Mechanism and prevention of port-site tumor recurrence after laparoscopy in a murine model

Functional activation of somatosensory cortex was studied in alpha-chloralose anesthetized rats by functional magnetic resonance imaging (fMRI), using both perfusion-weighted and T2*-weighted (blood oxygenation level dependent, BOLD) imaging. The sensitivity of functional activation was altered by ventilating animals for 3 minutes with 6% CO2. Before hypercapnic conditioning, electrical stimulation of the left forepaw at a frequency of 3 Hz led to an increase of signal intensity (relative to the unstimulated baseline condition) in the right somatosensory cortex by 6+/-2% (means+/-SD) in T2*-weighted images and by 45%+/-48% in perfusion-weighted images. After hypercapnic conditioning the signal intensity increase in perfusion-weighted images doubled to 91%+/-62% (P=0.034), whereas that of T2*-weighted images only marginally increased to 7+/-4% (not significant). This different behavior in both imaging modalities is interpreted as evidence for an increased flow response in combination with a higher oxygen extraction. Thus, the fMRI data reflect hypercapnia-induced resetting of the functional-metabolic coupling of the tissue during activation.     

Resting and stimulated states in functional imaging studies: evidence of differences in attentional and intentional set

In a [99mTc]-hexamethylpropyleneamine oxime single photon emission computed tomography study of cerebral blood flow (CBF) in a visual activation paradigm (awake, eyes closed versus eyes open viewing a reversing checkerboard pattern), the authors systematically measured previously observed qualitative alterations in frontal blood flow associated with visual stimulation (experiment 1). They confirmed a trend toward reductions in CBF throughout precentral cortex that approached significance in areas 9 and 46, in conjunction with significant increases in CBF in postcentral cortices, including visual association area PO, and areas 3-1-2, 22, and 23. The authors posited that these changes may be related to differences in attentional and intentional state in the eyes-closed and eyes-open conditions. Such differences should be associated with alterations in motor preparedness, leading to changes in response times and to alterations in thalamocortical gating of somatosensory information, which in turn lead to changes in somatosensory-evoked potential amplitudes. In experiment 2, the authors measured simple motor response times to a 1500-Hz tone stimulus and early components of somatosensory-evoked potentials under the same experimental conditions. In the visual stimulation condition, there was a significant increase in the evoked potential amplitude (t = 2.686, p = 0.021), and a significant decrease in response time (t = -2.464, p = 0.031). These observations provided tentative support for their hypothesis. The authors also demonstrated the major effect of normalization assumptions on regional blood flow measurements.     

Effect of neuronal NO synthase inhibition on the cerebral vasodilatory response to somatosensory stimulation

Whether nitric oxide (NO) mediates--or not--the local cerebral blood flow (CBF) increases occurring during functional brain activation is still a controversial issue. In the present study, we sought to determine whether neuronal NO synthase is involved in the cerebrovascular response to activation of the trigeminal pathway in the rat. Local CBF was measured using the autoradiographic [14C]iodoantipyrine technique in control alpha-chloralose anesthetized rats and 30 min following administration of 7-nitroindazole (7-NI), an inhibitor of the neuronal NO synthase. Unilateral whiskers stroking increased local CBF in all six regions of the trigeminal pathway. Under 7-NI, CBF was slightly decreased and the vasodilatatory response to whisker stimulation was unaltered in the four trigeminal nuclei studied. In contrast, no significant vasodilatation was noted in the ventral posteromedial thalamic nucleus and somatosensory cortex. These results suggest that the neuronal NO synthase mediates the hyperemia associated with somatosensory activation in second order relay stations but not in the site of termination of primary afferents.     

Responses of neurons of the first and second somatosensory zones of the cortex to peripheral, thalamic and cortical stimulation

Experiments were performed on cats immobilized with d-tubocurarine or myorelaxin. Neuronal responses were studied in the first somatosensory cortex (SI) to the second somatosensory cortex (SII), ventroposterior nucleus (VP) and contralateral forepaw stimulation. Besides, neuronal responses in SII to SI, VP and contralateral forepaw stimulation were also studied. It was shown that in SII the percentage of neurons excited by afferent volley with two or more synaptic change-overs in the cerebral cortex was larger than in SI. Neurons of SI and SII responded to cortical stimulation ortho- and antidromically, thus confirming the existence of bilateral cortico-cortical connections. Both in SI and SII, PSPs to cortical stimulation were similar in character to PSPs in the same neurons to VP stimulation. In 50.0% of SI neurons and 37.1 of SII neurons the difference in latencies of orthodromic spike potentials to VP and cortical stimulation was less than 1.0 ms. In 19.6% of SI neurons and 41.4% of SII neurons the latency of the response to cortical stimulation was 1.6-4.7 ms shorter than that of the response in the same neuron to VP stimulation. It is supposed that impulses from SI participate significantly in afferent activation of SII neurons.     

