rCBF Changes Research Articles

Beyond Patient Reported Pain: Perfusion Magnetic Resonance Imaging Demonstrates Reproducible Cerebral Representation of Ongoing Post-Surgical Pain

Development of treatments for acute and chronic pain conditions remains a challenge, with an unmet need for improved sensitivity and reproducibility in measuring pain in patients. Here we used pulsed-continuous arterial spin-labelling [pCASL], a relatively novel perfusion magnetic-resonance imaging technique, in conjunction with a commonly-used post-surgical model, to measure changes in regional cerebral blood flow [rCBF] associated with the experience of being in ongoing pain. We demonstrate repeatable, reproducible assessment of ongoing pain that is independent of patient self-report. In a cross-over trial design, 16 participants requiring bilateral removal of lower-jaw third molars underwent pain-free pre-surgical pCASL scans. Following extraction of either left or right tooth, repeat scans were acquired during post-operative ongoing pain. When pain-free following surgical recovery, the pre/post-surgical scanning procedure was repeated for the remaining tooth. Voxelwise statistical comparison of pre and post-surgical scans was performed to reveal rCBF changes representing ongoing pain. In addition, rCBF values in predefined pain and control brain regions were obtained. rCBF increases (5–10%) representing post-surgical ongoing pain were identified bilaterally in a network including primary and secondary somatosensory, insula and cingulate cortices, thalamus, amygdala, hippocampus, midbrain and brainstem (including trigeminal ganglion and principal-sensory nucleus), but not in a control region in visual cortex. rCBF changes were reproducible, with no rCBF differences identified across scans within-session or between post-surgical pain sessions. This is the first report of the cerebral representation of ongoing post-surgical pain without the need for exogenous tracers. Regions of rCBF increases are plausibly associated with pain and the technique is reproducible, providing an attractive proposition for testing interventions for on-going pain that do not rely solely on patient self-report. Our findings have the potential to improve our understanding of the cerebral representation of persistent painful conditions, leading to improved identification of specific patient sub-types and implementation of mechanism-based treatments.

Vascular risk factors are associated with faster decline of Alzheimer disease: a longitudinal SPECT study

We investigated the effects of cardiovascular risk factors, such as hypertension, diabetes mellitus, and hypercholesterolemia, on longitudinal regional cerebral blood flow (rCBF) changes in Alzheimer's disease (AD). We followed 68 outpatients with probable AD for an average of 40 months. They were divided into three groups based on no (n = 24), single (n = 27), and multiple (n = 17) vascular risk factors. We assessed longitudinal changes on the Mini-Mental State Examination, Functional Assessment Staging scores, and in rCBF deficits using repeated single photon emission computed tomography (SPECT) using N-isopropyl-p-[(123)I] iodoamphetamine. During follow-up, the multiple vascular risk factor group showed faster cognitive and functional decline than the no and single vascular risk factor groups. When compared with the initial SPECT, the follow-up SPECT showed a significant rCBF reduction in widespread regions, including the parietotemporal, frontal, and limbic lobes, in the multiple and single vascular risk factor groups, while there was rCBF reduction in small scattered regions of the temporoparietal lobe in the no vascular risk factor group. Multiple vascular risk factors are associated with a greater rate of decline in cognition, function, and rCBF in patients with AD. Our results highlight the contribution of vascular risk factors on the progression of AD.

Effect of dialysis on cerebral blood flow in depressive end-stage renal disease patients

