Kaoru Sakatani

Cerebral blood oxygenation changes induced by auditory stimulation in newborn infants measured by near infrared spectroscopy.

Recent neuronal activation studies on newborns using functional MRI or near infrared spectroscopy (NIRS) have suggested that the increase in O2 consumption accompanying neuronal activation exceeds the increase in O2 delivery in the visual cortex during photic stimulation. In the present study, we evaluated the cerebral blood oxygenation (CBO) changes induced by auditory stimulation in the frontal lobe of newborns using NIRS. We studied 28 newborns; the postnatal age at CBO measurements was 3.1+/-0.3 days (mean+/-S.E.M.). We measured concentration changes of deoxyhemoglobin (Deoxy-Hb), oxyhemoglobin (Oxy-Hb), and total hemoglobin (Total-Hb) induced by auditory (music) stimulation in the bilateral frontal lobes of the newborns. Twenty-six (92.9%) out of 28 subjects showed increases of Oxy-Hb and Total-Hb during the stimulation. In these subjects, 17 (60.7%) subjects showed an increase of Deoxy-Hb associated with increases of Oxy-Hb and Total-Hb, while nine (32.1%) subjects showed a decrease of Deoxy-Hb. Although the direction of the Deoxy-Hb differed, these two groups did not differ for Oxy-Hb and Total-Hb (P > 0.05). Two (7.1%) subjects showed other changes. The frontal lobe of newborns shows CBO responses similar to those observed in the visual cortex, specifically neuronal activation causes an increase of Deoxy-Hb associated with increases of Oxy-Hb and Total-Hb. These results support the hypothesis that increments in O2 consumption exceed increments in O2 delivery during neuronal activity in newborns.

Neural damage in the rat thalamus after cortical infarcts.

Histopathologic changes in the thalamus of 23 rats after somatosensory cortical infarction produced by middle cerebral artery occlusion were examined using the Fink-Heimer silver staining method, immunohistochemistry with antibodies against glial fibrillary acidic protein and laminin, and conventional stains. Middle cerebral artery occlusion produced cortical infarcts in the lateral parietal region, with variable involvement of the frontoparietal parasagittal sensorimotor cortex. Within 3 days after occlusion, massive terminal degeneration but no neuronal changes were apparent in the ipsilateral thalamus. By 1 week after occlusion, abnormal neurons with darkly stained, shrunken nuclei and atrophic perikarya were present in the ipsilateral thalamic nuclei. These neurons were densely argyrophilic in Fink-Heimer sections. Rats with small lateral parietal cortical lesions had degenerating neurons limited to the medial ventroposteromedial nucleus. Large lesions involving the parasagittal sensorimotor cortex resulted in widespread neuronal damage in the ventroposteromedial, ventroposterolateral, intralaminar, and posterior nuclear regions but nowhere else. Immunoreactivity to laminin antibody decreased, and astrocytic proliferation was abundant in affected thalamic areas. These findings are consistent with retrograde neuronal degeneration due to thalamocortical fiber damage in ischemic cortical regions. Such lesions remote from the infarct may influence functional recovery in patients with stroke.

Relation between asymmetry of prefrontal cortex activities and the autonomic nervous system during a mental arithmetic task: near infrared spectroscopy study

The present study evaluated the relationship between asymmetry of the prefrontal cortex activity and the automatic nervous system (ANS) response during a mental arithmetic (MA) task. Employing near infrared spectroscopy, we compared cerebral blood oxygenation changes in the right and left prefrontal cortices during a mental arithmetic task with HR changes. During the MA task, eight subjects (high-HR group) showed large HR increases (14.2 +/- 3.0) while eight subjects (low-HR group) showed small HR increases (3.6 +/- 2.8) (P < 0.00001). In both the high-HR and low-HR groups, near infrared spectroscopy (NIRS) demonstrated increases of oxyhemoglobin and total hemoglobin (=oxyhemoglobin + deoxyhemoglobin) associated with decreases of deoxyhemoglobin in the bilateral prefrontal cortices during MA task. In the high-HR group, the laterality ratio scores, i.e., [(R - L)/(R + L) of oxyhemoglobin and total hemoglobin], showed positive values (0.17 +/- 0.11 and 0.17 +/- 0.17, respectively), while in the low-HR group, the laterality ratio scores showed negative values (-0.28 +/- 0.21 and -0.35 +/- 0.24, respectively). In addition, there were significant positive correlations between HR changes and the laterality ratio scores of oxyhemoglobin (r = +0.87, P < 0.0001) and total hemoglobin (r = +0.85, P < 0.0001). These results indicate that the MA task-induced activity in the right prefrontal cortex was larger than that in the left prefrontal cortex in the subject with high HR increases, suggesting that the right prefrontal cortex activity during the MA task has a greater role in cerebral regulation of HR by virtue of decreasing parasympathetic effects or increasing sympathetic effects.

