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Functional anatomy of autobiographical memory recall deficits in depression.

ABSTRACT: BACKGROUND:Major depressive disorder (MDD) is associated with deficits in recalling specific autobiographical memories (AMs). Extensive research has examined the functional anatomical correlates of AM in healthy humans, but no studies have examined the neurophysiological underpinnings of AM deficits in MDD. The goal of the present study was to examine the differences in the hemodynamic response between patients with MDD and controls while they engage in AM recall. METHOD:Participants (12 unmedicated MDD patients; 14 controls) underwent functional magnetic resonance imaging (fMRI) scanning while recalling AMs in response to positive, negative and neutral cue words. The hemodynamic response during memory recall versus performing subtraction problems was compared between MDD patients and controls. Additionally, a parametric linear analysis examined which regions correlated with increasing arousal ratings. RESULTS:Behavioral results showed that relative to controls, the patients with MDD had fewer specific (p=0.013), positive (p=0.030), highly arousing (p=0.036) and recent (p=0.020) AMs, and more categorical (p<0.001) AMs. The blood oxygen level-dependent (BOLD) response in the parahippocampus and hippocampus was higher for memory recall versus subtraction in controls and lower in those with MDD. Activity in the anterior insula was lower for specific AM recall versus subtraction, with the magnitude of the decrement greater in MDD patients. Activity in the anterior cingulate cortex was positively correlated with arousal ratings in controls but not in patients with MDD. CONCLUSIONS:We replicated previous findings of fewer specific and more categorical AMs in patients with MDD versus controls. We found differential activity in medial temporal and prefrontal lobe structures involved in AM retrieval between MDD patients and controls as they engaged in AM recall. These neurophysiological deficits may underlie AM recall impairments seen in MDD.

SUBMITTER: Young KD

PROVIDER: S-EPMC3226869 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

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Functional anatomy of autobiographical memory recall deficits in depression.

Young K D KD Erickson K K Nugent A C AC Fromm S J SJ Mallinger A G AG Furey M L ML Drevets W C WC

Psychological medicine 20110729 2

<h4>Background</h4>Major depressive disorder (MDD) is associated with deficits in recalling specific autobiographical memories (AMs). Extensive research has examined the functional anatomical correlates of AM in healthy humans, but no studies have examined the neurophysiological underpinnings of AM deficits in MDD. The goal of the present study was to examine the differences in the hemodynamic response between patients with MDD and controls while they engage in AM recall.<h4>Method</h4>Participa ...[more]

PMID: 21798113

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Project description:Inflammation-related changes in the concentrations of inflammatory mediators such as c-reactive protein (CRP), interleukin 1β (IL-1), and IL-6 as well as kynurenine metabolites are associated with major depressive disorder (MDD) and affect depressive behavior, cognition, and hippocampal plasticity in animal models. We previously reported that the ratios of kynurenic acid (KynA) to the neurotoxic metabolites, 3-hydroxykynurenine (3HK) and quinolinic acid (QA), were positively correlated with hippocampal volume in depression. The hippocampus is critical for autobiographical memory (AM) recall which is impaired in MDD. Here we tested whether the ratios, KynA/3HK and KynA/QA were associated with AM recall performance as well as hippocampal activity during AM recall. Thirty-five unmedicated depressed participants and 25 healthy controls (HCs) underwent fMRI scanning while recalling emotionally-valenced AMs and provided serum samples for the quantification of kynurenine metabolites, CRP, and cytokines (IL-1 receptor antagonist - IL-1RA; IL-6, tumor necrosis factor alpha - TNF, interferon gamma -IFN-γ, IL-10). KynA/3HK and KynA/QA were lower in the MDD group relative to the HCs. The concentrations of the CRP and the cytokines did not differ significantly between the HCs and the MDD group. Depressed individuals recalled fewer specific AMs and displayed increased left hippocampal activity during the recall of positive and negative memories. KynA/3HK was inversely associated with left hippocampal activity during specific AM recall in the MDD group. Further, KynA/QA was positively correlated with percent negative specific memories recalled in the MDD group and showed a non-significant trend toward a positive correlation with percent positive specific memories recalled in HCs. In contrast, neither CRP nor the cytokines were significantly associated with AM recall or activity of the hippocampus during AM recall. Conceivably, an imbalance in levels of KynA versus QA-pathway metabolites may adversely impact the function of the hippocampus and AM recall, raising the possibility that kynurenine pathway may affect emotion-dependent memory within the context of depression.

