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Review
. 2008;10(2):153-63.
doi: 10.31887/DCNS.2008.10.2/lclark.

Cognitive neuroscience and brain imaging in bipolar disorder

Luke Clark  1 , Barbara J Sahakian
Affiliations
Review

Cognitive neuroscience and brain imaging in bipolar disorder

Luke Clark et al. Dialogues Clin Neurosci. 2008.

Abstract
in English, Spanish, French

Bipolar disorder is characterized by a combination of state-related changes in psychological function that are restricted to illness episodes, coupled with trait-related changes that persist through periods of remission, irrespective of symptom status. This article reviews studies that have investigated the brain systems involved in these state- and trait-related changes, using two techniques: (i) indirect measures of neurocognitive function, and (ii) direct neuroimaging measures of brain function during performance of a cognitive task. Studies of neurocognitive function in bipolar disorder indicate deficits in three core domains: attention, executive function, and emotional processing. Functional imaging studies implicate pathophysiology in distributed neural circuitry that includes the prefrontal and anterior cingulate cortices, as well as subcortical limbic structures including the amygdala and the ventral striatum. Whilst there have been clear advances in our understanding of brain changes in bipolar disorder, there are limited data in bipolar depression, and there is limited understanding of the influence of clinical variables including medication status, illness severity, and specific symptom dimensions.

El trastorno bipolar se caracteriza por la combinación de cambios en la función psicológica estado-dependiente, la que está restringida a los episodios de la enfermedad, y cambios rasgo-dependientes que persisien a través de los períodos de remisión independiente de la sintomatología. En este artículo se revisan estudios que han investigado los sistemas cerebrales involucrados en estes cambios esiado y rasgo-dependienies utilizando dos técnicas: 1) mediciones indirectas de la función neurocognitiva y 2) mediciones directes con neuroimágenes de la función cerebral durante el rendimiento frente a una prueba cognitiva. Los estudios de la función neurocognitiva en el trastorno bipolar revelan déficit en très áreas principales: atención, función ejecutiva y procesamiento emocional. Los estudios de imágenes funcionales incorporan la fisiopatología de circuitos neurales distribuidos en las cortezas prefrontal y del cíngulo anterior, como también de estructuras límbicas subcorticales que incluyen la amigdala y el esiriado ventral. Aunque han existido claras evidencias acerca de nuestra comprensión de los cambios cerebrales en el trastorno bipolar, hay datos limitados para la depresión bipolar, y hay una comprensión reducida de la influencia de variables clínicas como la medicación, la gravedad de la enfermedad y las dimensiones de síntomas específicos.

Les troubles bipolaires sont caractérisés par une association de modifications psychologiques liées à l'état qui sont limitées aux épisodes de la maladie, et de modifications « trait » qui persistent lors des périodes de rémission, indépendamment du statut thymique. Cet article passe en revue les études qui ont utilisé deux techniques pour observer les mécanismes cérébraux impliqués dans ces modifications irait et état dépendantes: 1) des mesures indirectes de la fonction neurocognitive et 2) des mesures directes par neuro-imagerie de la fonction cérébrale pendant l'exécution d'une tâche cognitive. Les études de la fonction neurocognitive dans les troubles bipolaires montrent des déficits dans trois domaines clés: l'attention, les fonctions executives et les processus émotionnels. Les études d'imagerie fonctionnelle impliquent la physiopaihologie de la distribution des circuits neuronaux, dont les cortex cingulaire antérieur et pré frontal, comme celle des structures limbiques sous-corticales, dont l'amygdale et le striatum ventral. Les connaissances sur les modifications cérébrales dans la maladie bipolaire ont bien progressé mais les données sur la dépression bipolaire sont peu nombreuses et l'influence de variables cliniques comme le traitement, la sévérité de la maladie et l'importance des symptômes spécifiques est mal comprise.

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Figures

Figure 1.
Figure 1.. Brain responses during risky decision-making in patients with mania, patients with depression, and healthy controls. A: Screen display for the Risk Task. Subjects are instructed that a token has been hidden at random under one of the six boxes. They must guess whether the token is hidden under a red or blue box, in order to win points. The less likely option (blue, in this example) is also associated with a higher win value, to create conflict between reward and uncertainty. Blocks of decision-making were contrasted with a visuomotor baseline condition. B: Activations during decision-making in healthy controls. C: Activations during decision-making in patients with mania. D: Activations during decision-making in patients with major depressive disorder. E: Areas of increased activity in healthy controls relative to patients with mania. Reproduced from ref 68: Rubinsztein JS, Fletcher PC, Rogers RD, et al. Decision-making in mania; a PET study. Brain. 2001;124:2550-2263. Copyright © Oxford University Press 2001
Figure 2.
Figure 2.. Brain responses during the affective Go-No Go task in patients with mania and healthy controls. This section shows areas of increased activity in patients relative to controls, in blocks when positive (happy) words were distracters compared with blocks where neutral valenced words were distracters, consistent with increased brain activity to mood-congruent, task-irrelevant information. Reproduced from ref 70: Elliott R, Ogilvie A, Rubinsztein JS, Calderon G, Dolan RJ, Sahakian BJ. Abnormal ventral frontal response during performance of an affective go/no go task in patients with mania. Biol Psychiatry. 2004;55:1 163-1 170. Copyright © Elsevier 2004
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