Language-Activated Cerebral Blood Oxygenation and Hemodynamic Changes of the Left Prefrontal Cortex in Poststroke Aphasic Patients: A Near-Infrared Spectroscopy Study

BACKGROUND AND PURPOSE In normal subjects, regional cerebral blood flow (rCBF) is greatly increased by neuronal activity, whereas the cerebral metabolic rate for O2 is increased only slightly. However, it is not clear what kinds of cerebral blood oxygenation and hemodynamic changes can be induced by language activities in language-relevant areas of poststroke aphasics. In the present study, we investigated the difference in the changes of cerebral blood oxygenation and hemodynamics in the left prefrontal cortex induced by language activities between normal subjects, poststroke nonaphasic patients, and nonfluent aphasic patients using near-infrared spectroscopy (NIRS). METHODS Twenty-nine participants performed speech tasks, such as confrontational naming, to evaluate changes among poststroke nonfluent (Brocas) aphasia patients (10 cases; mean+/-SEM, 56.9+/-2.2 years), age-matched normal subjects (13 cases; 50.7+/-2.2 years) and poststroke nonaphasic patients (6 cases; 52.5+/-3.9 years). The optodes of NIRS were placed over the left prefrontal cortex. We analyzed the NIRS parameter (oxyhemoglobin [oxy-Hb], deoxyhemoglobin [deoxy-Hb], and total hemoglobin [total-Hb]) changes by qualitative pattern analysis of the parameter changes and quantitative analysis of the parameter values among the groups. RESULTS The most common NIRS parameter change was an increase in oxy-Hb and total-Hb, with a slight decrease or no change in deoxy-Hb in the normal subjects (5 of 13 cases, 38.5%) and the nonaphasic cerebrovascular disease (CVD) patients (3 of 6 cases, 50.0%). In contrast, the most common pattern in the aphasic patients was an increase of deoxy-Hb, with an increase of oxy-Hb and total-Hb (5 of 10 cases, 50%). However, this pattern was observed in only 3 of 13 cases (23.1%) in the normal subjects and 1 of 6 cases (16.7%) in the nonaphasic CVD patients. The mean (+/-SEM) changes of deoxy-Hb of the aphasic patients, the normal subjects, and the nonaphasic CVD patients were 0.78+/-0.29, 0.06+/-0.16, and -0.18 +/- 0.22, respectively. The statistical analysis demonstrated a significant effect for deoxy-Hb (P<0.05), with the aphasic patients differing significantly from the normal subjects and the nonaphasic CVD patients, while the 2 nonaphasic groups did not differ from each other. CONCLUSIONS The present results demonstrate a multiplicity of language-activated cerebral blood oxygenation and hemodynamic changes in the left prefrontal cortex in the nonaphasic and aphasic groups. The increase of deoxy-Hb with increases of oxy-Hb and total-Hb in the aphasics during language tasks suggests that the left prefrontal cortex of the aphasics utilizes more oxygen than the nonaphasics during language tasks. Finally, functional MRI, which images the activation area in the brain by detecting the reduced concentration of deoxy-Hb during neuronal activation, should be performed on the patients with cerebral dysfunction, giving special consideration to the possible multiplicity of the rCBF and cerebral oxygen metabolism responses to functional tasks.

Evoked-cerebral blood oxygenation changes in false-negative activations in BOLD contrast functional MRI of patients with brain tumors.

Blood oxygenation level dependent contrast functional MRI (BOLD-fMRI) has been used to define the functional cortices of the brain in preoperative planning for tumor removal. However, some studies have demonstrated false-negative activations in such patients. We compared the evoked-cerebral blood oxygenation (CBO) changes measured by near-infrared spectroscopy (NIRS) and activation mapping of BOLD-fMRI in 12 patients with brain tumors who had no paresis of the upper extremities. On the nonlesion side, NIRS demonstrated a decrease in deoxyhemoglobin (Deoxy-Hb) with increases in oxyhemoglobin (Oxy-Hb) and total hemoglobin (Total-Hb) during a contralateral hand grasping task in the primary sensorimotor cortex (PSMC) of all patients. On the lesion side, NIRS revealed a decrease in Deoxy-Hb in five patients (Deoxy-decrease group), and an increase in Deoxy-Hb in seven patients (Deoxy-increase group); the Oxy-Hb and Total-Hb were increased during activation in both groups, indicating the occurrence of rCBF increases in response to neuronal activation. BOLD-fMRI demonstrated clear activation areas in the PSMC on the nonlesion side of all patients and on the lesion side of the Deoxy-decrease group. However, in the Deoxy-increase group, BOLD-fMRI revealed only a small activation area or no activation on the lesion side. Intraoperative brain mapping identified the PSMC on the lesion side that was not demonstrated by BOLD-fMRI. The false-negative activations might have been caused by the atypical evoked-CBO changes (i.e. increases in Deoxy-Hb) and the software employed to calculate the activation maps, which does not regard an increase of Deoxy-Hb (i.e., a decrease in BOLD-fMRI signal) as neuronal activation.

