A reproducible method for automated extraction of brain volumes from 3D human head MR images

An automated method for extracting brain volumes from three commonly acquired three-dimensional (3D) MR images (proton density, T1 weighted, and T2-weighted) of the human head is described. The procedure is divided into four levels: preprocessing, segmentation, scalp removal, and postprocessing. A user-provided reference point is the sole operator-dependent input required, The method's parameters were first optimized and then fixed and applied to 30 repeat data sets from 15 normal older adult subjects to investigate its reproducibility. Percent differences between total brain volumes (TBVs) for the subjects' repeated data sets ranged from .5% to 2.2%. We conclude that the method is both robust and reproducible and has the potential for wide application.

Novel guidance cues during neuronal pathfinding in the early scaffold of axon tracts in the rostral brain

A scaffold of axons consisting of a pair of longitudinal tracts and several commissures is established during early development of the vertebrate brain. We report here that NOC-2, a cell surface carbohydrate, is selectively expressed by a subpopulation of growing axons in this scaffold in Xenopus. NOC-2 is present on two glycoproteins, one of which is a novel glycoform of the neural cell adhesion molecule N-CAM. When the function of NOC-2 was perturbed using either soluble carbohydrates or anti-NOC-2 antibodies, axons expressing NOC-2 exhibited aberrant growth at specific points in their pathway. NOC-2 is the first-identified axon guidance molecule essential for development of the axon scaffold in the embryonic vertebrate brain.

Brain region-specific studies of the excitatory behavioral effects of morphine-3-glucuronide

This study was designed to determine in rats whether morphine-3-glucuronide (M3G) produces its neuro-excitatory effects most potently in the ventral hippocampus (as has been reported previously for subanalgesic doses of opioid peptides). Guide cannulae were implanted into one of seven regions of the rat brain: lateral ventricle; ventral, CA1 and CA2-CA3 regions of the hippocampus; amygdala; striatum or cortex. After a 7 day recovery period, rats received intracerebral injections of (i) M3G (1.1 or 11 nmol) (ii) DADLE ([D-Ala(2),D-Leu(5)]enkephalin), (45 nmol, positive controls) or (iii) vehicle (deionised water), and behavioral excitation was quantified over 80 min. High-dose M3G (11 nmol) evoked behavioral excitation in all brain regions but the onset, severity and duration of these effects varied considerably among brain regions. By contrast, low-dose M3G (1.1 nmol) evoked excitatory behaviors only when administered into the ventral hippocampus and the amygdala, with the most potent effects being observed in the ventral hippocampus. Prior administration of the nonselective opioid antagonists, naloxone and beta-funaltrexamine into the ventral hippocampus, markedly attenuated low-dose M3G's excitatory effects but did not significantly alter levels of excitation evoked by high-dose M3G. Naloxone given 10 min after M3G (1.1 or 11 nmol) did not significantly attenuate behavioral excitation. Thus, M3G's excitatory behavioral effects occur most potently in the ventral hippocampus as reported previously for subanalgesic doses of opioid peptides, and appear to be mediated through at least two mechanisms, one possibly involving excitatory opioid receptors and the other, non-opioid receptors.

Relationships between movement initiation times and movement-related cortical potentials in Parkinson's disease

Movement-related cortical potentials recorded from the scalp reveal increasing cortical activity occurring prior to voluntary movement. Studies of set-related cortical activity recorded from single neurones within premotor and supplementary motor areas in monkeys suggest that such premovement activity may act to prime activity of appropriate motor units in readiness to move, thereby facilitating the movement response. Such a role of early stage premovement activity in movement-related cortical potentials was investigated by examining the relationship between premovement cortical activity and movement initiation or reaction times. Parkinson's disease and control subjects performed a simple button-pressing reaction time task and individual movement-related potentials were averaged for responses with short compared with long reaction times. For Parkinson's disease subjects but not for the control subjects, early stage premovement cortical activity was significantly increased in amplitude for faster reaction times, indicating that there is indeed a relationship between premovement cortical activity amplitude and movement initiation or reaction times. In support of studies of set-related cortical activity in monkeys, it is therefore suggested that early stage premovement activity reflects the priming of appropriate motor units of primary motor cortex, thereby reducing movement initiation or reaction times. (C) 1999 Elsevier Science B.V. All rights reserved.

