A Dual-Mode Multifunctional Pulsed Radio-Frequency Stimulator for Trigeminal Neuralgia Relief and its Animal Model.

This work proposed a programmable pulsed radio-frequency (PRF) stimulator for trigeminal neuralgia (TN) relief on demand. The implantable stimulator is a miniaturized micro-system which integrates a wireless interface circuit, a sensor interface circuit, a PRF pattern generation circuit and a logic controller. The multifunctional stimulator capable of delivering current/voltage stimulation provides the choice of the biphasic sinusoidal, square and patterned waveform for PRF treatment researches. The external handheld device can wirelessly transmit the parameters of frequency, amplitude, pulse duration and repetition rate of the pulse train to the implanted stimulator. While stimulating, the temperature sensor can monitor the operating temperature. The feedback signal is transmitted in medical implanted communication system (MICS). The micro-system is fabricated in a 0.35 µm CMOS process with a chip size of 3.1 × 2.7 mm2. The fabricated chip was mounted on a 2.6 × 2.1 cm2 test board for studying the in vivo efficacy of pain relief by PRF. Animal studies of PRF stimulation and commonly-used medication for trigeminal neuralgia are also demonstrated and the presented results prove that PRF stimulation has greater effectiveness on trigeminal neuralgia relief comparing to the medication. The effectiveness period lasts at least 14 days. The results of neural recording show that the PRF stimulation of trigeminal ganglion (TG) attenuated neuron activities without being severely damaged. Pathology also revealed no lesion found on the stimulated area.

The application of data mining techniques to oral cancer prognosis.

This study adopted an integrated procedure that combines the clustering and classification features of data mining technology to determine the differences between the symptoms shown in past cases where patients died from or survived oral cancer. Two data mining tools, namely decision tree and artificial neural network, were used to analyze the historical cases of oral cancer, and their performance was compared with that of logistic regression, the popular statistical analysis tool. Both decision tree and artificial neural network models showed superiority to the traditional statistical model. However, as to clinician, the trees created by the decision tree models are relatively easier to interpret compared to that of the artificial neural network models. Cluster analysis also discovers that those stage 4 patients whose also possess the following four characteristics are having an extremely low survival rate: pN is N2b, level of RLNM is level I-III, AJCC-T is T4, and cells mutate situation (G) is moderate.

Effects of spike sorting error on the Granger causality index.

Accurately sorting individual neurons is a technical challenge and plays an important role in identifying information flow among neurons. Spike sorting errors are almost unavoidable and can roughly be divided into two types: false positives (FPs) and false negatives (FNs). This study investigates how FPs and FNs affect results of the Granger causality (GC) analysis, a powerful method for detecting causal interactions between time series signals. We derived an explicit formula based on a first order vector autoregressive model to analytically study the effects of FPs and FNs. The proposed formula was able to reveal the intrinsic properties of the GC, and was verified by simulation studies. The effects of FPs and FNs were further evaluated using real experimental data from the ventroposterior medial nucleus of the thalamus. Some practical suggestions for spike sorting are also provided in this paper.

Long-term changes in trigeminal ganglionic and thalamic neuronal activities following inferior alveolar nerve transection in behaving rats.

The transection of the inferior alveolar nerve (IANx) produces allodynia in the whisker pad (V2 division) of rats. Ectopic discharges from injured trigeminal ganglion (TG) neurons and thalamocortical reorganization are possible contributors to the sensitization of uninjured V2 primary and CNS neurons. To test which factor is more important, TG and ventroposterior medial nucleus (VPM) neurons were longitudinally followed before, during, and after IANx for up to 80 d. Spontaneous discharges and mechanical stimulation-evoked responses were recorded in conscious and in anesthetized states. Results show (1) a sequential increase in spontaneous activities, first in the injured TG neurons of the IAN (2-30 d), followed by uninjured V2 ganglion neurons (6-30 d), and then VPM V2 neurons (7-30 d) after IANx; (2) ectopic discharges included burst and regular firing patterns in the IAN and V2 branches of the TG neurons; and (3) the receptive field expanded, the modality shifted, and long-lasting after-discharges occurred only in VPM V2 neurons. All of these changes appeared in the late or maintenance phase (7-30 d) and disappeared during the recovery phase (40-60 d). These observations suggest that ectopic barrages in the injured IAN contribute more to the development of sensitization, whereas the modality shift and evoked after-discharges in the VPM thalamic neurons contribute more to the maintenance phase of allodynia by redirecting tactile information to the cortex as nociceptive.

A bundled microwire array for long-term chronic single-unit recording in deep brain regions of behaving rats.

Chronic single-unit recording in subcortical brain regions is increasingly important in neurophysiological studies. However, methods for long-term, stable recording of multiple single-units in deep brain regions and in dura-surrounded ganglion have not yet been established. In the present study, we propose a bundled microwire array design which is capable of long-term recording of the trigeminal ganglion and deep-brain units. This electrode set is easy to construct from common materials and tools found in an electrophysiological laboratory. The salient features of our design include: (1) short and separated tungsten microwires for stable chronic recording; (2) the use of a 30-guage stainless steel guide tube for facilitating penetration and aiming for deep targets as well as electrical grounding; (3) the inclusion of a reference of the same microwire material inside the bundle to enhance common mode rejection of far field noises; and (4) an adjustable connector. In our case, we used a 90° backward bending connector so that implanted rats could perform the same hole-seeking behavior and their faces and the whiskers could be stimulated in the behaving state. It was demonstrated that this multi-channel electrode caused minimal tissue damage at the recording site and we were able to obtain good, stable single-unit recordings from the trigeminal ganglion and ventroposterior medial thalamus areas of freely moving rats for up to 80 days. This methodology is useful for the studies that require long term and high quality unit recording in the deep brain or in the trigeminal system.

