Thalamic Diaschisis in Acute Ischemic Stroke: Occurrence, Perfusion Characteristics, and Impact on Outcome.

BACKGROUND AND PURPOSE: Ipsilateral thalamic diaschisis (ITD) describes the reduction of thalamic function, metabolism, and perfusion resulting from a distant lesion of the ipsilateral hemisphere. Our aim was to evaluate the perfusion characteristics and clinical impact of ITD in acute middle cerebral artery stroke, which does not directly affect the thalamus. METHODS: One hundred twenty-four patients with middle cerebral artery infarction were selected from a prospectively acquired cohort of 1644 patients who underwent multiparametric computed tomography (CT), including CT perfusion for suspected stroke. Two blinded readers evaluated the occurrence of ITD, defined as ipsilateral thalamic hypoperfusion present on ≥2 CT perfusion maps. Perfusion alterations were defined according to the Alberta Stroke Program Early CT Score regions. Final infarction volume and subacute complications were assessed on follow-up imaging. Clinical outcome was quantified using the modified Rankin Scale. Multivariable linear and ordinal logistic regression analysis were applied to identify independent associations. RESULTS: ITD was present in 25/124 subjects (20.2%, ITD+). In ITD+ subjects, perfusion of the caudate nucleus, internal capsule, and lentiform nucleus was more frequently affected than in ITD- patients (each with P<0.001). In the ITD+ group, larger cerebral blood flow (P=0.002) and cerebral blood volume (P<0.001) deficit volumes, as well as smaller cerebral blood flow-cerebral blood volume mismatch (P=0.021) were observed. There was no independent association of ITD with final infarction volume or clinical outcome at discharge in treatment subgroups (each with P>0.05). ITD had no influence on the development of subacute stroke complications. CONCLUSIONS: ITD in the form of thalamic hypoperfusion is a frequent CT perfusion finding in the acute phase in middle cerebral artery stroke patients with marked involvement of subcortical areas. ITD does not result in thalamic infarction and had no independent impact on patient outcome. Notably, ITD was misclassified as part of the ischemic core by automated software, which might affect patient selection in CT perfusion-based trials.

Cerebrovascular reactivity in the caudate nucleus, lentiform nucleus and thalamus in patients with carotid artery disease.

BACKGROUND AND PURPOSE: To assess the effect of unilateral large vessel disease upon the cerebral hemodynamic autoregulatory status in the basal ganglia of patients with steno-occlusive internal carotid artery (ICA) disease. MATERIALS AND METHODS: Twenty-five healthy volunteers and 38 patients with a unilateral symptomatic steno-occlusive ICA lesion and were investigated; 20 with a stenosis >50% and 18 with an occlusion. Cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) were assessed with pseudo-continuous arterial spin labeling (ASL) magnetic resonance (MR) imaging before and after administration of acetazolamide. RESULTS: When compared to controls, the CVR in patients with ICA stenosis was significantly lower in the middle cerebral artery (MCA) territory (P<0.05), and in the caudate (P<0.05) and lentiform nucleus (P<0.05) of the hemisphere ipsilateral to the stenosis. The CVR in the caudate nucleus contralateral to the stenosis was significantly lower (P<0.05) as well. In patients with ICA occlusion, the CVR in the hemisphere ipsilateral to the occlusion as well as in the contralateral hemisphere was significantly lower in the MCA territory (P<0.05), the caudate (P<0.05) and lentiform nucleus (P<0.05), and in the thalamus (P<0.05). CONCLUSION: Perfusion ASL MR imaging shows impaired cerebral hemodynamic autoregulation of the basal ganglia in patients with steno-occlusive ICA disease both in the hemisphere ipsilateral as well as in the hemisphere contralateral to the stenosis or occlusion.

Beyond cognitive reserve: behavioural reserve hypothesis in Frontotemporal Dementia.