The aim of this study was to investigate regional cerebral blood flow (rCBF) changes of end-stage renal disease (ESRD) patients with depressive symptoms during dialysis. Fourteen patients with ESRD underwent Tc-99m ethylcysteinate dimer (Tc-99m ECD) brain single photon emission computed tomography (SPECT) and were evaluated the severity of depressive mood at pre-dialytic period and at least 6months after dialysis initiation. rCBF was analyzed using statistical parametric mapping (SPM) in brain SPECT image. The responder was defined as a decrease of ≥25% in Hamilton Depression Rating Scale (HDRS) score from baseline HDRS score. Pre-dialysis brain SPECT did not show any rCBF differences between responders and non-responders. The follow-up brain SPECT revealed a significant higher perfusion in left middle temporal gyrus of responder group when compared with non-responder (hemisphere coordinate X, Y, Z; -58, -2, -16, peak Z=3.36, p=0.046). In responder, a significant increase in rCBF was found in right parahippocampal gyrus (hemisphere coordinate X, Y, Z; 30, -40, -14, peak Z=3.51, p=0.043). In non-responder, there were significant decreases in rCBF in left superior frontal gyrus (hemisphere coordinate X, Y, Z; -22, 30, 42, peak Z=3.86, p=0.032) and right orbitofrontal cortex (hemisphere coordinate X, Y, Z; 10, 58, -6, peak Z=3.81, p=0.046). The present findings showed the characteristic patterns of rCBF changes in depressive ESRD patients having maintenance dialysis. Further investigations in brain blood flow and glucose metabolism are needed to elucidate the effect of dialysis itself and the difference of according to dialysis modality in patients having depression and ESRD.

Exploring the after‐effects of theta burst magnetic stimulation on the human motor cortex: A functional imaging study

Theta burst stimulation (TBS) is a protocol of subthreshold repetitive transcranial magnetic stimulation (rTMS) inducing changes in cortical excitability. From functional imaging studies with conventional subthreshold rTMS protocols, it remains unclear what type of modulation occurs (direction and dependency to neural activity) and whether putative effects are bound to unspecific changes in cerebral perfusion or require a functional challenge. In a within-subjects (n = 17) repeated measurement design including real TBS and a control session without stimulation, we examined neural activation in a choice-reaction task after application of intermittent TBS, a protocol, which enhances cortical excitability over the left motor cortex (M1). Brain activity was monitored by blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging interleaved with measuring regional cerebral blood flow (rCBF) at rest using MR-based perfusion imaging. On a separate day, TMS-induced compound muscle action potentials (cMAPs) amplitude of the right hand was measured after excitatory TBS. Compared to control, a significant decrease in BOLD signal due to right hand motor activity during the choice-reaction task was observed mainly in the stimulated M1 and motor-related remote areas after stimulation. This decrease might represent a facilitating effect, because cMAPs amplitude increased upon TBS compared to control. No changes in rCBF at rest were observed. The data demonstrate that subthreshold intermittent TBS targets both the stimulated cortical area as well as remote areas. The facilitation changing the efficacy of neural signal transmission seems to be reflected by a BOLD signal decrease, whereas the network at rest does not appear to be affected.

Regional cerebral blood flow changes in patients with idiopathic REM sleep behavior disorder

Recent studies have shown an association between rapid eye movement sleep behavior disorder (RBD) and neurodegenerative disorders, especially alpha-synucleinopathies. We investigated regional cerebral blood flow (rCBF) changes using single photon emission computed tomography (SPECT) in patients with idiopathic RBD (iRBD), to determine functional brain alterations associated with the disorder. The SPECT data of 24 patients with iRBD were compared with those of 18 age-matched normal controls using statistical parametric mapping 2. We found decreased rCBF in the parietooccipital lobe (precuneus), limbic lobe, and cerebellar hemispheres in patients with iRBD, which is commonly seen in patients with Lewy body disease (Parkinson's disease and dementia with Lewy bodies) or multiple system atrophy. Our SPECT study suggests that iRBD can be a presymptomatic stage of alpha-synucleinopathies.

Brain activation associated with ratings of the hedonic component of thermal sensation during whole-body warming and cooling

Thermal sensation has both discriminative and hedonic components. The neural network associated with thermal discrimination has been described, but the representation of the hedonic component of thermal sensation in the brain has yet to be demonstrated. This study measured regional cerebral blood flow (rCBF) with Positron Emission Tomography in human participants during whole-body cooling and warming. Ratings of the hedonic dimension of thermal sensation were correlated with rCBF and compared to brain activation maps of skin and core temperature changes. The hedonic dimension of thermal sensation was represented in a widely distributed network that included somatosensory, limbic, paralimbic, and associative cortices. Changes in rCBF associated with ratings of the hedonic dimension of thermal sensation were contrasted with changes in rCBF associated with skin and core temperature to identify brain regions that were uniquely activated by the hedonic dimension of thermal sensation. The contrast between the correlates of the hedonic dimension of thermal sensation and the correlates of skin and core temperatures identified a region in the posterior part of the mid cingulate cortex (pMCC). The independent relationship between rCBF changes in the pMCC with ratings of the hedonic dimension of thermal sensation may indicate an important role for the pMCC in the integration of temperature-related signals from receptors in the skin and core.

