**2. Positron Emission Tomography**

In the 1980s, Positron Emission Tomography (PET) was used for the first time to detect focal neuronal activation within the primary somatosensory cortex of humans induced by

<sup>\*</sup> M. Seidl1, M. Christova2, E. Gallasch2, A.B. Kunz1,5, R. Nardone1,3, E. Trinka1 and F. Gerstenbrand4,5

*<sup>1</sup>Department of Neurology and Neuroscience Institute, Paracelsus Medical University Salzburg, Austria 2Institute of Physiology, Medical University Graz, Austria 3Department of Neurology, F. Tappeiner Hospital Meran, Italy 4Department of Neurology, Medical University Innsbruck, Austria 5Karl Landsteiner Institute for Neurorehabilitation and Space Neurology Vienna, Austria* 

Somatosensory Stimulation in Functional Neuroimaging: A Review 335

model of spatial attention in which potential signal enhancement may rely on generalized

In the same year, Ibanez et al. demonstrated in a PET study that there is no evidence that the primary motor and supplementary motor area are involved in the generation of the P22 and N30 components of somatosensory evoked potentials (SSEPs) caused by electrical stimulation of the median nerve at the wrist (Ibanez et al., 1995). PET was performed in normal subjects to study the cerebral areas activated by median nerve electrical stimulation at frequencies of up to 20 Hz. Stimulation evoked a single focus of activation in the primary somatosensory area. An increase of the regional cerebral blood flow in this area was linearly correlated with stimulus frequencies of up to 4 Hz and then reached a plateau. The supplementary motor area was not significantly activated by stimulation at any of the frequencies tested. In contrast to the primary somatosensory area, the supplementary motor area showed no trend toward a correlation between the regional cerebral blood flow changes and the stimulus repetition rate. These results suggested that a contribution of the primary motor cortex and the supplementary motor area to the generation of the P22 and

H215O PET studies with different application forms and intensities of innocuous and noxious thermal stimuli were performed by Casey et al (Casey et al., 1994;Casey et al., 1996) to identify the forebrain and brain stem structures that are active during the perception of acute heat pain in humans. Healthy subjects received repetitive noxious (50°C) and innocuous (40°C) heat pulses with duration of five seconds to the forearm and each subject rated the subjective intensity of each stimulation series. Significant regional cerebral blood flow with a maximum at 50°C stimuli was found in the thalamus, the cingulate cortex, the secondary and primary somatosensory cortex, the insula, the medial dorsal midbrain and the cerebellar vermis. In the second study noxious and innocuous heat and cold thermal

A detailed analysis of somatosensory representations within the parietal postcentral gyral and the lateral sulcal-opercular cortex in a H215O PET study was performed by Burton et al. (Burton et al., 1997). To investigate the issue of possible multiple activation foci in these regions and possible differences due to stimulating skin directly or through an imposed tool, changes in the regional cerebral blood flow during passive tactile stimulation of one or two fingertips were studied. Restrained fingers were rubbed with embossed gratings using a rotating drum stimulator. For different scans, gratings touched the skin directly for optimal stimulation of cutaneous receptors (skin mode stimulation) or indirectly by using an imposed guitar plectrum snugly fitted to the same fingers (tool mode stimulation). The latter was expected to better stimulate deep receptors better. The subjects were asked to estimate the roughness after each scan. Direct skin contact activated statistically validated foci in both hemispheres, on the contralateral side these foci occurred in the anterior and posterior limbs of the postcentral gyrus and on the ipsilateral side only in the posterior limb. Tool mode stimulation activated one contralateral focus that was in the posterior limb of the postcentral gyrus. These results suggested at least two maps for distal fingertips in the primary somatosensory area with the anterior and posterior foci corresponding, respectively, to activations in the Brodmann area 3b and the junction between the Brodmann areas 1 and 2. In the contralateral secondary somatosensory area, skin mode stimulation activated a peak that was anterior and medial to a focus associated with tool mode stimulation. The magnitude of the PET counts contralateral to stimulation was higher in the anterior primary and secondary somatosensory regions during initial scans, but reversed to

stimuli to the non-dominant arm of healthy subjects were applied.

suppression of background activity.