BACKGROUND: The brain reserve hypothesis posits that there are individual differences in the ability to cope with brain pathology, and that brain damage extent and clinical symptoms are not tightly linked. If cognitive reserve hypothesis has been demonstrated in Alzheimer Disease and Frontotemporal Dementia (FTD), no evidence of reserve mechanisms on behavioural disturbances has been corroborated yet. In FTD, distinct behavioural phenotypes may be identified. OBJECTIVE: To test the behavioural reserve hypothesis in behavioural variant FTD (bvFTD). METHODS: As previously demonstrated, bvFTD patients were grouped into four behavioural phenotypes, i.e. "disinhibited", "apathetic", "language", and "aggressive", by means of Confirmatory Factor Analysis on behavioural assessment. Educational achievement was considered as proxy measure of reserve on behavioural disturbances, and cerebral SPECT as an indirect expression of brain pathology. On each group, the effect of education on brain damage was assessed by slope analysis. RESULTS: A specific effect of education attainment on "disinhibited" phenotype was observed, the higher the education, the greater the hypoperfusion in the right inferior frontal gyrus and the left medial frontal gyrus and right caudate (P<0.001). On the other behavioural phenotypes, no effect of education was reported in modulating brain damage. CONCLUSIONS: We suggest that in neurodegenerative diseases the concept of brain reserve might be extended, as compensatory mechanisms are in action not only for cognitive deficits but for behavioural disturbances as well.

Quantitative cerebral blood flow mapping and functional connectivity of postherpetic neuralgia pain: a perfusion fMRI study.

This article investigates the effects of postherpetic neuralgia (PHN) on resting-state brain activity utilizing arterial spin labeling (ASL) techniques. Features of static and dynamic cerebral blood flow (CBF) were analyzed to reflect the specific brain response to PHN pain. Eleven consecutive patients suffering from PHN and 11 age- and gender-matched control subjects underwent perfusion functional magnetic resonance imaging brain scanning during the resting state. Group comparison was conducted to detect the regions with significant changes of CBF in PHN patients. Then we chose those regions that were highly correlated with the self-reported pain intensity as "seeds" to calculate the functional connectivity of both groups. Absolute CBF values of these regions were also compared across PHN patients and control subjects. Significant increases in CBF of the patient group were observed in left striatum, right thalamus, left primary somatosensory cortex (S1), left insula, left amygdala, left primary somatomotor cortex, and left inferior parietal lobule. Significant decreases in CBF were mainly located in the frontal cortex. Regional CBF in the left caudate, left insula, left S1, and right thalamus was highly correlated with the pain intensity, and further comparison showed that the regional CBF in these regions is significantly higher in PHN groups. Functional connectivity results demonstrated that the reward circuitry involved in striatum, prefrontal cortex, amygdala, and parahippocampal gyrus and the circuitry among striatum, thalamus, and insula were highly correlated with each element in PHN patients. In addition, noninvasive brain perfusion imaging at rest may provide novel insights into the central mechanisms underlying PHN pain.

Distribution of cerebral blood flow in the caudate nucleus, lentiform nucleus and thalamus in patients with carotid artery stenosis.

OBJECTIVE: To investigate the influence of internal carotid artery (ICA) stenosis on the distribution of blood flow to the caudate nucleus, lentiform nucleus, and thalamus. METHODS: We studied 18 healthy control subjects, 20 patients with a unilateral asymptomatic ICA stenosis, and 15 patients with a recently symptomatic unilateral ICA stenosis. The contribution of the ICAs and the basilar artery to the perfusion of the deep brain structures was assessed by perfusion territory selective arterial spin labeling (ASL) MRI. Differences were tested with a two-tailed Fishers' exact test. RESULTS: The caudate nucleus was predominantly supplied with blood by the ipsilateral ICA in all groups. In 4 of the 15 (27%) the symptomatic patients, the caudate nucleus partially received blood from the contralateral ICA, compared to none of the 18 healthy control subjects (p = 0.03). The lentiform nucleus and the thalamus were predominantly supplied with blood by the ipsilateral ICA and basilar artery respectively in all groups. CONCLUSION: In patients with a symptomatic ICA stenosis, the caudate nucleus may be supplied with blood by the contralateral ICA more often than in healthy controls.

Cerebral blood flow differences between long-term meditators and non-meditators.

We have studied a number of long-term meditators in previous studies. The purpose of this study was to determine if there are differences in baseline brain function of experienced meditators compared to non-meditators. All subjects were recruited as part of an ongoing study of different meditation practices. We evaluated 12 advanced meditators and 14 non-meditators with cerebral blood flow (CBF) SPECT imaging at rest. Images were analyzed with both region of interest and statistical parametric mapping. The CBF of long-term meditators was significantly higher (p<.05) compared to non-meditators in the prefrontal cortex, parietal cortex, thalamus, putamen, caudate, and midbrain. There was also a significant difference in the thalamic laterality with long-term meditators having greater asymmetry. The observed changes associated with long-term meditation appear in structures that underlie the attention network and also those that relate to emotion and autonomic function.

