Preliminary communication
Preliminary evidence for increased frontosubcortical activation on a motor impulsivity task in mixed episode bipolar disorder

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Abstract

Background

Of all mood states, patients in mixed episodes of bipolar disorder are at the greatest risk for impulsive behaviors including attempted suicide. The aim of this study was to examine whether the neural correlates of motor impulsivity are distinct in patients with mixed mania.

Methods

Ten patients with bipolar disorder in a mixed episode (BP-M), 10 bipolar comparison participants in a depressed episode (BP-D), and 10 healthy comparison (HC) participants underwent functional MRI while performing a Go/No-Go task of motor impulsivity.

Results

Both patient groups had elevated, self-rated motor impulsiveness scores. The BP-M group also had a trend-level increase in commission errors relative to the HC group on the Go/No-Go task. While the full sample strongly activated a ventrolateral prefrontal–subcortical brain network, the BP-M group activated the amygdala and frontal cortex more strongly than the HC group, and the thalamus, cerebellum, and frontal cortex more strongly than the BP-D group.

Limitations

This study is primarily limited by a relatively small sample size.

Conclusions

Higher commission error rates on the Go/No-Go task suggest increased vulnerability to impulsive responding during mixed episodes of bipolar disorder. Moreover, the distinct pattern of increased brain activation during mixed mania may indicate a connection between behavioral impulsivity and a failure of neurophysiological “inhibition”, especially in the amygdala.

Introduction

Bipolar disorder (BD) is characterized by impulse control problems. Clinical studies have identified poor impulse control as a factor associated with greater risk-taking, including attempted suicide, in BD (Michaelis et al., 2004). The occurrence of manic symptoms during depressive episodes is associated with even greater impulsivity and a higher probability of suicide attempts (Swann et al., 2007). This suggests that manic symptoms may provide the catalyst to act impulsively on negative thoughts during depression. Therefore, a better understanding of the neurological underpinnings of poor impulse control in mixed relative to depressed episodes of BD is an important empirical goal.

Impulsiveness is reported following damage to the orbitofrontal cortex (OFC) or ventrolateral prefrontal cortex (VLPFC), and practical and social judgment problems are also observed (Eslinger, 1999, Grafman et al., 1996). Lesions of prefrontal cortex can disrupt the ability to be guided by the future consequences of one's actions leading to poor decisions, presumably by “disconnecting” frontal monitoring systems from limbic input. Abnormalities within prefrontal–subcortical brain circuits also result in motor disruption, especially when the basal ganglia are involved (Lichter and Cummings, 2001).

Motor impulsivity tasks, such as Go/No-Go tasks, have been used extensively in the behavioral assessment of both higher-order frontal lobe and subcortical motor functions. Functional magnetic resonance imaging (fMRI) studies of acutely manic patients with BD have generally demonstrated decreased activation in VLPFC on non-emotional Go/No-Go tasks (Altshuler et al., 2005, Mazzola-Pomietto et al., 2009) and on non-emotional contrasts within affective Go/No-Go tasks (Elliot et al., 2004). However, to our knowledge, fMRI has not been used to examine motor impulsivity in mixed episodes of BD.

With these considerations in mind, we compared the neurophysiological response on a Go/No-Go motor inhibition task in patients with mixed mania to that of healthy and psychiatric control participants. We assessed neurofunctional variations within a VLPFC-subcortical emotional network previously implicated in BD (Strakowski et al., 2005, Strakowski et al., 2011) using both exploratory voxel-wise and hypothesis driven region-of-interest (ROI) analyses. We predicted that relative to both healthy and bipolar depressed comparison groups, bipolar mixed participants would demonstrate (a) greater motor impulsivity on a Go/No-Go task, and (b) abnormal activation within the VLPFC-subcortical network.

Section snippets

Subjects

Ten adults with bipolar I disorder in a current mixed episode (BP-M) were the focus of this study and 10 adults with bipolar I disorder in a current depressed episode (BP-D) served as a patient comparison group. All patients were recruited from the inpatient psychiatry units at the University Hospital. Ten demographically matched healthy comparison (HC group) participants without any history of Axis-I psychiatric disorders in themselves or first-degree relatives were also recruited.

All

Demographic and clinical measures

As Table 1 shows, the BP-M, BP-D, and HC groups were matched on all demographic and clinical measures with the exception of premorbid IQ [F(2,27) = 4.32, p < 0.05] and, as expected, Barrett Impulsivity Scale-Version 11 (BIS-11) motor impulsiveness (Patton et al., 1995) [F(2,27) = 8.22, p < 0.01]. Overall manic severity was greater in the BP-M group by definition [t(17) = 11.48, p < 0.001], and depressive symptoms were more severe in the BP-D group [t(17) = 3.14, p < 0.01]. Because our intent was to match the

Discussion

This study was designed to examine brain activation within the VLPFC-subcortical mood circuit during a Go/No-Go task in patients with BD. We expected that patients in a mixed episode would exhibit greater behavioral deficits and neurophysiological abnormalities relative to healthy and psychiatric comparison groups.

Consistent with previous signal-detection findings in acute BD, both patient groups were less able to discriminate targets from non-targets relative to the healthy group (Fleck et

Role of funding source

This work was supported in part by a Translational Research Grant through the Dean's Discovery Fund, University of Cincinnati College of Medicine (DEF), and by National Institute of Mental Health (NIMH) grants MH071931 and MH077138 (SMS). The NIMH had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.

Conflict of interest

Dr. Strakowski served as a consultant to Pfizer and Consensus Medical Communications, and spoke for Adamed and CME Outfitters. Dr. Adler served as a speaker for Johnson & Johnson and Schering Plough/Merck. Dr. DelBello served as a speaker or consultant for Eli Lilly, Schering Plough/Merck, and Bristol-Myers Squibb. No other investigators have any financial relationships to report. The investigators have also received research grants from AstraZeneca, Eli Lilly, Johnson & Johnson, Shire,

Acknowledgements

This research was presented, in part, at the Annual Meeting of the Central Society for Clinical Research, Chicago, April, 2009.

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