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Behavioral and antiepileptic effect of acute administration of the extract of the aquatic plant Echinodorus berteroi (Sprengel) Fassett (upright burhead).

Echinodorus berteroi is an aquatic plant found in Central America and the Caribbean to which antiepileptic action has been attributed by folk medicine. The aim of the present study was to investigate the potential behavioral and antiepileptic effect of decoctions (1, 5, and 30%, intraperitoneally) of the dried roots. One and five percent decoctions produced hypoactivity in mice. Hyperactivity induced by amphetamine (3mg/kg, subcutaneously) was significantly reduced by the 30% decoction, in rats. The extracts did not modify the latency to the first clonic convulsion or the survival time of isoniazid (210 mg/kg, ip)-treated mice. The 30% decoction significantly increased the latency to the first picrotoxin-induced clonic convulsion (7 mg/kg, intraperitoneally), as well as survival time. Repeated administration of the 5% decoction (30-minute intervals) significantly reduced the amplitude (muV) of the epileptic spikes induced by topical application of penicillin to sensorimotor cortex, in curare-treated rats. In summary, the root decoctions of E. berteroi paradoxically exhibited neuroleptic and antiepileptic actions. Nevertheless, these results partly justify the use of the plant for the treatment of epilepsy by practitioners of folk medicine.

Alismataceae↗

Bimanual coordination and interhemispheric interaction.

Bimanual coordination of skilled finger movements requires intense functional coupling of the motor areas of both cerebral hemispheres. This coupling can be measured non-invasively in humans with task-related coherence analysis of multi-channel surface electroencephalography. Since bimanual coordination is a high-level capability that virtually always requires training, this review is focused on changes of interhemispheric coupling associated with different stages of bimanual learning. Evidence is provided that the interaction between hemispheres is of particular importance in the early phase of command integration during acquisition of a novel bimanual task. It is proposed that the dynamic changes in interhemispheric interaction reflect the establishment of efficient bimanual 'motor routines'. The effects of callosal damage on bimanual coordination and learning are reviewed as well as functional imaging studies related to bimanual movement. There is evidence for an extended cortical network involved in bimanual motor activities which comprises the bilateral primary sensorimotor cortex (SM1), supplementary motor area, cingulate motor area, dorsal premotor cortex and posterior parietal cortex. Current concepts about the functions of these structures in bimanual motor behavior are reviewed.

Adult↗

Answering questions with an electroencephalogram-based brain-computer interface.

OBJECTIVE: To demonstrate that humans can learn to control selected electroencephalographic components and use that control to answer simple questions. METHODS: Four adults (one with amyotrophic lateral sclerosis) learned to use electroencephalogram (EEG) mu rhythm (8 to 12Hz) or beta rhythm (18 to 25Hz) activity over sensorimotor cortex to control vertical cursor movement to targets at the top or bottom edge of a video screen. In subsequent sessions, the targets were replaced with the words YES and NO, and individuals used the cursor to answer spoken YES/NO questions from single- or multiple-topic question sets. They confirmed their answers through the response verification (RV) procedure, in which the word positions were switched and the question was answered again. RESULTS: For 5 consecutive sessions after initial question training, individuals were asked an average of 4.0 to 4.6 questions per minute; 64% to 87% of their answers were confirmed by the RV procedure and 93% to 99% of these answers were correct. Performances for single- and multiple-topic question sets did not differ significantly. CONCLUSIONS: The results indicate that (1) EEG-based cursor control can be used to answer simple questions with a high degree of accuracy, (2) attention to auditory queries and formulation of answers does not interfere with EEG-based cursor control, (3) question complexity (at least as represented by single versus multiple-topic question sets) does not noticeably affect performance, and (4) the RV procedure improves accuracy as expected. Several options for increasing the speed of communication appear promising. An EEG-based brain-computer interface could provide a new communication and control modality for people with severe motor disabilities.

Adult↗

Hippocampal transection attenuates kainic acid-induced amygdalar seizures in rats.