Project description:Impaired emotion regulation is increasingly recognized as a core feature of depressive disorders. Indeed, currently and previously depressed adults both report greater problems in attenuating sadness (mood repair) in daily life than healthy controls. In contrast, studies of various strategies to attenuate sad affect have mostly found that currently or previously depressed adults and controls were similarly successful at mood repair in the laboratory. But few studies have examined mood repair among depression-prone youths or the effects of trait characteristics on mood repair outcomes in the laboratory.Adolescents, whose first episode of major depressive disorder (MDD) had onset at age 9, on average (probands), and were either in remission or depressed, and control peers, watched a sad film clip. Then, they were instructed to engage in refocusing attention (distraction) or recalling happy memories. Using affect ratings provided by the youths, we tested two developmentally informed hypotheses about whether the subject groups would be similarly able to attenuate sadness via the two mood repair strategies. We also explored if self-reported habitual (trait) mood repair influenced laboratory performance.Contrary to expectations, attention refocusing and recall of happy memories led to comparable mood benefits across subjects. Control adolescents reported significantly greater reductions in sadness than did depressed (Cohen's d = .48) or remitted (Cohen's d = .32) probands, regardless of mood repair strategy, while currently depressed probands remained the saddest after mood repair. Habitual mood repair styles moderated the effects of instructed (state) mood repair in the laboratory.Whether depressed or in remission, adolescents with MDD histories are not as efficient at mood repair in the laboratory as controls. But proband-control group differences in mood repair outcomes were modest in scope, suggesting that the abilities that subserve affect regulation have been preserved in probands to some degree. Further information about the nature of mood repair problems among youths with depression histories would help to better understand the clinical course of MDD and to design personalized interventions for depression.

Project description:Humans can vividly recall and re-experience events from their past, and these are commonly referred to as episodic or autobiographical memories. fMRI experiments reliably associate autobiographical event recall with activity in a network of "default" or "core" brain regions. However, as prior studies have relied on covert (silent) recall procedures, current understanding may be hampered by methodological limitations that obscure dynamic effects supporting moment-to-moment content retrieval. Here, fMRI participants (N = 40) overtly (verbally) recalled memories for ?2 min periods. The content of spoken descriptions was categorized using a variant of the Autobiographical Interview (AI) procedure (Levine et al., 2002) and temporally re-aligned with BOLD data so activity accompanying the recall of different details could be measured. Replicating prior work, sustained effects associated with autobiographical recall periods (which are insensitive to the moment-to-moment content of retrieval) fell primarily within canonical default network regions. Spoken descriptions were rich in episodic details, frequently focusing on physical entities, their ongoing activities, and their appearances. Critically, neural activity associated with recalling specific details (e.g., those related to people or places) was transient, broadly distributed, and grounded in category-selective cortex (e.g., regions related to social cognition or scene processing). Thus, although a single network may generally support the process of vivid event reconstruction, the structures required to provide detail-related information shift in a predictable manner that respects domain-level representations across the cortex.SIGNIFICANCE STATEMENT Humans can vividly recall memories of autobiographical episodes, a process thought to involve the reconstruction of numerous distinct event details. Yet how the brain represents a complex episode as it unfolds over time remains unclear and appears inconsistent across experimental traditions. One hurdle is the use of covert (silent) in-scanner recall to study autobiographical memory, which prevents experimenter knowledge of what information is being retrieved, and when, throughout the remembering process. In this experiment, participants overtly described autobiographical memories while undergoing fMRI. Activity associated with the recall and description of specific details was transient, broadly distributed, and grounded in category-selective cortex. Thus, it appears that as events unfold mentally, structures are dynamically reactivated to support vivid recollection.

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Functional anatomy of autobiographical memory recall deficits in depression.

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Functional anatomy of autobiographical memory recall deficits in depression.

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