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OBJECTIVE: Recently, there have been several approaches to utilize a brain-computer interface (BCI) for rehabilitation with stroke patients or as an assistive device for the paralyzed. In this study we investigated whether up to seven different hand movement intentions can be decoded from epidural electrocorticography (ECoG) in chronic stroke patients. APPROACH: In a screening session we recorded epidural ECoG data over the ipsilesional motor cortex from four chronic stroke patients who had no residual hand movement. Data was analyzed offline using a support vector machine (SVM) to decode different movement intentions. MAIN RESULTS: We showed that up to seven hand movement intentions can be decoded with an average accuracy of 61% (chance level 15.6%). When reducing the number of classes, average accuracies up to 88% can be achieved for decoding three different movement intentions. SIGNIFICANCE: The findings suggest that ipsilesional epidural ECoG can be used as a viable control signal for BCI-driven neuroprosthesis. Although patients showed no sign of residual hand movement, brain activity at the ipsilesional motor cortex still shows enough intention-related activity to decode different movement intentions with sufficient accuracy.

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The effect of caffeine (single oral doses of 200 mg and 400 mg) on the CNS was tested under resting conditions and while performing a concentration performance test in a placebo-controlled pilot study on ten healthy males. The EEG was evaluated quantitatively by spectral analysis with a Computer Aided Topographical ElectroEncephaloMetry system. Comparison of the averaged frequency content revealed a clear difference between the change in the functional state of the brain due to the mental arithmetics, on the one hand, and the caffeine effect, on the other. Both states of altered brain activity were reflected in a particular topographical distribution of the frequency change with respect to a frontal-occipital accentuation. Comparison of the two periods of mental arithmetics in the absence or presence of caffeine showed a tendency to concentration-dependent differences from each other. Administration of 200 mg and 400 mg caffeine in the relaxed state effected the decrease in spectral power in the theta and alpha ranges. The concentration performance test without caffeine effected decreases in power in the alpha range in frontal to parietal cortex and enhanced theta power in frontal and occipital regions and the alpha power in occipital cortex. The caffeine-dependent decrease in theta power and the decrease in delta power seen under relaxation conditions after 400 mg are not observed during the concentration performance test in the presence of caffeine.

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The objective of the study was to evaluate the prevalence of and the factors associated with cardiovascular autonomic diabetic neuropathy (CADN) and peripheral neuropathy in patients attending clinical and outpatient diabetes centers. The design was a multicenter cross section study with random selection of patients with Type 1 or Type 2 diabetes from seventeen German, three Swiss, and two Austrian inpatient and outpatient diabetes centers. A total of 1,642 patients were recruited, 1,171 of whom (Type 1: n = 647, age: 11-69 years; Type 2: n = 524, age: 16-72 years) were studied. Measurements and results. The following six autonomic function tests based on heart rate variation were used for the diagnosis of CADN: coefficient of variation and power spectrum in the low- and mid-frequency bands at rest, mean circular resultant during deep breathing, Valsalva ratio, and max/min 30:15 ratio to standing. The age-dependent lower limit of the normal range in these tests had previously been defined at the 2.3 centile in 120 healthy subjects. Definite CADN defined by the strict criterion of abnormal results in > or = 3 of these 6 tests was detected in 16.8% of the Type 1 and 22.1% of the Type 2 diabetic patients (p < 0.05). The corresponding rates of borderline CADN defined as the presence of 2 abnormalities were 8.5% and 12.2%, respectively (p < 0.05). Peripheral neuropathy defined as the presence of > or = 2 abnormalities among 3 criteria (neuropathic symptoms, absent tendon reflexes, and abnormal malleolar vibration perception threshold) was observed in 17.1% of Type 1 and 34.8% of Type 2 diabetic patients (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