Body-weight supported treadmill training for improving lower limb function in elderly hemiplegia patients after cerebral infarction

Objective To observe the effect of body-weight supported treadmill training (BWSTT) on the lower limb motor function of elderly hemiplegia patients with acute cerebral infarction using semi-quantitative analysis of regional cerebral blood flow (rCBF) through single photon emission computed tomography (SPECT). Methods Seven patients with cerebral infarction were given comprehensive rehabilitation therapy for 10 weeks in three stages: a baseline period of 2 weeks ( conventional rehabilitation therapy), an intervention period of 6 weeks ( conventional rehabilitation therapy plus BWSTT) and a withdrawal period of 2 weeks (conventional rehabilitation therapy). During the intervention period the exercise duration increased gradually from 15 to 30 minutes, once a day, 5 times a week,for 6 consecutive weeks. Dynamic changes in rCBF in the cortex were observed with SPECT before and after treat ment. Results During the baseline period there was no significant change in average MWS (maximum walking speed) or BBS ( Berg balance scale) scores. During the intervention period both scores improved significantly. During the withdrawal period there were some changes in MWS and BBS scores, but they were not significant. There was a significant change in average rCBF in the cortex after treatment compared with before. Conclusions BWSTT is effective for improving the walking speed and balance of elderly patients with acute cerebral infarction. There is a positive correlation between the recovery of lower limb motor function and changes in rCBF in the cortex. Key words: Single photon emission computed tomography; Body-weight supported treadmill training; Elderly; Cerebral infarction; Walking speed

Assessment of perihematomal hypoperfusion injury in subacute and chronic intracerebral hemorrhage by CT perfusion imaging

Objective: To study alterations of perihematomal cerebral perfusion associated to subacute and chronic intracerebral hemorrhage (ICH) by means of computed tomography perfusion (CTP) imaging.Methods: Non-enhanced CT scan and CTP examination were performed in 12 patients with subacute and chronic supratentorial ICH. The hematoma volume was measured, and the regional cerebral blood flow (rCBF), regional cerebral blood volume (rCBV), mean transit time (MTT) and time-to-peak (TTP) adjacent to hematoma were measured in 11 of 12 cases.Results: Eleven patients with mean age of 58·1 years were finally analysed. Mean time interval from symptom onset to initial CTP scanning was 18·4 days; mean hematoma volume was 26·8 ml. The gradient of hypoperfusion around the hematoma was revealed by rCBF maps in 11 cases, and by rCBV maps in ten cases. The areas of delayed TTP and MTT were showed in 11 and ten cases, respectively. The degree of reduction in rCBV correlated strongly with the hematoma volume (rinner=0·764, p=0·006;router=0·703, p=0·016). There was no correlation between the changes in rCBF, rCBV, MTT and TTP and the time interval from symptom onset to initial CTP examination.Conclusion: We have concluded that the gradient of hypoperfusion surrounding the hematoma may still exist during the subacute and chronic phases after ICH. The alterations in rCBV correlate with the hematoma volume. We believe that the reperfusion injury marked by increased rCBV contributes to the perilesional brain injury. The quantitative CT perfusion measurements can provide valuable information in individual management and prognostic evaluation of ICH.

Modulation of somatosensory‐evoked cortical blood flow changes by GABAergic inhibition of the nucleus basalis of Meynert in urethane‐anaesthetized rats

Vascular changes associated with brain functions are thought to be tightly coupled with neuronal activity through neuronal glucose consumption or the local release of vasoactive agents. In contrast, another view suggests that cortical blood flow is strongly regulated by the nucleus basalis of Meynert (NBM), independently of regional metabolism. Thus, although cortical regional cerebral blood flow (rCBF) variations induced by somatosensory stimulation are strongly linked to neuronal activity, they may also be partly controlled by the NBM. In the present study, cortical rCBF alterations in response to innocuous brushing of the hindlimb (HL) were investigated by laser speckle contrast imaging. The contribution of NBM to these changes was examined after injection of the GABAergic agonist muscimol into the right NBM, allowing comparison of somatosensory-evoked cortical rCBF modifications before and after NBM inactivation. As expected, HL brushing elicited a robust rCBF increase in the contralateral parietal cortex (PC), over the representation of the HL. However, these alterations were decreased, by approximately 40%, in the hemisphere ipsilateral to muscimol inactivation of NBM, whereas vehicle injection did not produce any significant variation. The results demonstrate that cortical rCBF changes induced by somatosensory stimulation are partly regulated by NBM.

