Relationships Between Altered Functional Magnetic Resonance Imaging Activation and Cortical Thickness in Patients With Euthymic Bipolar I Disorder

Abstract

Background Performance during cognitive control functional magnetic resonance imaging (fMRI) tasks are associated with frontal lobe hypoactivation in patients with bipolar disorder, even while euthymic. Here, we study the structural underpinnings for this functional abnormality simultaneously with brain activation data. Methods In a sample of ninety adults (45 with inter-episode Bipolar I disorder and 45 healthy controls), we explored whether abnormal functional activation patterns in bipolar euthymic subjects during a Go-NoGo fMRI task are associated with regional deficits in cortical gray matter thickness in the same regions. Cross-sectional differences in fMRI activation were used to form a-priori hypotheses for region-of-interest cortical gray matter thickness analyses. fMRI BOLD to structural magnetic resonance imaging (sMRI) thickness correlations were conducted across the sample and within patients and controls separately. Results During response inhibition (NoGo minus Go), bipolar subjects showed significant hypoactivation and reduced thickness in the inferior frontal cortex (IFC), superior frontal gyrus and cingulate compared to controls. Cingulate hypoactivation corresponded with reduced regional thickness. A significant activation by disease state interaction was observed with thickness in left prefrontal areas. Conclusions Reduced cingulate fMRI activation is associated with reduced cortical thickness. In the left frontal lobe, a thinner cortex was associated with increased fMRI activation in patients, but showed a reverse trend in controls. These findings suggest that reduced activation in the IFC and cingulate during a response inhibition task may have an underlying structural etiology, which may explain task-related functional hypoactivation that persists even when patients are euthymic.

Longitudinal Cortical Thickness Changes in Bipolar Disorder and the Relationship to Genetic Risk, Mania, and Lithium Use

“…In the present study, we observed cortical thickening in visual/somatosensory areas. Given that greater CT is commonly interpreted as better cortical integrity and has been positively related to cognitive function (33,35,38,(82)(83)(84)(85)(86)(87)(88)(89)(90)(91), it is tempting to speculate that cortical thickening reflects a structural normalization process. This line of reasoning is supported by results from our secondary analyses indicating that the increase of CT in visual/somatosensory areas may be related to lithium use.…”

Bipolar disorder type I and II show distinct relationships between cortical thickness and executive function

“…Leaning on observations of previous studies providing important links between cortical thickness and neural activity in task relevant brain regions , the correlations observed could potentially reflect functional involvements, and the observed clusters might overlap with areas of regional activation. One could speculate that if a specific level of structural impairment is reached in a task relevant region (here medial prefrontal cortex), other brain regions might take a compensatory role (as possible in BDII).…”

“…The medial prefrontal cortex has been shown to be involved in response inhibition, inhibitory control, and task switching . Patients with bipolar disorder showed both hypoactivation during response inhibition and reduced thickness in (medial) prefrontal brain regions compared to controls . Interestingly, our explorative post hoc analyses of individual D‐KEFS subtests indicates that CWIT and TMT (i.e., tasks with a strong inhibition component) may be the tasks driving to the associations with medial prefrontal brain areas in controls and BDII (Figure ).…”

“…More specifically, a recent meta‐analysis reported that thicker prefrontal cortices are commonly associated with better executive performance , which is of particular interest for bipolar disorder research. Importantly, relationships between regional cortical thickness and functional patterns of brain activation have been demonstrated . For example, during response inhibition, which requires executive control, patients with bipolar disorder showed both hypoactivation and reduced thickness in (medial) prefrontal brain regions compared to controls, suggesting that abnormal neural activation underlies structural etiology .…”

“…Importantly, relationships between regional cortical thickness and functional patterns of brain activation have been demonstrated . For example, during response inhibition, which requires executive control, patients with bipolar disorder showed both hypoactivation and reduced thickness in (medial) prefrontal brain regions compared to controls, suggesting that abnormal neural activation underlies structural etiology . Thus, cortical thickness correlates of executive function can provide important insights into brain structure–function relationships.…”