N30 components of SSEPs is unlikely.

cutaneous vibratory stimulation with a vibration frequency of 50 Hz and an amplitude of 1 mm (Fox et al., 1987). H215O labeled water was used as a blood flow tracer. The cutaneous surfaces of lips, fingers, and toes were tested. Intense and highly focal distinct responses within the primary somatosensory cortex with a medial-to-lateral homunculus were seen in each subject. The study demonstrated that eliciting regional cerebral blood flow responses within the somatosensory cortex by cutaneous vibration provides a safe, rapid, and reproducible tool for locating and assessing its functional status and for the localization of the central sulcus that is crucial in preoperative neurosurgical planning. The study has established normative values for future applications of the vibration paradigm in functional brain imaging.

In 1990, Tempel and Perlmutter compared the regional cerebral blood flow responses to vibrotactile stimulation in patients with predominantly unilateral idiopathic focal dystonia and normal subjects using H215O PET (Tempel and Perlmutter, 1990). The somatosensory stimulation led to consistently localized and robust peak response in the primary sensorimotor cortex, contralateral to hand vibration in normal subjects. The sensorimotor response in dystonic patients was also consistently localized to the same area, but significantly reduced in magnitude when vibrating the affected as well as the unaffected hand. Furthermore, vibration induced a dystonic cramp in the stimulated arm and hand in some patients, but in no normal subjects. This abnormal sensorimotor response had important implications for the understanding of the pathophysiology of idiopathic dystonia. Two years later, Tempel and Perlmutter performed another significant H215O PET study with vibration-induced regional cerebral blood flow responses in healthy young and elder subjects in order to investigate whether vibration-induced regional cerebral blood flow responses change with increasing age (Tempel and Perlmutter, 1992). Left and right hand vibration led to consistent responses within the contralateral primary sensorimotor cortex and the supplementary motor area with no changes in the physiologically aging brain.

In the same year, Seitz and Roland were able to demonstrate with a vibratory stimulus to the right hand palm of healthy volunteers and H215O PET that activation of some cerebral structures is accompanied by deactivations of corresponding other structures elsewhere in the brain (Seitz and Roland, 1992). Increases in the regional cerebral blood flow were localized in the left primary somatosensory area, the left secondary somatosensory area, the left retroinsular field, the left anterior parietal cortex, the left primary motor area, and the left supplementary motor area. The decreases occurred bilaterally within the superior parietal cortex, paralimbic association areas, and the left globus pallidus. The mean global cerebral blood flow did not change compared with rest. The decreases in cerebral oxidative metabolism were interpreted as regional depressions of synaptic activity.

In an H215O PET study by Drevets et al., changes in the human primary and secondary somatosensory cortices during the period when somatosensory stimuli were expected were investigated (Drevets et al., 1995): In anticipation of either focal or innocuous touching, or localized, painful shocks, the blood flow decreased in the parts of the primary somatosensory cortex located outside the representation of the skin locus of the expected stimulus. Specifically, attending to an impending stimulus to the fingers produced a significant decrease in blood flow in the somatosensory zones for the face, whereas attending to stimulation of the toe produced decreases in the zones for the fingers and face. Decreases were more prominent in the side ipsilateral to the location of the expected stimulus. No significant changes in the blood flow occurred in the region of the cortex representing the skin locus of the expected stimulation. These results were concurrent with a

cutaneous vibratory stimulation with a vibration frequency of 50 Hz and an amplitude of 1 mm (Fox et al., 1987). H215O labeled water was used as a blood flow tracer. The cutaneous surfaces of lips, fingers, and toes were tested. Intense and highly focal distinct responses within the primary somatosensory cortex with a medial-to-lateral homunculus were seen in each subject. The study demonstrated that eliciting regional cerebral blood flow responses within the somatosensory cortex by cutaneous vibration provides a safe, rapid, and reproducible tool for locating and assessing its functional status and for the localization of the central sulcus that is crucial in preoperative neurosurgical planning. The study has established normative values for future applications of the vibration paradigm in functional

