Brain imaging correlates of cognitive impairment in depression (original) (raw)
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Psychological Medicine, 1997
Introduction. Patients with unipolar depression show impaired performance on the Tower of London planning task. Positron emission tomography, which has previously identified resting state blood flow abnormalities in depression, was used to investigate neural activity associated with performance of this task in depressed patients and normal controls. Methods. Six patients with unipolar depression and six matched controls were scanned while performing easy and hard Tower of London problems in a one-touch computerized paradigm and while performing a perceptuomotor control task. Results. The patients in this study showed an expected task-related performance deficit compared with normal subjects. In normal subjects, the task engaged a network of prefrontal cortex, anterior cingulate, posterior cortical areas and subcortical structures including the striatum, thalamus and cerebellum. Depressed patients failed to show significant activation in the cingulate and striatum ; activation in the other prefrontal and posterior cortical regions was significantly attenuated relative to controls. Crucially, patients also failed to show the normal augmentation of activation in the caudate nucleus, anterior cingulate and right prefrontal cortex associated with increasing task difficulty. Conclusions. These findings provide evidence for cingulate, prefrontal and striatal dysfunction associated with impaired task performance in depression. The present results are consistent with a central role of cingulate dysfunction in depression as well as suggesting impaired frontostriatal function.
Cognitive impairment and fMRI in major depression
Neurotoxicity Research, 2006
Cognitive impairment in depression may be one of the more practically important aspects of the illness, responsible for much of its morbidity. It also is at the heart of its psychopathology, may contribute to strategies of treatment, and may give us a more easily quantifiable measure of impaired function to correlate with brain activity. Functional magnetic resonance imaging (fMRI) is ideally suited to examine brain function in depression. It has the correct time window to repeatedly sample cognitive task performance; it does not require exposure to radioactive tracers and can therefore be repeated many times; it also can be linked with high resolution structural images acquired in the same imaging session that help identify the regions of activation and support the spatial transformation necessary to compare the scans of different subjects. fMRI has already produced a series of consistent results in depression, identifying increased activity of rostral anterior cingulate and other medial prefrontal structures during effortful tasks and on occasion also increased dorsolateral prefrontal activity, suggesting increased possibly compensatory activity to maintain task performance. Investigating the interplay between limbic (orbitomedial) and 'cognitive' dorsolateral structures clearly has the potential to clarify important illness mechanisms of depressive illness.
Limbic over-activity in depression during preserved performance on the n-back task
NeuroImage, 2006
The profile of cognitive dysfunction observed in patients with major depressive disorder (MDD) may be partially attributed to a deficit in the central executive component of working memory (WM). This could be the consequence of a functional deficit in regions of cortex that are associated with WM function in healthy adults. In order to investigate this assertion, ten patients with a diagnosis of MDD and ten matched healthy controls undertook a parametric WM task (i.e. the n-back task) during the acquisition of blood oxygen level dependent echo planar magnetic resonance images (BOLD EPI fMRI). There was no significant difference in the behavioral performance of depressed patients and controls. This was true for both accuracy and reaction time on the nback task. Random effects analysis of the functional imaging data (using SPM99) revealed a significant difference in load-dependent activation in the medial orbitofrontal cortex/rostral anterior cingulate between patients and controls (cluster size (K E)/volume = 128/1024 mm 3 , P (corrected) = 0.025). While both participant groups exhibited a significant decrease in activation in this region with increased task difficulty, the magnitude of this decrease was smaller in patients with MDD than in controls. Therefore, this study implies that the performance of WM tasks is associated with a dysfunctional activation of the medial orbitofrontal and rostral anterior cingulate cortex in MDD. The study thus offers a rationale for explaining depressive cognitive impairment by the abnormal fronto-limbic activation found in clinical depression.
Human Brain Mapping, 2008
Objective: Previous research has provided conflicting information regarding the pattern of brain activation associated with cognitive performance in depressed people. We aimed to assess brain activation related to cognitive performance during planning and working memory tasks. Method: fMRI scans were conducted using a modified Tower of London task and a 2-back task in 13 patients with major depressive disorder and a matched control group. Results: Task performance was impaired in the depressed group on the Tower of London task but there were no differences between the groups in task performance on the n-back task. The patient group showed widespread increased brain activation in both tasks. There was considerable overlap in increased activation between the two tasks, especially in right prefrontal cortical regions. Conclusions: Patients with depression exhibit increased brain activation, especially in right prefrontal regions, across several types of cognitive task activity. Patients with depression may recruit greater brain regions to achieve similar or even poorer task performance than control subjects. Hum Brain Mapp, 2008. © 2007 Wiley-Liss, Inc.
The Role of Functional Neuroimaging in the Neuropsychology of Depression
2010
Depressed individuals show impaired performance in tests of attention and concentration. They also exhibit PET resting state abnormalities in dorsal prefrontal cortex and anterior cingulate, regions known to be substrates of attentional processing in healthy individuals. This chapter outlines a strategy to study neuropsychological mechanisms in emotional disorders using functional imaging methods. It reviews evidence strongly implicating the dorsolateral prefrontal cortex, particularly in the right hemisphere, as a key brain structure in emotion/cognition interactions in negative mood states. It will be argued that this neocortical region is a crucial convergence zone, being the substrate of sustained attention to the external environment, and the main target of limbic-cortical in¯uences during changes in mood state across health and disease.