Relation between mental stress-induced prefrontal cortex activity and skin conditions: a near-infrared spectroscopy study.

Although psychological stress affects skin condition, the neurophysiological mechanism involved is unclear. In this study, we evaluated the relationship between skin condition and left/right asymmetry in prefrontal cortex (PFC) activity during mental stress tasks since recent studies have suggested that the right PFC dominates the regulation of the stress response system, including the hypothalamic-pituitary-adrenal (HPA) axis. Using near-infrared spectroscopy, we measured hemoglobin concentration changes in the bilateral PFC during a mental arithmetic task in normal adults and evaluated the laterality scores (i.e., [(right-left)/(right+left)]) of oxyhemoglobin concentration changes. Elicitation of stress was verified by the State-Trait Anxiety Inventory (STAI) and heart rate. The sebum levels and Propionibacterium acnes populations in the facial skin were measured before the task. The task significantly increased the STAI-II scores (p=0.00079) and heart rate (p=0.0000049). The oxyhemoglobin concentration increased in the bilateral PFC during the task, associated with a decrease in deoxyhemoglobin concentration. The laterality scores of oxyhemoglobin concentration changes were positively correlated with sebum levels (r=+0.50, p=0.026) and P. acnes populations (r=+0.49, p=0.029) in the facial skin before the task. There was a significant positive correlation between heart rate changes and the laterality scores of oxyhemoglobin concentration changes (r=+0.54, p=0.015). These results demonstrate that the subjects with higher sebum levels and higher P. acnes populations in the facial skin have a right dominant PFC activity during a mental stress task and suggest that such subjects are sensitive to mental stress associated with hyperactivity of the stress response system, including the HPA axis system.

Somatosensory evoked potentials in rat cerebral cortex before and after middle cerebral artery occlusion.

We recorded somatosensory evoked potentials in pentobarbital-anesthetized rats before and after middle cerebral artery occlusion. Trigeminal (vibrissae), median (forelimb), and sciatic (hind limb) nerve stimuli produced consistent, robust, and sharply localized responses in the trigeminal, forelimb, and hind limb regions of the somatosensory cortex of 18 rats. These regions are situated at sequentially greater distances from the center of infarcts produced by middle cerebral artery occlusion. In eight rats, occlusion 1-2 mm below the rhinal fissure abolished somatosensory evoked potentials in all three cortical region within minutes. Positive wavelets preceding the primary cortical response were also diminished by the occlusion, suggesting that ischemia affected the thalamocortical white matter. Four of these eight rats did not show histologically apparent ischemic involvement of the hind limb cortical region at 3 hours after occlusion; sciatic nerve evoked potentials recovered substantially in all four rats, and the amplitudes exceeded baseline (129 +/- 30% at 1 hour, 173 +/- 33% at 3 hours) in three of the four rats. Three of the eight rats did not have gross ischemic involvement of the forelimb cortical region; median nerve evoked potentials recovered fully in all eight rats, but the amplitudes did not exceed baseline. All eight rats had evidence of ischemic damage in the trigeminal cortex; no rat showed full recovery in this region, and all but one had trigeminal evoked potentials that were less than 20% of baseline amplitudes by 3 hours after occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of blood-oxygen-level–dependent functional magnetic resonance imaging and near-infrared spectroscopy recording during functional brain activation in patients with stroke and brain tumors