Simultaneous oxygenation and perfusion imaging study of functional activity in primary visual cortex at different visual stimulation frequency: quantitative correlation between BOLD and CBF changes

A relationship between regional cerebral blood flow (CBF) and blood oxygenation level dependent (BOLD) changes in the primary visual cortex (V1) at varied visual stimulation frequency has been examined quantitatively using the multislice FAIR technique. A linear correlation in the common activation areas between functional BOLD and CBF maps was observed. This supports the hypothesis that the task-stimulated BOLD changes in microvasculature are correlated with the CBF changes that presumably reflect the degree of neuronal activity. The linear correlation coefficients for intrasubject comparisons are more significant than those for intersubject comparisons. This suggests that using intrasubject comparisons for quantitative studies of neuronal activity related to different task stimuli and task performances should be more reliable than using intersubject comparisons.     

Cerebral extracellular lactate concentration and blood flow during chemical stimulation of the nucleus tractus solitarii in anesthetized rats

The extracellular lactate concentration and blood flow in the cerebral cortex of urethane-anesthetized, paralyzed and artificially ventilated rats were monitored continuously and simultaneously using an enzyme electrode and a laser Doppler flowmeter (LDF), respectively, during chemical stimulation of the nucleus tractus solitarii (NTS) by microinjection of L-glutamate (1.7 nmol 50 nl). Chemical stimulation of the NTS significantly decreased the arterial blood pressure (ABP) from 85 +/- 17 to 68 +/- 14 mmHg, heart rate from 418 +/- 13 to 402 +/- 19 beats x min(-1) and cerebral blood flow (CBF) by 17.9 +/- 6.2% (P < 0.001). However, chemical stimulation of the NTS significantly increased the lactate concentration by 58.9 +/- 17.3 microM (P < 0.001). Barostat maneuver, which held systemic ABP constant during chemical stimulation of the NTS attenuated the responses in CBF and lactate concentration by 30 and 27%, respectively. The onset of the increase in lactate concentration was delayed about 19 s after that of the CBF decrease. Circulatory lactate produced no significant change in the cerebral extracellular lactate concentration. These results indicate that chemical stimulation of the NTS induces an increase in extracellular lactate concentration in the cerebral cortex through a decrease in CBF via cerebral vasoconstriction.     

Effects of dipyridamole in spontaneously hypertensive rabbits with diffuse chronic cerebral ischemia

The effect of intravenous dipyridamole (0.7 mg/kg) on cerebral blood flow (CBF), mean arterial blood pressure (MABP), heart rate, respiration rate, cerebral electrical activity, arterial blood gases, pH, and glucose was investigated in 14 normotensive and 14 stroke-prone spontaneously hypertensive anesthetized rabbits. CBF was measured by hydrogen and heat clearance. In both groups, MABP decreased (normotensive: -24 mm Hg, hypertensive: -47 mm Hg; ANOVA: P < 0.0001) and CBF increased (normotensive: +59 ml/100 g/min, hypertensive: +72 ml/100 g/min; ANOVA: P < 0.0002). CBF returned to the initial level 21 min later in hypertensive than in normotensive rabbits. Changes in other parameters were insignificant. In additional experiments, 30 mg/kg theophylline entirely prevented the cerebral vasodilator and systemic hypotensive effects of dipyridamole in both normotensive and hypertensive rabbits. We conclude that, in stroke-prone spontaneously hypertensive rabbits, the longer-lasting and larger CBF increase in response to dipyridamole may be attributed to reversible functional changes in the cerebral vasculature resulting from hypertension.     

