Cerebral perfusion mapping during retrieval of spatial memory in rats.

Studies of brain functional activation during spatial navigation using electrophysiology and immediate-early gene responses have typically targeted a limited number of brain regions. Our study provides the first whole brain analysis of cerebral activation during retrieval of spatial memory in the freely-moving rat. Rats (LEARNERS) were trained in the Barnes maze, an allocentric spatial navigation task, while CONTROLS received passive exposure. After 19 days, functional brain mapping was performed during recall by bolus intravenous injection of [14C]-iodoantipyrine using a novel subcutaneous minipump triggered by remote activation. Regional cerebral blood flow (rCBF)-related tissue radioactivity was analyzed by statistical parametric mapping from autoradiographic images of the three-dimensionally reconstructed brains. Functional connectivity was examined between regions of the spatial navigation circuit through interregional correlation analysis. Significant rCBF increases were noted in LEARNERS compared to CONTROLS broadly across the spatial navigation circuit, including the hippocampus (anterior dorsal CA1, posterior ventral CA1-3), subiculum, thalamus, striatum, medial septum, cerebral cortex, with decreases noted in the mammillary nucleus, amygdala and insula. LEARNERS showed a significantly greater positive correlation of rCBF of the ventral hippocampus with retrosplenial, lateral orbital, parietal and primary visual cortex, and a significantly more negative correlation with the mammillary nucleus, amygdala, posterior entorhinal cortex, and anterior thalamic nucleus. The complex sensory component of the spatial navigation task was underscored by broad activation across visual, somatosensory, olfactory, auditory and vestibular circuits which was enhanced in LEARNERS. Brain mapping facilitated by an implantable minipump represents a powerful tool for evaluation of mammalian behaviors dependent on locomotion.

Early life stress elicits visceral hyperalgesia and functional reorganization of pain circuits in adult rats.

Early life stress (ELS) is a risk factor for developing functional gastrointestinal disorders, and has been proposed to be related to a central amplification of sensory input and resultant visceral hyperalgesia. We sought to characterize ELS-related changes in functional brain responses during acute noxious visceral stimulation. Neonatal rats (males/females) were exposed to limited bedding (ELS) or standard bedding (controls) on postnatal days 2-9. Age 10-11 weeks, animals were implanted with venous cannulas and transmitters for abdominal electromyography (EMG). Cerebral blood flow (rCBF) was mapped during colorectal distension (CRD) using [14C]-iodoantipyrine autoradiography, and analyzed in three-dimensionally reconstructed brains by statistical parametric mapping and functional connectivity. EMG responses to CRD were increased after ELS, with no evidence of a sex difference. ELS rats compared to controls showed a greater significant positive correlation of EMG with amygdalar rCBF. Factorial analysis revealed a significant main effect of 'ELS' on functional activation of nodes within the pain pathway (somatosensory, insular, cingulate and prefrontal cortices, locus coeruleus/lateral parabrachial n. [LC/LPB], periaqueductal gray, sensory thalamus), as well as in the amygdala, hippocampus and hypothalamus. In addition, ELS resulted in an increase in the number of significant functional connections (i.e. degree centrality) between regions within the pain circuit, including the amygdala, LC/LPB, insula, anterior ventral cingulate, posterior cingulate (retrosplenium), and stria terminalis, with decreases noted in the sensory thalamus and the hippocampus. Sex differences in rCBF were less broadly expressed, with significant differences noted at the level of the cortex, amygdala, dorsal hippocampus, raphe, sensory thalamus, and caudate-putamen. ELS showed a sexually dimorphic effect ('Sex x ELS' interaction) at the LC/LPB complex, globus pallidus, hypothalamus, raphe, septum, caudate-putamen and cerebellum. Our results suggest that ELS alters functional activation of the thalamo-cortico-amydala pathway, as well as the emotional-arousal network (amygdala, locus coeruleus), with evidence that ELS may additionally show sexually dimorphic effects on brain function.

The Effects of Exercise on Dopamine Neurotransmission in Parkinson's Disease: Targeting Neuroplasticity to Modulate Basal Ganglia Circuitry.

