Frontal lobe function in bipolar disorder: A multichannel near-infrared spectroscopy study
Introduction
Bipolar disorder and major depressive disorder (major depression) are two of the principal disorders among mood disorders. Although their etiology and pathophysiology have not yet been completely elucidated, a number of structural and functional neuroimaging studies suggest the importance of the frontal lobe. For example, a reduction in the volume of cerebral regions (Beyer and Krishnan, 2002, Fossati et al., 2004, Sheline, 2003, Strakowski et al., 2002), particularly the gray matter and glial cell density (Davidson et al., 2002) in the frontal lobe, has been reported in structural neuroimaging studies. In functional neuroimaging studies using positron emission tomography (PET), single-photon emission computed tomography (SPECT), or functional magnetic resonance imaging (fMRI), abnormal changes in cerebral glucose metabolism and cerebral blood flow have been demonstrated, particularly in the prefrontal cortex (Drevets, 2000, Stoll et al., 2000, Videbech, 2000), and they were often reported to be associated with cognitive dysfunctions in some studies (Sweeney et al., 2000, Veiel, 1997).
In many of the functional neuroimaging studies demonstrating abnormal prefrontal functions, mixed patients with bipolar disorder and major depression were examined; that is, different diagnostic groups (e.g., bipolar disorder and major depression) with various mood states (e.g., depressed and manic) were often classified into one patient group (Strakowski et al., 2000). Differences in abnormalities in frontal lobe functions between patients with bipolar disorder and those with major depression have been suggested in recent studies, in which depressed patients with bipolar disorder and those with major depression were examined separately. Decreased prefrontal activity (hypofrontality) both at rest and during an activation task has been consistently demonstrated in depressed patients with major depression in a number of PET, SPECT, and fMRI studies (Brody et al., 2001, Drevets, 2000, Liotti and Mayberg, 2001, Malhi et al., 2004b, Rogers et al., 2004).
On the other hand, in depressed patients with bipolar disorder, the reported changes in the frontal lobe function during an activation task are so far inconsistent (Strakowski et al., 2000, Strakowski et al., 2004) although changes at rest are consistent in showing decreased activity (Blumberg et al., 2002): increased activity (visuospatial working memory task, Chang et al., 2004), decreased activity (Stroop task, Blumberg et al., 2003; auditory discrimination continuous performance task, Ketter et al., 2001; positive affect induction, Malhi et al., 2004a; emotional recognition, Yurgelun-Todd et al., 2000), and unchanged frontal lobe functions (semantic decision task, Curtis et al., 2001) compared to healthy controls have been reported, even within the same task, that is the verbal fluency task (increased activity, Curtis et al., 2001; decreased activity, Matsuo et al., 2002, Matsuo et al., 2004; unchanged function, Dye et al., 1999).
As far as the authors surveyed, only two research groups have directly contrasted the frontal lobe functions between depressed patients with bipolar disorder and those with major depression, but these studies showed inconsistent results. In near-infrared spectroscopy (NIRS) studies, Matsuo et al. found reduced [oxy-Hb] increases in the prefrontal region during a verbal fluency task in both the bipolar disorder and major depression groups compared with the healthy control groups, and found no significant differences between the bipolar disorder and major depression groups (Matsuo et al., 2000, Matsuo et al., 2002, Matsuo et al., 2004, Matsuo et al., 2005). However, in fMRI study, Lawrence et al. (2004) found larger prefrontal activations in response to emotional stimuli in the bipolar disorder group than in the major depression group. The reasons for the differences in the results of these research groups have not been clarified.
NIRS is a recently developed noninvasive functional neuroimaging technique. NIRS can detect regional cerebral blood volume (rCBV) changes in terms of changes in oxy hemoglobin concentration ([oxy-Hb]) and deoxy hemoglobin concentration ([deoxy-Hb]). The principle of NIRS is based on the modified Lambert–Beer law, and NIRS monitors the absorption of near-infrared light by oxy and deoxy hemoglobin using two different wavelengths. Both the [oxy-Hb] increase and [deoxy-Hb] decrease detected by NIRS have been shown to reflect cortical activation by simultaneous measurements using other methodologies (Hock et al., 1997, Kleinschmidt et al., 1996, Mehagnoul-Schipper et al., 2002, Toronov et al., 2001). The correlations with cerebral blood flow have been shown to be stronger for [oxy-Hb] than for [deoxy-Hb] (Malonek et al., 1997, Strangman et al., 2002b). In an animal study using a perfused brain rat model, [oxy-Hb] was also demonstrated to be the most sensitive marker of CBF changes among [oxy-Hb], [deoxy-Hb], and [total-Hb] (Hoshi et al., 2001).