Cognitive control and brain resources in major depression: An fMRI study using the n-back task
NeuroImage, 2005
Several neuroimaging studies have reported dhypofrontalityT in depressed patients performing a cognitive challenge compared to control subjects. Hypofrontality in depression is likely associated with an impaired behavioral performance. It is unclear whether this impaired performance is the consequence or the cause of hypofrontality. Consequently, we proposed to compare the cerebral activity of depressed patients and healthy subjects while controlling for the level of performance. Ten individuals meeting DSM-IV criteria for Major Depression and 10 healthy controls were tested with a verbal version of the n-back task during fMRI scanning. The working memory load was manipulated across the experiment (1,2,3-back) to increase the cognitive demands. fMRI data were acquired on a 1.5-T GE scanner and analyzed using SPM99 software. We did not find any difference between groups in both performance and reaction times for each level of complexity of the n-back task. Depressed patients and control subjects showed bilateral activation of the lateral prefrontal cortex, anterior cingulate and parietal cortex. Activation of these regions was modulated by the complexity of the task. Within this n-back neural network, depressed patients showed greater activation of the lateral prefrontal cortex and the anterior cingulate compared to healthy subjects. This study provides evidence that depressed patients need greater activation within the same neural network to maintain a similar level of performance as controls during a working memory task. Our findings suggest that depression may impair the cognitive capacity of depressed patients by recruiting more brain resources than controls during cognitive control. D
Cognitive deficits in depression: Possible implications for functional neuropathology
British Journal of Psychiatry, 2001
BackgroundWhile depression is known to involve a disturbance of mood, movement and cognition, its associated cognitive deficits are frequently viewed as simple epiphenomena of the disorder.AimsTo review the status of cognitive deficits in depression and their putative neurobiological underpinnings.MethodSelective computerised review of the literature examining cognitive deficits in depression and their brain correlates.ResultsRecent studies report both mnemonic deficits and the presence of executive impairment – possibly selective for set-shifting tasks – in depression. Many studies suggest that these occur independent of age, depression severity and subtype, task ‘difficulty’, motivation and response bias: some persist upon clinical ‘recovery’.ConclusionsM nemonic and executive deficits do not appear to be epiphenomena of depressive disorder. A focus on the interactions between motivation, affect and cognitive function may allow greater understanding of the interplay between key as...
Acta Neuropsychiatrica, 2010
Heinzel A, Northoff G, Boeker H, Boesiger P, Grimm S. Emotional processing and executive functions in major depressive disorder: dorsal prefrontal activity correlates with performance in the intra–extra dimensional set shift. Objective: Major depressive disorder (MDD) is characterised by predominately negatively valenced emotional symptoms that are often accompanied by cognitive impairments. We posited that cognitive impairments in MDD are related to altered emotional processing in prefrontal cortex. Methods: We compared 20 medication-free patients with MDD and 29 matched healthy controls. Both groups performed an emotional task during functional magnetic resonance imaging (fMRI). Furthermore, they completed the intra–extra dimensional set shift (IED) test probing for cognitive impairments. Then we correlated the results of the IED with the changes in fMRI BOLD signal in MDD patients and healthy subjects. Results: The subcategory of the IED applying extradimensional shift (EDS) show...
Neuropsychopharmacology, 2013
Functional neuroimaging studies have implicated dysregulation of prefrontal circuits in major depressive disorder (MDD), and these circuits are a viable target for predicting treatment outcomes. However, because of the heterogeneity of tasks and samples used in studies to date, it is unclear whether the central dysfunction is one of prefrontal hyperreactivity or hyporeactivity. We used a standardized battery of tasks and protocols for functional magnetic resonance imaging, to identify the common vs the specific prefrontal circuits engaged by these tasks in the same 30 outpatients with MDD compared with 30 matched, healthy control participants, recruited as part of the International Study to Predict Optimized Treatment in Depression (iSPOT-D). Reflecting cognitive neuroscience theory and established evidence, the battery included cognitive tasks designed to assess functions of selective attention, sustained attentionworking memory and response inhibition, and emotion tasks to assess explicit conscious and implicit nonconscious viewing of facial emotion. MDD participants were distinguished by a distinctive biosignature of: hypoactivation of the dorsolateral prefrontal cortex during working memory updating and during conscious negative emotion processing; hyperactivation of the dorsomedial prefrontal cortex during working memory and response inhibition cognitive tasks and hypoactivation of the dorsomedial prefrontal during conscious processing of positive emotion. These results show that the use of standardized tasks in the same participants provides a way to tease out prefrontal circuitry dysfunction related to cognitive and emotional functions, and not to methodological or sample variations. These findings provide the frame of reference for identifying prefrontal biomarker predictors of treatment outcomes in MDD.