Pauline Favre

fMRI evidence for abnormal resting-state functional connectivity in euthymic bipolar patients

BACKGROUND Neural substrates of bipolar disorder (BD) have frequently been characterized by dysregulation of fronto-limbic networks that may persist during euthymic periods. Only a few studies have investigated euthymic bipolar patients (BP) functional connectivity at rest. The current study aims to assess resting-state functional connectivity in euthymic BP in order to identify trait abnormalities responsible for enduring mood dysregulation in these patients. METHODS Medial prefrontal cortex (mPFC) functional connectivity was investigated in 20 euthymic BP and 20 healthy subjects (HS). The functional connectivity maps were compared across groups using a between-group random effect analysis. Additional region of interest (ROI) analysis focused on mPFC-amygdala functional connectivity as well as correlations between the clinical features in euthymic BP was also conducted. RESULTS A significant difference between euthymic BP and HS was observed in terms of connectivity between the mPFC and the right dorsolateral prefrontal cortex (dlPFC). A significant negative correlation between the activity of these regions was found in HS but not in euthymic BP. In addition, euthymic BP showed greater connectivity between mPFC and right amygdala compared to HS, which was also correlated with the duration of the disease. LIMITATIONS The BP group was heterogeneous with respect to the bipolarity subtype and the medication. The robustness of results could be improved with an increased sample size. CONCLUSIONS Compared to HS, the euthymic BP showed abnormal decoupling (decreased functional connectivity) activity between mPFC-dlPFC and hyperconnectivity (increased functional connectivity) and between mPFC and amygdala. These abnormalities could underlie the pathophysiology of BD, and may deteriorate further in accordance with disease duration.

Modulation of fronto-limbic activity by the psychoeducation in euthymic bipolar patients. A functional MRI study

Bipolar disorders (BD) are mainly characterized by emotional and cognitive processing impairment. The cerebral substrate explaining BD impairment and the action mechanisms of therapies are not completely understood, especially for psychosocial interventions. This fMRI study aims at assessing cerebral correlates of euthymic bipolar patients (EBP) before and after psychoeducation therapy. Sixteen EBP and 16 matched healthy subjects (HS) performed a word-face emotional Stroop task in two separate fMRI sessions at 3-month interval. Between fMRI sessions, EBP underwent psychoeducation. Before psychoeducation, the comparison of EBP vs. HS in fMRI data revealed (a) significant decreased activity of cognitive control regions such as bilateral inferior and left superior frontal gyri, right insula, right fusiform gyrus and bilateral occipital gyri and (b) significant increased activity of emotion-related processing regions such as bilateral hippocampus, parahippocampal gyri and the left middle temporal gyrus. After psychoeducation, EBP showed significant clinical improvement, increased activity of inferior frontal gyri and a tendency toward decreased activity of right hippocampus and parahippocampal gyrus. These results suggest that the imbalance between cognitive control and emotion processing systems characterizing BD acute episodes may persist during euthymic periods. Moreover, this imbalance may be improved by psychoeducation, which enhances the cognitive control and modulates emotional fluctuations in EBP.

Cerebral Correlates of Abnormal Emotion Conflict Processing in Euthymic Bipolar Patients: A Functional MRI Study

Background Patients with bipolar disorder experience cognitive and emotional impairment that may persist even during the euthymic state of the disease. These persistent symptoms in bipolar patients (BP) may be characterized by disturbances of emotion regulation and related fronto-limbic brain circuitry. The present study aims to investigate the modulation of fronto-limbic activity and connectivity in BP by the processing of emotional conflict. Methods Fourteen euthymic BP and 13 matched healthy subjects (HS) underwent functional magnetic resonance imaging (fMRI) while performing a word-face emotional Stroop task designed to dissociate the monitoring/generation of emotional conflict from its resolution. Functional connectivity was determined by means of psychophysiological interaction (PPI) approach. Results Relative to HS, BP were slower to process incongruent stimuli, reflecting higher amount of behavioral interference during emotional Stroop. Furthermore, BP showed decreased activation of the right dorsolateral prefrontal cortex (DLPFC) during the monitoring and a lack of bilateral amygdala deactivation during the resolution of the emotional conflict. In addition, during conflict monitoring, BP showed abnormal positive connectivity between the right DLPFC and several regions of the default mode network. Conclusions Overall, our results highlighted dysfunctional processing of the emotion conflict in euthymic BP that may be subtended by abnormal activity and connectivity of the DLPFC during the conflict monitoring, which, in turn, leads to failure of amygdala deactivation during the resolution of the conflict. Emotional dysregulation in BP may be underpinned by a lack of top-down cognitive control and a difficulty to focus on the task due to persistent self-oriented attention.