The relation of regional cerebral perfusion and atrophy in mild cognitive impairment (MCI) and early Alzheimer's dementia

The spatial and temporal relations between regional cerebral blood flow (rCBF) and brain volume (rVOL) changes in incipient and early Alzheimer's dementia (AD) are not fully understood. The participants comprised 30 subjects with mild cognitive impairment (MCI) and 15 with mild AD who were examined using structural and perfusion-weighted magnetic resonance imaging (MRI) at 1.5 Tesla. Hippocampus and amygdala volumes were measured by manual volumetry. A region-of-interest co-localisation method was used to calculate rCBF values. DNA samples were genotyped for apolipoprotein E (APO E). In comparisons of AD with MCI, rCBF was reduced in the posterior cingulum only, while profound rVOL reductions occurred in both right and left amygdala and in the right hippocampus, and as a trend, in the left hippocampus. Brain volumes of the hippocampus and the amygdala were uncorrelated with the respective rCBF variables in both MCI and AD. Hippocampal but not amygdalar volumes were associated with presence of one or two APOE ε4 alleles in MCI and mild AD, while there was no association of APOE ε4 allele with rCBF. These data support earlier indications that rCBF and rVOL changes are at least partly dissociated in the early pathogenesis of AD and heterogeneously associated with the APOE risk allele. The data also support the concept of functional compensatory brain activation and the diaschisis hypothesis as relevant in incipient and early AD.

Changes in Regional Cerebral Blood Flow and Three-Phase Bone Scan After Repeated Somatic Nerve Blocks for Sympathetically Independent Pain

The pathophysiology of complex regional pain syndrome type 1 (CRPS 1) correlates with variances in both the peripheral and central nerve system. We attempted to explore the topographic correlation between changes in regional cerebral blood flow (rCBF) and 3-phase bone scans during treatments of a series of somatic nerve blocks. The case we present here is a 24-year-old man, who suffered CRPS 1 in his right upper extremity for 4 months, and conservative therapy proved to be ineffectual to him. As he did not respond to stellate ganglion block, the syndrome was regarded as sympathetically independent pain (SIP). However, after administering a series of brachial plexus block and local anesthetics, complete resolution of pain, and restoration of function were manifested. In addition, an increase in rCBF, evidenced by single-photon emission computed tomography (SPECT), and changes in the 3 phase bone scan before and after the nerve block appear to correlate well with the clinical improvement. The changes in rCBF seem to support the theory that the pathogenesis of CRPS is also related to the central nervous system. Multiple somatic nerve blocks (SNB) not only improved physical function but also reversed the CRPS symptoms, for which we presume that reduced nociceptive input signals led to cortical reorganization.

Correlations between Z‐scores of VSRAD and regional cerebral blood flow of SPECT in patients with Alzheimer's disease and mild cognitive impairment

The purpose of the present study was to investigate whether there were correlations between atrophy of the entorhinal cortex and individual regional cerebral blood flow (rCBF) in patients with Alzheimer's disease (AD) and amnestic mild cognitive impairment (MCI) to better clarify the relationships between morphological and functional changes in AD. Twenty-six patients including sixteen AD and 10 amnestic MCI patients were enrolled. Z scores of voxel-based specific regional analysis system for AD (VSRAD) were determined to assess the degree of atrophy of the entorhinal cortex. Single-photon emission computed tomography (SPECT) and 3-D stereotaxic region of interest template (3DSRT) were used to quantify absolute rCBF. The Z scores of the entorhinal cortex were found to have significant negative correlations with the absolute rCBF in the bilateral hippocampus, thalamus and temporal regions. A negative correlation between Z scores and rCBF of the cerebellum region, especially on the right side, was also noted. Atrophy of the entorhinal cortex had an obvious functional relationship with rCBF changes in the hippocampus, thalamus, temporal lobe and cerebellum in AD and MCI patients, which was attributed to their close anatomical and physiological connections.