In 1990, Tempel and Perlmutter compared the regional cerebral blood flow responses to vibrotactile stimulation in patients with predominantly unilateral idiopathic focal dystonia and normal subjects using H215O PET (Tempel and Perlmutter, 1990). The somatosensory stimulation led to consistently localized and robust peak response in the primary sensorimotor cortex, contralateral to hand vibration in normal subjects. The sensorimotor response in dystonic patients was also consistently localized to the same area, but significantly reduced in magnitude when vibrating the affected as well as the unaffected hand. Furthermore, vibration induced a dystonic cramp in the stimulated arm and hand in some patients, but in no normal subjects. This abnormal sensorimotor response had important implications for the understanding of the pathophysiology of idiopathic dystonia. Two years later, Tempel and Perlmutter performed another significant H215O PET study with vibration-induced regional cerebral blood flow responses in healthy young and elder subjects in order to investigate whether vibration-induced regional cerebral blood flow responses change with increasing age (Tempel and Perlmutter, 1992). Left and right hand vibration led to consistent responses within the contralateral primary sensorimotor cortex and the supplementary motor area with no changes in the physiologically aging brain. In the same year, Seitz and Roland were able to demonstrate with a vibratory stimulus to the right hand palm of healthy volunteers and H215O PET that activation of some cerebral structures is accompanied by deactivations of corresponding other structures elsewhere in the brain (Seitz and Roland, 1992). Increases in the regional cerebral blood flow were localized in the left primary somatosensory area, the left secondary somatosensory area, the left retroinsular field, the left anterior parietal cortex, the left primary motor area, and the left supplementary motor area. The decreases occurred bilaterally within the superior parietal cortex, paralimbic association areas, and the left globus pallidus. The mean global cerebral blood flow did not change compared with rest. The decreases in cerebral oxidative

metabolism were interpreted as regional depressions of synaptic activity.

In an H215O PET study by Drevets et al., changes in the human primary and secondary somatosensory cortices during the period when somatosensory stimuli were expected were investigated (Drevets et al., 1995): In anticipation of either focal or innocuous touching, or localized, painful shocks, the blood flow decreased in the parts of the primary somatosensory cortex located outside the representation of the skin locus of the expected stimulus. Specifically, attending to an impending stimulus to the fingers produced a significant decrease in blood flow in the somatosensory zones for the face, whereas attending to stimulation of the toe produced decreases in the zones for the fingers and face. Decreases were more prominent in the side ipsilateral to the location of the expected stimulus. No significant changes in the blood flow occurred in the region of the cortex representing the skin locus of the expected stimulation. These results were concurrent with a

brain imaging.

model of spatial attention in which potential signal enhancement may rely on generalized suppression of background activity.

In the same year, Ibanez et al. demonstrated in a PET study that there is no evidence that the primary motor and supplementary motor area are involved in the generation of the P22 and N30 components of somatosensory evoked potentials (SSEPs) caused by electrical stimulation of the median nerve at the wrist (Ibanez et al., 1995). PET was performed in normal subjects to study the cerebral areas activated by median nerve electrical stimulation at frequencies of up to 20 Hz. Stimulation evoked a single focus of activation in the primary somatosensory area. An increase of the regional cerebral blood flow in this area was linearly correlated with stimulus frequencies of up to 4 Hz and then reached a plateau. The supplementary motor area was not significantly activated by stimulation at any of the frequencies tested. In contrast to the primary somatosensory area, the supplementary motor area showed no trend toward a correlation between the regional cerebral blood flow changes and the stimulus repetition rate. These results suggested that a contribution of the primary motor cortex and the supplementary motor area to the generation of the P22 and N30 components of SSEPs is unlikely.

H215O PET studies with different application forms and intensities of innocuous and noxious thermal stimuli were performed by Casey et al (Casey et al., 1994;Casey et al., 1996) to identify the forebrain and brain stem structures that are active during the perception of acute heat pain in humans. Healthy subjects received repetitive noxious (50°C) and innocuous (40°C) heat pulses with duration of five seconds to the forearm and each subject rated the subjective intensity of each stimulation series. Significant regional cerebral blood flow with a maximum at 50°C stimuli was found in the thalamus, the cingulate cortex, the secondary and primary somatosensory cortex, the insula, the medial dorsal midbrain and the cerebellar vermis. In the second study noxious and innocuous heat and cold thermal stimuli to the non-dominant arm of healthy subjects were applied.

A detailed analysis of somatosensory representations within the parietal postcentral gyral and the lateral sulcal-opercular cortex in a H215O PET study was performed by Burton et al. (Burton et al., 1997). To investigate the issue of possible multiple activation foci in these regions and possible differences due to stimulating skin directly or through an imposed tool, changes in the regional cerebral blood flow during passive tactile stimulation of one or two fingertips were studied. Restrained fingers were rubbed with embossed gratings using a rotating drum stimulator. For different scans, gratings touched the skin directly for optimal stimulation of cutaneous receptors (skin mode stimulation) or indirectly by using an imposed guitar plectrum snugly fitted to the same fingers (tool mode stimulation). The latter was expected to better stimulate deep receptors better. The subjects were asked to estimate the roughness after each scan. Direct skin contact activated statistically validated foci in both hemispheres, on the contralateral side these foci occurred in the anterior and posterior limbs of the postcentral gyrus and on the ipsilateral side only in the posterior limb. Tool mode stimulation activated one contralateral focus that was in the posterior limb of the postcentral gyrus. These results suggested at least two maps for distal fingertips in the primary somatosensory area with the anterior and posterior foci corresponding, respectively, to activations in the Brodmann area 3b and the junction between the Brodmann areas 1 and 2. In the contralateral secondary somatosensory area, skin mode stimulation activated a peak that was anterior and medial to a focus associated with tool mode stimulation. The magnitude of the PET counts contralateral to stimulation was higher in the anterior primary and secondary somatosensory regions during initial scans, but reversed to

