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Implementation of quantitative perfusion imaging techniques for functional brain mapping using pulsed arterial spin labeling.

We describe here experimental considerations in the implementation of quantitative perfusion imaging techniques for functional MRI using pulsed arterial spin labeling. Three tagging techniques: EPISTAR, PICORE, and FAIR are found to give very similar perfusion results despite large differences in static tissue contrast. Two major sources of systematic error in the perfusion measurement are identified: the transit delay from the tagging region to the imaging slice; and the inclusion of intravascular tagged signal. A modified technique called QUIPSS II is described that decreases sensitivity to these effects by explicitly controlling the time width of the tag bolus and imaging after the bolus is entirely deposited into the slice. With appropriate saturation pulses the pulse sequence can be arranged so as to allow for simultaneous collection of perfusion and BOLD data that can be cleanly separated. Such perfusion and BOLD signals reveal differences in spatial location and dynamics that may be useful both for functional brain mapping and for study of the BOLD contrast mechanism. The implementation of multislice perfusion imaging introduces additional complications, primarily in the elimination of signal from static tissue. In pulsed ASL, this appears to be related to the slice profile of the inversion tag pulse in the presence of relaxation, rather than magnetization transfer effects as in continuous arterial spin labeling, and can be alleviated with careful adjustment of inversion pulse parameters.

Arteries↗

Automated PET attenuation correction model for functional brain imaging.

UNLABELLED: The failure to compensate for subject motion between attenuation correction scans and emission scans precludes the optimization of functional brain imaging techniques. We have developed an automated method for attenuation correction that compensates for subject motion by deriving each set of correction factors from the corresponding emission study. METHODS: The technique consists of generation of an estimated skull image by filtered backprojection of the reciprocal of an emission sinogram; estimation of the thickness and radius of the skull on profiles extracted from the image; scaling the radius and thickness values to generate a model of the brain, skull, and scalp; and assignment of attenuation coefficients to the head model for generation of attenuation correction factors. Values for scale factors and tissue attenuation coefficients were determined empirically by fitting the emission-derived head model to measured transmission data in five subjects using nonlinear regression (group A). The average model parameters, across five datasets (group A), were then used to generate attenuation maps for five independent emission studies (group B). Mean-squared-error values were calculated between the measured transmission data and the two model groups. For comparison, mean squared error values were calculated between the measured transmission data and homogeneous ellipses that were manually fitted to emission images. RESULTS: The difference between the mean squared error for groups A and B was not significant (P>0.8), indicating that model parameters from a small group can be used for other subjects without further fitting. The mean squared error for the automated method was significantly lower than that of the ellipse method (P<0.001). The method reduced emission image variance, resulting in a higher peak Z value in activation images. The elimination of measured transmission scans resulted in a reduction in scan time ( approximately 15 min) and radiation exposure ( approximately 0.5-1.6 mrem). CONCLUSION: We have developed an automated attenuation correction method that compensates for subject motion between scans, accurately reproduces the characteristics of the head, and eliminates the use of measured transmission data to reduce scan duration, statistical noise propagation, and radiation dose.

Acoustic Stimulation↗

Design and performance of the UCLH mark 1b 64 channel electrical impedance tomography (EIT) system, optimized for imaging brain function.

The UCLH Mark 1b is a portable EIT system that can address up to 64 electrodes, which has been designed for imaging brain function with scalp electrodes. It employs a single impedance-measuring circuit and multiplexer so that electrode combinations may be addressed flexibly using software. It operates in the relatively low frequency band between 225 Hz and 77 kHz, as lower frequencies produce larger changes during brain activity, and has a videocassette-sized headbox on a lead 10 m long, connected to a base box the size of a video recorder, and notebook PC, so that recordings may be made in ambulant subjects. Its performance was assessed using a resistor-capacitor network, and two saline-filled tanks-a cylindrical Perspex one and a latex one which contained a human skull. System signal-to-noise ratio was better than 50 dB and the maximum reciprocity error less than 10% for most frequencies. The CMMR was better than 80 dB at 38 kHz and a sponge, 20 mm across, which caused a local 12% impedance increase, was correctly localized in images. This suggests that the system has adequate performance to image impedance changes of 5-50% known to occur in the brain during normal activity, epilepsy or stroke; clinical trials to image these conditions are in progress.