약용식물 추출물이 흰쥐의 뇌혈류학적 변화에 미치는 영향

As an attempt to develop new functional health beverage by using medicinal herb, we investigated the effect of medicinal plant extract (MPE) on mean arterial blood pressure (MABP) and regional cerebral blood flow (rCBF) of rats. The changes of MABP and rCBF were determined by LDF methods. LDF allows for real time, noninvasive, continuous recordings of local CBF. MABP in MPE treated rats showed significant change of MPE 1.0 and 10.0 mg/kg. MPE i.v. administration showed significant increase of rCBF in a dose-dependent manner. Propranolol pretreated MABP showed significant change in the increase of MPE. rCBF of propranolol pretreated rats showed significant change from the i.v. injection concentration of 1.0 and 10.0 mg/kg. The ischemia/ reperfusion induced oxidative stress may have contributed to cerebral damage in rats, and the present study provides clear evidence for the beneficial effect of MPE on ischemia induced brain injury. Also, the action mechanism in elevation effect of MPE on rCBF might be concerned with the role of β-adrenoceptor. The exact component and mechanism remains for the future study.

Abstract 2698: The parametric response map as an imaging biomarker for identifying progression from pseudoprogression in glioma patients

Abstract We assessed whether a new method of quantifying therapeutic-associated hemodynamic alterations may help to distinguish pseudoprogression from true progression in patients with high grade glioma. Patients from a prospective IRB-approved trial with high grade glioma received concurrent chemoradiation. Relative cerebral blood volume (rCBV) and blood flow (rCBF) maps were acquired prior and at week 3 mid-treatment. Pseudoprogression was defined as imaging changes 1-3 months after chemoradiation that mimic tumor progression but stabilized or improved without change in treatment or for which resection revealed radiation effects only. Clinical and conventional MR parameters, including average percent change of rCBV and CBF, were evaluated as potential predictors of pseudoprogression. Parametric response map (PRM), an innovative, voxel-by-voxel method of image analysis, was also performed. Median radiation dose was 72 Gy (range: 60-81). Of 27 patients, stable disease/partial response was noted in 13 and apparent progression in 14. Adjuvant temozolomide was continued in all patients. Pseudoprogression occurred in 6 patients. Based upon PRM analysis, a significant portion of the tumor volume had reduced rCBV (PRMrCBV) at week 3 in patients with progressive disease compared to those with pseudoprogression (p<0.01). In contrast, change in average percent rCBV or rCBF, MR tumor volume changes, age, extent of resection, and RTOG RPA classification did not distinguish progression from pseudoprogression. PRMrCBV at week 3 during chemoradiation is a potential early imaging biomarker of response that may be helpful in distinguishing pseudoprogression from true progression in glioma patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2698.

Hippocampal deep brain stimulation induces decreased rCBF in the hippocampal formation of the rat

Deep brain stimulation (DBS) is a promising experimental approach to treat various neurological disorders. However, the optimal stimulation paradigm and the precise mechanism of action of DBS are unknown. Neuro-imaging by means of Single Photon Emission Computed Tomography (SPECT) is a non-invasive manner of evaluating regional cerebral blood flow (rCBF) changes, which are assumed to reflect changes in neural activity. In this study, rCBF changes induced by hippocampal DBS are evaluated by subtraction analysis of stimulation on/off using small animal µSPECT of the rat brain. Rats (n=13) were implanted with a multi-contact DBS electrode in the right hippocampus and injected with 10mCi of HMPAO-Tc99m during application of various hippocampal DBS paradigms and amplitudes and during sham stimulation. Subtraction analysis revealed that hippocampal DBS caused a significant decrease in relative rCBF, both in the ipsi- (the side of the implanted electrode) and contralateral hippocampus. Hypoperfusion spread contralaterally with increasing stimulation amplitude. A clear distinction in spatial extent and intensity of hypoperfusion was observed between stimulation paradigms: bipolar Poisson Distributed Stimulation induced significant hypoperfusion ipsi- and contralaterally (p<0.01), while during other stimulation paradigms, rCBF-changes were less prominent. In conclusion, small animal µSPECT allows us to draw conclusions on the location, spatial extent and intensity of the hypoperfusion observed in the ipsi- and contralateral hippocampus, induced by hippocampal DBS. Our study demonstrates an innovative approach to visualize the effects of DBS and can be a useful tool in evaluating the effect of various stimulation paradigms and target areas for DBS.