Circulating levels of Locusta diuretic hormone: the effects of feeding

The most widely-used functional magnetic resonance imaging (fMRI) technique is based on the blood oxygenation level dependent (BOLD) effect, which requires at least partial uncoupling between cerebral blood flow (CBF) and oxygen consumption changes during increased mental activity. To compare BOLD and CBF effects during tasking, BOLD and flow-sensitive alternating inversion recovery (FAIR) images were acquired during visual stimulation with red goggles at a frequency of 8 Hz in an interleaved fashion. With the FAIR technique, absolute and relative CBF changes were determined. Relative oxygen consumption changes can be estimated using the BOLD and relative CBF changes. In gray matter areas in the visual cortex, absolute and relative CBF changes in humans during photic stimulation were 31 +/- 11 SD ml/100 g tissue/min and 43 +/- 16 SD % (n = 12), respectively, while the relative oxygen consumption change was close to zero. These findings agree extremely well with previous results using positron emission tomography. The BOLD signal change is not linearly correlated with the relative CBF increase across subjects and negatively correlates with the oxygen consumption change. Caution should be exercised when interpreting the BOLD percent change as a quantitative index of the CBF change, especially in inter-subject comparisons.     

Electrical stimulation of precentral cortical area in the treatment of central pain: electrophysiological and PET study

The clinical, electrophysiological and haemodynamic effects of precentral gyrus stimulation (PGS) as a treatment of refractory post-stroke pain were studied in 2 patients. The first patient had a right hemibody pain secondary to a left parietal infarct sparing the thalamus, while the second patient had left lower limb pain developed after a right mesencephalic infarct. In both cases, spontaneous pain was associated with hyperpathia, allodynia and hypoaesthesia in the painful territory involving both lemniscal and extra-lemniscal sensory modalities in patient 1, extra-lemniscal sensory modality only in patient 2. Both patients were treated with electrical PGS by means of a 4-pole electrode, the central sulcus being per-operatively located using the phase-reversal of the N20 wave of somatosensory evoked potentials. No sensory side effect, abnormal movement or epileptic seizure were observed during PGS. The analgesic effects were somatotopically distributed according to the localization of electrode on motor cortex. A satisfactory long-lasting pain control (60-70% on visual analog scale) as well as attenuation of nociceptive reflexes were obtained during PGS in the first patient. Pain relief was less marked and only transient (2 months) in patient 2, in spite of a similar operative procedure. In this patient, in whom PGS eventually evoked painful dysethesiae, no attenuation of nociceptive RIII reflex could be evidenced during PGS. Cerebral blood flow (CBF) was studied using emission tomography (PET) with O-labeled water. The sites of CBF increase during PGS were the same in both patients, namely the thalamus ipsilateral to PGS, cingulate gyrus, orbito-frontal cortex and brainstem. CBF increase in brainstem structures was greater and lasted longer in patient 1 while patient 2 showed a greater CBF increase in orbito-frontal and cingular regions. Our results suggest that PGS-induced analgesia is somatotopically mediated and does not require the integrity of somatosensory cortex and lemniscal system. PGS analgesic efficacy may be mainly related to increased synaptic activity in the thalamus and brainstem while changes in cingulate gyrus and orbito-frontal cortex may be rather related to attentional and/or emotional processes. The inhibitory control on pain would involve thalamic and/or brainstem relays on descending pathways down to the spinal cord segments, leading to a depression of nociceptive reflexes. Painful dysesthesiae during stimulation have to be distinguished from other innocuous sensory side effects, since they may compromise PGS efficacy.     

The influence of DNA glycosylases on spontaneous mutation

In the present study we examined the effects of phasic activation of the nucleus locus coeruleus (LC) on transmission of somatosensory information to the rat cerebral cortex. The rationale for this investigation was based on earlier findings that local microiontophoretic application of the putative LC transmitter, norepinephrine (NE), had facilitating actions on cortical neuronal responses to excitatory and inhibitory synaptic stimuli and more recent microdialysis experiments that have demonstrated increases in cortical levels of NE following phasic or tonic activation of LC. Glass micropipets were used to record the extracellular activity of single neurons in the somatosensory cortex of halothane-anesthetized rats. Somatosensory afferent pathways were activated by threshold level mechanical stimulation of the glabrous skin on the contralateral forepaw. Poststimulus time histograms were used to quantitate cortical neuronal responses before and at various time intervals after preconditioning burst activation of the ipsilateral LC. Excitatory and postexcitatory inhibitory responses to forepaw stimulation were enhanced when preceded by phasic activation of LC at conditioning intervals of 200-500 ms. These effects were anatomically specific in that they were only observed upon stimulation of brainstem sites close to (>150 micron) or within LC and were pharmacologically specific in that they were not consistently observed in animals where the LC-NE system had been disrupted by 6-OHDA pretreatment. Overall, these data suggest that following phasic activation of the LC efferent system, the efficacy of signal transmission through sensory networks in mammalian brain is enhanced.     