Somatosensory Stimulation in Functional Neuroimaging: A Review 337

the lateral premotor cortex, the contralateral secondary somatosensory area, the contralateral posterior cingulate cortex, the bilateral prefrontal cortex (Brodmann area 10) and in the contralateral basal ganglia. In Huntington's disease, decreased activation was detected contralateral in the secondary somatosensory area, the parietal Brodmann areas 39 and 40, the lingual gyrus, the bilateral prefrontal cortex (Brodmann areas 8, 9, 10 and 44), the primary somatosensory area, and the contralateral basal ganglia. In both clinical diseases, relative enhanced activation of the ipsilateral somatosensory cortical areas, notably the caudal primary and secondary somatosensory regions as well as the insular cortex, could also be detected. The data show that Parkinson's and Huntington's disease, beyond wellestablished deficits in the central motor control, are characterized by abnormal cortical and subcortical activation on passive somatosensory stimulation. Furthermore, the finding that the activation increases in the ipsilateral somatosensory cortical areas may be interpreted as an indication of either altered central focusing and gating of the somatosensory impulses, or

A 18F-fluorodeoxyglucose PET study with somatosensory stimulation in patients suffering from spinal cord injuries was performed by Roelcke et al. (Roelcke et al., 1997a) to assess the effect of a transverse spinal cord lesion on cerebral energy metabolism in view of sensorimotor reorganisation. PET was used to study resting cerebral glucose metabolism in patients with complete paraplegia or tetraplegia after spinal cord injury compared with healthy subjects. The global absolute glucose metabolism rate was lower in the spinal cord injury patients than in the healthy subjects. A relatively increased glucose metabolism was discovered particularly in the supplementary motor area, the anterior cingulate, and the putamen. A relatively reduced glucose metabolism was found in patients with spinal cord injury was found in the midbrain, the cerebellar hemispheres, and the temporal cortex. It was concluded that cerebral deafferentation due to reduction or loss of sensorimotor function results in the low level of an absolute global glucose metabolism rate found in patients with spinal cord injury. Relatively increased glucose metabolism in brain regions involved in attention and initiation of movement may be related to secondary disinhibition

PET studies using noxious electrical stimuli to the median nerve were also performed on patients in persistent vegetative state (actually referred to as unresponsive wakefulness syndrome) to assess cortical pain processing (Kassubek et al., 2003;Laureys et al., 2002). Even though cortical metabolism (in FDG-PET) was decreased up to 40% of normal values, both studies showed reliable activations in residual parts of the pain processing networks in H215O PET. Compared to age-matched controls, noxious stimuli activated the primary somatosensory cortex, contralateral thalamus and midbrain, but failed to activate higherorder associative cortices (secondary somatosensory, bilateral posterior parietal, premotor, polysensory superior temporal and prefrontal cortices). These findings help to understand cortical processing after severe brain injury, however, but they can neither prove nor

Somatosensory stimuli were applied in many functional magnetic resonance imaging (fMRI) studies. Especially light stimulation using air puffs (Stippich et al., 1999b) or other tactile stimuli (Hodge et al., 1998;Moore et al., 2000;Rausch et al., 1998;Servos et al., 1998), scratching of the hand palm (Hoeller et al., 2002), vibration (Gelnar et al., 1998b;Golaszewski

disprove awareness of pain or any other stimulus in this patient group.

**3. Functional Magnetic Resonance Imaging** 

enhanced compensatory recruitment of the somatosensory areas.

of these regions.

more activation in the posterior primary somatosensory region during later scans. These short-term practice effects suggested changes in neural activity with stimulus novelty.