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To establish a test battery for the detection and characterization of cardiovascular autonomic neuropathy (CADN) and to evaluate its prevalence, a number of autonomic function tests based on spectral analysis, vector analysis, and standard tests of heart rate variation and blood pressure responses were performed in 261 diabetic patients aged 11-76 years with various stages of peripheral neuropathy. The percentages of abnormal results in the individual tests based on heart rate variation were 6-31% in 115 patients without peripheral neuropathy, 16-45% in 61 patients with subclinical neuropathy, 22-59% in 73 patients with symptomatic peripheral neuropathy, and 67-100% in 12 patients with the latter in conjunction with autonomic symptoms (p < 0.05). The most frequently abnormal indices, each representing a different physiological basis, were the coefficient of variation, low-frequency and mid-frequency power spectrum at rest, mean circular resultant, postural change in systolic blood pressure, and, in particular, the max/min 30:15 ratio and Valsalva ratio. CADN, defined as the presence of > or = 3 abnormalities among these seven parameters was detected in none of 120 control subjects, 13.0% of the patients without peripheral neuropathy, 34.4% of those with subclinical neuropathy, 49.3% of those with symptomatic peripheral neuropathy, and in 100% of the subjects with the latter and concomitant autonomic symptoms (p < 0.05). The overall prevalence of CADN in 103 patients completing all parameters was 46.6%. The corresponding rate of CADN defined as > or = 2 abnormalities among the five tests included in an optimized version of the battery proposed by Ewing and Clarke was 38.8%.(ABSTRACT TRUNCATED AT 250 WORDS)

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OBJECTIVE: To determine the prevalence of cardiovascular autonomic nerve dysfunction in patients with newly diagnosed insulin-dependent diabetes mellitus (IDDM) compared with healthy nondiabetic subjects. RESEARCH DESIGN AND METHODS: A battery of cardiovascular reflex tests was performed in 130 newly diagnosed IDDM patients aged 12-40 yr at mean blood glucose levels of 7.2 mM after insulin had been administered for 3-39 days. Age-dependent lower limits of normal of these tests were defined at the 2.3 percentile in 120 nondiabetic subjects. Tests of heart-rate variation (HRV) included the coefficient of variation (C.V.) and the low-frequency (LF), midfrequency (MF), and high-frequency (HF) bands of spectral analysis at rest, HRV during deep breathing (C.V., expiratory-inspiratory ratio, and mean circular resultant), Valsalva ratio, and maximum/minimum 30:15 ratio. In addition, spectral analysis on standing, the change in systolic blood pressure to standing, and diastolic blood pressure response to sustained handgrip were determined in 50 patients. RESULTS: A significantly higher percentage of abnormal test responses in the diabetic group compared with the control group was noted for power spectrum in the LF band (7.3 vs. 0.8%, P less than 0.05) and MF band (10.6 vs. 0%, P less than 0.001) at rest and HF band on standing (10.0 vs. 0.9%, P less than 0.05), maximum/minimum 30:15 ratio (25.4 vs. 5.0%, P less than 0.001), and Valsalva ratio (17.5 vs. 4.2%, P less than 0.001). There were no significant differences between both groups in regard to the remaining parameters. Ten (7.7%) diabetic patients but none of the nondiabetic subjects had cardiovascular autonomic neuropathy defined by the strict criterion of abnormal results in more than three of six tests (P less than 0.001). In addition, 12 (9.2%) patients but only 2 (1.7%) control subjects had abnormal results in two of six tests (P less than 0.01). CONCLUSIONS: Cardiovascular autonomic nerve dysfunction is relatively common in newly diagnosed IDDM patients after correction of the initial metabolic imbalance. A combination of tests based on spectral and conventional analysis of HRV appears suitable for detection of early abnormalities in autonomic function in diabetes.

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Cyclandelate and flunarizine, two vasoactive Ca2+ channel or Ca2+ overload blockers have been compared with respect to their in vivo action on field potentials recorded from the depths of the brain in freely moving rats. Whereas cyclandelate showed a dose dependent rapid onset of action in the range of 15 to 120 mg/kg i.p., flunarizine only induced weak effects very slowly, not reaching statistical relevance before the fourth hour after the injection (0.1 to 1.6 mg/kg). Even then no clear dose dependence could be recognized for flunarizine. With respect to the frequency content of the recorded signals a rather close similarity between both drugs could be seen. Comparison of the drug effects to our reference data base of more than 80 compounds revealed a close relationship to memantine, an antiparkinson drug, suspected to act on the NMDA (N-methyl-d-aspartate) receptor-ionophor complex controlling Ca2+ fluxes. There is some indication that cyclandelate might also act in a similar way at the molecular level.

