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PubMed1993

Suppression of plasma testosterone and prostate carcinoma size by a redox-based, brain-targeted estrogen delivery system in the rat.

Studies were undertaken to examine the effects of an estradiol-chemical delivery system (E2-CDS) or castration (CAST) on plasma testosterone (T) and growth of the Segaloff 11095 carcinoma. Fischer 344 rats were implanted subcutaneously with the Segaloff 11095 tumor and tumor growth was monitored thereafter. After optimal tumor growth, when the average tumor size was approximately 25 x 15 mm (length x width; 4-5 g wet weight), rats were randomized into (1) testis-intact controls; (2) CAST; (3) intact+E2-CDS groups (rats received weekly injection of the E2-CDS at 0.5 mg/kg). Animals were killed 7 or 14 days after the initiation of treatments. Blood and tissue samples were collected for subsequent analysis. Plasma T levels were suppressed by 98% and 97% through 14 days after CAST or E2-CDS treatment. CAST increased plasma gonadotropin (LH) concentrations, while E2-CDS reduced LH compared to intact control levels. E2-CDS treatment increased plasma E2 levels to 24 (one injection) or 75 pg/ml (two injections) at 7 or 14 days, respectively. E2-CDS, given once a week for 2 consecutive weeks, resulted in a decreased growth of the prostate tumor by 61%, while CAST reduced the weights of these tumors by only 20%. In response to E2-CDS (one or two injections), weights of the in situ ventral prostate and seminal vesicles were significantly reduced by 70% and 50%, respectively, in tumor-bearing rats. Similarly, CAST reduced the weights of these tissues by 80% (prostate) or 52% (seminal vesicle) at 7 or 14 days after treatment. Pituitary weight increased, while testes weight decreased by 20% with two injections of E2-CDS, compared with intact control rats. Collectively, these data indicate that E2-CDS is effective in reducing the growth rate of prostatic tumors in the rat.

Animals↗
PubMed2002

Stereotaxy-based regional brain volumetry applied to segmented MRI: validation and results in deficit and nondeficit schizophrenia.

A method for postprocessing of segmented routine brain MRI studies providing automated definition of major structures (frontal, parietal, occipital, and temporal lobes; cerebellar hemispheres; and lateral ventricles) according to the Talairach atlas is presented. The method was applied to MRI studies from 25 normal subjects (NV), 14 patients with deficit schizophrenia (DS), and 14 with nondeficit schizophrenia (NDS), to evaluate their gray matter and CSF regional volumes. The two patient groups did not differ in mean age at illness onset, duration of illness, severity of psychotic symptoms, or disorganization; DS had more severe avolition and worse social functioning than NDS. For validation purposes, brain structures were manually outlined on original MR images in 10 studies, thus obtaining reference measures. Manual and automated measures were repeated 1 month apart to measure reproducibilities of both methods. The automated method required less than 1 min/operator per study vs more than 30 min for manual assessment. Mean absolute difference per structure between the two techniques was 4.8 ml. Overall reproducibility did not significantly differ between the two methods. In subjects with schizophrenia, a significant decrease in GM and increase in CSF were found. GM loss was confined to frontal and temporal lobes. Lateral ventricles were significantly larger bilaterally in NDS compared to NV and only on the right in NDS compared to DS. The finding of greater structural brain abnormalities in NDS adds to the evidence that deficit schizophrenia does not represent just the more severe end of the schizophrenia continuum.

Adolescent↗
PubMed1999

Temporal and spatial complexity measures for electroencephalogram based brain-computer interfacing.