Movement-related potentials in Parkinson's disease: External cues and attentional strategies

Hypokinetic movement can be greatly improved in Parkinson's disease patients by the provision of external cues to guide movement. It has recently been reported, however, that movement performance in parkinsonian patients can be similarly improved in the absence of external cues by using attentional strategies, whereby patients are instructed to consciously attend to particular aspects of the movement which would normally be controlled automatically. To study the neurophysiological basis of such improvements in performance associated with the use of attentional strategies, movement-related cortical potentials were examined in Parkinson's disease and control subjects using a reaction time paradigm. One group of subjects were explicitly instructed to concentrate on internally timed responses to anticipate the presentation of a predictably timed go signal. Other subjects were given no such instruction regarding attentional strategies. Early-stage premovement activity of movement-related potentials was significantly increased in amplitude and reaction times were significantly faster for Parkinson's disease subjects when instructed to direct their attention toward internally generating responses rather than relying on external cues. It is therefore suggested that the use of attentional strategies may allow movement to be mediated by less automatic and more conscious attentional motor control processes which may be less impaired by basal ganglia dysfunction, and thereby improve movement performance in Parkinson's disease.

Detection of dimethyl sulfone in the human brain by in vivo proton magnetic resonance spectroscopy

We wish to report the detection of dimethyl sulfone (methylsulfonylmethane, C2H6O2S) in the brain of a normal 62-year-old male using in vivo proton magnetic resonance spectroscopy. The presence of this exogenous metabolite resulted from ingestion of a dietary supplement containing dimethyl sulfone. The concentration of this compound in the brain was measured to be 2.4 mmol, with a washout half life of approximately 7.5 days. The in vivo T-1 and T-2 relaxation times of dimethyl sulfone were measured to be 2180 ms and 385 ms, respectively. The concentration of major brain metabolites, namely N-acetylaspartate, total Creatine and Choline, and myo-Inositol were within normal limits. (C) 2000 Elsevier Science Inc. All rights reserved.

Development and standardization of the Self-regulation Skills Interview (SRSI): A new clinical assessment tool for acquired brain injury

The Self-regulation Skills Interview (SRSI) is a clinical tool designed to measure a range of metacognitive skills essential for rehabilitation planning, monitoring an individual's progress, and evaluating the outcome of treatment interventions. The results of the present study indicated that the SRSI has sound interrater reliability and test-retest reliability. A principle components analysis revealed three SRSI factors: Awareness, Readiness to Change, and Strategy Behavior. A comparison between a group of 61 participants with acquired brain injury (ABI) and a group of 43 non-brain-injured participants indicated that the participants with ABI had significantly lower levels of Awareness and Strategy Behavior, but that level of Readiness to Change was not significantly different between the two groups. The significant relationship observed between the SRSI factors and measures of neuropsychological functioning confirmed the concurrent validity of the scale and supports the value of the SRSI for post-acute assessment.

Chronic ethanol has region-selective effects on Egr-1 and Egr-3 DNA-binding activity and protein expression in the rat brain

