Change in prefrontal activity and executive functions after action-based cognitive remediation in bipolar disorder: a randomized controlled trial

Ott, Caroline V.; Macoveanu, Julian; Bowie, Christopher R.; Fisher, Patrick M.; Knudsen, Gitte M.; Kessing, Lars Vedel; Miskowiak, Kamilla Woznica

doi:10.1038/s41386-020-00901-7

Cited by 23 publications

(30 citation statements)

References 47 publications

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“…46 Indeed, this prediction is in line with the emerging demonstrations of treatment-related modulation of dlPFC activity in response to pharmacological treatment with erythropoietin (EPO) and vortioxetine, and the psychological intervention Action-Based Cognitive Remediation (ABCR). 25,45,47,48 Future longitudinal studies assessing the predictive validity of dPFC target engagement for cognitive improvement are therefore warranted.…”

Section: Discussionmentioning

confidence: 99%

Neuronal underpinnings of cognitive impairment in bipolar disorder: A large data‐driven functional magnetic resonance imaging study

et al. 2021

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Objectives: Cognitive impairment occurs in approximately 50% of remitted patients with bipolar disorder (BD). However, there exists no treatment with replicated and robust efficacy on cognition in BD. This is partially due to limited insight into the neuronal underpinnings of cognitive impairment in these patients. This is the first study to investigate neuronal underpinnings of cognitive impairment in a large functional magnetic resonance imaging (fMRI) dataset comparing neural activity patterns between distinct neurocognitive subgroups of partially or fully remitted patients with BD. Methods: Patients (n = 153) and healthy controls (HC) (n = 52) underwent neuropsychological assessment and fMRI, during which they performed a verbal N-back working memory (WM) task. Based on hierarchical cluster analysis of neuropsychological test performance, patients were grouped into one of two neurocognitive subgroups (cognitively impaired, n = 91; cognitively normal compared to HC, n = 62) that were compared on WM-related neural activity. Results: Cognitively impaired patients displayed WM-related hypo-activity in left dorsolateral prefrontal cortex and frontal and parietal regions within a cognitive control network (CCN) as well as hyper-activity in the default mode network (DMN) compared to cognitively normal patients. In contrast, cognitively normal patients only exhibited hypo-activity within a small cluster in the superior frontal gyrus relative to HC.

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Section: Discussionmentioning

confidence: 99%

Neuronal underpinnings of cognitive impairment in bipolar disorder: A large data‐driven functional magnetic resonance imaging study

et al. 2021

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“…The functional MRI scan was relatively short based on current standards, and a longer multiband acquisition would improve the precision of signal estimation. For cluster-based analyses, we applied a threshold commonly used in clinical trials and studies with modest sample sizes, 43 , 44 , 45 , 46 , 47 , 48 although a more conservative threshold would further reduce the risk of type I error. We applied a hypothesis-driven, seed-to-whole-brain rsFC approach focused on the SN.…”

Section: Discussionmentioning

confidence: 99%

“…Group-level inferential models were conducted to compare the seed-based connectivity maps of participants with and without apathy. We implemented cluster-based inference using Gaussian random field theory with a height z score greater than 2.3 43 , 44 , 45 , 46 , 47 , 48 and a Bonferroni cluster correction of P < .0125 (2-tailed) to account for the number of seeds analyzed (n = 4).…”

Section: Methodsmentioning

confidence: 99%

Comparison of Functional and Structural Neural Network Features in Older Adults With Depression With vs Without Apathy and Association With Response to Escitalopram

et al. 2022

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IMPORTANCEApathy is prevalent among individuals with late-life depression and is associated with poor response to pharmacotherapy, including chronicity and disability. Elucidating brain networks associated with apathy and poor treatment outcomes can inform intervention development. OBJECTIVES To assess the brain network features of apathy among individuals with late-life depression and identify brain network abnormalities associated with poor antidepressant response. DESIGN, SETTING, AND PARTICIPANTS This secondary analysis of a single-group, open-label nonrandomized clinical trial of escitalopram conducted at an outpatient geriatric psychiatry clinic enrolled 40 adults aged 59 to 85 years with major depressive disorder from July 1, 2012, to July 31, 2019. INTERVENTIONS After a 2-week washout period, participants received escitalopram titrated to a target of 20 mg/d for 12 weeks. MAIN OUTCOMES AND MEASURES Baseline and posttreatment magnetic resonance imaging (MRI), clinical, and cognitive assessments were conducted. Functional MRI was used to map group differences in resting state functional connectivity (rsFC) of the salience network, and diffusion MRI connectometry was performed to evaluate pathway-level disruptions in structural connectivity. The Apathy Evaluation Scale was used to quantify apathy, and the Hamilton Depression Rating Scale (HAM-D) was used to quantify the primary outcome of depression severity. RESULTS Forty participants (26 women [65%]; mean [SD] age, 70.0 [6.6] years [range, 59-85 years]) with depression were included; 20 participants (50%) also had apathy. Relative to nonapathetic participants with depression, those with depression and apathy had lower rsFC of salience network seeds with the dorsolateral prefrontal cortex (DLPFC), premotor cortex, midcingulate cortex, and paracentral lobule and greater rsFC with the lateral temporal cortex and temporal pole (z score >2.7; Bonferroni-corrected threshold of P < .0125). Compared with participants without apathy, those with apathy had lower structural connectivity in the splenium, cingulum, and fronto-occipital fasciculus (t score >2.5; false discovery rate-corrected P = .02). Twenty-seven participants completed escitalopram treatment; 16 (59%) achieved remission (HAM-D score <10). Lower insula-DLPFC/midcingulate cortex rsFC was associated with less symptomatic improvement (HAM-D % change) (β [df] = 0.588 [26]; P = .001) and a higher likelihood of nonremission (odds ratio, 1.041 [95% CI, 1.003-1.081]; P = .04) after treatment and, in regression models, was a mediator of the association between baseline apathy and persistence of depression.(continued) Key Points Question What are the brain network features of apathy in late-life depression, and how are they associated with treatment outcomes? Findings In this secondary analysis of a 12-week nonrandomized single-group trial of escitalopram titrated to 20 mg/d, compared with 20 older adults with depression without apathy, 20 older adults with depression and apathy showed distinct alterations in ne...

