**1. Introduction**

352 Neuroimaging – Cognitive and Clinical Neuroscience

Roelcke, U., Curt, A., Otte, A., Missimer, J., Maguire, R.P., Dietz, V., and Leenders, K.L.

Roelcke, U., Curt, A., Otte, A., Missimer, J., Maguire, R.P., Dietz, V., and Leenders, K.L.

Ruben, J., Schwiemann, J., Deuchert, M., Meyer, R., Krause, T., Curio, G., Villringer, K.,

Seifert, F. and Maihofner, C. (2007). Representation of cold allodynia in the human brain--a

Seitz, R.J. and Roland, P.E. (1992). Vibratory stimulation increases and decreases the

Servos, P., Zacks, J., Rumelhart, D.E., and Glover, G.H. (1998). Somatotopy of the human

Sterr, A., Shen, S., Zaman, A., Roberts, N., and Szameitat, A. (2007). Activation of SI is

Stippich, C., Hofmann, R., Kapfer, D., Hempel, E., Heiland, S., Jansen, O., and Sartor, K.

Stippich, C., Hofmann, R., Kapfer, D., Hempel, E., Heiland, S., Jansen, O., and Sartor, K.

Takanashi, M., Abe, K., Yanagihara, T., Oshiro, Y., Watanabe, Y., Tanaka, H., Hirabuki, N.,

Tempel, L.W. and Perlmutter, J.S. (1990). Abnormal vibration-induced cerebral blood flow

Tempel, L.W. and Perlmutter, J.S. (1992). Vibration-induced regional cerebral blood flow

Tharin, S. and Golby, A. (2007). Functional brain mapping and its applications to

Toga, A. W. and Mazziotta, J. C. Brain Mapping. The Methods. Second Edition. Academic

Wienbruch, C., Candia, V., Svensson, J., Kleiser, R., and Kollias, S.S. (2006). A portable and low-

Xu, X., Fukuyama, H., Yazawa, S., Mima, T., Hanakawa, T., Magata, Y., Kanda, M., Fujiwara, N.,

system in clinical and research environments. Neurosci Lett *398*, 183-8.

perception in the human brain studied by PET. Neuroreport *8*, 555-9.

cost fMRI compatible pneumatic system for the investigation of the somatosensensory

Shindo, K., Nagamine, T., and Shibasaki, H. (1997). Functional localization of pain

responses in idiopathic dystonia. Brain *113 ( Pt 3)*, 691-707.

neurosurgery. Neurosurgery *60*, 185-201; discussion 201-2.

responses in normal aging. J Cereb Blood Flow Metab *12*, 554-61.

study. J Neurol Neurosurg Psychiatry *62*, 61-5.

study. J Neurol Neurosurg Psychiatry *62*, 61-5.

somatosensory cortex. Cereb Cortex *11*, 463-73.

functional MRI study. Neuroimage *35*, 1168-80.

arm using fMRI. Neuroreport *9*, 605-9.

study in humans. Brain Res Bull *54*, 125-9.

Neuroreport *18*, 607-11.

Neurosci Lett *277*, 25-8.

Neurosci Lett *277*, 25-8.

Press, San Diego, CA, 2002.

tomography (PET) study. Acta Neurol Scand *86*, 60-7.

(1997a). Influence of spinal cord injury on cerebral sensorimotor systems: a PET

(1997b). Influence of spinal cord injury on cerebral sensorimotor systems: a PET

Kurth, R., and Villringer, A. (2001). Somatotopic organization of human secondary

regional cerebral blood flow and oxidative metabolism: a positron emission

modulated by attention: a random effects fMRI study using mechanical stimuli.

(1999a). Somatotopic mapping of the human primary somatosensory cortex by fully automated tactile stimulation using functional magnetic resonance imaging.

(1999b). Somatotopic mapping of the human primary somatosensory cortex by fully automated tactile stimulation using functional magnetic resonance imaging.

Nakamura, H., and Fujita, N. (2001). Effects of stimulus presentation rate on the activity of primary somatosensory cortex: a functional magnetic resonance imaging CO is a tasteless, odorless and colorless gas. The existence of endogenous CO in the human body arises from heme catabolism (Meredith and Vale 1988; Ernst and Zibrak 1998) and oxidation of organic molecules (Marilena 1997). Endogenous CO acts as a neurotransmitter for long-term potentiation, consequently playing a key role in memory and learning (Marilena 1997). It also plays a role in modulating inflammation, apoptosis, cell proliferation, mitochondrial biogenesis (Weaver 2009) and vascular relaxation (Marilena 1997).