Functional activation of cerebral blood flow abolished by scopolamine is reversed by cognitive enhancers associated with cholinesterase inhibition: a positron emission tomography study in unanesthetized monkeys

The effects of somatosensory stimulation on the regional cerebral blood flow (rCBF) response were studied in unanesthetized monkeys before and after treatment with scopolamine and three cognitive enhancers (physostigmine, E2020 and tacrine) that inhibit cholinesterase, using 15O-labeled water and high-resolution positron emission tomography. Under control conditions, somatosensory stimulation induced a significant increase in the rCBF response in the contralateral somatosensory cortex of monkey brain. Intravenous administration of scopolamine (50 microg/kg) resulted in abolishment of the rCBF response to stimulation. The rCBF response abolished by pretreatment with scopolamine was recovered by administration of physostigmine (1 or 10 microg/kg), E2020 (10 or 100 microg/kg) or tacrine (100 or 1000 microg/kg), in a dose-dependent manner. The effect of E2020 (100 microg/kg) on the rCBF response lasted for >4 hr, whereas the effects of physostigmine and tacrine were of shorter duration. These findings suggest that these compounds reversed the scopolamine-abolished rCBF response to somatosensory stimulation via enhancement of cholinergic neurotransmission, which was mainly induced by cholinesterase inhibition.     

Cholinergic modulation of cerebral cortical blood flow changes induced by trauma

These experiments tested the role of cholinergic mechanisms in the changes of cerebral cortical blood flow (CBF) induced by brain trauma. CBF was measured with Iodo-14C-antipyrine autoradiography, in 128 cerebral cortex regions of both hemispheres, distributed in eight coronal slices. The effects of a 6.3-mm diameter craniotomy over the left motor-sensory cortex with no weight drop, and of trauma (drop weight of 20 g from 30 cm height on left motor-sensory cortex through a 6.3 mm circular craniotomy) on CBF were studied at 2 and 24 h after the interventions. A group of control animals that received no intervention was also set up. Animals were treated with the cholinesterase inhibitor physostigmine salicylate (3.3 microg/kg/min i.v. infusion started 60 min before CBF measurements), the cholinergic blocker scopolamine hydrobromide (1 mg/kg i.v. pulse, 18 min before CBF measurements), or with the drugs vehicle (saline). A focus of decreased CBF at the site of impact was observed 2 h after trauma, extending caudally as far as the occipital cortex. CBF on the contralateral cerebral cortex was also decreased. Both phenomena reversed partially at 24 h. This spontaneous recovery of CBF was blocked by scopolamine. Physostigmine reversed the decrease in CBF of the traumatized cortex, partially around the contused area and completely in more distant regions. The cerebral cortex contralateral to the trauma showed significantly higher CBF 24 h after trauma when compared to intact controls or craniotomy that peaked at the area symmetrical to the center of trauma. This phenomenon was also enhanced by physostigmine and completely blocked by scopolamine. These results suggest a prominent role of cholinergic mechanisms in the vascular adjustments that accompany cerebral trauma.     

Dynamic functional imaging of relative cerebral blood volume during rat forepaw stimulation

Dynamic measurements of regional changes in cerebral blood volume (CBV) were performed in rat models of hypercarbia and focal neuronal activation using T2-weighted imaging after injection of an intravascular contrast agent with a very long blood half-life. Calculated percent CBV change during hypercarbia was consistent with literature results from other non-invasive modalities. Equivalent percent CBV increases were found using spin- and gradient-echo images, suggesting proportional changes in blood volume for capillaries and small veins. During electrical stimulation of rat forepaw, focal CBV response to stimulation (24+/-4%) was significantly delayed relative to blood oxygen level dependent (BOLD) signal after both onset and cessation of stimulation. Poststimulus CBV decay was temporally consistent with the BOLD poststimulus undershoot. The use of exogenous agent increased the functional contrast-to-noise ratio relative to BOLD imaging by 5.7+/-1.3 at a magnetic field strength of 2 Tesla and 1.5+/-0.2 at 4.7 Tesla.     

