Wireless and batteryless biomedical microsystem for neural recording and epilepsy suppression based on brain focal cooling.

This work presents a biomedical microsystem with a wireless radiofrequency (RF)-powered electronics and versatile sensors/actuators for use in nanomedicinal diagnosis and therapy. The cooling of brain tissue has the potential to reduce the frequency and severity of epilepsy. Miniaturised spiral coils as a wireless power module with low-dropout linear regulator circuit convert RF signals into a DC voltage, can be implanted without a battery in monitoring free behaviour. A thermoelectric (TE) cooler is an actuator that is employed to cool down brain tissue to suppress epilepsy. Electroencephalogram (EEG) electrodes and TE coolers are integrated to form module that is placed inside the head of a rat and fastened with a bio-compatible material. EEG signals are used to identify waveforms associated with epilepsy and are measured using readout circuits. The wireless part of the presented design achieves a low quiescent current and line/load regulation and high antenna/current efficiency with thermal protection to avoid damage to the implanted tissue. Epilepsy is suppressed by reducing the temperature to reduce the duration of this epileptic episode. Related characterisations demonstrate that the proposed design can be adopted in an effective nanomedicine microsystem.

Depression- and anxiety-like behaviors of a rat model with absence epileptic discharges.

Depression and/or anxiety are major comorbidities of epilepsy. However, the contribution of absence epileptic discharges in psychiatric syndromes is inconclusive. This study aimed to clarify the influence of absence seizure in anxiety- and depression-like behaviors using normal Wistar rats and Long-Evans rats with spontaneous spike-wave discharges (SWDs). Anxiety-like behaviors were evaluated by the open field (OF) and elevated plus maze (EPM) tests, and depression-like behaviors by the forced swimming (FS) and sucrose consumption (SC) tests. Long-Evans rats displayed significantly higher frequency and longer duration in the open arms of the EPM and in the center zone of the OF than did Wistar rats. Normalized behavioral indexes by movement also were significantly higher in Long-Evans rats. An excess of SWD numbers was associated with lower indexes and worse movement in the two behavioral tests. Ethosuximide eliminated the seizure frequency-dependent relationship and also significantly increased all indexes of the EPM test. Additionally, Long-Evans rats revealed significantly longer immobility in the FS test and lower consumption of sucrose solution in the SC test than did Wistar rats. Meanwhile, no relationship was found between immobility of the FS test and SWD number. Ethosuximide ameliorated depression-like behavior of Long-Evans rats that was equal to that of Wistar rats. Thus, Long-Evans rats showed seizure frequency-related exacerbation in anxiety-like behavior; and they displayed a depressive propensity. Our data suggest that generalized SWDs may have distinct influences in anxious and depressive behaviors.

Effects of age and gender on intravenous midazolam premedication: a randomized double-blind study.

BACKGROUND: Given the potentially important effects that age and gender may have on midazolam premedication, this study aimed at determining if these factors alter anxiety, sedation, and cardiorespiratory outcomes when administering two different doses of i.v. midazolam. METHODS: After randomization, patients were premedicated 1 h before surgery with either i.v. midazolam 0.02 or 0.06 mg kg(-1) depending on their age and gender group. Levels of anxiety and sedation, heart rate, respiratory rate (RR), mean blood pressure (MBP), and oxygen saturation (Sp(O2)) were measured before and 15 min after midazolam administration. RESULTS: A higher level of preoperative anxiety was more often observed in women than in men, and in young than in older patients. The female or younger patients showed significant anxiolytic benefits from midazolam. A deeper sedation level was found in men compared with women. Forty-two of 45 patients (93.3%) with excessive sedation received midazolam 0.06 mg kg(-1). The elderly patients receiving midazolam 0.06 mg kg(-1) showed significant reductions in MBP, RR, and Sp(O2). Of the patients with an Sp(O2)<90%, 72.7% had received midazolam 0.06 mg kg(-1). CONCLUSIONS: Age and gender differences in neuropsychological and physiological responses after midazolam premedication were evident. Midazolam is effective for producing sedation and anxiolysis at a dose of 0.02 mg kg(-1), with minimal effects on cardiorespiration and oxygen saturation to patients. Dosage adjustments based on these covariates are, therefore, necessary.

Dynamic changes of touch- and laser heat-evoked field potentials of primary somatosensory cortex in awake and pentobarbital-anesthetized rats.

In this investigation, changes of mechanical- (MEP) and laser-evoked potentials (LEP) in rat primary somatosensory cortex during the course of pentobarbital (PB) anesthesia were examined. Temporal analysis of changes in the magnitude and latency of MEP and LEP, EEG activity, gross motor behaviors, and the tail flick response following laser stimulation before, during, and after PB administration (50 mg/kg, i.p.) was performed and correlated in chronically implanted rats. During the wakeful condition, there were two major cortical components each following mechanical stimulation (MEP1 and MEP2, n=17) and laser stimulation (LEP1 and LEP2, n=10), respectively. After PB administration, the positive peak in MEP1 was enhanced, and all other components disappeared. These components returned with different time courses. Two hours after PB administration, when the rat had spontaneous movements and flexor reflexes, LEP2 showed reversed polarity. MEP2 returned gradually 3 h after PB administration when the rat regained its ability to execute coordinated movements. After 4 h, LEP1 began to reappear and LEP2 returned to its negative polarity. We found that PB facilitated Abeta fiber-related cortical evoked potential (MEP1), while differentially inhibited Adelta and C fiber-related components (MEP2, LEP1 and LEP2). Characterization of these anesthesia-induced changes in cortical output may be useful in studying the neural basis of tactile and pain sensations.