Exogenous sources of CO intoxication include smoking, forest fires, pollutants, and improper usage of heaters or furnaces (Weaver 2009; Kumar, Prakash et al. 2010). CO intoxication usually indicates exposure to exogenous sources and is considered one of the most common causes of poisoning worldwide (Prockop and Chichkova 2007; Weaver 2009), with 1000 deaths annually in Britain (Meredith and Vale 1988), and 4000-6000 deaths annually in the United States (Tibbles and Perrotta 1994; Ernst and Zibrak 1998; Weaver 1999). In Asia, the exact epidemiology remains unclear. In Japan, Hong Kong and Taiwan, a common CO etiology of intoxication is charcoal burning suicide (Lee, Chan et al. 2002). In Japan, poisoning by charcoal burning is the most lethal form of suicide and is a highly prevalent method among men aged 25-64 years of age (Kamizato, Yoshitome et al. 2009), in contrast to a high rate of drug poisoning as a method of suicide in women. In Hong Kong, the risk factors of suicide by charcoal burning are male and living alone with financial stress (Lee and Leung 2009). In Taiwan, charcoal burning was not a common method of suicide before 1998, with a rate of only 0.14 per 105 people per year (Lin and Lu 2008). With the dissemination of media and the internet, the rate of charcoal burning suicides dramatically increased by 40-fold, reaching a rate of 5.38 per 105 people per year in 2005 (Lin and Lu 2008).

Neuroimaging Studies in Carbon Monoxide Intoxication 355

1998), cerebral cortical (Choi, Lee et al. 1992; Kao, Hung et al. 1998), and white matter (WM) (Sesay, Bidabe et al. 1996) areas have been noticed. Cerebral WM and the globus pallidum (GPi) were noted to have relatively low cerebral blood flow after acute CO intoxication in

Hypoxia in the CNS induces decreased adenosine-5'-triphosphate, influx of Ca2+ and Na+, release of glutamate, noradrenaline and acetylcholine and causes cell swelling and death (Weinachter, Blavet et al. 1990; Kluge 1991). Increased glutamate with both neuronal necrosis and apoptosis was noted immediately after CO intoxication in one animal study (Piantadosi, Zhang et al. 1997). However, how hypoxia affects the CNS in the acute stage of CO intoxication has not been well established (Piantadosi, Zhang et al. 1997; Gorman, Drewry et al. 2003). Aside from changes of cerebral blood flow and hypoxia, increasing intracranial pressure and brain tissue necrosis have been noted in animals and humans after acute CO intoxication (Jiang and Tyssebotn 1997; Piantadosi, Zhang et al. 1997; Uemura,

The pathogenesis of delayed CNS injury in CO intoxication is complicated. Hypoperfusion (Sesay, Bidabe et al. 1996; Watanabe, Nohara et al. 2002; Chu, Jung et al. 2004) and hypoxia (Opeskin and Drummer 1994) still play an important role. Demyelination (Murata, Kimura et al. 2001; Kamijo, Soma et al. 2007; Ide and Kamijo 2008), cytotoxic edema (Kim, Chang et al. 2003; Chu, Jung et al. 2004; Kwon, Chung et al. 2004), hemorrhage (Ramsey 2001) and infarction (Schwartz, Hennerici et al. 1985; Sung, Yu et al. 2010) have also been associated with delayed neurological deficits. Hypoperfusion and cytotoxic edema in delayed CNS injury have been noted in WM areas and the cerebral cortex (Chu, Jung et al. 2004), and ischemia and necrosis have been noted in the globus pallidus (Chang, Han et al. 1992). Although demyelination and axonal damage might co-exist in CO intoxication, demyelination more than axonal damage is suggested in the literature (Chang, Han et al.

1992; Murata, Kimura et al. 2001; Kamijo, Soma et al. 2007; Ide and Kamijo 2008).

CO also inhibits a number of proteins essential for cells. Myoglobin in the heart and skeletal muscle systems, neuroglobin in the brain, cytochrome P450 (Weiner 1986), dopamine and tryptophan oxygenase (Raub and Benignus 2002) have all been reported to be affected. A high CO concentration transforms xanthine dehydrogenase to xanthine oxidase and produces more free radicals in tissues (Piantadosi, Tatro et al. 1995). Inhibiting the normal function of these intracellular proteins causes further damage or systemic injury in CO

The diagnosis of CO intoxication is based on the clinical history of exposure or elevated carboxyhemoglobin level (> 10%) (Handa and Tai 2005; Chang, Lee et al. 2009). There is currently no definition of clinical staging in CO intoxication in the literature, although the pathophysiology follows that of hypoxic–ischemic encephalopathy (Gutierrez, Rovira

one animal study (Okeda, Matsuo et al. 1987).

Harada et al. 2001; Lo, Chen et al. 2007).

**2.4.2 Chronic CNS injury** 

**2.5 Other mechanisms** 

**3. Clinical manifestation** 

**3.1 The diagnosis of CO intoxication** 

intoxication.

et al.).