Distribution of cerebral blood flow in the nucleus caudatus, nucleus lentiformis, and thalamus: a study of territorial arterial spin-labeling MR imaging.

PURPOSE: To investigate the effect of variations in anatomic features of the circle of Willis on the perfusion territory to deep structures, including the nucleus caudatus, the nucleus lentiformis, and the thalamus. MATERIALS AND METHODS: The ethics committee of the study institution approved the study protocol. A total of 159 patients with first-time clinical symptoms of cerebral ischemia were recruited. Contributions to the perfusion territory were visualized with territorial arterial spin-labeling magnetic resonance (MR) imaging. The anatomic features of the circle of Willis were evaluated with time-of-flight MR angiography. Perfusion territory contributions were compared among circle of Willis variants by using the Cochran-Mantel-Haenszel test. RESULTS: The perfusion territory contributions to the deep-brain structures could be evaluated in 119 of 159 patients (75%). With a fetal-type circle of Willis (41 of 238 hemispheres; 17%), there was a contribution from the ipsilateral internal carotid artery to the thalamus in all 41 hemispheres (100%), compared with 96 of the 197 hemispheres (49%) without a fetal-type circle of Willis. In the 19 patients with a hypoplastic A1 segment, there was more often a contribution of the contralateral internal carotid artery to the perfusion of the nucleus caudatus (10 of 19; 53%) and the nucleus lentiformis (5 of 19; 26%). CONCLUSION: The perfusion territory contributions to deep-brain structures vary widely. These differences can be partly explained by variations in the anatomic features of the circle of Willis. (c) RSNA, 2010.

Transcranial brain sonography findings predict disease progression in multiple sclerosis.

OBJECTIVE: In multiple sclerosis (MS), an early neurodegenerative affection of subcortical gray matter has been suggested. Transcranial sonography (TCS) shows hyperechogenic lesions of substantia nigra (SN) and basal ganglia, thought to reflect iron accumulation, in a number of primary neurodegenerative diseases. The present study deals with the question of whether TCS can also display deep gray matter lesions in patients with MS and whether sonographic findings relate to severity and progression of MS. METHODS: We prospectively studied 75 patients with different courses of MS and 55 age-matched healthy subjects clinically and with TCS. Twenty-three patients additionally had 1.5-T MRI at the time of TCS. Disease progression was assessed clinically 2 years after TCS. RESULTS: Abnormal hyperechogenicity of SN, lenticular nucleus (LN), caudate nucleus, and thalamus was found in 41%, 54%, 40%, and 8% of the patients with MS, with similar frequency in patients with relapsing-remitting and primary or secondary progressive MS if corrected for disease duration, but only in 13%, 13%, 5% (each, p < 0.001), and none (p = 0.028) of the control subjects. Hyperechogenicity of SN and LN correlated with more pronounced MRI T2 hypointensity, thought to reflect iron deposition. Larger bilateral SN echogenic area was related to higher rate of disease progression, whereas small SN echogenic area (SN hypoechogenicity) predicted a disease course without further progression within 2 years. CONCLUSIONS: Neurodegenerative disease-like deep gray matter lesions can be frequently detected by transcranial sonography (TCS) in patients with multiple sclerosis (MS). Findings suggest that TCS shows changes of brain iron metabolism which correlate with future progress of MS.

Motor cortex stimulation in patients with deafferentation pain: activation of the posterior insula and thalamus.

OBJECT: The mechanisms underlying deafferentation pain are not well understood. Motor cortex stimulation (MCS) is useful in the treatment of this kind of chronic pain, but the detailed mechanisms underlying its effects are unknown. METHODS: Six patients with intractable deafferentation pain in the left hand were included in this study. All were righthanded and had a subdural electrode placed over the right precentral gyrus. The pain was associated with brainstem injury in one patient, cervical spine injury in one patient, thalamic hemorrhage in one patient, and brachial plexus avulsion in three patients. Treatment with MCS reduced pain; visual analog scale (VAS) values for pain were 82 +/- 20 before MCS and 39 +/- 20 after MCS (mean +/- standard error). Regional cerebral blood flow (rCBF) was measured by positron emission tomography with H2(15)O before and after MCS. The obtained images were analyzed with statistical parametric mapping software (SPM99). RESULTS: Significant rCBF increases were identified after MCS in the left posterior thalamus and left insula. In the early post-MCS phase, the left posterior insula and right orbitofrontal cortex showed significant rCBF increases, and the right precentral gyrus showed an rCBF decrease. In the late post-MCS phase, a significant rCBF increase was detected in the left caudal part of the anterior cingulate cortex (ACC). CONCLUSIONS: These results suggest that MCS modulates the pathways from the posterior insula and orbitofrontal cortex to the posterior thalamus to upregulate the pain threshold and pathways from the posterior insula to the caudal ACC to control emotional perception. This modulation results in decreased VAS scores for deafferentation pain.