The relationship between hyperproliferation and epidermal thickening in a mouse model for BCIE

This study examined the hypothesis that the cerebrovascular response to asphyxia of the late gestation sheep fetus is characterized by an increase in cerebrovascular resistance and a fall in cerebral blood flow (CBF) rather than the fall in resistance and increase in CBF which occurs in acute hypoxemia. In eight unanesthetized late gestation fetal sheep (123- to 125-d gestation) we evaluated continuous changes in carotid blood flow (CaBF) as an index of global CBF and total cerebral Hb concentrations as an index of global cerebral blood volume (CBV) using ultrasound flow probes and near infrared spectroscopy respectively. Asphyxia was induced by rapid and complete occlusion of the umbilical cord for 10 min. We also examined the fetal response to 1 h of acute 9% isocapnic hypoxia for comparison purposes. During hypoxia we observed a sustained increase in CaBF (p < 0.05) and CBV (p < 0.01) and a fall in carotid vascular resistance (p < 0.05). During asphyxia there was no significant rise in CBV, a fall in CaBF (p < 0.05), and a rise in carotid vascular resistance (p < 0.01). CaBF fell at a time when mean arterial pressure was elevated (p < 0.01). These data strongly suggest that fetal CBF does not increase and may even fall during severe asphyxia of rapid onset. Furthermore, our near infrared spectroscopy data show that the relative changes in total cerebral Hb concentrations may reflect the type and severity of the insult to which the fetus is exposed.     

Measurement of nitric oxide in the rat cerebral cortex during hypercapnoea

Changes in nitric oxide (NO) concentration and cerebral blood flow (CBF) in the parietal cortex during hypercapnoea were investigated in anaesthetized rats, using a NO-selective electrode and laser Doppler flowmetry. When hypercapnoea was induced by inhalation of 5% CO2 for 10 min, both the NO concentration and CBF increased. After administration of 7-nitroindazole, a neuronal NO synthase (nNOS) inhibitor, both the basal NO and CBF decreased, and responses to hypercapnoea were also significantly suppressed by 70.1% and 73.2%, respectively, compared with the control state. These results suggest that NO derived from nNOS is involved not only in maintaining resting cerebral circulation but also in regulating CBF response during hypercapnoea.     

Stimulation of human thalamus for pain relief: possible modulatory circuits revealed by positron emission tomography

Stimulation of human thalamus for pain relief: possible modulatory circuits revealed by positron emission tomography. J. Neurophysiol. 80: 3326-3330, 1998. Stimulation of the somatosensory thalamus was used for more than 2 decades to treat chronic pain in the human. However, despite clinical reports of successful results, little is known about the actual mechanisms mediating this form of stimulation-produced analgesia. To reveal possible neuronal pathways evoked by thalamic stimulation, we measured regional changes in cerebral blood flow (rCBF) in five patients who received successful long-term relief of chronic pain with somatosensory thalamic stimulation. Positron emission tomography during thalamic stimulation revealed significant activation of the thalamus in the region of the stimulating electrodes as well as activation of the insular cortex ipsilateral to the thalamic electrodes (contralateral to the patients' clinical pain). For these patients, thalamic stimulation also evoked paresthesiae that included thermal sensations in addition to tingling sensations. Results of this study indicate that in some cases somatosensory thalamic stimulation may activate a thalamocortical pain modulation circuit that involves thermal pathways. These results are consistent with other recent reports suggesting that activation of thermal pathways may contribute to modulation of nociceptive information.     

An attempt at reversibility and increase of the virulence of axenic strains of Entamoeba histolytica

Sequential changes of cerebral autoregulation were studied in 20 cats after recirculation of cerebral ischemia. The cerebral autoregulation was evaluated by autoregulation index (A.I.), calculating % delta cerebral blood flow (CBF)/delta cerebral perfusion pressure (CPP), with changing the mean arterial blood pressure (MABP) within 80-130 mmHg. Duration of ischemic insult was 15 min after disappearance of direct cortical response (DCR). Following recovery of cerebral circulation, MABP, CBF and intracranial pressure (ICP) were observed sequentially for at least 48 hours. In 6 of 20 cats the autoregulation was disturbed early after recirculation, and the ICP was increased, resulting in no cerebral blood flow (early deteriorated group). In the other 14 cats the autoregulation was restored immediately, but in 7 of the 14 cats it was disturbed again after 24 hours following recirculation (delayed deteriorated group), finally the ICP was elevated and the CBF became 0 as same as early deteriorated group. In another 7 cats it was not disturbed until 5 days. The changes in CBF following insult were five patterns. These were classified into type A (Gradual decrease), type B (Transient increase), type C (Constant maintenance), type D (Relatively rapid decrease) and type E (Rapid decrease). The delayed cerebral dysautoregulation occurred in the types except for type A and type E. These results suggested there was close relation between delayed dysautoregulation and delayed neuronal dysfunction that we reported previously. Moreover, we considered the delayed dysautoregulation could be speculated from the value of ICP/CBF immediately after recirculation and the pattern of the changes in CBF during ischemic insult.     