Animal studies have been instrumental in providing evidence for exercise-induced neuroplasticity of corticostriatal circuits that are profoundly affected in Parkinson's disease. Exercise has been implicated in modulating dopamine and glutamate neurotransmission, altering synaptogenesis, and increasing cerebral blood flow. In addition, recent evidence supports that the type of exercise may have regional effects on brain circuitry, with skilled exercise differentially affecting frontal-striatal related circuits to a greater degree than pure aerobic exercise. Neuroplasticity in models of dopamine depletion will be reviewed with a focus on the influence of exercise on the dorsal lateral striatum and prefrontal related circuitry underlying motor and cognitive impairment in PD. Although clearly more research is needed to address major gaps in our knowledge, we hypothesize that the potential effects of exercise on inducing neuroplasticity in a circuit specific manner may occur through synergistic mechanisms that include the coupling of an increasing neuronal metabolic demand and increased blood flow. Elucidation of these mechanisms may provide important new targets for facilitating brain repair and modifying the course of disease in PD.

Prone positioning decreases cardiac output and increases systemic vascular resistance in neonates.

OBJECTIVE: To evaluate the cardiovascular response to short-term prone positioning in neonates. STUDY DESIGN: In this prospective study, we continuously monitored heart rate (HR), stroke volume (SV) and cardiac output (CO) by electrical velocimetry in hemodynamically stable neonates in each of the following positions for 10 min: supine, prone and back-to-supine position. Skin blood flow (SBF) was also continuously assessed on the forehead or foot using Laser Doppler technology. Systemic vascular resistance (SVR) index was calculated as mean blood pressure (BP)/CO. Data were analyzed using repeated measures analysis of variance. RESULTS: Thirty neonates (gestational age: 35±4 weeks; postmenstrual age: 36±3 weeks) were enrolled. HR did not change in response to positioning. However, in prone position, SV, CO and SBF decreased and SVR index increased from 1.5±0.3 to 1.3±0.3 ml kg(-1) (mean ±s.d., P<0.01), 206±44 to 180±41 ml kg(-1) min(-1) (P<0.01), 0.54±0.30 to 0.44±0.29 perfusion units (P<0.01) and 0.25±0.06 to 0.30±0.07 mm Hg ml(-1) kg(-1) min(-1) (P<0.01), respectively. After placing the infants back-to-supine position, SV, CO, SBF and SVR index returned to baseline. The above pattern of cardiovascular changes was consistent in vast majority of the studied neonates. CONCLUSIONS: Short-term prone positioning is associated with decreased SV, CO and SBF and increased calculated SVR index.

Changes in regional brain perfusion during functional brain activation: comparison of [(64)Cu]-PTSM with [(14)C]-Iodoantipyrine.

A dilemma in behavioral brain mapping is that conventional techniques immobilize the subject, extinguishing all but the simplest behaviors. This is avoided if brain activation is imaged after completion of the behavior and tissue capture of the tracer. A single-pass flow tracer proposed for positron emission tomography (PET) is a radiolabeled copper(II) complex of pyruvaldehyde bis(N(4)-methylthiosemicarbazone), [Cu(64)]-PTSM. [Cu(64)]-PTSM reaches steady-state cerebral distribution more rapidly than the metabolic tracer [(18)F]-fluorodeoxyglucose, allowing imaging with substantially greater temporal resolution. Using dual-label autoradiography, this study compares the relative regional cerebral blood flow tracer distribution (CBF-TR) of [(64)Cu]-PTSM to that of the classic perfusion tracer [(14)C]-iodoantipyrine in a rat model during treadmill walking. Rats were exposed to continuous walking on a treadmill and compared to quiescent controls. [(64)Cu]-PTSM was bolus injected (iv) after 1 min, followed by a 5-minute uptake and subsequent bolus injection of [(14)C]-iodoantipyrine. CBF-TR was quantified by autoradiography and analyzed in the three-dimensionally reconstructed brain by statistical parametric mapping, as well as by region-of-interest analysis. A high homology was found between the [(64)Cu]-PTSM and [(14)C]-iodoantipyrine patterns of cerebral activation in cortical and subcortical regions. For white matter, however, [(64)Cu]-PTSM showed lower perfusion than [(14)Cu]-iodoantipyrine. [(64)Cu]-PTSM is a useful tracer for functional brain mapping in freely-moving subjects. Its application in conjunction with PET promises to increase our understanding of the neural circuitry of behaviors dependent on locomotion.

Brain maps on the go: functional imaging during motor challenge in animals.