Another method for selectively activating the cortical projections of deep receptors for proprioceptive perception in a study with H215O PET was presented by Mima et al. (Mima et al., 1999). Functional brain maps during active and passive finger movements driven by a servo-motor were compared. The authors were able to selectively activate proprioception with a minimal contribution from the epicritic sensation with a newly developed device. Proprioception was represented only within the contralateral primary and secondary somatosensory areas, whereas active movements were cortically represented within the contralateral primary sensorimotor cortex, the premotor cortex, the supplementary motor area, the bilateral secondary somatosensory areas, the basal ganglia and the ipsilateral cerebellum. In this study, differential brain maps for cortical representations of different components of the sensorimotor system were displayed for the first time in the field of functional neuroimaging.

Xu et al. elucidated the functional localization and somatotopic organization of pain perception in the human cerebral cortex with PET during selective painful stimulation. Response to painful stimuli to the hand and foot were elicited using a special CO2 laser, which selectively activates nociceptive receptors (Xu et al., 1997). Multiple brain areas, including the bilateral secondary somatosensory areas and both insulas, the frontal lobe, and thalamus contralateral to the stimulus side were found to be involved in the response to painful stimulation. While the data indicate that the bilateral secondary somatosensory area plays an important role in pain perception, they also indicate that there is no pain-related somatotopic organization in the human secondary somatosensory cortex or insula. Pain processing during three levels of noxious stimulation that produced differential patterns of central activity was investigated by Derbyshire et al. (Derbyshire et al., 1997).

Bittar et al. investigated presurgical mapping of the primary somatosensory cortex compared with intraoperative cortical stimulation with H215O PET (Bittar et al., 1999a;Bittar et al., 1999b). PET scanning with vibrotactile stimulation of the face, the hands or the feet to localize the primary somatosensory area before surgical resection of the mass lesions or epileptogenic foci affecting the central area was performed in patients with brain tumor. With the aid of image-guided surgical systems, the location of significant activation foci on the PET scanning were compared with those of positive intraoperative cortical stimulation performed at craniotomy. In 95%, the PET activation foci were spatially concordant with the intraoperative cortical stimulation. Intraoperative cortical stimulation was positive in 40% of the stimulation sites where the PET did not result in statistically significant activation. According to these results, it was concluded that PET is an accurate method for mapping the primary somatosensory area prior to surgery.

Boecker et al. investigated the functional anatomy of somatosensory processing in two clinical conditions characterized by basal ganglia dysfunction in Parkinson's and Huntington's disease (Boecker et al., 1999) in a H2 15O PET study. Continuous unilateral high-frequency vibratory stimulation was applied to the immobilized metacarpal joint of the index finger. In the control subjects, the activation pattern was lateralized to the side opposite to the stimulus presentation, including the primary and secondary somatosensory areas, as well as subcortical (globus pallidus, ventrolateral thalamus) regions. Inter-group comparisons of the vibration-induced changes of the regional cerebral blood flow between patients and control subjects revealed differences in central somatosensory processing. In Parkinson's disease, decreased activation was found in the contralateral sensorimotor cortex,

more activation in the posterior primary somatosensory region during later scans. These short-term practice effects suggested changes in neural activity with stimulus novelty. Another method for selectively activating the cortical projections of deep receptors for

al., 1999). Functional brain maps during active and passive finger movements driven by a servo-motor were compared. The authors were able to selectively activate proprioception with a minimal contribution from the epicritic sensation with a newly developed device. Proprioception was represented only within the contralateral primary and secondary somatosensory areas, whereas active movements were cortically represented within the contralateral primary sensorimotor cortex, the premotor cortex, the supplementary motor area, the bilateral secondary somatosensory areas, the basal ganglia and the ipsilateral cerebellum. In this study, differential brain maps for cortical representations of different components of the sensorimotor system were displayed for the first time in the field of

Xu et al. elucidated the functional localization and somatotopic organization of pain perception in the human cerebral cortex with PET during selective painful stimulation. Response to painful stimuli to the hand and foot were elicited using a special CO2 laser, which selectively activates nociceptive receptors (Xu et al., 1997). Multiple brain areas, including the bilateral secondary somatosensory areas and both insulas, the frontal lobe, and thalamus contralateral to the stimulus side were found to be involved in the response to painful stimulation. While the data indicate that the bilateral secondary somatosensory area plays an important role in pain perception, they also indicate that there is no pain-related somatotopic organization in the human secondary somatosensory cortex or insula. Pain processing during three levels of noxious stimulation that produced differential patterns of