Brain↗

Functional brain imaging and neuropsychological testing in Lyme disease.

Differentiating neuropsychiatric Lyme disease from a primary psychiatric disorder can be a daunting task. This article describes how functional brain imaging and neuropsychological testing can be particularly valuable in helping to make diagnostic distinctions. In addition to a review of the relevance of functional imaging to neuropsychiatry in general, recent findings are presented regarding the use of single photon emission computed tomographic (SPECT) imaging in Lyme disease.

Brain↗

Sensitivity to chlorpromazine effects on brain function of schizophrenics and normals. A preliminary report.

For the purpose of quantitative demonstration of the sensitivity to chlorpromazine (CPZ) effects on brain functions of schizophrenics and normal subjects, polygraphic recordings of electroencephalogram (EEG) and electrodermal response (EDR) were performed before and 3 h after oral administration of 25 mg of CPZ: percent time waking EEG (per cent W-EEG) and number per minute of EDR were measured during the resting period and the period of calculation. In 10 normal adult subject, both per cent W-EEG and number of EDR showed remarkable decrease after CPZ administration. In 22 schizophrenics, however, per cent W-EEG showed no significant decrease after CPZ administration. Number of EDR in schizophrenics during the period of calculation did not show any significant decrease. The neural mechanism underlying the lower sensitivity to CPZ effects in schizophrenics was discussed.

Adolescent↗

Behind the scenes of functional brain imaging: a historical and physiological perspective.

At the forefront of cognitive neuroscience research in normal humans are the new techniques of functional brain imaging: positron emission tomography and magnetic resonance imaging. The signal used by positron emission tomography is based on the fact that changes in the cellular activity of the brain of normal, awake humans and laboratory animals are accompanied almost invariably by changes in local blood flow. This robust, empirical relationship has fascinated scientists for well over a hundred years. Because the changes in blood flow are accompanied by lesser changes in oxygen consumption, local changes in brain oxygen content occur at the sites of activation and provide the basis for the signal used by magnetic resonance imaging. The biological basis for these signals is now an area of intense research stimulated by the interest in these tools for cognitive neuroscience research.

Animals↗

Brain function as revealed by current density analysis of magnetoencephalography signals.

Magnetoencephalography signals are used to extract two-dimensional estimates of the cortical current density associated with spontaneous and steady state brain activity as well as auditory and visual evoked responses. The results provide clues about the organization of the electrical activity across wide cortical regions. Similarities and differences in spontaneous and evoked responses are highlighted and related to findings from other techniques, raising the possibility that volume conduction currents may play some role in coordinating brain function across widely separated cortical regions.

Brain↗

Preliminary evaluation of dual wavelength phased array imaging on neonatal brain function.

Imaging of human tissue using noninvasive techniques has been of great interest in biomedical fields. Optical imaging has attracted a lot of attention because of its portability and economy. The possibility that a highly portable, fast, safe, and affordable imaging system which could obtain interpretable images of brain function for pre- and full-term neonates in a few seconds, has been explored in this article. We have used a sensitive optical topography system, termed phased array, in which a pair of equal-amplitude and antiphase light sources are applied to generate a sharp amplitude null and phase transition plane. This two-wavelength (750 and 830 nm), frequency encoded (50 and 52 MHz) phased array imaging system can indicate the blood concentration and oxygenation changes in blood model studies and during parietal brain activation in neonates. Significant functional responses, particularly to parietal stimulation in normal and pathological states of neonatal brain, have been revealed in our study. The preliminary clinical results are presented in this article.

Blood Flow Velocity↗

Maturation of widely distributed brain function subserves cognitive development.