Brain mapping in the freely moving animal is useful for studying motor circuits, not only because it avoids the potential confound of sedation or restraints, but because activated brain states may serve to accentuate differences that only manifest partially while a subject is in the resting state. Perfusion or metabolic mapping using autoradiography allows one to examine changes in brain function at the circuit level across the entire brain with a spatial resolution (approximately 100 micro) appropriate for the rat or mouse brain, and a temporal resolution (seconds-minutes) sufficient for capturing acute brain changes. Here we summarize the application of these methods to the functional brain mapping of behaviors involving locomotion of small animals, methods for the three-dimensional reconstruction of the brain from autoradiographic sections, voxel based analysis of the whole brain, and generation of maps of the flattened rat cortex. Application of these methods in animal models promises utility in improving our understanding of motor function in the normal brain, and of the effects of neuropathology and treatment interventions such as exercise have on the reorganization of motor circuits.

Flattened cortical maps of cerebral function in the rat: a region-of-interest approach to data sampling, analysis and display.

We describe a method for the measurement, analysis and display of cerebral cortical data obtained from coronal brain sections of the adult rat. In this method, regions-of-interest (ROI) are selected in the cortical mantle in a semiautomated fashion using a radial grid overlay, spaced in 15 degrees intervals from the midline. ROI measurements of intensity are mapped on a flattened two-dimensional surface. Topographic maps of statistical significance at each ROI allow for the rapid viewing of group differences. Cortical z-scores are displayed with the boundaries of brain regions defined according to a standard atlas of the rat brain. This method and accompanying software implementation (Matlab, Labview) allow for compact data display in a variety of autoradiographic and histologic studies of the structure and function of the rat brain.

Reorganization of functional brain maps after exercise training: Importance of cerebellar-thalamic-cortical pathway.

Exercise training (ET) causes functional and morphologic changes in normal and injured brain. While studies have examined effects of short-term (same day) training on functional brain activation, less work has evaluated effects of long-term training, in particular treadmill running. An improved understanding is relevant as changes in neural reorganization typically require days to weeks, and treadmill training is a component of many neurorehabilitation programs. Adult, male rats (n=10) trained to run for 40 min/day, 5 days/week on a Rotarod treadmill at 11.5 cm/s, while control animals (n=10) walked for 1 min/day at 1.2 cm/s. Six weeks later, [(14)C]-iodoantipyrine was injected intravenously during treadmill walking. Regional cerebral blood flow-related tissue radioactivity was quantified by autoradiography and analyzed in the three-dimensionally reconstructed brain by statistical parametric mapping. Exercised compared to nonexercised rats demonstrated increased influence of the cerebellar-thalamic-cortical (CbTC) circuit, with relative increases in perfusion in deep cerebellar nuclei (medial, interposed, lateral), thalamus (ventrolateral, midline, intralaminar), and paravermis, but with decreases in the vermis. In the basal ganglia-thalamic-cortical circuit, significant decreases were noted in sensorimotor cortex and striatum, with associated increases in the globus pallidus. Additional significant changes were noted in the ventral pallidum, superior colliculus, dentate gyrus (increases), and red nucleus (decreases). Following ET, the new dynamic equilibrium of the brain is characterized by increases in the efficiency of neural processing (sensorimotor cortex, striatum, vermis) and an increased influence of the CbTC circuit. Cerebral regions demonstrating changes in neural activation may point to alternate circuits, which may be mobilized during neurorehabilitation.

Changes in brain functional activation during resting and locomotor states after unilateral nigrostriatal damage in rats.

To evaluate functional neuronal compensation after partial damage to the nigrostriatal system, we lesioned rats unilaterally in the striatum with 6-hydroxydopamine. Five weeks later, cerebral perfusion was mapped at rest or during treadmill walking using [(14)C]-iodoantipyrine. Regional CBF-related tissue radioactivity (CBF-TR) was quantified by autoradiography and analyzed by statistical parametric mapping and region-of- interest analysis. Lesions were confirmed by tyrosine hydroxylase immunohistochemistry and changes in rotational locomotor activity. Functional compensations were bilateral and differed at rest and during treadmill walking. Consistent with the classic view of striatopallidal connections, CBF-TR of lesioned compared to sham-lesioned rats increased in the ipsilateral subthalamic nucleus (STN) and internal globus pallidus, and decreased in the striatum and external globus pallidus. Contrary to the classic view, CBF-TR increased in the ipsilateral ventral lateral, ventral anterior thalamus and motor cortex, as well as in the central medial thalamus, midline cerebellum, and contralateral STN. During walking, perfusion decreased in lesioned compared to sham-lesioned rats across the ipsilateral striato-pallidal-thalamic-cortical motor circuit. Compensatory increases were seen bilaterally in the ventromedial thalamus and red nucleus, in the contralateral STN, anterior substantia nigra, subiculum, motor cortex, and in midline cerebellum. Enhanced recruitment of associative sensory areas was noted cortically and subcortically. Future models of compensatory changes after nigrostriatal damage need to address the effects of increased neural activity by residual dopaminergic neurons, interhemispheric interactions and differences between resting and locomotor states. Identification of sites at which functional compensation occurs may define useful future targets for neurorehabilitative or neurorestorative interventions in Parkinson's disease.

