Neural correlates of cognitive remediation in patients with mood disorders

https://doi.org/10.1016/j.pscychresns.2013.06.007Get rights and content

Abstract

Little is known about the brain changes that mediate improvement following cognitive remediation. We used neuropsychological tests and functional magnetic resonance imaging to study working memory and recollection memory in patients with mood disorders, before (PRE) and after (POST) 10 weeks of cognitive remediation. Thirty-eight patients completed a recollection memory task at PRE (28 had complete PRE and POST scans) and 35 patients completed an n-back working memory task at PRE (23 had complete PRE and POST scans). We also compared patients at PRE with two groups of healthy controls subjects (n=18 for the recollection memory task and n=15 for the working memory task). At PRE, compared to controls, patients had (i) poorer backward digit span scores, (ii) lower accuracy scores and weaker frontopolar activation during the 2-back condition, and (iii) poorer recollection scores and altered medial temporal activation on the recollection memory task. Following remediation, patients (i) improved on the backward digit span, (ii) activation increased in lateral and medial prefrontal, superior temporal, and lateral parietal regions in the 2-back condition, and (iii) recollection-related activation increased in the bilateral hippocampus. Improvements in 2-back accuracy correlated with activation increases in lateral and medial prefrontal and lateral parietal regions, and improved recollection scores correlated with activation increases in the left hippocampus. PRE–POST improvements on the backward digit span correlated with PRE–POST improvements in 2-back task accuracy; however, there was no direct association between improvement on the backward digit span following training and change in functional activation. These findings suggest that cognitive remediation may lead to behavioural improvements on tests of working memory. The relation between behavioural change and changes in functional activation following remediation requires further study.

Introduction

Cognitive remediation may be an effective means of improving neuropsychological deficits in many different populations (e.g., Grynszpan et al., 2011, Naismith et al., 2010, McGurk et al., 2007), and there are a growing number of studies focused on understanding the neurobiological changes that mediate improvements following this type of intervention. Much of this work has been conducted in patients with schizophrenia (e.g., Penadés et al., 2013, Bor et al., 2011, Wexler et al., 2000) or multiple sclerosis (Filippi et al., 2012, Leavitt et al., 2012), but some studies have examined training-induced functional change in healthy adults (Schweizer et al., 2013) and adults with mild cognitive impairment (Rosen et al., 2011).

The purpose of the present study was to examine the functional correlates of computer-assisted cognitive remediation (CACR) in patients with bipolar disorder (BD) or major depressive disorder (MDD). Deficits in working memory and recollection memory are frequently reported in these patients (e.g., Kurtz and Gerraty, 2009, Paelecke-Habermann et al., 2005), and imaging studies have identified key alterations in the neural substrates that subserve task performance. For instance, patients with mood disorders often show attenuated activation in lateral prefrontal regions during working memory (e.g., Garrett et al., 2011, Townsend et al., 2010), and deficits in recollection memory have been linked to weaker hippocampal activation (Milne et al., 2011), and smaller hippocampal volumes (Kaymak et al., 2010). Yet, only a few studies have explored the potential efficacy of cognitive remediation for these patients (e.g., Naismith et al., 2010, Elgamal et al., 2007, also see Anaya et al., 2012), and none have examined the functional correlates of cognitive training.

Accordingly, we used functional magnetic resonance imaging (fMRI) during an n-back working memory task and a recollection memory task to investigate the potential for change within these networks following a CACR intervention. We also compared functional activation in the patient sample prior to remediation with that of a normative sample. We expected to find altered functional activation in patients, relative to controls, in frontal regions during the n-back task and in medial temporal lobe (MTL) regions during the recollection memory task. Following remediation, we predicted increased task-related activation in frontal and MTL regions, improved task performance, and improvements on neuropsychological tests of working memory and recollection memory.

Section snippets

Patients

Patients diagnosed with a primary mood disorder according to DSM-IV criteria were recruited through the Mood Disorders Clinic at St. Joseph′s Healthcare to participate in a study examining the efficacy of a 10-week computer-assisted cognitive remediation (CACR) program. Patients were eligible to participate if they: (i) had a Structured Interview for DSM-IV, Axis I Disorders, Patient version (SCID-I/P; First et al., 1995) confirmed diagnosis of BD or MDD; (ii) were euthymic or had stable

Results

We scanned 44 patients on the recollection memory task at PRE. Four scans were lost to excessive movement, and two scans were discarded because the subjects were responding irregularly. We scanned 42 patients and 20 healthy controls on the n-back task at PRE. Five of the patient scans were lost to technical issues (malfunctioning response box) and two were lost to movement. In the healthy control sample, two scans were lost to the same technical issue, and three were lost to movement. Thus, at

Discussion

We measured functional activation during an n-back working memory task and a recollection memory task, before and after 10 weeks of cognitive remediation in patients with a primary mood disorder. We also compared patients at PRE to healthy control subjects on the same tasks.

Acknowledgements

This work was supported in part by the Ontario Mental Health Foundation, in the form of a research studentship awarded to Liesel-Ann Meusel, and an operating grant from Astra Zeneca.

We greatly appreciate the assistance of Andrea Milne and Shelley Ferris with data collection, and the assistance of Caitlin Gregory with data analysis. All authors had full access to all of the data collected in this study.

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