NIRS has some advantages and disadvantage over other functional neuroimaging methodologies such as PET, SPECT, and fMRI. The three advantages of NIRS are (1) the complete noninvasiveness of the measurement enabling repeated measurements, (2) the high time resolution of 0.1 s enabling a detailed clarification of temporal changes in rCBV, and (3) the portability and compactness of its apparatus enabling measurements under natural conditions with subjects sitting on a comfortable chair. The disadvantages of NIRS are that it measures hemoglobin concentrations (1) only as relative changes, not as absolute values, (2) only in the cortex immediately beneath the probes but not in deeper brain structures, (3) with a high time resolution but with a low spatial resolution, and (4) not only in the brain but also in other surface structures, such as the skin and skull. Considering the advantages and disadvantages described above, NIRS is assumed to be particularly useful in assessing the dynamic aspects of cortical activation in rather broad areas.
NIRS has been demonstrated to enable the detection of brain activations during cognitive tasks in healthy controls (reviewed by Hoshi, 2003, Obrig and Villringer, 2003, Strangman et al., 2002a). For mood disorders, several NIRS studies have been conducted. Okada et al. (1996) reported no dominant hemispheric changes in [total-Hb] in the prefrontal area of patients with major depression during a mirror drawing task. In addition to Matsuo et al., 2000, Matsuo et al., 2002, Matsuo et al., 2005 as described above, both Suto et al. (2004) and Herrmann et al. (2004) reported reduced frontal activation during a verbal fluency task in patients with major depression. Eschweiler et al. (2000) found that reduced [oxy-Hb] increases predict a good therapeutic efficacy of repetitive transcranial magnetic stimulation in patients with major depression.
In the present study, we evaluated the spatial and temporal characteristics of rCBV changes during cognitive activation in patients with bipolar disorder by multichannel NIRS, and compared them with those in patients with major depression. The verbal fluency task was employed as cognitive activation and the finger-tapping task as cognitively undemanding control activation. The inconsistency in frontal lobe activation in bipolar disorder has not been clarified in any functional neuroimaging methodologies as described above, and there have been no studies that assessed the temporal characteristics of cerebral activation in mood disorders except a NIRS study in our laboratory (Suto et al., 2004). The objectives of the present study are (1) to clarify the characteristics of brain activations in patients with bipolar disorder along the task time course with the aid of the high time resolution of NIRS and (2) to compare them with those in healthy controls as well as patients with major depression of similar psychopathology. We hypothesized that (1) the characteristics of the frontal lobe function are expressed more clearly in cognitive activation than in control motor activation, (2) cognitive activations in bipolar disorder are consistent in some time segments and inconsistent in other time segments with those in major depression, and (3) such differences in activations along the time course can explain, at least in part, the inconsistent results in cognitive activation regarding bipolar disorder.
Section snippets
Subjects
Seventeen patients with bipolar disorder, 11 patients with major depression, and 17 healthy controls participated in the present study (Table 1). The patients with bipolar disorder and those with major depression were recruited among the outpatients and inpatients at Gunma University Hospital, and were diagnosed according to the criteria in the Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (American Psychiatric Association 1994).
The patients with bipolar disorder included 11
Cognitive activation
The numbers of words generated during the verbal fluency task were not significantly different among the three groups (healthy control: mean, 16.5; SD, 3.6; bipolar disorder: mean, 14.7; SD, 4.4; major depression: mean, 14.2; SD, 5.6; one-way ANOVA F = 1.15, P = 0.33). The grand averaged waveforms of [oxy-Hb], [deoxy-Hb], and [total-Hb] during the verbal fluency task in the healthy control, bipolar disorder, and major depression groups are shown in Fig. 1, Fig. 2, Fig. 3, respectively. The
Summary of obtained results
In the present study, the rCBV changes during the cognitive and motor tasks in the bipolar disorder group were compared with those in the healthy control and major depression groups. rCBV increases were successfully demonstrated by NIRS during both the cognitive and motor activations in all the three groups. Their time courses were different among the three groups: the [oxy-Hb] increases in the bipolar disorder group were smaller in the early task period but larger in the late task period than
Acknowledgments
This research was supported in part by a Grant-in-Aid for Scientific Research (C) from the Japanese Ministry of Education, Culture, Sports, Science and Technology (MF), a Health and Labor Sciences Research Grant for Research on Psychiatric and Neurological Diseases and Mental Health (MF), and a Health and Labor Sciences Research Grant for Special Research from the Japanese Ministry of Health, Labor and Welfare (MM).
We thank Dr. Itsuro Ida, Dr. Akihiko Oshima, and Mr. Suguru Hattori of the
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