic psychomotor slowing. These data converge with currently influential models on the neuropathophysiology of MDD. Moreover, this study reports differential neural patterns in frontal-striatal and paralimbic structures on this task between MDD and OCD, confirming previous findings regarding the neural correlates of deficient reversal learning in OCD.

Distinct brain systems underlie the processing of valence and arousal of affective pictures.

Valence and arousal are thought to be the primary dimensions of human emotion. However, the degree to which valence and arousal interact in determining brain responses to emotional pictures is still elusive. This functional MRI study aimed to delineate neural systems responding to valence and arousal, and their interaction. We measured neural activation in healthy females (N=23) to affective pictures using a 2 (Valence) x 2 (Arousal) design. Results show that arousal was preferentially processed by middle temporal gyrus, hippocampus and ventrolateral prefrontal cortex. Regions responding to negative valence included visual and lateral prefrontal regions, positive valence activated middle temporal and orbitofrontal areas. Importantly, distinct arousal-by-valence interactions were present in anterior insula (negative pictures), and in occipital cortex, parahippocampal gyrus and posterior cingulate (positive pictures). These data demonstrate that the brain not only differentiates between valence and arousal but also responds to specific combinations of these two, thereby highlighting the sophisticated nature of emotion processing in (female) human subjects.

Neuropsychological investigation into the carcinoid syndrome.

RATIONALE: In patients suffering from metastatic carcinoid tumors, chronic disturbances of serotonergic metabolism are frequently present. Serotonin is supposed to influence a range of cognitive functions. OBJECTIVES: The present study evaluated the cognitive performance of carcinoid patients. METHODS: In 14 patients with proven carcinoid syndrome, neuropsychological functioning was studied. Visual search, sustained attention, set shifting ability and spatial working memory were assessed using tests from the CANTAB neuropsychological battery. This was compared with the performance of matched healthy controls. RESULTS: Plasma tryptophan levels were lower than controls. Patients showed an enhanced ability to learn new stimulus-response associations. Sustained visual attention, however, was impaired. CONCLUSION: Cognitive patterns were different from those found in depressive patients and partly mimicked those found in tryptophan depletion experiments. Further investigation has to point out the role of serotonergic changes in the accomplishment of affective states.

Decision making performance in obsessive compulsive disorder.

BACKGROUND: Neuro-imaging studies in OCD report the orbitofrontal cortex to be functionally abnormal. As these areas are presumed to be involved in decision making, studying this behavior in OCD may provide further insight into the cognitive deficits accompanying the disorder. METHODS: Performance of 27 drug-free OCD patients and 26 healthy volunteers was compared on the decision making task of Bechara et al. [Cognition, 50 (1994) 7-15]. RESULTS: OCD patients and volunteers displayed comparable decision-making behavior. Within OCD patients, risk taking was independently related to both anxiety and OCD severity. LIMITATIONS: Results must be regarded as preliminary, due to the limited number of OCD patients included and the lack of a clinical control group. CONCLUSIONS: Although VMpfc function is not generally impaired, it seems to be involved in OCD; possibly in another way than could be measured with this task. CLINICAL RELEVANCE: Clarification of cognitive distortions underlying OCD may guide development of new strategies for cognitive-behavioral therapy.

Five-minute recordings of heart rate variability in obsessive-compulsive disorder, panic disorder and healthy volunteers.

BACKGROUND: Recent studies have used spectral analysis of heart rate variability (HRV) to study autonomous nervous system (ANS) function in panic disorder (PD). Most studies reported a reduced HRV in resting PD patients, suggesting increased sympathetic and decreased parasympathetic tone. In obsessive-compulsive disorder (OCD) inconsistent findings have been reported on ANS function and to date no studies have been carried out with spectral analysis of HRV. In this HRV study we compared ANS function in patients with PD, OCD and normal controls. METHODS: Standardized HRV measurement was carried out in 24 PD patients, 26 OCD patients and 24 age-matched normal controls. All patients were drug free. As this comparison yielded unexpected results, the PD and normal control samples were enlarged to 53 and 54 subjects, respectively, to verify our first measurement. RESULTS: OCD patients were not characterized by a reduced HRV, as compared to normal controls. This was also found in PD patients, even in the enlarged sample. CONCLUSIONS: HRV analysis in patients with OCD or PD showed that these patients were not characterized by ANS abnormalities, as no evidence was found of diminished HRV in a large sample of resting OCD and PD patients, measured sitting on a hospital bed.

Neuropsychological performance of OCD patients before and after treatment with fluoxetine: evidence for persistent cognitive deficits.

BACKGROUND: There is an ongoing debate about the nature of executive dysfunction that accompanies obsessive-compulsive disorder (OCD). One reason for this may be that state-related factors, such as use of medication or co-morbid symptoms, confound with task performance. This study tried to isolate trait- from state-dependent cognitive impairments by examining variability of cognition following treatment. METHOD: Nineteen OCD patients were tested on the Cambridge Neuropsychological Test Automated Battery (CANTAB) before and after treatment with fluoxetine. Their pattern of performance was compared to the one observed in healthy volunteers (N = 24). RESULTS: OCD patients displayed impairments in planning ability, spatial memory and motor speed that persisted after clinical improvement. With treatment, OCD performance diverged from that of controls on measures of focused attention and strategic ability. However, these effects were rather mild as they did not entail a significant deterioration of performance within the OCD sample. CONCLUSIONS: Our data suggest that cognitive impairments in OCD are not secondary to symptoms and therefore form a trait feature of the disorder. The nature of the deficits refers to a chronic dysfunction of the dorsolateral-striatal circuit. The minor effects of treatment on task performance is in line with recent evidence that serotonin mediates cognitive functions of orbitofrontal cortex to a greater extent than those associated with dorsolateral prefrontal regions.