Stimulation of subgenual cingulate area decreases limbic top-down effect on ventral visual stream: A DBS-EEG pilot study.

Abstract Deep brain stimulation (DBS) of the subgenual cingulate gyrus (area CG25) is beneficial in treatment resistant depression. Though the mechanisms of action of Cg25 DBS remain largely unknown, it is commonly believed that Cg25 DBS modulates limbic activity of large networks to achieve thymic regulation of patients. To investigate how emotional attention is influenced by Cg25 DBS, we assessed behavioral and electroencephalographic (EEG) responses to an emotional Stroop task in 5 patients during ON and OFF stimulation conditions. Using EEG source localization, we found that the main effect of DBS was a reduction of neuronal responses in limbic regions (temporal pole, medial prefrontal and posterior cingulate cortices) and in ventral visual areas involved in face processing. In the dynamic causal modeling (DCM) approach, the changes of the evoked response amplitudes are assumed to be due to changes of long range connectivity induced by Cg25 DBS. Here, using a simplified neural mass model that did not take explicitly into account the cytoarchitecture of the considered brain regions, we showed that the remote action of Cg25 DBS could be explained by a reduced top‐down effective connectivity of the amygdalo‐temporo‐polar complex. Overall, our results thus indicate that Cg25 DBS during the emotional Stroop task causes a decrease of top‐down limbic influence on the ventral visual stream itself, rather than a modulation of prefrontal cognitive processes only. Tuning down limbic excitability in relation to sensory processing might be one of the biological mechanisms through which Cg25 DBS produces positive clinical outcome in the treatment of resistant depression. HighlightsCG25 DBS does not modulate significantly the emotional Stroop effect in depression.CG25 decreases N170 event related potential amplitude.CG25 DBS decreases activity in occipital face processing areas.CG25 DBS decreases connection strength to and from temporal pole.

White matter plasticity induced by psychoeducation in bipolar patients: A controlled diffusion tensor imaging study

Bipolar disorder (BD) is a severe mood disorder which is often difficult to treat. Pharmacological treatments are often effective in symptom management, but their effects are generally insufficient on a functional level [1] . Among psychosocial interventions, psychoeducation has recently shown significant and long-lasting effects on treatment adherence, relapse prevention and global functioning [2] . Consequently, psychoeducation is now positioned as an essential part of therapeutic strategies in BD, although its mechanistic neural action has not yet been precisely identified. The evidence for frontolimbic disconnectivity, responsible for emotional disturbance in BD, has been highlighted by functional magnetic resonance imaging (fMRI) [3, 4] as well as by diffusion tensor imaging (DTI) studies that reported abnormalities in white matter (WM) tracts linking frontal and limbic regions, such as the uncinate fasciculus [5] . However, to date, no study has investigated WM plasticity in patients with BD after a psychotherapeutic intervention, while dynamic changes in WM organization have been highlighted after various trainings in healthy subjects (HS), Received: February 23, 2015 Accepted after revision: September 10, 2015 Published online: November 27, 2015

Neurodevelopmental subtypes of bipolar disorder are related to cortical folding patterns: An international multicenter study

Brain sulcation is an indirect marker of neurodevelopmental processes. Studies of the cortical sulcation in bipolar disorder have yielded mixed results, probably due to high variability in clinical phenotype. We investigated whole‐brain cortical sulcation in a large sample of selected patients with high neurodevelopmental load.