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To establish normal ranges for assessment of autonomic dysfunction, a battery of cardiovascular reflex tests was performed in 120 healthy subjects aged 15-67 years using a computer-based technique. Tests of heart rate variation (HRV) included 8 measures at rest: coefficient of variation (CV), root mean squared successive difference (RMSSD), spectral analysis of HRV in the low frequency, mid frequency, and high frequency bands in the supine and standing postures; 5 measures during deep breathing: CVb, RMSSDb, Expiration-Inspiration (E-I) difference, E/I ratio, and mean circular resultant of vector analysis; Valsalva ratio, and max/min 30:15 ratio. In addition, the change in systolic and diastolic blood pressure in response to standing and the diastolic blood pressure response to sustained handgrip were determined. The results of all measures, the blood pressure tests excepted, declined significantly with increasing age (r = -0.16 to -0.59; p less than 0.05). Moreover, RMSSD, RMSSDb, and E-I difference decreased considerably with increasing heart rate (r = -0.37 to -0.52; p less than 0.001). The longest and shortest R-R intervals in response to standing were distributed within beats 21-39 and 6-24, respectively. All tests were independent of sex. Log transformation was used to define the age-related lower limits of normal at the 2.3 centile for all tests of HRV, except for the E/I, Valsalva, and max/min 30:15 ratios. The results of these tests had to be analysed using a log(y-1) transformation. The intra-individual reproducibility determined on two consecutive days in 20 healthy subjects and 21 diabetic patients indicated that there were no major differences between the two groups regarding the day-to-day variation of test results, which was highest for the Valsalva ratio. We conclude that: (1) all indices of spectral and vector analyses of HRV are age-dependent and have the advantage of being independent of heart rate; (2) RMSSD, E-I difference, and the 30:15 ratio as it was used previously are not suitable for evaluation of autonomic dysfunction in diabetes; (3) log(y-1) transformation is required to determine age-dependent normal ranges and reproducibility for the three ratios.

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Although neuropathy has long been recognized as a complication of diabetes, the impact of this condition has not been adequately established. The prevalence of diabetic neuropathy is virtually unknown because the published studies differ considerably with regard to definition, method of assessment, and patient selection. Furthermore, the determination of prevalence has been hampered by the fact that there is no generally accepted classification of the variety of manifestations of diabetic neuropathy. The introduction of new sensitive diagnostic methods aids in the detection of less severe stages of neuropathy, as compared with clinically based assessment, and renders the disease more prevalent. The prevalence of diabetic neuropathy in the few reported population-based studies was approximately 30%. We have evaluated the prevalence of cardiovascular autonomic neuropathy in a group of approximately 1000 diabetic patients randomly included from 21 hospitals in Germany, Austria, and Switzerland. The results of this study and those of a prospective study on the natural history of neural dysfunction during the first 5 years after diagnosis of type 1 diabetes will be presented.

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Under the assumption that field potentials recorded from particular brain areas reflect the net balance of neurotransmitter activities, the dose- and time-dependent responses induced by intraperitoneal application of different neuroleptic drugs are quantified by spectral analysis of the electroencephalogram recorded from frontal cortex, hippocampus, striatum and reticular formation. The actions of haloperidol, chlorpromazine, clozapine, prothipendyl and thioridazine in general were characterized by increases of the spectral power in the alpha 1 and beta range, at higher dosages also in the theta range. This observed pattern of changes is in line with the neuroleptic induced spectral changes reported in the literature for other animals and man. In the light of the already known effects of other psychoactive drugs on the frequency content of field potentials in the rat, it should now be possible to classify different drugs in terms of their clinical indication. With respect to the type of neurotransmitter control underlying the changes produced by various neuroleptics, it is quite obvious from the comparisons with the respective drug effects that dopamine-D1-receptor controlled transmission is not responsible for this action. On the basis of earlier findings a possible interaction between dopamine-D2 receptor or glutamatergic transmitter control is discussed.