A multichannel system for recording and analysis of cortical field potentials in freely moving rats.

A system has been developed to record and analyze the cortical electrical activity from 16 different sites in freely moving rats. The hardware includes a 16-channel amplifier system whose high input impedance, low noise, small size, light weight and shielded multistrand connecting cable allow high quality multichannel recording of field potentials. The software developed for this system consists of data acquisition, data analysis and topographic mapping of cortical-evoked potentials as well as electroencephalograms. Cortical field potentials evoked by CO2-laser stimulation were compared between wakeful and pentobarbital-treated conditions. To investigate the background interference produced by sleep spindle, three kinds of reference-free methods (the Wilson, local average and weighted average methods) were utilized to compare the coherence between field potentials obtained from two cerebral hemispheres using monopolar vs. reference-free recordings.

Quantitative relationship between fluctuations of blood pressure and sympathetic nerve activity in pentobarbital anesthetized rats.

Transfer function analysis was used to examine the coupling between the sympathetic nerve activity (SNA) and the blood pressure (BP) fluctuations. In pentobarbital anesthetized Wistar rats, linear regression of the relationship between frequency (X-axis) and the logarithmic transfer magnitude, i.e. log (BP power density/renal SNA power density) (Y-axis), in the low frequency range (0.016-0.85 Hz) revealed an excellent fit (r = 0.97-0.98). Comparing the regression lines, rats under large dose of pentobarbital anesthesia (40 mg/kg, i.v. single dose) had significantly smaller intercept and slope values compared to rats under small dose of pentobarbital anesthesia (12.5 mg/kg). When intercept and slope values were compared between intact and acutely sinoaortic denervated rats, no significant difference were found. The results suggest that sympathetic modulation of vasomotor tone may be a major factor in generating BP fluctuations between 0.016 and 0.85 Hz in rats. Furthermore, these results support the possibility of using low frequency spectral power of BP to quantitatively estimate the fluctuations of SNA for rats under pentobarbital anesthesia if anesthetic depth is controlled.

Comparison of touch- and laser heat-evoked cortical field potentials in conscious rats.

Field potentials and multiunit activities from chronically implanted cortical electrodes were used to study tactile and nociceptive information processing from the tail of the rat. Fourteen stainless steel screws implanted in the skull were used as electrodes to record field potentials in different cortical areas. Electrical, mechanical, and laser pulses were applied to the tail to induce evoked cortical field potentials. Evoked responses were compared before and after sodium pentobarbital anesthesia (50 mg/kg, i.p.). In both electrical- and mechanical-evoked potential (EEP and MEP) studies, two major peaks were found in the conscious animal. The polarity of the late component was modified after pentobarbital anesthesia. In the laser-evoked potential (LEP) study, two distinct negative peaks were found. Both peaks were very sensitive to anesthesia. Following quantitative analysis, our data suggest that the first positive peak of EEP and MEP corresponded to the activation of the Abeta fiber, the second negative peak of MEP and the first peak of LEP corresponded to Adelta fiber activation, while the second peak of LEP corresponded to C fiber activation. The absolute magnitudes of all cortical components were positively related to the intensity of the stimulation. From spatial mapping analysis, a localized concentric source of field potential was observed in the primary somatosensory cortex (SI) only after activation of the Abeta fiber. Larger responsive cortical areas were found in response to Adelta and C fiber activation. In an intracortical recording experiment, both tactile and nociceptive stimulation evoked heightened unit activity changes at latencies corresponding to respective field potentials. We conclude that different cortical areas are involved in the processing of A and C fiber afferent inputs, and barbiturate anesthesia modifies their processing.

Algorithmic complexity as an index of cortical function in awake and pentobarbital-anesthetized rats.

This study introduces algorithmic complexity to measure characteristics of brain functions. The EEG of the rat was recorded with implanted electrodes. The normalized complexity value was relatively independent of data length, and it showed a simpler and easier calculation characteristic than other non-linear indexes. The complexity index revealed significant differences among awake, asleep, and anesthetized states. It may be useful in tracking short-term and long-term changes in brain functions, such as anesthetized depth, drug effects, or sleep-wakefulness.

A new automated method for detection and recording of animal moving path.

A new electronic system has been developed to trace the location and movement of small animals in an open-field environment. The system, incorporated with a conventional touch panel position sensor (TPPS) and an IBM AT compatible computer, automtically digitizes and records the moving path of the animal. The detection principle of the TPPS is based on the pressure effect. Whenever an animal is put on the TPPS, the location of the animal can be detected. The personal computer system is in corporate to record the locomotion data of the animal. The system described here is shown to be a reliable and accurate tool to record the moving path of an animal. This measurement did not require extra light or other stimuli, and the apparatus is low priced, and simple to build up and user friendly.