Cognitive and brain maturational changes continue throughout late childhood and adolescence. During this time, increasing cognitive control over behavior enhances the voluntary suppression of reflexive/impulsive response tendencies. Recently, with the advent of functional MRI, it has become possible to characterize changes in brain activity during cognitive development. In order to investigate the cognitive and brain maturation subserving the ability to voluntarily suppress context-inappropriate behavior, we tested 8-30 year olds in an oculomotor response-suppression task. Behavioral results indicated that adult-like ability to inhibit prepotent responses matured gradually through childhood and adolescence. Functional MRI results indicated that brain activation in frontal, parietal, striatal, and thalamic regions increased progressively from childhood to adulthood. Prefrontal cortex was more active in adolescents than in children or adults; adults demonstrated greater activation in the lateral cerebellum than younger subjects. These results suggest that efficient top-down modulation of reflexive acts may not be fully developed until adulthood and provide evidence that maturation of function across widely distributed brain regions lays the groundwork for enhanced voluntary control of behavior during cognitive development.

Adolescent↗

Medial prefrontal cortex and self-referential mental activity: relation to a default mode of brain function.

Medial prefrontal cortex (MPFC) is among those brain regions having the highest baseline metabolic activity at rest and one that exhibits decreases from this baseline across a wide variety of goal-directed behaviors in functional imaging studies. This high metabolic rate and this behavior suggest the existence of an organized mode of default brain function, elements of which may be either attenuated or enhanced. Extant data suggest that these MPFC regions may contribute to the neural instantiation of aspects of the multifaceted "self." We explore this important concept by targeting and manipulating elements of MPFC default state activity. In this functional magnetic resonance imaging (fMRI) study, subjects made two judgments, one self-referential, the other not, in response to affectively normed pictures: pleasant vs. unpleasant (an internally cued condition, ICC) and indoors vs. outdoors (an externally cued condition, ECC). The ICC was preferentially associated with activity increases along the dorsal MPFC. These increases were accompanied by decreases in both active task conditions in ventral MPFC. These results support the view that dorsal and ventral MPFC are differentially influenced by attentiondemanding tasks and explicitly self-referential tasks. The presence of self-referential mental activity appears to be associated with increases from the baseline in dorsal MPFC. Reductions in ventral MPFC occurred consistent with the fact that attention-demanding tasks attenuate emotional processing. We posit that both self-referential mental activity and emotional processing represent elements of the default state as represented by activity in MPFC. We suggest that a useful way to explore the neurobiology of the self is to explore the nature of default state activity.

Adult↗

Assessment of brain function in clinical pediatric research: behavioral and biological strategies.

Psychobiological research in child psychiatry requires rigorous assessment of behavior and multiple perspectives on brain function through neurochemical, neuroendocrine, psychophysiological, and other advanced methods. The serious neuropsychiatric disorders of childhood, such as autism, attention deficit disorder, and language disorders, can be studied in complementary clinical protocols aimed at explicating patterns of behavioral and metabolic dysfunction which characterize various clinical syndromes. Clinical research with children raises sensitive ethical issues; the ethical problems can be addressed when children and families are active collaborators with the investigators and a long-term relationship is established. In this setting, participation in research can facilitate better treatment for a child. The use of novel biological strategies, such as pharmacological challenge tests, permits evaluation of the relation of specific neuronal systems to behavioral dimensions in clinical disorders. The development of a new treatment for Tourette's syndrome illustrates the integration of basic and clinical research methods.

Catecholamines↗

History of zinc as related to brain function.

Zinc (Zn) is essential for synthesis of coenzymes that mediate biogenic-amine synthesis and metabolism. Zn from vesicles in presynaptic terminals of certain glutaminergic neurons modulates postsynaptic N-methyl-D-aspartate (NMDA) receptors for glutamate. Large amounts of Zn released from vesicles by seizures or ischemia can kill postsynaptic neurons. Acute Zn deficiency impairs brain function of experimental animals and humans. Zn deficiency in experimental animals during early brain development causes malformations, whereas deficiency later in brain development causes microscopic abnormalities and impairs subsequent function. A limited number of studies suggest that similar phenomena can occur in humans.

Animals↗

[Brain function and blood flow velocity in the middle cerebral artery in subarachnoid hemorrhage: evaluation with multimodality evoked potentials (MEPs) and transcranial Doppler (TCD) ultrasound].

