Frontal and temporal cortical functional recovery after electroconvulsive therapy for depression: A longitudinal functional near-infrared spectroscopy study

https://doi.org/10.1016/j.jpsychires.2017.02.018Get rights and content

Highlights

  • This is the first longitudinal study to investigate the effect of ECT, using NIRS.

  • ECT normalized functional responses to a cognitive task in the frontal cortices.

  • Cortical responsiveness was positively correlated with improved depression.

  • NIRS is an appropriate technique for evaluating severe psychiatric conditions.

Abstract

While the efficacy and tolerability of electroconvulsive therapy (ECT) for depression has been well established, the acute effects of ECT on brain function remain unclear. Particularly, although cognitive dysfunction has been consistently observed after ECT, little is known about the extent and time course of ECT-induced brain functional changes, as observed during cognitive tasks. Considering the acute antidepressant effects of ECT on depression, aberrant brain functional responses during cognitive tasks in patients with depression may improve immediately after this treatment. To clarify changes in cortical functional responses to cognitive tasks following ECT, we used task-related functional near-infrared spectroscopy (NIRS) to assess 30 patients with major depressive disorder or bipolar depression before and after an ECT series, as well as 108 healthy controls. Prior to ECT, patients exhibited significantly smaller [oxy-Hb] values in the bilateral frontal cortex during a letter verbal fluency task (VFT) compared with healthy controls. We found a significant increase in [oxy-Hb] values in the bilateral frontal cortex during the VFT after ECT in the patient group. A decrease in depression severity was significantly correlated with an increase in [oxy-Hb] values in the right ventrolateral prefrontal cortex following ECT. This is the first NIRS study to evaluate brain functional changes before vs. after ECT. Impaired functional responses, observed during the cognitive task in depressed patients, were normalized after ECT. Thus, recovery from abnormal functional responses to cognitive tasks in the frontal brain regions may be associated with the acute therapeutic effects of ECT for depression.

Introduction

Approximately 350 million individuals worldwide suffer from depression, which is reportedly the leading cause of disability in the world, and a major contributor to the overall global burden of disease (World Health Organization, 2016). Despite developments in psychopharmacology and psychotherapy, up to 30% of patients poorly respond to these treatments (Rush et al., 2006). Patients with treatment resistant depression are considered candidates for electroconvulsive therapy (ECT). ECT is known as the most acutely effective treatment for depression, and has been employed for over 70 years. Although the clinical efficacy and tolerability of this treatment have been well established (Gazdag et al., 2009, UK ECT Review Group, 2003), the mechanisms underlying the therapeutic effects of ECT remain elusive (Abbott et al., 2014, Bolwig, 2014, Farzan et al., 2014, Zhuo and Yu, 2014).

Previous neuroimaging studies of depression have consistently found a general pattern of increased activity in the limbic regions, including the amygdala, with reduced activity in the prefrontal regions, particularly the lateral prefrontal cortex (Fitzgerald et al., 2008, Hamilton et al., 2012, Koenigs and Grafman, 2009). Reversal or normalization of these processes has also been demonstrated following treatment with antidepressants (Delaveau et al., 2011). Additionally, previous neuroimaging studies using, positron emission tomography (PET), single photon emission computed tomography (SPECT), and functional magnetic resonance image (fMRI) have revealed functional changes in the brain following ECT (Abbott et al., 2014, Bolwig, 2014, Farzan et al., 2014, Zhuo and Yu, 2014). These neuroimaging data have consistently demonstrated short-term decreases in frontal perfusion and metabolism, and increased slow wave electroencephalography (EEG) oscillations after ECT (Abbott et al., 2014, Bolwig, 2014, Zhuo and Yu, 2014), indicating that ECT may induce hypofrontality. This additional hypofrontality in the lateral prefrontal cortex observed after ECT is contradictory given the acute antidepressant effects of ECT (Nobler et al., 2001). This discrepancy may be attributable to the methodological limitations of previous studies. Severely depressed patients may have difficulty engaging in time-consuming neuroimaging studies, especially those that involve being restrained, such as fMRI and EEG. As a result, neuroimaging studies have mainly investigated resting-state brain function, and functional neuroimaging studies that assess tasks with a high cognitive load are scarce (Abbott et al., 2014, Zhuo and Yu, 2014). However, although evidence of cognitive dysfunction has been consistently observed after ECT (Bodnar et al., 2015, Semkovska and McLoughlin, 2012), the associations between such cognitive dysfunctions and brain function have not been thoroughly investigated. Indeed, only three longitudinal ECT studies have investigated task-related brain function (Christ et al., 2008, Beall et al., 2012, Zwanzger et al., 2016), and only one study investigated brain function during a cognitive task (2-back task) after ECT (Beall et al., 2012). However, this study had a very small sample size (n = 6) and lacked a healthy control group (Beall et al., 2012).