Since the dorsal and ventral hippocampus in the rat may act differently from one another in limbic seizures, we studied effects of orthogonal transection between the dorsal and ventral hippocampus upon kainic acid-induced amygdalar seizures. A total of 26 rats were divided into three groups. Ten rats underwent transection using a modified wire knife (transection group); 16 others were untransection group (n=10) and controls (n=6). All the rats then underwent stereotactic implantation of electrodes in the left amygdala (LA), left dorsal hippocampus (LdH), left ventral hippocampus (LvH), and the left sensorimotor cortex (LCx). A stainless steel cannula also was introduced into the LA. Rats except controls later received 1.0 microg of kainic acid (KA) via the cannula. Controls received phosphate buffer solution alone. In the untransection group, multiple spike discharges in the LA immediately propagated concurrently to the LvH and LdH. Propagation involved the LCx to become status epilepticus 1 to 2 h after KA injection. Seizures, characterized by mastication, salivation, facial twitching, forelimb clonus, and sometimes rearing and falling, lasted 1 to 2 days. Microscopic examination revealed severe neuronal cell damage in the LA, LvH, and LdH. In the transection group, multiple spike discharges initiated from the LA and were propagated to LvH, but LdH as well as LCx involvement was slight. Status epilepticus involved only the LA and LvH 1 to 2 h following KA injection. Seizures subsided within 24 h, showing no ictal manifestations except for aggressiveness. Overall, seizures were weak and transient compared with those in controls. Histologically, hippocampal neuronal damage was slight, but damage to amygdalar neurons was similar to that in untransection group. No electroclinical and histological changes were seen in controls. These results indicated that connections between the dorsal and ventral hippocampus are important for full development of KA-induced amygdalar seizures.

Amygdala↗

Kainic acid-induced dorsal and ventral hippocampal seizures in rats.

Despite reports of differing regional seizure susceptibility in the hippocampus, hippocampal initiation of limbic seizures has not been precisely localized. We compared seizures induced by kainic acid microinjection into the left dorsal and ventral hippocampus of rats. Discharges following ventral injections rapidly propagated to the left amygdala and sensorimotor cortex unlike seizures following dorsal injections. The ventral group showed various ictal behaviors including motor manifestations, while dorsally injected rats showed only immobilization.

Amygdala↗

Electrophysiological, behavioral and metabolical features of globus pallidus seizures induced by a microinjection of kainic acid in rats.

There has been few studies of the globus pallidus in relation to epilepsy. In this study, kainic acid (KA)-induced globus pallidus seizure was electrophysiologically, electroencephalographically, histopathologically and metabolically investigated in rats. Sixteen Wistar rats weighing 250-350 g were used. Under intraperitoneal pentobarbital anesthesia, a stainless-steel cannula was inserted stereotaxically into the left globus pallidus pars externa (GPe) for KA injection. For recording EEG, a depth electrode was inserted into the left GPe, just posterior to the tip of the injection guide cannula. Electrodes were also inserted into the right globus pallidus and bilateral sensorimotor cortex (SMC). EEG changes after KA injection were classified as follows: Continuous low-voltage spikes were observed in the left GPe on EEG at stage 1. Intermittent multiple spikes and wave complexes began to propagate to the left SMC at stage 2. Continuous spikes and wave complexes began to propagate to the bilateral SMC at stage 3. Secondary generalized seizures were observed at stage 4. Globus pallidus seizures recurred every 7-9 min and lasted for 4-6 h. However, the seizures gradually subsided and became normal within 18 h. No spontaneous seizure was detected for the next 30 days. Histopathological study revealed a small gliotic lesion with neuronal cell loss around the cannula tip. Neither degeneration nor neuronal cell loss in the ipsilateral hippocampus were observed. The autoradiogram using [14C]2-deoxyglucose during seizure status demonstrated a remarkable increase of local cerebral glucose utilization not only in the GPe but also in the GPi. An increase glucose metabolism was also found in the follows: the medial and lateral septal nucleus, substantia nigra, hippocampus, frontal cortex, parietal cortex, piriform cortex, entorhinal cortex, accumbens nucleus, ventral and lateral nucleus of the thalamus, amygdala, and ventral nucleus of hypothalamus. KA injection into the unilateral GPe evoked not only epileptic excitation of the cortex but also transient enhancement of the globus pallidus-substantia nigra circuit.

Action Potentials↗

Behavioral training increases local astrocytic metabolic activity but does not alter outcome of mild transient ischemia.

