Hypoactivation of the prefrontal cortex during verbal fluency test in PTSD: a near-infrared spectroscopy study

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Abstract

Several studies have suggested that there is frontal dysfunction in subjects with posttraumatic stress disorder (PTSD). We investigated the relationship between alterations of the hemodynamic response of the prefrontal cortex during a cognitive task (verbal fluency task; VFT) and memory function measured using the Wechsler Memory Scale-Revised (WMS-R). The subjects were victims of the Tokyo Subway Sarin attack with (n=8) or without (n=26) PTSD. Hemodynamic response in the prefrontal cortex was measured using a 24-channel near-infrared spectroscopy (NIRS) system. Subjects with PTSD had a significantly smaller response of oxygenated hemoglobin and total hemoglobin during the VFT compared with those without PTSD, although there was no significant difference in performance on the VFT. Subjects with PTSD had significantly lower scores on attention and concentration in the WMS-R, which was positively correlated with the increase of total hemoglobin during the VFT. The ‘frontal dysfunction’ observed in subjects with PTSD may be a secondary phenomenon to reduced attentional capacity.

Introduction

Near-infrared spectroscopy (NIRS) can non-invasively and continuously monitor alterations in oxygenated (oxyHb) and deoxygenated (deoxyHb) hemoglobin using near-infrared light, which penetrates biological tissues (Jobsis, 1977). When a brain region is activated, the blood vessels are dilated and the volume of regional cerebral blood flow increases. Oxygen consumption also increases in the activated region, but it is smaller than the increase of cerebral blood volume (Gsell et al., 2000). The dilatation of blood vessels also results in an increase of blood flow velocity. Increased blood flow efficiently flushes deoxyHb from the activated brain region. As a result, cognitive activation usually causes increased oxyHb and regional cerebral blood volume, i.e. totalHb measured by NIRS, accompanied by decreased deoxyHb. Although the exact extent of the brain region examined by each set of NIRS probes cannot be determined, the region examined is thought to be a banana-shaped region between the two optodes (Gratton et al., 1994), with a depth of 0.9 to 1.3 cm from the brain surface (Villringer et al., 1997, Koizumi et al., 1999).

Many NIRS studies have shown increases of oxyHb in the forebrain during cognitive activation in normal subjects (Hoshi and Tamura, 1993, Hoshi et al., 1994, Villringer et al., 1993, Hock et al., 1995, Villringer et al., 1997) and in patients with psychiatric disorders (Okada et al., 1994, Okada et al., 1996, Hock et al., 1996, Hock et al., 1997, Fallgatter and Strik, 2000, Matsuo et al., 2000, Matsuo et al., 2002, Matsuo et al., 2003). For example, Matsuo et al. (2002) showed that the increase of oxyHb during the verbal fluency task in the left frontal region measured by NIRS was significantly smaller in elderly patients with mood disorders than in controls, which supported our hypothesis that hypofrontality in elderly depressed patients is due to impaired vascular reactivity.

Posttraumatic stress disorder (PTSD) is an anxiety disorder elicited by exposure to a traumatic event and characterized by three categories of symptoms: persistent re-experience, avoidance and increased arousal. Functional neuroimaging studies have found prefrontal hypoactivation in subjects with PTSD during both traumatic stimuli (Shin et al., 1997, Shin et al., 1999, Lucey et al., 1997, Bremner et al., 1999, Zubieta et al., 1999, Rauch et al., 2000, Fernandez et al., 2001, Lanius et al., 2001) and cognitive tasks (Semple et al., 1996, Shaw et al., 2002, Clark et al., 2002). However, neuropsychological studies have shown cognitive impairment in subjects with PTSD (Vasterling et al., 1998, Vasterling et al., 2002, Koenen et al., 2001, Brandes et al., 2002). Vasterling et al. showed that subjects with chronic PTSD (2002) or acute onset PTSD (1998) had deficits of both attention and memory on several cognitive tasks. To our knowledge, however, there has been no functional neuroimaging study of PTSD that examined the association between the functional neuroimaging findings during frontal activation tasks and neuropsychological tests of attention and memory. The aim of our study was to investigate the relationship between the hemodynamic response of the prefrontal cortex during cognitive tasks and attention and memory, in an attempt to characterize the neuropsychological deficit in PTSD.

Section snippets

Subjects

We recruited 34 victims of the Tokyo Subway Sarin Attack, with or without PTSD, who were treated in an emergency room for acute sarin intoxication and were followed up at St Luke's International Hospital in Tokyo. This study was performed in 2000–2001, 5–6 years after the attack. None of the subjects had ever received psychiatric treatment for PTSD related to this attack. Trained psychiatrists interviewed the victims using a structured interview employing the Clinician-Administered PTSD Scale

Results

Fig. 2 presents typical time courses of the NIRS variables in subjects with or without a history of PTSD. The numbers of words answered during the VFT in the two groups were not significantly different (t=1.28, P=0.20 by Student's t-test). There was no significant correlation between the number of words answered in the VFT and the serum cholinesterase level (n=33, r=0.09) after the sarin intoxication.

Four-way repeated measures analysis of variance showed a significant main effect of task in

Discussion

We showed that the PTSD group had significantly poorer responses of oxyHb and totalHb during the VFT while their performance on the VFT did not differ from that of the non-PTSD group. The PTSD group had significantly lower scores in the category of attention and concentration in the WMS-R, which was positively correlated with the increase of totalHb during the VFT.

There have been a few neuroimaging studies of prefrontal function in subjects with PTSD during cognitive tasks. A PET study (Shaw et

Acknowledgements

This research was performed through Special Coordination Funds for Promoting Science and Technology from the Ministry of Education, Culture, Sports, Science and Technology. The authors are grateful to Dr Shin-ichi Ishimatsu (St. Luke's International Hospital, Emergency Unit), who helped us enroll the subjects, and other staff of the project, who performed interviews (Dr Noriko Maruta and Dr Shunichi Furukawa), psychological assessment (Mr Riichi Someya) and MRI examinations (Dr Haruyasu Yamada

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