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Rare side effects on the central nervous system including dizziness, restlessness, and even very rare convulsions as reported during the course of antibiotic treatment with quinolones were the topic of a well-controlled in vitro approach. The excitability of brain matter was tested by electrically evoking field potentials in the CA1 region of the rat hippocampus in vitro. Direct effects of nalidixic acid, enoxacin, pefloxacin, norfloxacin, ofloxacin, and ciprofloxacin were found to occur as a dose-dependent increase in amplitude of this field potential, which is in line with the view that the quinolones increase excitability. The highest increase was found with enoxacin and nalidixic acid, and the lowest increase was found with ciprofloxacin. In order to keep the potential risk of the antibiotic therapy as low as possible, ciprofloxacin might be the drug of choice of the quinolones. In contrast to the quinolones, which only increased the amplitudes of electrically evoked potentials, fenbufen induced spontaneous firing in the pyramidal cell layer without stimulation in addition to its dose-dependent effects on the amplitudes of the evoked potentials. Threshold doses of the quinolones tested (0.25 microM) increased the amplitudes of evoked potentials in the presence of an otherwise ineffective concentration of fenbufen (1 microM) to different degrees, ranging from 39.2% for ciprofloxacin to 72.6% for enoxacin.

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The effect of cyclandelate (Natil) on the CNS was tested in a double-blind, placebo-controlled pilot study on 48 healthy males using a single oral dosage of 1200 mg. The EEG was evaluated quantitatively by spectral analysis before and one hour as well as two and a half hours after drug or placebo administration under resting conditions and while performing a test of mental arithmetic. Under resting conditions the power in the alpha 2 frequency band of the signals from the frontal and central recordings was increased in the cyclandelate group in comparison to the placebo group. This effect was still observed two and a half hours after drug intake. Under the condition of mental arithmetic no drug related effect was observed in the EEG. The cyclandelate induced increase of spectral power in the alpha 2 frequency band under resting conditions demonstrates a general effect of cyclandelate on the CNS. The results are discussed with respect to the known age related decrease of spectral power in the alpha frequency band. The established effect of cyclandelate in young healthy subjects calls for a study with chronic treatment in elderly subjects or patients with cognitive deficits.

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Recording of field potentials from different brain areas of freely behaving rats and subsequent spectral analysis of the signals has proved to be a most sensitive method in pharmacology. This new model is used to measure the effect on the electrical activity of the brain of repeated daily injections of 1 ml/kg of a vitamin B mixture (Neurobion, 1 ml containing 33.3 mg B1, 33.3 mg B6, and 0.333 mg B12). Subacute application of the vitamin B combination for 1 week in a group of six rats resulted in changes in the power spectra, which became more prominent from day to day. Particularly increases in the power of the alpha 1 and beta range from the thalamus dominated the vitamin-induced changes. From the comparison with earlier results obtained with centrally acting serotonergic drugs, it is concluded that the pharmacodynamic action of the vitamin B mixture predominantly influences this transmitter system. The same group of animals, once challenged with a single dose of 0.2 mg/kg morphine before the repeated vitamin treatment, responded to the same challenge after the treatment in a more sensitive manner. Particularly power changes in the beta range were more pronounced. This higher sensitivity to a morphine challenge persisted for more than 1 week after the end of the vitamin treatment which points to a plastic change in serotonergic neurotransmitter control processes. The results obtained here may be linked to the antinociceptive properties of the vitamin B mixture and practical consequences may include a reduction of morphine dose for analgesia during repeated vitamin B treatment.

