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Cannabis and brain function.

Current literature and practice experience has been reviewed to clarify what is known about the effects of cannabis on brain function, the risk that cannabis use may pose for young people during their adolescence, and risk factors within the individual or their environment that may predispose to long-term abuse and dependence. There is sound evidence that cannabis intoxication has an adverse effect on cognitive function and behaviour, and may, in vulnerable individuals, lead to a psychotic reaction. Regular use may have an adverse effect on learning, with possible mid- to long-term psychological and cognitive impairment. Heavy use may lead to emotional dependence with consequent social and psychological dysfunction. Intervention strategies must go beyond the conventional education and public health measures that appear to have been unsuccessful so far in influencing cannabis use in teenagers. Such strategies may more usefully aim at assessment of risk factors in individuals and groups for dependence on the drug, and the combined and cooperative intervention of parents, schools, health professionals and teenagers themselves.

Adolescent↗

Alpha oscillations in brain functioning: an integrative theory.

The old concept stating that EEG alpha (10-Hz) activity reflects passive or idling states of the brain is giving way to modern views of 10-Hz oscillations in relation to diverse brain functions comprising sensory, motor, and memory processes: (1) Spontaneous alpha activity is not pure noise as shown by methods of chaos analysis. (2) Evoked alpha oscillations patterns (precisely time-locked to a stimulus; duration approx. 200-300 ms) depend on the modality of stimulation and the recording site. (3) Induced alpha oscillations are initiated by, but not closely time-locked to a stimulus. (4) 10-Hz oscillations are recorded in nervous systems of different complexities, from the human brain to isolated ganglia of invertebrates. The neural origins of 10-Hz oscillations are demonstrated by recordings at the cellular level. (5) Rather than trying to locate a unique alpha generator, it is preferable to assume that a 'diffuse and distributed alpha system' exists. A particular support for this hypothesis is given by stimulus-dependent hippocampal alpha responses in the cat brain. (6) The major physiological meaning of 10-Hz oscillations may be comparable to the putative universal role of gamma responses in brain signaling.

Alpha Rhythm↗

Effects of calcium channel blockers on impairment of brain function in senescence-accelerated mice.

The effects of the L-type calcium channel blockers, nicardipine, nimodipine, nilvadipine and amlodipine, on brain dysfunction were examined in senescence-accelerated-prone mice. A disturbed brain function in passive avoidance response, forced swimming, rota-rod and traction tests was observed in senescence-accelerated-prone mice compared to senescence-accelerated-resistant mice. A single oral administration of the four calcium channel blockers tested had little effect on the brain dysfunction in senescence-accelerated-prone mice. In contrast, the daily oral administration of nicardipine (1 and 3 mg/kg), nimodipine (3 mg/kg) and nilvadipine (3 mg/kg), once a day for three weeks, prolonged the shortened latency of step-through in the passive avoidance response and falling time in rota-rod tests. Brain dysfunction in forced swimming and traction tests was not influenced by repeated administration of these blockers. Repeated administration of amlodipine for three weeks in senescence-accelerated-prone mice showed little pharmacological actions in all four tests. Thus, we found that repeated administration of nicardipine, nimodipine and nilvadipine ameliorated the brain dysfunction in these mice. Furthermore, the present study suggests that senescence-accelerated-prone mice can be used as an appropriate model for evaluating the pharmacological effects of calcium channel blockers on brain dysfunction.

Amlodipine↗

Level of ischemia and brain functions in the Mongolian gerbil in vivo.

The Mongolian gerbil (Meriones unguiculatus) provides a very useful animal model to study the effects of ischemia on brain functions. In this model it is possible to induce two levels of ischemia in the same animal. Thus, monitoring the brain in vivo in real-time will provide meaningful information regarding the development of ischemic injury as well as the follow-up during the recirculation period. The aims of the study were as follows: (1) To elucidate the mechanism behind the development of ischemic depolarization under unilateral and bilateral carotid artery occlusion. (2) To exclude the possibility that removal of the dura mater will affect the results. (3) To correlate the kinetics of the recovery processes to the level of ischemia. We tested the correlation between energy depletion level (evaluated by intramitochondrial NADH redox state) and the development of ischemic depolarization (ID) and vasospasm (evaluated by extracellular K+, DC potential and 366 nm reflectance changes, respectively) under partial and complete ischemia (induced by unilateral or bilateral carotid artery occlusion) using the multiparametric monitoring system (MPA). In 12 out of 32 gerbils monitored by the MPA, the dura mater remained intact, while in the other 20, it was removed very gently before connecting the MPA to the brain. Two types of responses to unilateral carotid artery occlusion were recorded and the gerbils were divided into groups according to the development of the ID. In a third group of 5 gerbils we tested the effect of 1-5 min of bilateral occlusion on the various parameters monitored.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Functional brain imaging in neuropsychiatric disorders of childhood.

This review article presents a summary of the current state-of-the-art of functional brain imaging, with a primary focus on childhood neuropsychiatric disorders. Coverage is emphasized for developments that appear to be of current or potential future importance for the child neurologist and related pediatric specialist, and also from the perspective of the developmental neuroscientist. Emphasis is placed on the modalities of single photon emission computed tomography (SPECT), positron emission tomography (PET), and both "conventional" and "functional" magnetic resonance imaging, (MRI) including reference to the major new radiopharmaceutical and magnetic resonance-based imaging agents and techniques. The fundamental physicochemical processes underlying such studies are outlined, with citation of sources of more detailed information for the interested reader. A variety of imaging studies are reviewed for selected groups of childhood neuropsychiatric disorders, designed to illustrate the achievements and future promise of these imaging modalities. Areas of concentration are suggested for future imaging research in the field of childhood behavioral disorders, where these methods seem critical to improved understanding of pathogenetic mechanisms, as well as development of more effective treatment strategies.