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“…Specifically, encoding-related paradigms may be less ideal than paradigms that tap into executive aspects of cognitive functions, such as N-back WM tests. We therefore recommend WM fMRI paradigms for future cognition trials to examine neurocircuitry target engagement, based on their robust sensitivity to (i) activity differences in dPFC and DMN between cognitively impaired and cognitively normal patients (Petersen et al, 2021), (ii) illnessassociated changes in dPFC activity (Macoveanu et al, 2020) and (iii) dPFC and DMN activity in response to pharmacological and psychological treatments targeting cognition (Miskowiak et al, 2016c;Ott et al, 2020a;Smith et al, 2018). In keeping with this, it is, however, important to note that drug-induced target engagement modulation of neurocircuitries does not always translate into demonstrable treatment-related cognitive improvement at a behavioural level in phase III clinical trials (Nathan and Bakker, 2020).…”

Section: Discussionmentioning

confidence: 99%

“…In our recent fMRI study of 153 remitted BD patients with and without cognitive impairments, we found that patients who were cognitively impaired displayed hypo-activity in a dorsal CCN including dPFC and failure to switch off the default mode network (DMN) during N-back working memory (WM) (Petersen et al, 2021). We and others also found that distinct pharmacological and psychological treatments with beneficial effects on cognition, including erythropoietin (EPO), vortioxetine and action-based cognitive remediation, all modulated either verbal or spatial N-back WM-related dPFC activity in patients with mood disorders (Miskowiak et al, 2016c;Ott et al, 2020a;Smith et al, 2018). Importantly, we also detected change in dPFC activity during N-back WM performance after a mood episode in recently diagnosed BD patients, in the absence of performance decline on neuropsychological tests, suggesting that dPFC activity change is a more sensitive assay of change in brain function than overt cognitive performance (Macoveanu et al, 2020).…”

Section: Introductionmentioning

confidence: 88%

Assessment of the neuronal underpinnings of cognitive impairment in bipolar disorder with a picture encoding paradigm and methodological lessons learnt

et al. 2021

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Background: Mood disorders are often associated with persistent cognitive impairments. However, pro-cognitive treatments are essentially lacking. This is partially because of poor insight into the neurocircuitry abnormalities underlying these deficits and their change with illness progression. Aims: This functional magnetic resonance imaging (fMRI) study investigates the neuronal underpinnings of cognitive impairments and neuronal change after mood episodes in remitted patients with bipolar disorder (BD) using a hippocampus-based picture encoding paradigm. Methods: Remitted patients with BD ( n=153) and healthy controls ( n=52) were assessed with neuropsychological tests and underwent fMRI while performing a strategic picture encoding task. A subgroup of patients ( n=43) were rescanned after 16 months. We conducted data-driven hierarchical cluster analysis of patients’ neuropsychological data and compared encoding-related neuronal activity between the resulting neurocognitive subgroups. For patients with follow-up data, effects of mood episodes were assessed by comparing encoding-related neuronal activity change in BD patients with and without episode(s). Results: Two neurocognitive subgroups were revealed: 91 patients displayed cognitive impairments while 62 patients were cognitively normal. No neuronal activity differences were observed between neurocognitive subgroups within the dorsal cognitive control network or hippocampus. However, exploratory whole-brain analysis revealed lower activity within a small region of middle temporal gyrus in impaired patients, which significantly correlated with poorer neuropsychological performance. No changes were observed in encoding-related neuronal activity or picture recall accuracy with the occurrence of mood episode(s) during the follow-up period. Conclusion: Memory encoding fMRI paradigms may not capture the neuronal underpinnings of cognitive impairment or effects of mood episodes.

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Change in prefrontal activity and executive functions after action-based cognitive remediation in bipolar disorder: a randomized controlled trial

Cited by 23 publications

References 47 publications

Neuronal underpinnings of cognitive impairment in bipolar disorder: A large data‐driven functional magnetic resonance imaging study

Neuronal underpinnings of cognitive impairment in bipolar disorder: A large data‐driven functional magnetic resonance imaging study

Comparison of Functional and Structural Neural Network Features in Older Adults With Depression With vs Without Apathy and Association With Response to Escitalopram

Assessment of the neuronal underpinnings of cognitive impairment in bipolar disorder with a picture encoding paradigm and methodological lessons learnt

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