Blood-oxygen-level-dependent contrast functional magnetic resonance imaging (BOLD-fMRI) has been used to perform functional imaging in brain disorders such as stroke and brain tumors. However, recent studies have revealed that BOLD-fMRI does not image activation areas correctly in such patients. To clarify the characteristics of the evoked cerebral blood oxygenation (CBO) changes occurring in stroke and brain tumors, we have been comparing near-infrared spectroscopy (NIRS) and BOLD-fMRI recording during functional brain activation in these patients. We review our recent studies and related functional imaging studies on the brain disorders. In the primary sensorimotor cortex (PSMC) on the nonlesion side, the motor task consistently caused a decrease of deoxyhemoglobin (deoxy-Hb) with increases of oxyhemoglobin (oxy-Hb) and total hemoglobin (t-Hb), which is consistent with the evoked CBO response observed in normal adults. BOLD-fMRI demonstrated robust activation areas on the nonlesion side. In stroke patients, severe cerebral ischemia (i.e., misery perfusion) caused an increase of deoxy-Hb during the task, associated with increases of oxy-Hb and t-Hb, in the PSMC on the lesion side. In addition, the activation volume of BOLD-fMRI was significantly reduced on the lesion side. The BOLD signal did not change in some areas of the PSMC on the lesion side, but it tended to decrease in other areas during the tasks. In brain tumors, BOLD-fMRI clearly demonstrated activation areas in the PSMC on the lesion side in patients who displayed a normal evoked CBO response. However, the activation volume on the lesion side was significantly reduced in patients who exhibited an increase of deoxy-Hb during the task. In both stroke and brain tumors, false-negative activations (i.e., marked reductions of activation volumes) in BOLD imaging were associated with increases of deoxy-Hb, which could cause a reduction in BOLD signal. BOLD-fMRI investigations of patients with brain disorders should be performed while giving consideration to atypical evoked CBO changes.

Changes in cerebral blood oxygenation of the frontal lobe induced by direct electrical stimulation of thalamus and globus pallidus: a near infrared spectroscopy study

OBJECTIVE Blood oxygenation level dependent (BOLD) contrast functional MRI images show activated cortical areas by detecting a reduced concentration of deoxyhaemoglobin (deoxy-Hb) during neuronal activity; however, near infrared spectroscopy (NIRS) has shown various patterns of cerebral blood oxygenation (CBO) changes in the frontal lobe during cognitive tasks. To determine if various patterns of CBO changes occur in the frontal lobe when the brain is directly stimulated, changes in CBO in the frontal lobe induced by deep brain stimulation in patients with implanted electrodes were evaluated. METHODS Six patients were studied, including five with Parkinsons disease and one with essential tremor. To reduce tremor or rigidity, the electrodes were implanted at the thalamic nucleus ventralis intermedius (VIM: three Parkinsons disease and one essential tremor) or the globus pallidus internus (GPi: two Parkinsons disease). Using NIRS, changes of deoxy-Hb, oxyhaemoglobin (oxy-Hb) and total haemoglobin (total Hb) were measured in the bilateral frontal lobes during various stimulus conditions. RESULTS High frequency (120 Hz) GPi stimulation consistently increased oxy-Hb and total Hb with a decrease of deoxy-Hb in an intensity and time dependent manner. Oxy-Hb and total Hb increased immediately after the onset of stimulation and then gradually decreased when stimulation was continued. By contrast, high frequency (120 Hz) VIM stimulation decreased oxy-Hb, deoxy Hb and total Hb in an intensity dependent manner. In the severe tremor patient with VIM stimulation, frequency response was examined by decreasing stimulus frequencies; deoxy-Hb increased at high frequencies (70–40 Hz), and then decreased below the control level at low frequencies (30–0 Hz), whereas oxy-Hb and total Hb increased consistently at high and low frequencies. CONCLUSION The electrical stimulation of GPi and VIM caused various CBO changes in the frontal lobe, which were similar to those found during cognitive tasks. Such a multiplicity of CBO changes in the frontal lobe may be caused by complex neuronal circuits in the frontal lobe which has many neuronal connections to other cortical areas or the basal ganglia.

Transient presence and functional interaction of endogenous GABA and GABAA receptors in developing rat optic nerve

GABA (γ-aminobutyric acid) is a major inhibitory synaptic neurotransmitter with widespread distribution in the central nervous system (CNS). GABA can also modulate axonal excitability by activation of GABAA receptors in CNS white matter regions where synapses and neuronal cell bodies are not present. Studies on cultured glia cells have revealed the synthesis of GABA in rat optic nerve O-2A progenitor cells that give rise to oligodendrocytes and type 2 astrocytes in vitro. We report here that: (i) GABA is detected by immuno-electron microscopy in intact rat optic nerve and is localized to glia and pre-myelinated axons during the first few weeks of postnatal development, but is markedly reduced or absent in the adult; and (ii) neonatal optic nerve is depolarized by GABAA receptor agonists or by the inhibition of GABA uptake. These results demonstrate the presence of functional GABAA receptors, and GABA uptake and release mechanisms in developing rat optic nerve, and suggest that excitability of developing axons can be modulated by endogenous neurotransmitter at non-synaptic sites.