Near-infrared spectroscopy (NIRS) is a relatively new functional neuroimaging technique that has received increasing attention in the fields of psychiatry and neuroscience. Compared with PET and MRI, NIRS is advantageous in that it is noninvasive, safe, low-cost, restraint-free, and compact. Accordingly, NIRS is a suitable device for investigating brain function in individuals with severe psychiatric disorders during cognitive tasks. NIRS can identify changes in regional cerebral blood volume (rCBV) with a high temporal resolution (0.1 s), specifically, using near-infrared light to measure changes in the concentrations of oxy-hemoglobin ([oxy-Hb]) and deoxy-hemoglobin ([deoxy-Hb]) (Ohmae et al., 2006, Villringer and Chance, 1997).

Considering the acute antidepressant effects of ECT, it is possible that frontal functional responses to cognitive tasks are improved immediately after ECT treatment. To investigate such changes in frontal functional responses to cognitive tasks after ECT, we used a 52-channel NIRS to examine [oxy-Hb] values in the frontal and temporal cortices during a verbal fluency task (VFT) before and after ECT in patients with severe depression or bipolar disorder.

Section snippets

Trial setting

In this prospective study, we compared changes in [oxy-Hb] values in the frontal and temporal brain cortices before (T1) vs. after ECT (T2: within 2 weeks of the completion of the ECT series) in individuals with depression. This clinical trial was conducted at Keio University Hospital from June 2013 through December 2015. The study protocol was prepared in accordance to the ethical standards of the Declaration of Helsinki and approved by the Keio University Hospital review board. Written

Demographic and clinical characteristics

Of 36 patients evaluated, 30 were eligible for statistical analysis (11 men, mean age: 59.4 ± 14.2 years old). Of those excluded, 2 patients completed only one session of ECT (both voluntarily discontinued ECT), 3 patients were not able to complete the post-NIRS scan for logistical reasons, and 1 patient had incomplete pre-NIRS scan data. Patients were selected for ECT, due to treatment resistant depression (n = 27), past history of response to ECT treatment (n = 9). The age at onset of illness

Discussion

Prior to ECT, patients in the DEP group exhibited lower [oxy-Hb] values compared with those in the HC group, as measured via NIRS. However, the DEP group exhibited significantly increased [oxy-Hb] values after ECT in the frontal and temporal brain regions. The smaller [oxy-Hb] values at baseline were generally normalized at the endpoint. Specifically, it was evident that the waveform recorded at the FP and the left DLPFC was normalized at the endpoint (Fig. 2). In the right VLPFC, improvement

Conclusion

We found that hypofrontality during the VFT at baseline was normalized after ECT. Moreover, cortical functional responses to an activation task were positively correlated with the degree of improvement in depressive symptoms. Along with affirming the high level of safety, low cost, comfort, and high temporal resolution of NIRS, the present data may provide new neurobiological evidence for understanding the mechanisms of the acute antidepressant effects of ECT.

Role of the funding source

This study received funding from Elli Lilly (no grant number).

Contributors

J. Hirano designed the study, wrote the protocol, assessed depression severity, conducted the literature search, statistically analyzed the data, and wrote the first draft of manuscript. A. Takamiya was involved in patient recruitment, the assessment of depression severity, and the literature search. S. Hotta, and Y. Miyasaka conducted the NIRS scans. A. Iwanami and Shenghong Pu analyzed the healthy control data. B. Yamagata, H. Uchida, and M. Mimura wrote the final version of the manuscript.

Acknowledgements

The authors are grateful to Mr. Shingo Kawasaki at Hitachi Co. for technical support and to Dr. Hitoshi Sakurai at Keio University for advice regarding the manuscript.

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