Evaluation of basal ganglia haemodynamic changes with perfusion-weighted magnetic resonance imaging in patients with Parkinson's disease.

PURPOSE: The aim of our study was to assess the regional cerebral blood flow (rCBF) of basal ganglia and thalami in patients with Parkinson's disease (PD) using perfusion-weighted magnetic resonance imaging (PW-MRI). MATERIAL AND METHODS: Twenty subjects affected by idiopathic PD according to the United Kingdom Brain Bank criteria were enrolled in the study. Twenty normal subjects matched for age and gender were included as controls. After 20-day therapy withdrawal, the PD patients underwent PW-MRI. The rCBF was calculated both in patients and in controls. The regions of interest were manually positioned on rCBF maps over the caudate nucleus, the putamen, the external and internal globus pallidus, and over the ventrolateral nucleus of the thalamus. Data were normalised with those obtained from parieto-occipital white matter (POWM). Statistical analysis was performed using a parametric ANOVA test. RESULTS: Patients showed a significant (p<0.01) interhemispheric asymmetry; rCBF values were higher on the more severely affected side. Controls showed no interhemispheric asymmetry. CONCLUSION: Our study suggests that PW-MRI is a valuable tool for assessing haemodynamic changes in PD patients. Haemodynamic change pattern may be useful in the early diagnosis of PD.

[The peculiarities of speech disturbance in patients with arteriovenous malformations of the caudate nucleus and the thalamus].

Clinical and neuropsychological study of 28 patients with arteriovenous malformations (AVM) of the caudate nucleus and 36 patients with AVM of the thalamus has been conducted. After surgical removal of the caudate nucleus, speech disturbances developed in 4 out of 8 patients with left-side AVM and in 1 patient, a converted left-hander, with right-side AVM. All 5 patients had mild speech disturbances, which differed by character in dependence of the AVM location. In case of AVM location in the head of the caudate nucleus, the speech disturbances were represented by perseverations and were similar to those caused by the lesion in the Broca area. In case of the caudate nucleus lesion, naming was mildly affected that resembled temporal aphasia. After surgical removal of AVM in the left thalamus in 9 patients, complex and rather stable speech disturbances developed in 7 cases. They were featured by the signs of frontal and temporal aphasias, i.e. there were perseverations and disturbances of naming, auditory and speech memory. The peculiarities of speech disturbances in lesions of the caudate nucleus and the thalamus were well explained by their anatomic and functional correlations with different regions of brain speech cortex. Speech disturbances in various subcortical lesions are reviewed. In the authors' opinion, subcortical aphasias do not have any particular character but include the same factors in different combinations as cortical ones that is determined by the presence of common functional systems for speech support which comprise cortical and subcortical patterns.

Oral methylphenidate challenge selectively decreases putaminal T2 in healthy subjects.

Despite the recent rise in oral methylphenidate (MPH) abuse, few studies have characterized the time course of oral MPH brain effects in human subjects. Accordingly, this study assessed the hemodynamic effects of oral MPH effects in 11 healthy young adults (six women), by measuring brain transverse relaxation times (T2). T2 can be interpreted as a surrogate marker for, and inversely correlated with, steady-state cerebral blood volume (CBV). Data were acquired from the caudate nucleus, putamen, and thalamus, using a 1.5 T MRI scanner at baseline and serially for 2 h following oral MPH administration (0.5 mg/kg). Physiological and subjective measures and plasma MPH levels also were examined. MPH induced a selective T2 decrease (-1.65+/-0.53 ms) in the putamen (F(6,54)=2.68, P<0.03). Heartrate, blood pressure and plasma MPH levels increased significantly after drug administration, as well as subjective ratings of "feeling drug effect". T2 decreases may reflect MPH-induced increases in putaminal blood volume. These data suggest that T2 relaxometry can be used to study the time course of regional cerebral blood volume responses to MPH and perhaps to other stimulant drugs.

Regional cerebral hyperperfusion with ictal dystonic posturing: ictal-interictal SPECT subtraction.