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The effects of dizocilipine (MK-801), (+/-)-5-methyl-10,11-dihydro-5Hdibenzo-[a,d]-cyclohepten-5, 10-imine maleate, after IP injection into freely behaving rats, have been compared with the action of ketamine-chloride and phencyclidine (PCP). MK-801 produced strongly dose-dependent effects which could be followed quantitatively over a time of 4 h. During this time spectral analysis of the field potentials continuously recorded from frontal cortex, hippocampus, striatum, and reticular formation revealed a particular pattern of changes which was very stable over time, and after low doses of 0.05 and 0.1 mg/kg, matched that produced by phencyclidine (2 and 4 mg/kg) or ketamine chloride (10 and 20 mg/kg). With higher doses of MK-801 a continuous change from power decreases to power increases was observed. These increases were accompanied by strong behavioral effects in terms of impaired locomotor control. All three non-competitive NMDA antagonists showed a high degree of similarity with respect to the changes of the frequency content of the field potentials over time. The same pattern of electrical changes could be observed after the application of L-dopa (50 mg/kg) or amphetamine (0.2 mg/kg). This can be interpreted in the sense that the same population of cells within the recording area which is under dopaminergic control is at the same time under glutamate control. This leads to the hypothesis that it might be possible to bypass the missing dopaminergic control during parkinsonism by noncompetitive NMDA-receptor blocking drugs.

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Quantitative computer-assisted evaluation of thioctic acid-induced sprouting in Neuro-2a cells reveals a clear dose dependence with respect to several parameters of sprouting. At first predominantly the length of main sprouts per cell (neurites from cell soma to first branching) and the number of branchings per cell are increased. With the higher dosages, the length of branches per cell rises considerably, too. In contrast, the degree of branching (mean length of neurites per branching) seems to be independent of the concentration of thioctic acid. The capacity of thioctic acid to induce sprouting is discussed in terms of the involvement of SH groups and with regard to regeneration phenomena as they may occur in diabetogenic neuropathy.

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Rats were stereotactically implanted with electrodes into four brain areas (frontal cortex, hippocampus, striatum, and reticular formation) to allow registration of intracerebral field potentials. Connection of the electrodes to a microplug fixed to the skull of the animals allowed wireless transmission of the signals using a four-channel telemetric device. The potentials were subjected to a frequency analysis in real time, the power spectra obtained were segmented according to previous experience. Even in the low-dose range, budipine affected the power within these frequency bands: at 2 mg/kg i.p. in the hippocampus, at 4 mg/kg in the frontal cortex also. Power increases, observed mainly in the alpha-1 and beta-2 bands, became decreases in several bands when the dosage was raised to 8 mg/kg. Further power decreases, especially in the alpha-1 and beta-1 range, were observed after 12 mg/kg of budipine. It is notable that the reticular formation was affected only at the high dosage. The muscarinic anticholinergics biperiden and scopolamine provoked a pattern of electric brain activity changes which were to some extent similar to those obtained with the low dose of budipine, in terms of power increases the delta, alpha-1 and beta-2 frequencies in the hippocampus and frontal cortex. In the striatum and reticular formation, however, they were essentially different. Here the anticholinergics differed not only from budipine, but also from each other: biperiden caused decreases in theta and alpha-2 power comparable to the action of 2,3,4,5-tetrahydro-1-phenyl-1H-3-benzazepine-7,8-diol, a dopamine D1-agonist. Scopolamine, in contrast, displayed the familiar pattern of delta and alpha-1 increases in the striatum.(ABSTRACT TRUNCATED AT 250 WORDS)

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Telemetric recordings of field potentials from frontal cortex, hippocampus, striatum and reticular formation of freely moving rats were analysed before and after injection of the enantiomeric hallucinogenic amphetamine derivatives R-DOB [(-)-1-(2,5-dimethoxy-4-bromophenyl)-2-aminopropane], R-DOM [(-)-1-(2,5-dimethoxy-4-methylphenyl)-2-amino-propane] and R-DOI [(-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane] as well as the nonhallucinogenic amphetamine derivatives S-MBDB [(+)-N-methyl-1-(1,3-benzodioxol-5-yl)butanamine] and S-MDMA [(+)-3,4-methylenedioxymethamphetamine] and S-(+)-amphetamine. The frequency analysis of the field potentials revealed a clearcut difference between them. The spectral patterns emerging after injection of the non-hallucinogens were characterized by a general decrease of power, the changes in the alpha2 and delta band being the most prominent, whereas only after the application of the hallucinogenic compounds was a contrasting increase of power observed in the alpha 1 frequency band, especially in the striatum. As increases in alpha 1 power have been correlated in the same pharmacological model to serotonergic control mechanisms, the results are in line with the hypothesis that 5-HT2 receptors, predominantly occurring in the striatum, might be involved in the hallucinogenic action of drugs.