This study focused on the DNA-binding activity and protein expression of the transcription factors Egr-1 and Egr-3 in the rat brain cortex and hippocampus after chronic or acute ethanol exposure. DNA-binding activity was reduced in both regions after chronic ethanol exposure and was restored to the level of the pair-fed group at 16 h of withdrawal. Cortical Egr-1 protein levels were not altered by chronic ethanol exposure but increased 16 h after withdrawal, thus mirroring DNA-binding activity. In contrast, Egr-3 protein levels did not undergo any change. There was no change in the level of either protein in the hippocampus. Immunohistochemistry revealed a region-selective change in immunopositive cells in the cortex and hippocampus. Finally, an acute bolus dose of ethanol did not affect Egr DNA-binding activity and ethanol treatment did not alter the DNA-binding activity or protein levels of the transcription factor Spl. These observations suggest that chronic exposure to ethanol has region-selective effects on the DNA-binding activity and protein expression of Egr-1 and Egr-3 transcription factors in the rat brain. These changes occur after prolonged ethanol exposure and may thus reflect neuroadaptive changes associated with physical dependency and withdrawal. These effects are also transcription factor-selective. Clearly, protein expression is not the sole mediator of the changes in DNA-binding activity and chronic ethanol exposure must have effects on modulatory agents of Egr DNA-binding activity. (C) 2000 Elsevier Science Ltd, All rights reserved.

Self-awareness and psychosocial functioning following acquired brain injury: An evaluation of a group support programme

This study investigated a group support programme designed to improve self-awareness deficits and psychosocial functioning in a group of chronic patients (N = 21) with acquired brain injury (ABI). The participants were on average 8.6 years (range: 1-36 years) post-injury and were seen at the Brain Injury Association of Queensland, Australia. The assessment of participants involved two standardised measures of intellectual self-awareness with collateral reports from relatives. The present study introduced a new measure called the Self-Regulation Skills Interview (SRSI) which assessed higher levels of self awareness and self-regulation skills. Psychosocial functioning was assessed using a standardised self-report measure. At baseline the group had a relatively high level of intellectual self-awareness regarding their deficits, a low to moderate level of self-regulation skills, and significant psychosocial impairment. The participants were involved in a 16-week group programme which involved components of cognitive rehabilitation, cognitive-behavioural therapy, and social skills training. A post-intervention assessment indicated that participants had significantly improved levels of self-regulation skills and psychosocial functioning. A 6-month follow-up assessment indicated that overall, participants had maintained the gains made during the programme. The important role of self-regulation skills is emphasised as the principle factor contributing to the maintenance of the gains observed.

Referral to post-acute care following traumatic brain injury (TBI) in the Australian context

The study aimed to describe the types of care allocated at the end of acute care to people diagnosed with TBI and to identify the factors associated with variations in referral to care. A retrospective analysis of medical records of 61 patients was conducted based on a sample from two hospitals. While 60.7% of the study sample were referred to formal rehabilitation care, this was primarily non-inpatient rehabilitation care (32.8%). Discriminant analysis was used to determine medical and non-medical predictors of referral. Results indicated that place of treatment and age contribute to group differences and were significant in separating the inpatient rehabilitation group from the non-inpatient and no rehabilitation groups. Review by a rehabilitation physician was associated with referral to inpatient rehabilitation but was not adequate to explain referral to non-inpatient rehabilitation. An in-depth exploration of post-acute referral is warranted to improve policy and practice in relation to continuity of care following TBI.

Expression of POU, Sox, and Pax genes in the brain ganglia of the tropical abalone Haliotis asinina

In gastropod mollusks, neuroendocrine cells in the anterior ganglia have been shown to regulate growth and reproduction. As a first step toward understanding the molecular mechanisms underlying the regulation of these physiological processes in the tropical abalone Haliotis asinina, ive have identified sets of POU, Sox, and Pax transcription factor genes that are expressed in these ganglia. Using highly degenerate oligonucleotide primers designed to anneal to conserved codons in each of these gene families, we have amplified by reverse transcriptase polymerase chain reaction 2 POU genes (HasPOU-III and HasPOU-IV), 2 Sox genes (HasSox-B and HasSox-C), and two Pax genes (HasPax-258 and HaxPax-6). Analyses with gene-specific primers indicated that the 6 genes are expressed in the cerebral and pleuropedal ganglia of both reproductively active and spent adults, in a number of sensory structures, and in a subset of other adult tissues.