There has been much interest recently in the concept of using information from the motor cortex region of the brain, recorded using non-invasive scalp electrodes, to construct a crude interface with a computer. It is known that movements of the limbs, for example, are accompanied by desynchronisations and synchronisations within the scalp-recorded electroencephalogram (EEG). These event-related desynchronisations and synchronisations (ERD and ERS), however, appear to be present when volition to move a limb occurs, even when actual movement of the limb does not in fact take place. The determination and classification of the ERD/S offers many exciting possibilities for the control of peripheral devices via computer analysis. To date most effort has concentrated on the analysis of the changes in absolute frequency content of signals recorded from the motor cortex. The authors present results which tackle the issues of both the interpretation of changes in signals with time and across channels with simple methods which monitor the temporal and spatial 'complexity' of the data. Results are shown on synthetic and real data sets.

Computer User Training↗
PubMed1998

Clinical neurochemistry: developments in dementia research based on brain bank material.

Brain tissue obtained at autopsy continues to provide unique opportunities in current dementia research. Not only is tissue analysis still essential for diagnosis, but investigation of neurochemical pathology, at a level of resolution beyond current in vivo imaging, continues to provide new insights into the involvement of neurotransmitter signalling systems. These are relevant to therapy which, with respect to symptoms such as cognitive impairment, psychosis and depression, is currently targeted to specific transmitter (cholinergic, dopaminergic and serotonergic) systems. This paper focuses on dopaminergic, cholinergic and histaminergic parameters in Alzheimer's disease (AD), Dementia with Lewy bodies (DLB) and Parkinson's disease (PD). In the normal striatum the dopamine transporter and D2 receptor exhibit distinct rostral-caudal distributions and D2 binding is affected by genetic polymorphism at the Taq 1A locus. The transporter is reduced in both DLB and PD but not AD, correlating with severity of extrapyramidal dysfunction, and receptor abnormalities are apparent in DLB patients responding adversely to neuroleptics. Striatal nicotine receptors are lost in all 3 disorders, further reduced as a result of neuroleptic medication, and elevated as a result of tobacco use. In the thalamus there are selective reductions in presynaptic cholinergic activity in DLB in the reticular nucleus which relate to symptoms of hallucinations and fluctuating consciousness prevalent in this disorder. In the hippocampus coupling of muscarinic M1 receptors, relevant to response to cholinergic therapy, is impaired in areas most affected by beta-amyloid plaques and intact in less affected areas. Analysis of histamine H2 receptors indicates that, despite presynaptic histamine abnormalities in AD, receptor numbers are normal. Such clinically and therapeutically relevant observations on human brain neurochemistry provide a basis for improving therapeutic strategies and prospects of diagnostic in vivo chemical imaging.

Brain↗
PubMed1986

In vivo determination of extracellular concentration of amino acids in the rat hippocampus. A method based on brain dialysis and computerized analysis.

Extracellular (EC) concentrations of amino acids were determined in the rat dentate gyrus by means of non-linear regression analysis of 'in vivo' brain dialysis data, considering a simple model of diffusion through a dialysis membrane. The apparent diffusion constants (K) of several amino acids were also calculated in the 'in vivo' situation. While putative amino acid neurotransmitters (glutamate, aspartate and gamma-aminobutyric acid (GABA) were present in the EC fluid at the low micromolar range (0.8-2.9 microM), glutamine was by far the most prominent (193.4 microM). The values of intra/extracellular concentration ratios formed 3 groups: high (greater than 2000) for putative neurotransmitters; low (less than 100) for serine, glutamine, arginine and alpha-alanine; and intermediate (about 400) for taurine. The 'in vivo' calculated K values proved useful for estimation of both basal and changing EC concentrations of amino acids in relatively brief perfusions. These data were evaluated in terms of the functional significance of absolute EC concentrations and tissue-EC fluid ratios. Present findings indicate the simultaneous existence of both an inhibitory and an excitatory tonus as well as the utility of high intra/extracellular concentration ratios in determination of the possible neurotransmitter role of specific amino acids.

Amino Acids↗
PubMed2005

Integration of newly born dentate granule cells into adult brains: hypotheses based on normal and epileptic rodents.

