Abnormal neural activity in the patients with remitted geriatric depression: A resting-state functional magnetic resonance imaging study

Abstract

Objective

To investigate regional activity abnormalities of first-episode remitted geriatric depression (RGD) using a resting-state functional magnetic resonance imaging (fMRI) in closely matched patients and healthy controls, and to examine the relationship between performances on neuropsychological tests and regional activity abnormalities.

Method

A newly reported regional homogeneity approach was used to analyze blood oxygen level-dependent fMRI data on resting state in 18 patients with remitted geriatric depression and 14 well-matched healthy controls. All subjects were measured by neuropsychological tests.

Results

Decreased regional homogeneity (ReHo) in remitted geriatric depression distributed over the frontal, temporal and parietal lobes. In addition, increased ReHo were found mainly in the putamen, frontal and parietal lobes. The RGD patients performed significantly worse in the delayed recall of Rey Auditory Verbal Learning Test (RAVLT) and Trail Making Test A and B (seconds) when compared with the control group. And there are significant negative correlations between ReHo values of right putamen, left superior frontal gyrus and Trail Making Test A (seconds) (r = − 0.583, P = 0.023; r = − 0.598, P = 0.018, respectively), Trail Making Test B (seconds) (r = − 0.587, P = 0.021; r = − 0.545, P = 0.036, respectively) in the patients with RGD.

Limitations

This study is cross-sectional, therefore it cannot determine whether abnormal brain activation is a state marker or trait marker of RGD in resting-state fMRI.

Conclusion

Our study reveals that RGD is associated with abnormal activity of certain brain regions, which are believed to be involved in the psychopathology and pathophysiology of executive function in remitted geriatric depression.

Introduction

Depression is one of the most common mental disorders in the elderly. It is associated with a decline in both well-being and daily functioning and with a high risk of functional impairment, a high risk of mortality, and a high rate of service utilization (Taki et al., 2005).

Positron emission tomography (PET) and event-related functional magnetic resonance imaging (fMRI) studies have consistently reported abnormal activation in first episode or naive patient with major depressive disorder (MDD), with predominantly decreased activation of cortical regions including the dorsolateral prefrontal cortex (Anand and Shekhar, 2003, Ketter, 1996, Mayberg et al., 1999) and anterior cingulate cortex (Drevets et al., 1997), but increased activation of limbic regions such as medial thalamus, striatum, and amygdala (Mayberg et al., 1999, Drevets, 2000, Sheline et al., 2001, Siegle et al., 2002). In contrast, there is less consensus on the changes in functional brain activity in remitted depression. PET studies in remitted depression have also demonstrated abnormalities of focal metabolism, specifically increased metabolism in anterior cingulate, orbitofrontal cortex, and medial thalamus during tryptophan depletion (Neumeister et al., 2004) and reduced metabolism in the pregenual anterior cingulate during induced sadness (Liotti et al., 2002). These studies suggested that metabolic activity of several regions may serve as “signatures” not merely of a depressive “state”, but of a depressive “trait”.

In the first resting-state fMRI study, Biswal et al. (1995) found that low-frequency fluctuation was highly synchronous among motor cortices of healthy human, concluding that the low-frequency fluctuation of blood flow and oxygenation was indeed a neurophysiological index. Since then, resting-state fMRI is being increasingly widely researched in the human brain function and dysfunction. Most of these studies, however, have used functional connectivity analysis, measuring the correlation coefficients of all brain areas with a predefined region of interest (Greicius et al., 2007). An area showing abnormal functional connectivity with other areas may not be necessarily abnormal itself. Therefore, it is important to investigate the regional activity.

The assessment of regional homogeneity (ReHo), a data-driven method, assumes that a given voxel is temporally similar to its neighbors. It measures the ReHo of the time series of the regional blood oxygen level-dependent (BOLD) signal. Therefore, ReHo reflects the temporal homogeneity of the regional BOLD signal rather than its density. As the BOLD signal of fMRI may reflect neural activity (Logothetis et al., 2001), abnormal ReHo is possibly relevant to the changes of temporal aspects of neural activity in the regional brain, and thus ReHo may be used to detect the brain regions with abnormal activity. To update, The ReHo method has been used to explore regional neural activity pattern in the resting state in only four papers, including healthy volunteers (Zang et al., 2004), schizophrenia (Liu et al., 2006, Shi et al., 2007) and attention deficit hyperactivity disorder (ADHD) (Cao et al., 2006). Liu et al. (2006) reported that decreased ReHo was found in many brain areas in schizophrenic patients by using resting-state fMRI. Cao et al. (2006) indicated that boys with ADHD showed decreased regional homogeneity in the frontal–striatal–cerebellar circuits, but increased regional homogeneity mainly in the occipital cortex. Together, the two studies suggested that the ReHo approach could be potentially useful in revealing the pathophysiology of psychiatric disorders in the resting state. As yet there has been no report of regional neural activity pattern in MDD by resting-state fMRI with ReHo method. The aim of this study is to explore the regional brain activity of patients with remitted geriatric depression by using resting-state fMRI with ReHo method.