Parametric Response Map As an Imaging Biomarker to Distinguish Progression From Pseudoprogression in High-Grade Glioma

To assess whether a new method of quantifying therapy-associated hemodynamic alterations may help to distinguish pseudoprogression from true progression in patients with high-grade glioma. Patients with high-grade glioma received concurrent chemoradiotherapy. Relative cerebral blood volume (rCBV) and blood flow (rCBF) maps were acquired before chemoradiotherapy and at week 3 during treatment on a prospective institutional review board-approved study. Pseudoprogression was defined as imaging changes 1 to 3 months after chemoradiotherapy that mimic tumor progression but stabilized or improved without change in treatment or for which resection revealed radiation effects only. Clinical and conventional magnetic resonance (MR) parameters, including average percent change of rCBV and CBF, were evaluated as potential predictors of pseudoprogression. Parametric response map (PRM), an innovative, voxel-by-voxel method of image analysis, was also performed. Median radiation dose was 72 Gy (range, 60 to 78 Gy). Of 27 patients, stable disease/partial response was noted in 13 patients and apparent progression was noted in 14 patients. Adjuvant temozolomide was continued in all patients. Pseudoprogression occurred in six patients. Based on PRM analysis, a significantly reduced blood volume (PRM(rCBV)) at week 3 was noted in patients with progressive disease as compared with those with pseudoprogression (P < .01). In contrast, change in average percent rCBV or rCBF, MR tumor volume changes, age, extent of resection, and Radiation Therapy Oncology Group recursive partitioning analysis classification did not distinguish progression from pseudoprogression. PRM(rCBV) at week 3 during chemoradiotherapy is a potential early imaging biomarker of response that may be helpful in distinguishing pseudoprogression from true progression in patients with high-grade glioma.

Regional cerebral blood flow responses to hyperventilation during sevoflurane anaesthesia studied with PET

Arterial carbon dioxide tension (PaCO(2)) is an important factor controlling cerebral blood flow (CBF) in neurosurgical patients. It is still unclear whether the hypocapnia-induced decrease in CBF is a general effect on the brain or rather linked to specific brain regions. We evaluated the effects of hyperventilation on regional cerebral blood flow (rCBF) in healthy volunteers during sevoflurane anaesthesia measured with positron emission tomography (PET). Eight human volunteers were anaesthetized with sevoflurane 1 MAC, while exposed to hyperventilation. During 1 MAC sevoflurane at normocapnia and 1 MAC sevoflurane at hypocapnia, one H(2)(15)O scan was performed. Statistical parametric maps and conventional regions of interest analysis were used for estimating rCBF differences. Cardiovascular parameters were maintained constant over time. During hyperventilation, the mean PaCO(2) was decreased from 5.5 + or - 0.7 to 3.8 + or - 0.9 kPa. Total CBF decreased during the hypocapnic state by 44%. PET revealed wide variations in CBF between regions. The greatest values of vascular responses during hypocapnia were observed in the thalamus, medial occipitotemporal gyrus, cerebellum, precuneus, putamen and insula regions. The lowest values were observed in the superior parietal lobe, middle and inferior frontal gyrus, middle and inferior temporal gyrus and precentral gyrus. No increases in rCBF were observed. This study reports highly localized and specific changes in rCBF during hyperventilation in sevoflurane anaesthesia, with the most pronounced decreases in the sub cortical grey matter. Such regional heterogeneity of the cerebral vascular response should be considered in the assessment of cerebral perfusion reserve during hypocapnia.