The correlation of mean sympathetic activity with low-frequency blood pressure and sympathetic variability.

The low-frequency (0.2-0.8 Hz) component of blood pressure (BP) variability (LF(BP)) is used as an index of the low-frequency variability of sympathetic nerve activity (SNA) (LF(SNA)) in rats. It is unclear whether the LF(BP) can be used as an index of the mean SNA (mSNA). We investigated the correlation of the LF(BP) with different levels of the mSNA in this study to evaluate if it is a feasible tool for detecting differences in mSNA under physiological conditions. Correlation of the LF(SNA) with different mSNA levels was also investigated. The BP and renal SNA of rats were recorded in a nonanesthetized state. Values of the mSNA obtained from 531 recording epochs in six rats were graded into 30 levels with a bin resolution of 0.05 normalized units. A linear regression analysis showed that the correlation between the mSNA and LF(SNA) was higher than that between the mSNA and LF(BP). The mSNA was well correlated with the LF(SNA) over a wider mSNA range, while it was correlated with the LF(BP) only in a restricted range. These results demonstrated a restricted condition under which measuring the LF(BP) can be a definitive index of the mSNA, and further suggest the possibility of using the weighted LF(BP) as an index of the mSNA via intermediation by the LF(SNA) for a wider mSNA range.

Correlation of discharges of rostral ventrolateral medullary neurons with the low-frequency sympathetic rhythm in rats.

The rostral ventrolateral medulla (RVLM) is critically important in the generation of sympathetic activity. The purpose of this study was to investigate whether discharges of RVLM neurons contribute to low-frequency (LF) sympathetic rhythms. Blood pressure (BP), renal sympathetic nerve activity (SNA), and neuronal activity in the RVLM were simultaneously recorded in seven anesthetized, paralyzed, and artificially ventilated rats. Fifty-one RVLM neurons were recorded and classified into three differential functional groups according to their activities related to baroreceptor input. Those in the category of spike firing inhibited by a BP increase (BP(I)) and which excited sympathetic discharges was the most abundant (24%). Coherence analysis was used to examine the relationship of the firing frequency of RVLM neurons with the LF (0.2-0.8Hz) rhythm of SNA. Forty-one percent of RVLM neurons showed a significant correlation to LF rhythms, and BP(I) neurons with sympathoexcitatory properties were the major contributors. In another 4 baroreceptor-denervated rats, 36 RVLM neurons were recorded. In these rats, RVLM neuronal activities no longer changed with BP fluctuations. Nevertheless, more than 40% of RVLM neurons were sympathoexcitatory, and 36% of RVLM neurons were still correlated with the LF SNA rhythm. Our results suggest that there are RVLM neurons involved in generating the LF rhythm in SNA and that the baroreflex can induce the participation of more neurons in LF rhythm generation.

Neuroprotective effects of resveratrol on cerebral ischemia-induced neuron loss mediated by free radical scavenging and cerebral blood flow elevation.

Resveratrol is a natural phytoestrogen and possesses many biological functions such as anti-inflammatory activity and protection against atherosclerosis and myocardial infraction. The present study was carried out to elucidate the neuroprotective effect and possible mechanism of resveratrol on cerebral ischemia-induced hippocampus neuron loss. Sixty adult male rats underwent general anesthesia (urethane, 1.4 g/kg, i.p.) and were divided into three groups: sham operation, ischemia treatment, and ischemia combined with resveratrol administration (20 mg/kg, i.v.). The carotid artery was bilaterally ligated to induce cerebral ischemia. Microdialysis and high-performance liquid chromatography were used to analyze dihydroxybenzoic acid (DHBA) that reflected the hippocampal hydroxyl radical level. Hippocampal nitric oxide was assayed among different groups. During cerebral ischemia, the hydroxyl radical levels were elevated in rats and animals displayed severe neuronal loss. A single dose of resveratrol significantly increased the nitric oxide level and decreased the hydroxyl radical level. The reduction of cerebral blood flow and neuronal loss were also attenuated by resveratrol treatment. The results demonstrated that a single infusion of resveratrol could elicit neuroprotective effects on cerebral ischemia-induced neuron damage through free radical scavenging and cerebral blood elevation due to NO release.

Frequency response characteristic of sympathetic mediated low-frequency blood pressure fluctuations in conscious rats.

A quantitative relationship between power densities of blood pressure (PBP) and sympathetic nerve activity (PSNA) in a low-frequency range (LF, 0.016-0.85 Hz), expressed as PSNA=PBPxax10bx(frequency) was proposed in pentobarbital-anesthetized rats. For evaluating the general applicability of this equation, the quantitative relationship of power density ratio Hf=PBP/PSNA across frequency was tested in a conscious state. Wistar rats were chronically instrumented with a femoral artery catheter and recording electrode around the renal sympathetic nerve. The blood pressure and renal sympathetic nerve activity were monitored both under pentobarbital anesthesia and in a conscious state. Linear regression analysis of the relationship between the frequency and logarithmic magnitude of the power density ratio in the LF range revealed excellent fit in both conditions (r=-0.96+/-0.01 and -0.93+/-0.01 for anesthetized and conscious rats, respectively). Comparing the regression lines, rats under pentobarbital anesthesia had significantly larger values for the y-intercept and slope compared to rats in a conscious state (y-intercepts: 0.80+/-0.09>0.53+/-0.08; slopes: -2.86+/-0.26>-1.62+/-0.21). Our results demonstrate that it is also feasible to use the weighted PBP in LF as a quantitative index of sympathetic variability in conscious rats, but the evaluation of possible complications controlling the regression parameters is called for.