Brain dysfunction and blood flow velocity changes in the middle cerebral artery (MCAFV) were studied in 59 patients with ruptured cerebral aneurysms presenting subarachnoid hemorrhage. Brain function and blood flow velocity were evaluated by multimodality evoked potentials (MEPs) consisting of ABR, SEP and VEP as reported, and transcranial Doppler (TCD) ultrasound. The abnormality on MEPs were graded into 4 grades. Nearly normal, mildly abnormal, moderately abnormal and severely abnormal. The results on MEP study were compared with clinical Hunt and Hess (H. H) grade or Fisher's CT group of subarachnoid hemorrhage in 44 patients. MCAFV was measured in 15 patients and mean velocity as well as CO2 reactivity and effect of head elevation were studied. Control value of MCAFV was 64 +/- 13 cm/sec in 50 healthy adults. CO2 reactivity was determined by K values obtained from the modified formula of cerebral blood flow by Olesen et al. MEP grade in H. H grade III and IV patients showed, on admission, variations in their grades in comparison with those in H. H grade I II and V patients. There was no definite correlation between the abnormality in MEPs and the degree of subarachnoid hemorrhage in Fisher's group 3 and 4 patients. When the surgical results in early and late operation in H. H grade III and IV patients were compared, it was shown that the outcome was favourable in early operated patients of H. H grade III if initial MEP grades were between I-III.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Functional brain imaging study of mathematical reasoning abilities in velocardiofacial syndrome (del22q11.2).

PURPOSE: Children with velocardiofacial syndrome (VCFS) often have deficits in mathematical reasoning. Previous research has suggested that structural abnormalities in the parietal lobe region might underlie these deficits. The present study utilized functional magnetic resonance imaging (fMRI) to explore the relationship between brain function and mathematical performance in VCFS. METHODS: Eight children with VCFS and eight comparison subjects underwent fMRI scanning and completed an arithmetic computation task. RESULTS: In the VCFS group, increased activation was observed in the left supramarginal gyrus (LSMG) as the task difficulty increased. CONCLUSION: Aberrant LSMG activation, possibly due to structural deficits of the left parietal lobe, may explain decrements in arithmetic performance observed in VCFS.

Adolescent↗

Disturbed functional brain interactions underlying deficient tactile object discrimination in Parkinson's disease.

Somatosensory discrimination of cuboid objects was studied in a group of healthy volunteers and patients with Parkinson's disease using regional cerebral blood flow (rCBF) measurements obtained with positron emission tomography (PET) and 15O labeled water [H2 15O]. A 6-[18F]-fluoro-L-dopa (FDOPA) PET scan demonstrated that the patients may be grouped into those with normal and those with abnormally lowA FDOPA uptake in the caudate nucleus. The categorical group comparisons revealed that task-induced rCBF increases were deficient in bilateral motor and sensory cortical areas in the Parkinson patients. Moreover, deficient rCBF increases were evident in the mesial and right dorsolateral prefrontal cortex for patients in a more advanced disease state, who showed low FDOPA uptake in the caudate nucleus. A principal component analysis (PCA), performed on the rCBF data, identified three patterns (principal components, PCs) that differentiated patients from normals. The first PC represented a right-hemisphere dominant, bilateral group of brain areas known to be involved in tactile exploration. A second PC reflected a cortical-subcortical pattern of functional interactions, comprising cortical areas important for working memory processes. The third group-differentiating PC revealed a pattern of functional interactions involving bilateral temporo-parieto-occipital association cortices, which was consistent with a hypothesized supramodal network necessary for object discrimination. In an additional subgroup analysis, greater expression of the third PC pattern predicted greater caudate FDOPA uptake in patients. Our neuroimaging data revealed a disturbance of distinct patterns of brain functional interactions related to the sensorimotor deficit in Parkinson's disease and to deficits of cognitive information processing deficits in the more advanced stage of Parkinson's disease.

Adult↗

[Effects of nutritional intervention on brain functions and its related biochemical indexes in mice exposed to high +Gy].