Functional neurological outcome after transient ischemia might be improved by timely therapeutic intervention. To determine if restorative behavioral therapy influences damage, improves task learning, or alters astrocyte metabolic activity after ischemia, rats (food-restricted to 85% of free-feeding weight) were (a) first trained to respond on one of two levers under a fixed-ratio 20 schedule of food presentation (FR20), then (b) subjected to sham manipulation of carotid arteries or 10 min ischemia by four-vessel occlusion, followed by (c) 4 days of operant testing or inactivity, (d) then all rats were tested under a FR20 lever reversal task for 4 weeks, and (e) 3 days after the last behavioral session astrocyte metabolism was assayed by local uptake of [2-14C]acetate. Mild loss of hippocampal neurons occurred in ischemic rats with or without training after ischemia. Glial fibrillary acidic protein-positive astrocytes were present in similar numbers throughout brains of sham control and ischemic rats. Mild ischemia did not impair learning, and no changes in FR20 reversal learning were detected in sham vs. ischemic rats. Net [14C]acetate uptake was unaffected by ischemia but [14C]acetate uptake increased 15-24% (P<0.05; n=12-15/group) in specific structures (caudate, primary motor and sensorimotor cortex, CA1 hippocampus, subcortical white matter) in the pooled groups of rats that had 4 days FR20 testing vs. inactivity before reversal learning. 'Behavioral therapy' (operant testing on the 4 days immediately following either sham manipulation or ischemia) did not alter ischemic outcome, but was associated with higher acetate utilization in regions involved in motor activities.

Acetic Acid↗

Somatosensory evoked magnetic fields arising from sources in the human cerebellum.

Somatosensory evoked neuromagnetic activity of human cerebellum was recorded noninvasively with a 122-channel whole-scalp magnetometer. Cerebellar source areas activated 13-19 ms after unilateral electric stimulation of the median nerve. The first signals preceded those occurring in the primary sensorimotor cortex at around 20 ms and overlapped in time with the activation of thalamic sources. The orientation and location of most prominent cerebellar activation suggest that the detected signals represent synchronized postsynaptic activity of spinocerebellar cortex. These signals are probably elicited by the first afferent sensory volley from peripheral nerve endings and mediated by spinocerebellar (cuneocerebellar) tracts. The results imply strong coherent activation of cerebellar neuronal populations after purely sensory stimulation. Moreover, with presented methods the millisecond-scale temporal resolution of neurophysiological measurements can be more generally applied to the study of neuronal population activity in intact human cerebellum.

Adult↗

Non-invasive detection of ongoing neuronal population activity in normal human hippocampus.

A 122-channel magnetoencephalographic array was used to monitor ongoing neuronal population activity in six normal human subjects during the performance of a mental calculation and passive viewing of a picture. Signal-space projection was utilized to obtain waveforms and spectra for activity in anterior hippocampus and sensorimotor cortex. Hippocampal waveforms were complex. Spectral components below 12 Hz in hippocampus included task-dependent peaks superimposed on a broadband background of increasing amplitude at decreasing frequencies. MEG imaging of both waveforms and spectra for ongoing activity within hippocampus makes possible the investigation of the role of rhythmic and non-rhythmic hippocampal activity in normal human cognition.

Adult↗

Beneficial effects of TDN-345, a novel Ca2+ antagonist, on ischemic brain injury and cerebral glucose metabolism in experimental animal models with cerebrovascular lesions.

The effects of TDN-345 on mortality and ischemic neurological deficit following transient global cerebral ischemia in Mongolian gerbils and also the rate of local cerebral glucose utilization (LCGU) in stroke-prone spontaneously hypertensive rats (SHRSP) with cerebrovascular lesions were investigated. In Mongolian gerbils, ischemia was produced by clamping the bilateral common carotid arteries for 15 min. TDN-345 (0.1-1.0 mg/kg) dose-dependently decreased the mortality and ischemic neurological deficit score when administered orally twice, 60 min before ischemia and 90 min after recirculation. Additionally, TDN-345 (0.2 or 1.0 mg/kg, p.o. once daily for 3 weeks after the onset of stroke) decreased the mortality and recurrence of stroke in SHRSP. To determine the site of action of TDN-345 in the brain, the rate of LCGU in various brain regions in SHRSP with stroke was examined using a [14C]2-deoxy-D-glucose method. The rate of LCGU decreased significantly in all the brain regions in SHRSP with stroke compared with Wistar-Kyoto (WKY) control rats, whereas the reduction in the rate of LCGU in SHRSP with stroke was prevented by TDN-345 treatment, especially in the sensorimotor cortex and locus coeruleus. These results suggest that TDN-345 has therapeutic efficacy in the treatment of cerebrovascular disease.

Animals↗

Use-dependent exacerbation of brain damage occurs during an early post-lesion vulnerable period.