Mapping cerebral blood flow changes during auditory-cued conditioned fear in the nontethered, nonrestrained rat.

Conditioned fear (CF) is one of the most frequently used behavioral paradigms; however, little work has mapped changes in cerebral perfusion during CF in the rat-the species which has dominated CF research. Adult rats carrying an implanted minipump were exposed to a tone (controls, n = 8) or a tone conditioned in association with footshocks (CS group, n = 9). During reexposure to the tone 24 h later, animals were injected intravenously by remote activation with [14C]-iodoantipyrine using the pump. Significant group differences in regional CBF-related tissue radioactivity (CBF-TR) were determined by region-of-interest analysis of brain autoradiographs, as well as in the reconstructed, three-dimensional brain by statistical parametric mapping (SPM). CS animals demonstrated significantly greater, fear-enhanced increases in CBF-TR in auditory cortex than controls. The lateral amygdala was activated, whereas the basolateral/basomedial and central amygdala were deactivated. In the hippocampus and medial prefrontal cortex, CBF-TR increased significantly ventrally but not dorsally. Significant activations were noted in medial striatum and the thalamic midline and intralaminar nuclei. However, the ventrolateral/dorsolateral striatum and its afferents from motor and somatosensory cortex were deactivated, consistent with the behavioral immobility seen during CF. Significant activations were also noted in the lateral septum, periaqueductal gray, and deep mesencephalic nucleus/tegmental tract. Our results show that auditory stimuli endowed with aversive properties through conditioning result in significant redistribution of cerebral perfusion. SPM is a useful tool in the brain mapping of complex rodent behaviors, in particular the changes in activation patterns in limbic, thalamic, motor, and cortical circuits during CF.

Activation of cerebral cortex during acoustic challenge or acute foot-shock in freely moving, nontethered rats.

Most brain mapping techniques require immobilization of the subject, which extinguishes all but the simplest behaviors. We applied in freely moving rats an implantable microbolus infusion pump (MIP) which can be triggered by remote activation for the injection of the cerebral blood flow tracer [(14)C]iodoantipyrine during behavioral activation. Consistent with previous electrophysiological, metabolic and brain anatomic studies, CBF-related tissue radioactivity (CBF-TR) increased in acoustic cortex during a 1000 Hz/8000 Hz alternating tone. In response to an acute foot-shock, CBF-TR increased in visual cortex, parietal association cortex, and extended into primary motor cortex, and primary somatosensory cortex mapping the trunk. These results support the utility of implantable pumps as adjunct tools for studying cerebral activation during behavioral challenges in nontethered, nonrestrained animals.

Functional brain mapping in freely moving rats during treadmill walking.

A dilemma in functional neuroimaging is that immobilization of the subject, necessary to avoid movement artifact, extinguishes all but the simplest behaviors. Recently, we developed an implantable microbolus infusion pump (MIP) that allows bolus injection of radiotracers by remote activation in freely moving, nontethered animals. The MIP is examined as a tool for brain mapping in rats during a locomotor task. Cerebral blood flow-related tissue radioactivity (CBF-TR) was measured using [14C]-iodoantipyrine with an indicator-fractionation method, followed by autoradiography. Rats exposed to walking on a treadmill, compared to quiescent controls, showed increases in CBF-TR in motor circuits (primary motor cortex, dorsolateral striatum, ventrolateral thalamus, midline cerebellum, copula pyramis, paramedian lobule), in primary somatosensory cortex mapping the forelimbs, hindlimbs and trunk, as well as in secondary visual cortex. These results support the use of implantable pumps as adjunct tools for functional neuroimaging of behaviors that cannot be elicited in restrained or tethered animals.

An implantable bolus infusion pump for use in freely moving, nontethered rats.