Bittar et al. investigated presurgical mapping of the primary somatosensory cortex compared with intraoperative cortical stimulation with H215O PET (Bittar et al., 1999a;Bittar et al., 1999b). PET scanning with vibrotactile stimulation of the face, the hands or the feet to localize the primary somatosensory area before surgical resection of the mass lesions or epileptogenic foci affecting the central area was performed in patients with brain tumor. With the aid of image-guided surgical systems, the location of significant activation foci on the PET scanning were compared with those of positive intraoperative cortical stimulation performed at craniotomy. In 95%, the PET activation foci were spatially concordant with the intraoperative cortical stimulation. Intraoperative cortical stimulation was positive in 40% of the stimulation sites where the PET did not result in statistically significant activation. According to these results, it was concluded that PET is an accurate method for mapping the

Boecker et al. investigated the functional anatomy of somatosensory processing in two clinical conditions characterized by basal ganglia dysfunction in Parkinson's and Huntington's disease (Boecker et al., 1999) in a H215O PET study. Continuous unilateral high-frequency vibratory stimulation was applied to the immobilized metacarpal joint of the index finger. In the control subjects, the activation pattern was lateralized to the side opposite to the stimulus presentation, including the primary and secondary somatosensory areas, as well as subcortical (globus pallidus, ventrolateral thalamus) regions. Inter-group comparisons of the vibration-induced changes of the regional cerebral blood flow between patients and control subjects revealed differences in central somatosensory processing. In Parkinson's disease, decreased activation was found in the contralateral sensorimotor cortex,

central activity was investigated by Derbyshire et al. (Derbyshire et al., 1997).

15O PET was presented by Mima et al. (Mima et

proprioceptive perception in a study with H2

primary somatosensory area prior to surgery.

functional neuroimaging.

the lateral premotor cortex, the contralateral secondary somatosensory area, the contralateral posterior cingulate cortex, the bilateral prefrontal cortex (Brodmann area 10) and in the contralateral basal ganglia. In Huntington's disease, decreased activation was detected contralateral in the secondary somatosensory area, the parietal Brodmann areas 39 and 40, the lingual gyrus, the bilateral prefrontal cortex (Brodmann areas 8, 9, 10 and 44), the primary somatosensory area, and the contralateral basal ganglia. In both clinical diseases, relative enhanced activation of the ipsilateral somatosensory cortical areas, notably the caudal primary and secondary somatosensory regions as well as the insular cortex, could also be detected. The data show that Parkinson's and Huntington's disease, beyond wellestablished deficits in the central motor control, are characterized by abnormal cortical and subcortical activation on passive somatosensory stimulation. Furthermore, the finding that the activation increases in the ipsilateral somatosensory cortical areas may be interpreted as an indication of either altered central focusing and gating of the somatosensory impulses, or enhanced compensatory recruitment of the somatosensory areas.

A 18F-fluorodeoxyglucose PET study with somatosensory stimulation in patients suffering from spinal cord injuries was performed by Roelcke et al. (Roelcke et al., 1997a) to assess the effect of a transverse spinal cord lesion on cerebral energy metabolism in view of sensorimotor reorganisation. PET was used to study resting cerebral glucose metabolism in patients with complete paraplegia or tetraplegia after spinal cord injury compared with healthy subjects. The global absolute glucose metabolism rate was lower in the spinal cord injury patients than in the healthy subjects. A relatively increased glucose metabolism was discovered particularly in the supplementary motor area, the anterior cingulate, and the putamen. A relatively reduced glucose metabolism was found in patients with spinal cord injury was found in the midbrain, the cerebellar hemispheres, and the temporal cortex. It was concluded that cerebral deafferentation due to reduction or loss of sensorimotor function results in the low level of an absolute global glucose metabolism rate found in patients with spinal cord injury. Relatively increased glucose metabolism in brain regions involved in attention and initiation of movement may be related to secondary disinhibition of these regions.

PET studies using noxious electrical stimuli to the median nerve were also performed on patients in persistent vegetative state (actually referred to as unresponsive wakefulness syndrome) to assess cortical pain processing (Kassubek et al., 2003;Laureys et al., 2002). Even though cortical metabolism (in FDG-PET) was decreased up to 40% of normal values, both studies showed reliable activations in residual parts of the pain processing networks in H215O PET. Compared to age-matched controls, noxious stimuli activated the primary somatosensory cortex, contralateral thalamus and midbrain, but failed to activate higherorder associative cortices (secondary somatosensory, bilateral posterior parietal, premotor, polysensory superior temporal and prefrontal cortices). These findings help to understand cortical processing after severe brain injury, however, but they can neither prove nor disprove awareness of pain or any other stimulus in this patient group.
