Resting State Brain Network Disturbances Related to Hypomania and Depression in Medication-Free Bipolar Disorder

Abstract

Research on resting functional brain networks in bipolar disorder (BP) has been unable to differentiate between disturbances related to mania or depression, which is necessary to understand the mechanisms leading to each state. Past research has also been unable to elucidate the impact of BP-related network disturbances on the organizational properties of the brain (eg, communication efficiency). Thus, the present work sought to isolate network disturbances related to BP, fractionate these into components associated with manic and depressive symptoms, and characterize the impact of disturbances on network function. Graph theory was used to analyze resting functional magnetic resonance imaging data from 60 medication-free patients meeting the criteria for BP and either a current hypomanic (n=30) or depressed (n=30) episode and 30 closely age/sex-matched healthy controls. Correction for multiple comparisons was carried out. Compared with controls, BP patients evidenced hyperconnectivity in a network involving right amygdala. Fractionation revealed that (hypo)manic symptoms were associated with hyperconnectivity in an overlapping network and disruptions in the brain's 'small-world' network organization. Depressive symptoms predicted hyperconnectivity in a network involving orbitofrontal cortex along with a less resilient global network organization. Findings provide deeper insight into the differential pathophysiological processes associated with hypomania and depression, along with the particular impact these differential processes have on network function.

Aberrant brain network topology in fronto‐limbic circuitry differentiates euthymic bipolar disorder from recurrent major depressive disorder

“…Previous research indicated compromised FC especially between the amygdala and prefrontal regions in acutely depressed BD patients (Li et al, 2015;Liu et al, 2015;Spielberg et al, 2016). However, most studies examining euthymic BD individuals did not report any significant effects in amygdala FC, consistent with our results .…”

“…In contrast to our findings, many studies reported aberrations in the amygdala as a key component of the limbic network. Hyperactivation in the amygdala was not only reported in task‐based fMRI studies presenting emotionally arousing pictures (Townsend & Altshuler, ) but also in prior examinations of resting‐state FC: Previous research indicated compromised FC especially between the amygdala and prefrontal regions in acutely depressed BD patients (Li et al, ; Liu et al, ; Spielberg et al, ). However, most studies examining euthymic BD individuals did not report any significant effects in amygdala FC, consistent with our results (Townsend & Altshuler, ).…”

“…Studies identifying graph-theoretical network differences in BD (Kim et al, 2013;Leow et al, 2013;Roberts et al, 2017;Spielberg et al, 2016) and in MDD (Borchardt et al, 2016;Jin et al, 2011;Lord, Horn, Breakspear, & Walter, 2012;Luo et al, 2015;Meng et al, 2014;Ye et al, 2015;Zhang et al, 2011) have shown promising results distinguishing these patient groups from healthy individuals, implying a disturbed network organization in affective disorders. They predominantly reported alterations of regional topological properties while findings are inconsistent regarding global changes.…”

A MATLAB toolbox for multivariate analysis of brain networks

“…Thus, network analysis of the brain provides a profound perspective into understanding the structural and functional organizations of the brain in health and disease (Bassett and Bullmore 2009, Bullmore and Sporns 2009, Sporns 2010). Increasing numbers of studies indicate alterations in network configuration of the brain with aging (Meunier, Achard et al 2009, Micheloyannis, Vourkas et al 2009, Sala-Llonch, Bartres-Faz et al 2015), and in neurological disorders such as Alzheimer’s disease (He, Chen et al 2008, Supekar, Menon et al 2008, Stam, de Haan et al 2009, Fang, Yan et al 2015), schizophrenia (Bassett, Bullmore et al 2008, Liu, Liang et al 2008, Rubinov, Knock et al 2009), depression (Leistedt, Coumans et al 2009, Ye, Yang et al 2015, Spielberg, Beall et al 2016), and Parkinson’s disease (Gao and Wu 2016, Tessitore, Santangelo et al 2017). …”

Disrupted brain structural connectivity in Pediatric Bipolar Disorder with psychosis

“…Although abnormal functional connectivity is proposed to be a main feature in BD, few studies have focused on whether the underlying structural connectivity is altered in BD using state-of-the-art whole-brain network analysis [24][25][26][27][28][29][30] . As such, complementing the existing knowledge of anatomical and functional deficits in PBD with a comprehensive mapping of altered structural connectivity will inform how brain structure-function coupling is affected, and thus allow for an improved assessment of patients' cognition 27 .…”