Relationship Between Regional Cerebral Blood Flow and Electrocorticographic Activities Under Sevoflurane and Isoflurane Anesthesia

The aims of this study are (1) to assess the effects of volatile anesthetics on regional cerebral blood flow (rCBF) and electrocorticography (ECoG), and (2) to investigate the relationship between rCBF and ECoG influenced by volatile anesthetics. The authors measured rCBF using laser Doppler flowmetry and ECoG simultaneously and continuously from the same cortex during craniotomy, using the specially arranged probe. Patients received intravenous anesthetics with nitrous oxide until craniotomy, and after opening of dura, volatile anesthetic, either isoflurane or sevoflurane, was started and was gradually increased for the measurement. Four of the nine cases (44.4%) of the sevoflurane group showed no change both in rCBF and ECoG. In three cases (33.3%), rCBF increased as the frequency of the paroxysmal activities increased. In two cases (22.2%), decreased rCBF was accompanied by slow waves. In 12 cases of the isoflurane group, no apparent rCBF and ECoG changes were seen, except a case with decreased rCBF and slow waves. This is the first report of simultaneous recordings of regional CBF and neuronal activity under general anesthesia. During sevoflurane and isoflurane anesthesia <2.5 minimum alveolar anesthetic concentration, rCBF is affected by ECoG activities rather than pharmacologic action of inhalational anesthetics.

Altered Neural Cholinergic Receptor Systems in Cocaine-Addicted Subjects

Changes in the brain's cholinergic receptor systems underlie several neuropsychiatric disorders, including Alzheimer's disease, schizophrenia, and depression. An emerging preclinical literature also reveals that acetylcoholine may have an important function in addictive processes, including reward, learning, and memory. This study was designed to assess alterations in cholinergic receptor systems in limbic regions of abstinent cocaine-addicted subjects compared with healthy controls. On three separate days, 23 1- to 6-week abstinent, cocaine- (and mostly nicotine-) addicted subjects and 22 sex-, age-, and race-matched control subjects were administered the muscarinic and nicotinic cholinergic agonist physostigmine, the muscarinic antagonist scopolamine, and saline. Regional cerebral blood flow (rCBF) after each infusion was determined using single photon emission-computed tomography. Both cholinergic probes induced rCBF changes (p<0.005) in relatively distinct, cholinergic-rich, limbic brain regions. After physostigmine, cocaine-addicted subjects showed altered rCBF, relative to controls, in limbic regions, including the left hippocampus, left amygdala, and right insula. Group differences in the right dorsolateral prefrontal cortex, posterior cingulate, and middle temporal gyrus were also evident. Scopolamine also revealed group differences in the left hippocampus and right insula as well as the posterior cingulate and middle temporal gyrus. Cocaine addicted and controls differ in their subcortical, limbic, and cortical response to cholinergic probes in areas relevant to craving, learning, and memory. Cholinergic systems may offer a pharmacologic target for cocaine addiction treatment.

Regional cerebral blood flow changes induced by deep brain stimulation in secondary dystonia

The purpose of the present study is to investigate the effect of deep brain stimulation (DBS) on regional cerebral blood flow (rCBF) in cases of secondary dystonia as well as to correlate the rCBF changes with clinical outcomes. Six patients with medically intractable secondary dystonia who underwent DBS surgery were included in this study. Burke-Fahn-Mardsen Dystonia Rating Scale (BFMDRS) was used for the assessment of dystonia, before and after surgery. Single photon emission computed tomography (SPECT) of the brain was performed postoperatively in the two stimulation states (ON-DBS and OFF-DBS) and the changes of rCBF in the three following brain regions of interest (ROIs): primary motor cortex, premotor and supplementary motor cortex, and prefrontal cortex were evaluated. Two patients exhibited excellent response to DBS, two patients got moderate benefit after the procedure, and in two patients, no clinical improvement was achieved. A mean improvement of 49.1% (0-90.7%) in BFMDRS total scores was found postoperatively. Brain SPECT data analysis revealed an overall decrease in rCBF in the investigated ROIs, during the ON-DBS state. Clinical improvement was significantly correlated with the observed decrease in rCBF in the presence of DBS. When conservative treatment fails to relieve severely disabled patients suffering from secondary dystonia, DBS may be a promising therapeutic alternative. Moreover, this study indicates a putative role of brain SPECT imaging as a postoperative indicator of clinical responsiveness to DBS.