One of the current constraints on functional neuroimaging in animals is that to avoid movement artifacts during data acquisition, subjects need to be immobilized, sedated, or anesthetized. Such measures limit the behaviors that can be examined, and introduce the additional variables of stress or anesthetic agents that may confound meaningful interpretation. This study provides a description of the design and characteristics of a self-contained, implantable microbolus infusion pump (MIP) that allows triggering of a bolus injection at a distance in conscious, behaving rats that are not restrained or tethered. The MIP is externally triggered by a pulse of infrared light and allows in vivo bolus drug delivery. We describe application of this technology to the intravenous bolus delivery of iodo[(14)C]antipyrine in a freely moving animal, followed immediately by lethal injection, rapid removal of the brain, and analysis of regional cerebral blood flow tissue radioactivity with the use of autoradiography. The ability to investigate changes in brain activation in nonrestrained animals makes the MIP a powerful tool for evaluation of complex behaviors.

Heart rate dynamics in monoamine oxidase-A- and -B-deficient mice.

Heart rate (HR) dynamics were investigated in mice deficient in monoamine oxidase A and B, whose phenotype includes elevated tissue levels of norepinephrine, serotonin, dopamine, and phenylethylamine. In their home cages, spectral analysis of R-R intervals revealed more pronounced fluctuations at all frequencies in the mutants compared with wild-type controls, with a particular enhancement at 1-4 Hz. No significant genotypic differences in HR variability (HRV) or entropies calculated from Poincaré plots of the R-R intervals were noted. During exposure to the stress of a novel environment, HR increased and HRV decreased in both genotypes. However, mutants, unlike controls, demonstrated a rapid return to baseline HR during the 10-min exposure. Such modulation may result from an enhanced vagal tone, as suggested by the observation that mutants responded to cholinergic blockade with a decrease in HRV and a prolonged tachycardia greater than controls. Monoamine oxidase-deficient mice may represent a useful experimental model for studying compensatory mechanisms responsible for changes in HR dynamics in chronic states of high sympathetic tone.

Increased baroreceptor response in mice deficient in monoamine oxidase A and B.

The recent development of mice doubly deficient for monoamine oxidase A and B (MAO-A/B, respectively) has raised questions about the impact of these mutations on cardiovascular function, in so far as these animals demonstrate increased tissue levels of the vasoactive amines serotonin, norepinephrine, dopamine, and phenylethylamine. We recorded femoral arterial pressures and electrocardiograms in adult MAO-A/B-deficient mice during halothane-nitrous oxide anesthesia as well as 30 min postoperatively. During both anesthesia and recovery, systolic, diastolic, and mean arterial pressures were 10-15 mmHg lower in MAO-A/B-deficient mice compared with normal controls (P < 0.01). Mutants also showed a greater baroreceptor-mediated reduction in heart rate in response to hypertension after intravenous pulses of phenylephrine or angiotensin II. Tachycardia elicited in response to hypotension after nitroprusside was greater in mutants than in controls. Heart rate responsiveness to changes in arterial pressure was abolished after administration of glycopyrrolate, with no differences in this phenomenon noted between genotypes. These data suggest that prevention of hypertension may occur in chronic states of catecholaminergic/indoleaminergic excess by increased gain of the baroreflex.

Biochemical, behavioral, physiologic, and neurodevelopmental changes in mice deficient in monoamine oxidase A or B.

The availability of mutant mice that lack either MAO A or MAO B has created unique profiles in the central and peripheral availability of serotonin, norepinephrine, dopamine, and phenylethylamine. This paper summarizes some of the current known phenotypic findings in MAO A knock-out mice and contrast these with those of MAO B knock-out mice. Differences are discussed in relation to the biochemical, behavioral, and physiologic changes investigated to date, as well as the role played by redundancy mechanisms, adaptational responses, and alterations in neurodevelopment.

Fluorescence of indocyanine green in blood: intensity dependence on concentration and stabilization with sodium polyaspartate.