The granule cells of the dentate gyrus are a population of neurons continuously generated throughout life. In the rat, the morphological development of newly born granule cells generated in the adult share many similarities with granule cells generated during development. These include a specific migration pattern, orientation and progression of neurite outgrowth. It appears as though varied dendritic morphology occurs depending on the position of the granule cells within the granule cell layer. A hypothesis for granule cell migration and differentiation of their dendritic processes is proposed based on normal and epileptic rats. In this hypothesis, the granule cells are generated in the subgranular zone, and then they migrate into the granule cell layer. During this migration, the sequence of neurite outgrowth is described, where the newly born granule cell first sprouts rudimentary processes. One of these processes, the basal dendrite, is transiently present on developing rodent granule cells in rats. However, in seizure-induced rats the basal dendrite often fails to retract, which leads to the formation of hilar basal dendrites, and also perhaps, ectopic granule cells in the hilus. In this review, granule cell development is discussed with relevance to the creation of the recurrent excitatory circuitry in rodent models of temporal lobe epilepsy.

Animals↗
PubMed2001

Functional brain imaging based on ERD/ERS.

Sensory, cognitive and motor processing can result in changes of the ongoing EEG in form of an event-related desynchronization (ERD) or event-related synchronization (ERS). Both phenomena are time-locked but not phase-locked to the event and they are highly frequency-band specific. The ERD is interpreted as a correlate of an activated cortical area with increased excitability and the ERS in the alpha and lower beta bands can be interpreted, at least under certain circumstances, as a correlate of a deactivated cortical area. Spatial mapping of ERD/ERS can be used to study the dynamics of cortical activation patterns. Examples from a movement task are reported.

Alpha Rhythm↗
PubMed1999

Metabolism-based brain-targeting system for a thyrotropin-releasing hormone analogue.

Gln-Leu-Pro-Gly, a progenitor sequence for the thyrotropin-releasing hormone (TRH) analogue [Leu(2)]TRH (pGlu-Leu-Pro-NH(2)), was covalently and bioreversibly modified on its N- and C-termini (by a 1,4-dihydrotrigonellyl and a cholesteryl group, respectively) to create lipoidal brain-targeting systems for the TRH analogue. The mechanism of targeting and the recovery of the parent peptide at the target site involve several enzymatic steps, including the oxidation of the 1,4-dihydropyridine moiety. Due to the lipid insolublity of the peptide pyridinium conjugate obtained after this reaction, one of the rudimentary steps of brain targeting (i.e., trapping in the central nervous system) can be accomplished. Our design also included spacer amino acid(s) inserted between the N-terminal residue of the progenitor sequence and the dihydrotrigonellyl group to facilitate the posttargeting removal of the attached modification. The release of the TRH analogue in the brain is orchestrated by a sequential metabolism utilizing esterase/lipase, peptidyl glycine alpha-amidating monooxygenase (PAM), peptidase cleavage, and glutaminyl cyclase. In addition to in vitro experiments to prove the designed mechanism of action, the efficacy of brain targeting for [Leu(2)]TRH administered in the form of chemical-targeting systems containing the embedded progenitor sequence was monitored by the antagonistic effect of the peptide on the barbiturate-induced anesthesia (measure of the activational effect on cholinergic neurons) in mice, and considerable improvement was achieved over the efficacy of the parent peptide upon using this paradigm.

Animals↗
PubMed2006

Information-based functional brain mapping.

The development of high-resolution neuroimaging and multielectrode electrophysiological recording provides neuroscientists with huge amounts of multivariate data. The complexity of the data creates a need for statistical summary, but the local averaging standardly applied to this end may obscure the effects of greatest neuroscientific interest. In neuroimaging, for example, brain mapping analysis has focused on the discovery of activation, i.e., of extended brain regions whose average activity changes across experimental conditions. Here we propose to ask a more general question of the data: Where in the brain does the activity pattern contain information about the experimental condition? To address this question, we propose scanning the imaged volume with a "searchlight," whose contents are analyzed multivariately at each location in the brain.