For a period of time after unilateral brain injury, surviving neural tissue surrounding the lesion may be vulnerable to extremely high behavioral demand. Previously, we found that lesions of the forelimb representation area of the sensorimotor cortex (FL-SMC) in rats increase in size substantially when the intact forelimb is immobilized with a plaster of paris cast during the first 15 days after surgery, which forces overuse of the impaired forelimb. The present study was designed to determine whether the adult brain is more vulnerable to forced overuse of the impaired forelimb during the first 7 days post-lesion than during the second 7 days post-lesion. Using behavioral tests of forelimb use and stereological analysis of remaining tissue volume 40 days after FL-SMC lesions, we found that forced overuse of the impaired forelimb during the first 7 days after the initial damage caused expansion of neural injury and greatly interfered with restoration of function. In contrast, forced overuse of the impaired forelimb during the second 7 days had no significant effect on lesion size but nevertheless interfered with restoration of function. Thus, surviving neural tissue in the damaged hemisphere and recovery of function appear to be vulnerable to prolonged forced overuse of the impaired forelimb throughout the first 15 days, but tissue loss was detectable only when the animal was forced to use the impaired forelimb during the first 7 days after injury.

Animals↗

Rapid disappearance of zinc positive terminals in focal brain ischemia.

The study was undertaken to determine if the levels of vesicular zinc in neuronal terminals would decrease in response to focal brain ischemia. The middle cerebral artery was occluded distal to the striatal branches in male spontaneously hypertensive rats. At 7, 15, 30, 45, 60, 90, 120 min; 3, 6, 12, 24, 48 h and 7 days later the animals were sacrificed and the brains were stained for zinc-sulfides, cell bodies and AChE-positive cholinergic fibers. The density of zinc positive terminals significantly decreased in the neocortical ischemic zone 7 min after middle cerebral artery occlusion (MCAO). In the neocortical layers II and III most zinc positive neuronal terminals disappeared at 7 min after MCAO whereas the zinc positive terminals in layers V and VI remained positive at least 2 h. Beginning at 1 h after MCAO and progressing to 24 h a significant decrease in the density of zinc positive terminals was observed in the dorsolateral striatum, and ventrobasal thalamic nucleus, both major projection areas of the sensorimotor cortex. The disappearance of zinc positive neuronal terminals in the ischemic neocortex and related areas, is most likely due to a neuronal release of vesicular zinc in response to hypoxia. The high extracellular concentration of zinc is thought to be both neuroprotective by blocking the NMDA receptor and neurotoxic by activating neuronal influx of Ca2+ through voltage gated calcium channels. It seems evident that the latter effect of zinc is contributing to the neuronal death in focal brain ischemia.

Animals↗

The effects of pharmacological doses of 2-deoxyglucose on cerebral blood flow in healthy volunteers.

The effects of glucose deprivation on cerebral blood flow (CBF) have been extensively investigated during insulin-induced hypoglycemia in laboratory animals. Pharmacological doses of glucose analog, 2-deoxyglucose (2DG), is an alternative glucoprivic agent that in contrast to insulin, directly inhibits glycolysis and glucose utilization. Both glucoprivic conditions markedly increase CBF in laboratory animals. How 2DG affects CBF in humans is still undetermined. In the present study we have employed H215O positron emission tomography (PET) to examine the effects of pharmacological doses of 2DG (40 mg/kg) on regional and global cerebral blood flow in 10 brain areas in 13 healthy volunteers. 2DG administration significantly raised regional CBF (rCBF) in the cingulate gyrus, sensorimotor cortex, superior temporal cortex, occipital cortex, basal ganglia, limbic system and hypothalamus. 2DG produced a trend towards elevated CBF in whole brain and frontal cortex, while no changes were observed in the corpus callosum and thalamus. In addition, 2DG significantly decreased body temperature and mean arterial pressure (MAP). Maximal percent changes in hypothalamic rCBF were significantly correlated with maximal changes in body temperature but not with MAP. These results indicate that cerebral glucoprivation produced by pharmacological doses of 2DG is accompanied by widespread activation of cortical and subcortical blood flow and that the blood flow changes in the hypothalamus may be related to 2DG-induced hypothermia.

Adult↗

Lack of topographical organisation of the corticospinal tract in the cervical spinal cord of the adult rat.

The fluorescent dextran, Fluororuby, was injected into either the hindlimb or forelimb sensorimotor cortex to label corticospinal axons projecting to corresponding regions of spinal cord. In the rostral cervical spinal cord, labelled axons projecting to the lumbar or cervical grey matter were intermingled randomly. We conclude that there is no topographical organisation of the corticospinal tract in the cervical spinal cord.

Age Factors↗

Characterization of AMPA receptor populations in rat brain cells by the use of subunit-specific open channel blocking drug, IEM-1460.

