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

Abstract

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.

Study protocol – elucidating the neural correlates of functional remediation for older adults with bipolar disorder

“…Concerning verbal learning and memory, the neural correlates of treatment-related improvements remain unclear, with a dearth of studies and conflicting findings ( 30 , 68 , 69 ). In this sense, some studies used a picture encoding task, an fMRI paradigm that probes visual memory for investigating the neural correlates of verbal memory improvement.…”

Associations between aberrant working memory-related neural activity and cognitive impairments in somatically healthy, remitted patients with mood disorders

“…fMRI data analysis Definition of the region of interest anatomical masks: Based on our hypotheses, we constructed two volumes of interest (VOI) masks for (i) the DMN, and (ii) the dorsal CCN, respectively, in accordance with prior neuroimaging findings (Emch, Von Bastian, & Koch, 2019;Owen, McMillan, Laird, & Bullmore, 2005) and consistent with our previous methodological approach (Petersen et al, 2021;Zarp Petersen et al, 2022). The following regions were included in the DMN: hippocampal complex, cingulate gyrus (posterior division), frontal medial cortex.…”

Neural correlates of episodic memory decline following electroconvulsive therapy: An exploratory functional magnetic resonance imaging study

“…Functional MRI memory encoding task. The encodingrelated fMRI paradigm employed in this study was derived from the strategic memory encoding picture task developed by Hariri et al (2003) and consistent with the one utilized in our prior trials (Petersen et al, 2021). During this task, participants viewed a sequence of neutral pictures, were instructed to indicate with a button press whether each picture depicted an indoor or outdoor scene and try to encode and memorize them.…”

“…However, immediately following the fMRI scan, participants completed a free recall test outside of the scanner to register the number of correctly recalled pictures from the task. Since recall rates were low across patient and HC groups in our recent fMRI studies (Petersen et al, 2021), and hence expected to be even lower in this ECT patient cohort, we decided a priori not to correlate out-scanner memory recall rates with neural activity.…”