Adolescent↗
PubMed2004

Toward a direct brain interface based on human subdural recordings and wavelet-packet analysis.

Highly accurate asynchronous detection of movement related patterns in individual electrocorticogram channels has been shown using detection based on either event-related potentials (ERPs) or event-related desynchronization and synchronization (ERD/ERS). A method using wavelet-packet features selected with a genetic algorithm was proposed to simultaneously detect ERP and ERD/ERS and was tested on data from seven subjects and four motor tasks. The proposed wavelet method performed better than previous methods with perfect detection for four subject/task combinations and hit percentages greater than 90% with false positive percentages less than 15% for at least one task for all seven subjects.

Action Potentials↗
PubMed2003

Implementation of a telemonitoring system for the control of an EEG-based brain-computer interface.

By the use of a brain-computer interface (BCI), it is possible for completely paralyzed patients, who have lost their ability to speak, to have a new possibility to communicate with their environment. The training with such a BCI system can be performed at the patient's home, if there is a responsible person present who is familiar with the system. This person has to adjust different parameters and to adapt the training individually to each patient. Since this function is usually taken over by the developers of the system, the number of patients who can be included in regular BCI training is restricted due to geographical distances. This paper describes the implementation of a telemonitoring system, which makes it possible for the developer to control and supervise the BCI training from his or her own place of work. First experiences with a patient living far away from the developer's lab are reported.

Adult↗
PubMed2003

How many people are able to operate an EEG-based brain-computer interface (BCI)?

Ninety-nine healthy people participated in a brain-computer interface (BCI) field study conducted at an exposition held in Graz, Austria. Each subject spent 20-30 min on a two-session BCI investigation. The first session consisted of 40 trials conducted without feedback. Then, a subject-specific classifier was set up to provide the subject with feedback, and the second session--40 trials in which the subject had to control a horizontal bar on a computer screen--was conducted. Subjects were instructed to imagine a right-hand movement or a foot movement after a cue stimulus depending on the direction of an arrow. Bipolar electrodes were mounted over the right-hand representation area and over the foot representation area. Classification results achieved with 1) an adaptive autoregressive model (39 subjects) and 2) band power estimation (60 subjects) are presented. Roughly 93% of the subjects were able to achieve classification accuracy above 60% after two sessions of training.

Adaptation, Physiological↗
PubMed2005

Sensorimotor rhythm-based brain-computer interface (BCI): feature selection by regression improves performance.

People can learn to control electroencephalogram (EEG) features consisting of sensorimotor rhythm amplitudes and can use this control to move a cursor in one or two dimensions to a target on a screen. In the standard one-dimensional application, the cursor moves horizontally from left to right at a fixed rate while vertical cursor movement is continuously controlled by sensorimotor rhythm amplitude. The right edge of the screen is divided among 2-6 targets, and the user's goal is to control vertical cursor movement so that the cursor hits the correct target when it reaches the right edge. Up to the present, vertical cursor movement has been a linear function of amplitude in a specific frequency band [i.e., 8-12 Hz (mu) or 18-26 Hz (beta)] over left and/or right sensorimotor cortex. The present study evaluated the effect of controlling cursor movement with a weighted combination of these amplitudes in which the weights were determined by an regression algorithm on the basis of the user's past performance. Analyses of data obtained from a representative set of trained users indicated that weighted combinations of sensorimotor rhythm amplitudes could support cursor control significantly superior to that provided by a single feature. Inclusion of an interaction term further improved performance. Subsequent online testing of the regression algorithm confirmed the improved performance predicted by the offline analyses. The results demonstrate the substantial value for brain-computer interface applications of simple multivariate linear algorithms. In contrast to many classification algorithms, such linear algorithms can easily incorporate multiple signal features, can readily adapt to changes in the user's control of these features, and can accommodate additional targets without major modifications.

Adult↗