Adolescent↗

Neurostimulation and functional brain imaging.

Recent advancements in functional neuroimaging have furthered our understanding of the normal and pathological brain. These non-invasive imaging modalities have allowed us to study the human brain in vivo. Concurrently, the revival of neurostimulation in the treatment of pain, movement disorders, and epilepsy has allowed the synergistic combination of these two technologies. Several studies focusing on the use of functional imaging in patients with implanted neurostimulation devices are reviewed. The anticipated roles of these two disciplines are discussed.

Brain↗

Magnetic resonance imaging methods for study of human brain function and their application at high magnetic field.

Magnetic resonance imaging (MRI) sequences are finding a new application in the study of human brain function by monitoring localized changes in signal intensity which accompany neuronal activity. These sequences can be sensitized to changes in cerebral blood volume, cerebral blood flow, and blood oxygenation, all of which reflect aspects of neuronal activity in the brain. Many of these experiments benefit from being implemented at a higher magnetic field strength than conventional MRI. An overview of these techniques is presented, and examples of their use are given.

Blood Volume↗

The mechanism by which exercise modifies brain function.

The effect of exercise on central nervous system function was investigated in relation to the mechanism of calcium-calmodulin-dependent dopamine synthesis in the brain. It is shown here through animal experiments that exercise leads to an increase in the calcium level in the brain. This in turn enhances brain dopamine synthesis, and through this increased dopamine modifies and/or affects brain function, which might induce physiological, behavioral, and psychological changes.

Alcoholic Intoxication↗

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↗

Integration of functional brain information into stereotactic irradiation treatment planning using magnetoencephalography and magnetic resonance axonography.

PURPOSE: To minimize the risk of neurologic deficit after stereotactic irradiation, functional brain information was integrated into treatment planning. METHODS AND MATERIALS: Twenty-one magnetoencephalography and six magnetic resonance axonographic images were made in 20 patients to evaluate the sensorimotor cortex (n = 15 patients, including the corticospinal tract in 6), visual cortex (n = 4), and Wernicke's area (n = 2). One radiation oncologist was asked to formulate a treatment plan first without the functional images and then to modify the plan after seeing them. The pre- and postmodification values were compared for the volume of the functional area receiving > or =15 Gy and the volume of the planning target volume receiving > or =80% of the prescribed dose. RESULTS: Of the 21 plans, 15 (71%) were modified after seeing the functional images. After modification, the volume receiving > or =15 Gy was significantly reduced compared with the values before modification in those 15 sets of plans (p = 0.03). No statistically significant difference was found in the volume of the planning target volume receiving > or =80% of the prescribed dose (p = 0.99). During follow-up, radiation-induced necrosis at the corticospinal tract caused a minor motor deficit in 1 patient for whom magnetic resonance axonography was not available in the treatment planning. No radiation-induced functional deficit was observed in the other patients. CONCLUSION: Integration of magnetoencephalography and magnetic resonance axonography in treatment planning has the potential to reduce the risk of radiation-induced functional dysfunction without deterioration of the dose distribution in the target volume.

Adult↗

Models and theories of brain function in cognition within a framework of behavioral cognitive psychology.

The present article presents a nonexhaustive collection of contemporary models and theories on brain function and discusses these models and theories within a framework of explanatory formulations in behavioral cognitive psychology. Such a mission was accomplished by evaluating the cognitive implications in the explanatory formulations with respect to established laws/principles and models/theories of behavioral cognitive psychology. The article also points to problem areas of behavioral cognitive psychology for which the explanatory formulations have solutions to offer. The article shows that the cinematographic hypothesis, the new visual model, the synergetic model, and the theory of whole-brain-work emphasize various aspects of perception. The formulations on P300 theory emphasize attention and also working memory. The theory on cognits is a comprehensive account of memory. Characteristic to all of these explanatory formulations and also to that on the complexity and its evolution and that on neurocognitive networks is the emphasis on selective distribution, integration to the point of supersynergy, and dynamicity. Such a viewpoint was not only applied to the operations of the brain but also of cognition. With such a conceptualization, the explanatory formulations could account for cognitive processes other than the ones emphasized. A common aspect in a majority of the formulations is the utilization of the oscillatory activity as the valid activity of the brain. The article points out that a frontier in cognitive psychophysiology would be the study of the genetics of brain oscillations.

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↗

Nicotine effects on brain function and functional connectivity in schizophrenia.

BACKGROUND: Nicotine in tobacco smoke can improve functioning in multiple cognitive domains. High rates of smoking among schizophrenic patients may reflect an effort to remediate cognitive dysfunction. Our primary aim was to determine whether nicotine improves cognitive function by facilitating activation of brain regions mediating task performance or by facilitating functional connectivity. METHODS: Thirteen smokers with schizophrenia and 13 smokers with no mental illness were withdrawn from tobacco and underwent functional magnetic resonance imaging (fMRI) scanning twice, once after placement of a placebo patch and once after placement of a nicotine patch. During scanning, subjects performed an n-back task with two levels of working memory load and of selective attention load. RESULTS: During the most difficult (dichotic 2-back) task condition, nicotine improved performance of schizophrenic subjects and worsened performance of control subjects. Nicotine also enhanced activation of a network of regions, including anterior cingulate cortex and bilateral thalamus, and modulated thalamocortical functional connectivity to a greater degree in schizophrenic than in control subjects during dichotic 2-back task performance. CONCLUSIONS: In tasks that tax working memory and selective attention, nicotine may improve performance in schizophrenia patients by enhancing activation of and functional connectivity between brain regions that mediate task performance.

Adult↗