OBJECTIVE: To study the effects of nutritional intervention on changes of monoamines in rats brain, certain amino acids in rats serum and maze behaviors caused by high +Gy exposure. METHOD: The mice were arranged into control group (Group A), +Gy group (Group B) and +Gy nutritional intervention group (group C). Group A was not exposed to +Gy. Both Group B and group C were exposed to +10 Gy for 8 min. Three hours before +Gy exposure distilled water was given to mice in group B by gavage. The day before exposure pyridoxal fortified water was given and 3 h before exposure mixed amino acids solution were given by gavage to group C. Maze test scores were recorded for all groups. After the maze test was completed, blood was collected through the eyes for serum amino acids and brain tissue was collected by decollation for monoamines and gamma-glutamyl transferase (GGT) activity determinations. RESULT: After +Gy exposure maze test scores and brain NE concentrations decreased and abnormal behaviors were found. While other monoamine transmitters increased significantly. In group C maze behaviors improved and biochemical changes induced by +Gy exposure alleviated. CONCLUSION: High +Gy exposure can induce changes of neural transmitters coming from nutritional metabolites in central nervous system. As a result, brain functions are affected. Nutritional intervention can alleviate this negative effect to some extent.

Amino Acids↗

[Evaluation of brain function: electrophysiology of the motor system].

To evaluate brain motor function, transcranial magnetic stimulation and supraspinal control of spinal reflexes are reviewed. Motor evoked potentials (MEPs) is facilitated after movement, depending on muscles (arm, hand) and movements (isometric, precise, repetitive, sequential), which indicates specialization of cortical mechanisms. EMG triphasic pattern in ballistic movement is delayed by magnetic stimulation, but the pattern itself is preserved. Ballistic and associated posture-adjusting movements are delayed by magnetic stimulation in the same way, and similar cortical mechanisms appear to be included. Patients with motor neglect, normal MEPs and remarkably prolonged silent period show inability to initiate movement for several seconds after magnetic stimulation, and strong and long-lasting intracortical inhibition are observed. Motor neglect can be produced by strong inhibitory inputs to the motor cortex. Neural plasticity is studied in patients with brain and peripheral lesions; ipsilateral MEPs, enlargement of muscle representation in the cortex, and contribution of descending pathways other than corticospinal tract are reported. Central control of spinal reflex activities is also important in motor control. Reflex circuits contribute to reciprocal inhibition and to selective contraction, or function as an attenuator of activity of the motoneurone pool. Neural plasticity after daily exercise is reported also at the segmental level.

Electrophysiology↗

Functional brain imaging during anesthesia in humans: effects of halothane on global and regional cerebral glucose metabolism.

BACKGROUND: Propofol and isoflurane anesthesia were studied previously with functional brain imaging in humans to begin identifying key brain areas involved with mediating anesthetic-induced unconsciousness. The authors describe an additional positron emission tomography study of halothane's in vivo cerebral metabolic effects. METHODS: Five male volunteers each underwent two positron emission tomography scans. One scan assessed awake-baseline metabolism, and the other scan assessed metabolism during halothane anesthesia titrated to the point of unresponsiveness (mean +/- SD, expired = 0.7+/-0.2%). Scans were obtained using a GE2048 scanner and the F-18 fluorodeoxyglucose technique. Regions of interest were analyzed for changes in both absolute and relative glucose metabolism. In addition, relative changes in metabolism were evaluated using statistical parametric mapping. RESULTS: Awake whole-brain metabolism averaged 6.3+/-1.2 mg x 100 g(-1) x min(-1) (mean +/- SD). Halothane reduced metabolism 40+/-9% to 3.7+/-0.6 mg x 100 g(-1) x min(-1) (P< or =0.005). Regional metabolism did not increase in any brain areas for any volunteer. The statistical parametric mapping analysis revealed significantly less relative metabolism in the basal forebrain, thalamus, limbic system, cerebellum, and occiput during halothane anesthesia. CONCLUSIONS: Halothane caused a global whole-brain metabolic reduction with significant shifts in regional metabolism. Comparisons with previous studies reveal similar absolute and relative metabolic effects for halothane and isoflurane. Propofol, however, was associated with larger absolute metabolic reductions, suppression of relative cortical metabolism more than either inhalational agent, and significantly less suppression of relative basal ganglia and midbrain metabolism.

Anesthesia, General↗