Assessment of cerebral blood flow reserve using functional magnetic resonance imaging

Imaging of activated brain areas based on changes of blood deoxyhemoglobin levels is now possible with MRI. Acetazolamide (ACZ) increases cerebral blood flow (CBF) without changing cerebral oxygen consumption; this results in signal changes observed in gradient echo MR images from the areas with an increase in CBF. We assessed signal changes after ACZ application in seven healthy subjects with a conventional 1.5-T MRI scanner. The susceptibility-sensitized three-dimensional fast low-angle shot (FLASH) sequence was used to visualize signal changes induced by ACZ. We analyzed anatomic localization of different ranges of detected signal changes. ACZ caused significant signal changes in the gray matter and at the edge of the cerebral cortex, the latter corresponding to draining surface veins. No significant differences were seen among different brain areas within the same slice. Using the maximal intensity projection technique, we were able to partially separate signal changes originating in draining veins from signal originating in the gray matter microvasculature. Signal changes from the microvessels reflect cerebrovascular reserve. Blood-oxygen-level-dependent (BOLD) based MRI can evaluate CBF reserve with high spatial and temporal resolution. To assess cerebrovascular reserve, it is necessary to separate signal changes originating in large vessels from signal from brain microvasculature.     

The cochlear blood flow: a comparison between the laser Doppler and the microsphere surface methods

Since the introduction in the early 1980s, of the laser Doppler (LD) method for measuring cochlear blood flow (CBF) it has been debated whether the measured changes reflect the total or regional blood flow and whether the method per se influences the CBF. In order to answer those questions, the effect of one vasodilating drug, sodium nitroprusside, was investigated after topical application on the round window membrane (RWM) with respect to its influence on CBF. Two different techniques, the microspheres surface method and the LD method, were used. Untreated animals and animals which received saline or nicotine acid on the RWM were used as controls. The effects on CBF and blood pressure (BP) were continuously registered with LD. When a maximal flow had stabilized, 6 x 10(6) microspheres were injected into the left side of the heart. After the microspheres had been distributed within the body, the animals were killed. Both cochleae were microdissected and the microspheres counted turn by turn in the lateral wall. The number of spheres in the two ears was compared and the difference was recorded as the increase caused by the drug. The percentage change in CBF measured using the LD was compared with that obtained by using the microsphere surface method (MSM). No change in CBF measured by the two techniques was registered in the untreated animals, or after saline or nicotinic acid, while sodium nitroprusside induced a substantial increase in CBF. The mean percentage change of CBF measured with the LD method was compared with the calculated mean percentage change of microspheres for all turns in the cochlea, and in the first turn. Student's t-test and the linear correlation coefficient were calculated.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cocaine decreases cortical cerebral blood flow but does not obscure regional activation in functional magnetic resonance imaging in human subjects

The authors used functional magnetic resonance imaging (fMRI) to determine whether acute intravenous (i.v.) cocaine use would change global cerebral blood flow (CBF) or visual stimulation-induced functional activation. They used flow-sensitive alternating inversion recovery (FAIR) scan sequences to measure CBF and blood oxygen level-dependent (BOLD) sensitive T2* scan sequences during visual stimulation to measure neuronal activation before and after cocaine and saline infusions. Cocaine (0.6 mg/kg i.v. over 30 seconds) increased heart rate and mean blood pressure and decreased end tidal carbon dioxide (CO2). All measures returned to baseline by 2 hours, the interinfusion interval, and were unchanged by saline. Flow-sensitive alternating inversion recovery imaging demonstrated that cortical gray matter CBF was unchanged after saline infusion (-2.4 +/- 6.5%) but decreased (-14.1 +/- 8.5%) after cocaine infusion (n = 8, P < 0.01). No decreases were detected in white matter, nor were changes found comparing BOLD signal intensity in cortical gray matter immediately before cocaine infusion with that measured 10 minutes after infusion. Visual stimulation resulted in comparable BOLD signal increases in visual cortex in all conditions (before and after cocaine and saline infusion). Despite a small (14%) but significant decrease in global cortical gray matter CBF after acute cocaine infusion, specific regional increases in BOLD imaging, mediated by neurons, can be measured reliably.