Indocyanine green (ICG) has been widely used in cardiovascular, hepatic, and ophthalmologic studies. Application of this fluorescent dye has been handicapped by its poor stability in solution and by the complex dependence of its fluorescence intensity on concentration. Noncovalent interactions between ICG and sodium polyaspartate (PASP) stabilize ICG fluorescence in aqueous solution, but the effect of PASP on ICG fluorescence in blood has not been described. The current study had two main goals: first, to characterize in vitro in blood the relationship between fluorescence intensity and concentration of ICG-PASP (ICG) and the stability of this relationship over time; second, to test a new phenomenological model describing the dependence of ICG fluorescence on concentration. Freshly-prepared ICG and ICG-PASP solutions produced the same fluorescence intensity over a wide range of concentrations (0.0005-0.1271 mg/ml). The peak fluorescence of ICG was reduced by 11% after 10 h and by 72% at 7 days. In contrast, the peak fluorescence intensity of ICG-PASP solutions was nearly unchanged for up to 14 days. The dependence of the fluorescence intensity on concentration was accurately represented by our model that accounted for the generation of fluorescence following light absorption, and for the reabsorption of the emitted fluorescence by ICG.

Regional cerebral cortical activation in monoamine oxidase A-deficient mice: differential effects of chronic versus acute elevations in serotonin and norepinephrine.

Mice deficient in monoamine oxidase A have previously been shown to demonstrate a chronic elevation of serotonin and norepinephrine in the brain. Using the autoradiographic [14C]iodo-antipyrine method, we examined cerebral cortical blood flow in conscious, restrained four- to five-month-old knock-out and wild-type animals following the intraperitoneal administration of either saline or D-fenfluramine. Knock-out animals administered saline, compared to their wild-type counterparts, demonstrated a significantly higher regional cortical blood flow in somatosensory and barrel field neocortex, an area which previous histological studies have shown to be characterized by abnormal serotonergic projection fibers and absent barrel formation. Regional cortical blood flow was significantly lower in knock-out than in wild-type mice in the entorhinal and midline motor cortex, with non-significant decreases noted in the olfactory, piriform and retrosplenial cortices and the amygdala. We compared the above findings to those obtained in response to D-fenfluramine which, in conjunction with its metabolite D-norfenfluramine, results in acute elevations of brain levels of serotonin and norepinephrine. Administration of D-fenfluramine (21. 2mg/kg) resulted in changes in regional cortical perfusion in most brain regions of both knock-out and wild-type mice that were opposite to the genotypic differences seen in perfusion in response to saline. Fenfluramine significantly increased regional cortical blood flow in the allocortex (olfactory, piriform, entorhinal) and the amygdala, and significantly decreased regional cortical blood flow in the somatosensory, barrel field, midline motor and retrosplenial cortices. Changes in regional perfusion in response to fenfluramine were topographically equivalent in knock-out and wild-type mice, although in knock-out mice such changes were of greater magnitude. Our study suggests that the effects on regional cortical blood flow of a lifelong absence of monoamine oxidase A, and the consequent chronic increase in serotonin and norepinephrine, differ from those attributable to acute increases in these neurotransmitters following fenfluramine administration. Such a differential response may reflect neurodevelopmental abnormalities and/or effects of a chronic physiological adaptation on the regulation of cortical activation.

Attenuation of brain high frequency electrocortical response after thiopental in early stages of Alzheimer's dementia.

RATIONALE: Pathological brain regions generate proportionately less high-frequency (beta) activity than non-pathological regions, a phenomenon accentuated by barbiturate administration. OBJECTIVES: Previously, we reported a loss of high-frequency brain electrical response to thiopental in dementia of the Alzheimer's type (DAT). The current study examines whether this phenomenon may be detected in early stages of the illness. METHODS: Using quantitative electroencephalography, we examined power in the 20-28 Hz band in patients with early DAT (n=7, age 71.0+/-3.2 years, Folstein Mini Mental State Score, MMSE 26.2+/-0.8), normal controls (n=8, age 74.3+/-3.2 years, MMSE 29.0+/-0.3) and subjects with moderately severe DAT (n=6, age 76.6+/-3.0 years, MMSE=12.5+/-3.7) at baseline and following an intravenous bolus of thiopental (0.5 mg/kg). RESULTS: No significant group differences in beta power were detectable at baseline. In response to thiopental, early DAT subjects compared to controls showed a significantly smaller beta power response in the frontal region at 1-3 min postinjection. Losses were smaller than those of subjects with moderately severe DAT and demonstrated a non-linear correlation with decreases in cognitive function as assessed by the MMSE score (r2=0.75). CONCLUSION: In early stages of DAT, a barbiturate challenge may unmask abnormalities in brain electrical activity not seen at baseline. Such changes may reflect underlying cortical deafferentation.