Morphological and electrophysiological properties of principal neurons in the rat lateral amygdala in vitro

In this study, we characterize the electrophysiological and morphological properties of spiny principal neurons in the rat lateral amygdala using whole cell recordings in acute brain slices. These neurons exhibited a range of firing properties in response to prolonged current injection. Responses varied from cells that showed full spike frequency adaptation, spiking three to five times, to those that showed no adaptation. The differences in firing patterns were largely explained by the amplitude of the afterhyperpolarization (AHP) that followed spike trains. Cells that showed full spike frequency adaptation had large amplitude slow AHPs, whereas cells that discharged tonically had slow AHPs of much smaller amplitude. During spike trains, all cells showed a similar broadening of their action potentials. Biocytin-filled neurons showed a range of pyramidal-like morphologies, differed in dendritic complexity, had spiny dendrites, and differed in the degree to which they clearly exhibited apical versus basal dendrites. Quantitative analysis revealed no association between cell morphology and firing properties. We conclude that the discharge properties of neurons in the lateral nucleus, in response to somatic current injections, are determined by the differential distribution of ionic conductances rather than through mechanisms that rely on cell morphology.

Psychophysiological phenotypes of cognition: The P3 and SW components

As part of a large ongoing project, the Memory, Attention and Problem Solving (MAPS) study, we investigated whether genetic variability explains some of the variance in psychophysiological correlates of brain function, namely, the P3 and SW components of event-related potentials (ERPs). These ERP measures are minute time recordings of brain processes and, because they reflect fundamental cognitive processing, provide a unique window on the millisecondto- millisecond transactions that occur at the cognitive level and taking place in the human brain. The extent to which the variance in P3 and SW components is influenced by genetic factors was examined in 350 identical and nonidentical twin pairs aged 16 years. ERPs were recorded from 15 scalp electrodes during the performance of a visuospatial delayed response task that engages working memory. Multivariate genetic analyses using MX were used to estimate genetic and environmental influences on individual differences in brain functioning and to identify putative genetic factors common to the ERP measures and psychometric IQ. For each of the ERP measures, correlation among electrode sites was high, a spatial pattern was evident, and a large part of the genetic variation in the ERPs appeared to be mediated by a common genetic factor. Moderate within-pair concordance in MZ pairs was found for all ERP measures, with higher correlations found for P3 than SW, and the MZ twin pair correlations were approximately twice the DZ correlations, suggesting a genetic influence. Correlations between ERP measures and psychometric IQ were found and, although moderately low, were evident across electrode site. The analyses show that the ERP components, P3 and SW, are promising phenotypes of the neuroelectrical activity of the brain and have the potential to be used in linkage and association analysis in the search for QTLs influencing cognitive function.

Experimental methods for studying drug uptake in the head and brain

A number of techniques have been developed to study the disposition of drugs in the head and, in particular, the role of the blood-brain barrier (BBB) in drug uptake. The techniques can be divided into three groups: in-vitro, in-vivo and in-situ. The most suitable method depends on the purpose(s) and requirements of the particular study being conducted. In-vitro techniques involve the isolation of cerebral endothelial cells so that direct investigations of these cells can be carried out. The most recent preparations are able to maintain structural and functional characteristics of the BBB by simultaneously culturing endothelial cells with astrocytic cells,The main advantages of the in-vitro methods are the elimination of anaesthetics and surgery. In-vivo methods consist of a diverse range of techniques and include the traditional Brain Uptake Index and indicator diffusion methods, as well as microdialysis and positron emission tomography. In-vivo methods maintain the cells and vasculature of an organ in their normal physiological states and anatomical position within the animal. However, the shortcomings include renal acid hepatic elimination of solutes as well as the inability to control blood flow. In-situ techniques, including the perfused head, are more technically demanding. However, these models have the ability to vary the composition and flow rate of the artificial perfusate. This review is intended as a guide for selecting the most appropriate method for studying drug uptake in the brain.