PURPOSE: Ictal-interictal single-photon emission computed tomography (SPECT) subtraction was performed to find brain structures related to ictal dystonic posturing (DP) in patients with temporal lobe epilepsy (TLE). METHODS: Thirty-two patients with mesial TLE who had ictal and interictal SPECTs were included. They were divided into two groups; DP group with ictal dystonia during ictal SPECT (n = 15) and Non-DP group without ictal DP (n = 17). Ictal-interictal SPECT subtraction was performed, and then subtracted SPECT was coregistered with brain spoiled gradient recalled (SPGR) magnetic resonance imaging (MRI). The ictal hyperperfusion on subtracted SPECT was analyzed in basal ganglia, frontal cortex, thalamus, temporal lobe, and insular cortex. RESULTS: The incidences of ictal hyperperfusion on brain regions in DP versus Non-DP groups were 80.0% (12 of 15 patients) versus none (0 of 17), p = 0.001, chi2, in caudate nucleus; 93.3% (14 of 15) versus 47.0% (eight of 17), p = 0.005, in putamen; and 80.0% (12 of 15) versus 41.2% (seven of 17), p = 0.026, in thalamus. No significant difference of ictal hyperperfusion was found in globus pallidus, temporal lobes, insular and frontal cortices between DP and Non-DP groups. DP patients showed an earlier age at seizure onset [8.6 years (DP) vs. 15.7 years (Non-DP) (p = 0.015)] and a longer duration of seizure history [19.0 years (DP) vs. 11.9 years (Non-DP) (p = 0.015)]. CONCLUSIONS: Caudate nucleus, putamen, and thalamus were significantly related to the ictal DP during TLE seizures. Our study showed first an active involvement of the caudate nucleus in the generation of ictal DP.

Normal pressure hydrocephalus and cerebral blood flow: a PET study of baseline values.

Regional cerebral blood flow (CBF) was studied with O(15)-water positron emission tomography and anatomic region-of-interest analysis on co-registered magnetic resonance in patients with idiopathic (n = 12) and secondary (n = 5) normal pressure hydrocephalus (NPH). Mean CBF was compared with values obtained from healthy volunteers (n = 12) and with clinical parameters. Mean CBF was significantly decreased in the cerebrum and cerebellum of patients with NPH. The regional analysis demonstrated that CBF was reduced in the basal ganglia and the thalamus but not in white matter regions. The results suggest that the role of the basal ganglia and thalamus in NPH may be more prominent than currently appreciated. The implications for theories regarding the pathogenesis of NPH are discussed.

Early-onset anorexia nervosa: is there evidence of limbic system imbalance?

OBJECTIVE: This study, part of a continuing effort to understand the pathophysiology of the brain in early-onset anorexia nervosa, attempts to validate findings from an earlier study of regional cerebral blood flow and to correlate any abnormalities in blood flow with eating disorder psychopathology. METHOD: Fifteen newly referred children and adolescents with a diagnosis of anorexia nervosa (AN) underwent regional cerebral blood flow (rCBF) examination using single-photon computerized tomography (SPECT) and the Eating Disorders Examination (EDE) for children. RESULTS: Mean age was 14 years 11 months (SD = 1.35). Mean weight for height ratio was 82.79 % (SD = 10.66). SPECT findings showed that 11 (73%) had asymmetry (hypoperfusion) of blood flow in at least one area. Regions of the brain showing hypoperfusion included the temporal lobe (n = 9), parietal lobe (n = 5), frontal lobe (n = 3), thalamus (n = 3), and the caudate nuclei (n = 1). The median EDE subscale scores were high for all four subscales. Those patients with hypoperfusion had higher median EDE subscale scores than those without hypoperfusion, although the differences were not statistically significant. CONCLUSIONS: Most patients in our study had abnormal rCBF, predominantly affecting the temporal lobe, confirming our previous findings. There was no association with the EDE scores. The findings support earlier suggestions of an imbalance in neural pathways or circuits, possibly within the limbic system. This hypothesis is considered within the context of current knowledge and suggestions made with regard to how it might be tested.

The unilateral spatial neglect phenomenon in patients with arteriovenous malformations of deep brain structures.