Dicationic adamantane derivative, IEM-1460, which selectively blocks GluR2-lacking, Ca2+-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors, was used to characterize the distribution of AMPA receptors among populations of rat brain cells. IEM-1460 inhibited kainate-induced inward currents (at -80 mV) in a dose-dependent manner. IEM-1460 concentrations producing 50% inhibition of kainate-induced current amplitude (IC50) varied greatly depending on the cell type studied. Striatal giant cholinergic interneurons and putative Bergmann glial cells isolated from the cerebellum were found to be highly sensitive to IEM-1460 block (IC50=2.6 microM), indicating the expression of GluR2-lacking AMPA receptor subtype. Among hippocampal and cortical non-pyramidal neurons, there were cell-to-cell differences in the pattern of AMPA receptor subtype expression. Some cells which are known to express AMPA receptors lacking GluR2 subunit exhibited high sensitivity of IEM-1460 block (IC50 about 1 microM) but in the others, the part of AMPA receptor population seemed to be represented by GluR2-having receptor subtype. The latter subtype was mainly expressed by pyramidal neurons isolated from hippocampus (IC50=1102 microM) and sensorimotor cortex (IC50=357 microM) which showed low affinity for IEM-1460 block. In conclusion, IEM-1460 can be utilized as an indicator of the distribution of AMPA receptor subtypes among populations of rat brain cells, and pharmacological detection of the absence of GluR2 subunit in AMPA receptor assembly can provide useful information for the interpretation of physiological events.

Adamantane↗

Spatial filter selection for EEG-based communication.

Individuals can learn to control the amplitude of mu-rhythm activity in the EEG recorded over sensorimotor cortex and use it to move a cursor to a target on a video screen. The speed and accuracy of cursor movement depend on the consistency of the control signal and on the signal-to-noise ratio achieved by the spatial and temporal filtering methods that extract the activity prior to its translation into cursor movement. The present study compared alternative spatial filtering methods. Sixty-four channel EEG data collected while well-trained subjects were moving the cursor to targets at the top or bottom edge of a video screen were analyzed offline by four different spatial filters, namely a standard ear-reference, a common average reference (CAR), a small Laplacian (3 cm to set of surrounding electrodes) and a large Laplacian (6 cm to set of surrounding electrodes). The CAR and large Laplacian methods proved best able to distinguish between top and bottom targets. They were significantly superior to the ear-reference method. The difference in performance between the large Laplacian and small Laplacian methods presumably indicated that the former was better matched to the topographical extent of the EEG control signal. The results as a whole demonstrate the importance of proper spatial filter selection for maximizing the signal-to-noise ratio and thereby improving the speed and accuracy of EEG-based communication.

Adult↗

Perception of motion and qEEG activity in human adults.

This study was designed to relate visual perception of motion to cortical activity, by evaluation of the association of quantified electroencephalogram (qEEG) parameters with a video film projection. The EEG was recorded from 14 sites according to the International 10-20 system and a common average reference was used. Forty right-handed volunteers (mean age = 24 years) were examined. The video film consisted of 20 s sequences showing still shots and moving shots with human movements or object movements. The EEG was then subjected to spectral analysis; the spectral powers for the theta, alpha and beta bands were calculated for 14 s epochs and compared with sequences of the video film. All analyses were based on logarithmically transformed absolute spectral power values. The power values of each frequency band were analysed in a 3-way repeated measure ANOVA (Hemisphere x Electrode x Sequence). The results were represented by EEG cartography. Significant decreases in the alpha 1, beta 1 and beta 2 power values of EEG in centro-parietal regions of both hemispheres were shown during perception of human motion sequences. This suggests participation of the sensorimotor cortex during visual observation of human motion.

Adolescent↗

EEG-based communication: analysis of concurrent EMG activity.

OBJECTIVE: Recent studies indicate that people can learn to control the amplitude of mu or beta rhythms in the EEG recorded from the scalp over sensorimotor cortex and can use that control to move a cursor to targets on the computer screen. While subjects do not move during performance, it is possible that inapparent or unconscious muscle contractions contribute to the changes in the mu and beta rhythm activity responsible for cursor movement. We evaluated this possibility. METHODS: EMG was recorded from 10 distal limb muscle groups while five trained subjects used mu or beta rhythms to move a cursor to targets at the bottom or top edge of a computer screen. RESULTS: EMG activity was very low during performance, averaging 4.0+/-4.4% (SD) of maximum voluntary contraction. Most important, the correlation, measured as r2, between target position and EMG activity averaged only 0.01+/-0.02, much lower than the correlation between target position and the EEG activity that controlled cursor movement, which averaged 0.39+/-0.18. CONCLUSIONS: These results strongly support the conclusion that EEG-based cursor control does no depend on concurrent muscle activity. EEG-based communication and control might provide a new augmentative communication option for those with severe motor disabilities.

Adult↗