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The necessity of testing psychoactive drugs in awake freely moving animals has led to the development of a telemetry-based system which enables the pharmacologist to follow centrally active molecules in their time- and dose-dependent effects on electric brain activity in terms of changes in spectral power density of extracellularly recorded field potentials (tele-EEG). This report describes the effect of three analgesics with respect to bioelectric changes in frontal cortex, thalamus, striatum and reticular formation. Two opiate drugs, morphine and tramadol, behaved very similarly despite a tenfold difference in dosage, whereas flupirtine, a nonopiate analgesic, changed the frequency content of the EEG signals in an entirely different manner. The frequency pattern produced by the opiates closely resembles that of centrally acting serotonin uptake inhibitors and thus is consistent with the view of a serotonergic prevalence of neurochemical interactions within the recorded brain areas. In contrast, the action of flupirtine obviously can be attributed to a clonidine-like effect on noradrenergic alpha 2-receptors. The results are discussed with respect to already known influences of these drugs on indoleaminergic and catecholaminergic transmission.

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Streptozocin-diabetic rats were treated with a mixture of gangliosides (Cronassial, 21% GM1, 40%GD1a, 16% GD1b, 19% GT1b) in different application schemes: a) daily s.c. injection of 20 mg/kg gangliosides starting from the first day of diabetes and continued for 8 weeks; b) application of the same dose but only every second day over the same period of time; c) daily application of the same dose is started four weeks after induction of diabetes and continued for 4 weeks; d) daily injections of a corresponding volume of physiological saline. Serial in vivo determinations of conduction velocities in the tail nerve of these animals and of non-diabetic control animals gave the following results: 1. The nerve conduction velocities decreased in all diabetic groups which is evidence for the development of a peripheral diabetic neuropathy. 2. The finding from a previous study is reproduced showing that daily application of gangliosides counteracts this deceleration of nerve conduction. 3. Application of the same dose every second day is nearly as effective in inhibiting the development of the diabetic neuropathy as daily injections. 4. When a daily ganglioside treatment is started four weeks after the onset of diabetes, the existing neuropathy is reduced. The possible basis for this ganglioside effect on experimental peripheral neuropathy and its significance for the treatment of human diabetic polyneuropathies is discussed.

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Chronic implantation of four bipolar concentric electrodes into frontal cortex, hippocampus, striatum and reticular formation of the rat allows continuous recording of bioelectric potentials during the action of various drugs. Frequency analysis of the potentials serves to quantify EEG changes over longer periods of time. Segmentation of the spectra into six frequency bands and integration of their power provides parameters by which the different drugs can be differentiated from each other. The action of classic tricyclic antidepressants like amitriptyline and imipramine as well as the effect of doxepine is characterized by a general decrease in power with respect to all frequency bands and all brain areas. Amitriptylinoxide can be distinguished from them by its lack of decrease in beta-2 power and a smaller decrease in alpha-1 power. Amphetamine lacks decreases in alpha-1 frequencies in the striatum and the reticular formation. Both diazepam and haloperidol show increases in beta-2 power; haloperidol increases alpha-1 power, whereas diazepam diminishes it. LSD can be differentiated from amphetamine by its increases in alpha-1 power in the hippocampus and striatum. Thus all antidepressants show very similar changes with respect to the frequency patterns obtained after drug injection, whereas drugs used for other indications can be well distinguished from each other and also from antidepressants.

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