Clinical-neuropsychological investigations were performed in 187 patients with arteriovenous malformations (AVM) of deep brain structures; 28 had AVM of the caudate nucleus, 35 of the thalamus, 45 of the cingulate gyrus, 43 of the hippocampus, and 36 of the corpus callosum. A total of 47 patients displayed neglect phenomena of different modalities, while unfixed neglect was demonstrated in 40 cases using special tests. The vast majority of patients showed neglect of left-sided space and the left side of the body, while only three patients showed right-sided neglect. These three patients had signs of left-handedness. In the development of neglect in all patients was associated with post-hemorrhagic or post-operative damage to the white matter (the projections of sensory bundles of the parietal and occipital lobes, the periventricular white matter) or the thalamus and corpus callosum. In hemispheric lesions, neglect developed on the background of the corresponding derangements (hemihypesthesia hemianopsia) and were of the same modality. In cases of damage to the corpus callosum, neglect could develop without accompanying sensory disturbances or the phenomenon could occur on different sides (in cases of simultaneous left hemisphere damage). This supports the independent nature of the neglect phenomenon.

Differences in the extent of primary ischemic damage between middle cerebral artery coagulation and intraluminal occlusion models.

The authors studied the differences between heat-shock/stress protein 70 (hsp70) gene expression and protein synthesis in the unilateral middle cerebral artery (MCA) microsurgical direct occlusion (Tamura's) model and the unilateral intraluminal occlusion model. In Tamura's model, expression of hsp70 mRNA and HSP70 protein and decreased protein synthesis were detected in the ischemic areas, including the ipsilateral cortex and caudate. These phenomena, however, were not observed in the areas outside the MCA territory, including the ipsilateral thalamus, hippocampus, and substantia nigra. These results were consistent among the experimental rats. In the intraluminal occlusion model, however, induction of both hsp70 mRNA and HSP70 protein and impairment of protein synthesis were noted in the areas outside the MCA territory, including the ipsilateral thalamus, hypothalamus, hippocampus, and substantia nigra, as well as in the MCA territory, including the ipsilateral cortex and caudate. These results were not consistent among the experimental rats. These different results might be due to widespread damage resulting from internal carotid artery (ICA) occlusion in the intraluminal occlusion model. Accordingly, the authors suggest that this model be called an ICA occlusion model, rather than a pure MCA occlusion model.

Anticipation of increasing monetary reward selectively recruits nucleus accumbens.

Comparative studies have implicated the nucleus accumbens (NAcc) in the anticipation of incentives, but the relative responsiveness of this neural substrate during anticipation of rewards versus punishments remains unclear. Using event-related functional magnetic resonance imaging, we investigated whether the anticipation of increasing monetary rewards and punishments would increase NAcc blood oxygen level-dependent contrast (hereafter, "activation") in eight healthy volunteers. Whereas anticipation of increasing rewards elicited both increasing self-reported happiness and NAcc activation, anticipation of increasing punishment elicited neither. However, anticipation of both rewards and punishments activated a different striatal region (the medial caudate). At the highest reward level ($5.00), NAcc activation was correlated with individual differences in self-reported happiness elicited by the reward cues. These findings suggest that whereas other striatal areas may code for expected incentive magnitude, a region in the NAcc codes for expected positive incentive value.

Effects of anesthesia on functional activation of cerebral blood flow and metabolism.

Functional brain mapping based on changes in local cerebral blood flow (lCBF) or glucose utilization (lCMR(glc)) induced by functional activation is generally carried out in animals under anesthesia, usually alpha-chloralose because of its lesser effects on cardiovascular, respiratory, and reflex functions. Results of studies on the role of nitric oxide (NO) in the mechanism of functional activation of lCBF have differed in unanesthetized and anesthetized animals. NO synthase inhibition markedly attenuates or eliminates the lCBF responses in anesthetized animals but not in unanesthetized animals. The present study examines in conscious rats and rats anesthetized with alpha-chloralose the effects of vibrissal stimulation on lCMR(glc) and lCBF in the whisker-to-barrel cortex pathway and on the effects of NO synthase inhibition with N(G)-nitro-L-arginine methyl ester (L-NAME) on the magnitude of the responses. Anesthesia markedly reduced the lCBF and lCMR(glc) responses in the ventral posteromedial thalamic nucleus and barrel cortex but not in the spinal and principal trigeminal nuclei. L-NAME did not alter the lCBF responses in any of the structures of the pathway in the unanesthetized rats and also not in the trigeminal nuclei of the anesthetized rats. In the thalamus and sensory cortex of the anesthetized rats, where the lCBF responses to stimulation had already been drastically diminished by the anesthesia, L-NAME treatment resulted in loss of statistically significant activation of lCBF by vibrissal stimulation. These results indicate that NO does not mediate functional activation of lCBF under physiological conditions.