Neural correlates of cognitive remediation in patients with mood disorders
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.
References (56)
- et al.
A systematic review of cognitive remediation for schizo-affective and affective disorders
Journal of Affective Disorders
(2012) - et al.
Sex differences in the medial temporal lobe during encoding and recognition of pseudowords and abstract designs
Neuroimage
(2012) - et al.
Basic operations in working memory: contributions from functional imaging studies
Behavioral and Brain Research
(2010) - et al.
How can cognitive remediation therapy modulate brain activations in schizophrenia?
An fMRI study
(2011)Psychiatry Research
(2011) - et al.
Thresholding of statistical maps in functional neuroimaging using the false discovery rate
Neuroimage
(2002) - et al.
Reduced brain activation in euthymic bipolar patients during response inhibition: an event-related fMRI study
Psychiatry Research: Neuroimaging
(2009) - et al.
Control processes in verbal working memory: an event-related potential study
Brain Research
(2007) - et al.
Modulation of working-memory maintenance by directed attention
Neuropsychologia
(2011) - et al.
Gender differences in the neural correlates of response inhibition during a stop signal task
NeuroImage
(2006) - et al.
Cognitive training in affective disorders improves memory: a preliminary study using the NEAR approach
Journal of Affective Disorders
(2010)
Attention and executive functions in remitted major depression patients
Journal of Affective Disorders
Therapy-induced plasticity of cognitive functions in MS patients: insights from fMRI
Journal of Physiology
A hippocampal marker of recollection memory ability among healthy young adults: contributions of posterior and anterior segments
Neuron
Event-related fMRI studies of episodic encoding and retrieval: meta-analyses using activation likelihood estimation
Neuropsychologia
fMRI abnormalities in dorsolateral prefrontal cortex during a working memory task in manic, euthymic and depressed bipolar subjects
Psychiatry Research: Neuroimaging
Increased hippocampal head diffusivity predicts impaired episodic memory performance in early Alzheimer′s disease
Neuropsychologia
An inventory for measuring depression
Archives of General Psychiatry
Dose response and dose equivalence of antipsychotics
Journal of Clinical Psychopharmacology
Distinct brain networks for adaptive and stable task control in humans
Proceedings of the National Academy of Sciences of the United States of America
Successful computer-assisted cognitive remediation therapy in patients with unipolar depression: a proof of principle study
Psychological Medicine
Multiple sclerosis: effects of cognitive rehabilitation on structural and functional MR imaging measures—an explorative study
Radiology
Structured Interview for DSM- IV Axis I Disorders—Patient Edition, Version 2
Aberrant brain activation during a working memory task in psychotic major depression
American Journal of Psychiatry
Sex differences in prefrontal cortical brain activity during fMRI of auditory verbal working memory
Neuropsychology
Efficacy and specificity of computer-assisted cognitive remediation in schizophrenia: a meta-analytical study
Psychological Medicine
Effects of medication on neuroimaging findings in bipolar disorder: an updated review
Bipolar Disorders
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