BOLD responses to trigeminal nerve stimulation

The current study investigates a new model of barrel cortex activation using stimulation of the infraorbital branch of the trigeminal nerve. A robust and reproducible activation of the rat barrel cortex was obtained following trigeminal nerve stimulation. Blood oxygen level-dependent (BOLD) effects were obtained in the primary somatosensory barrel cortex (S1BF), the secondary somatosensory cortex (S2) and the motor cortex. These cortical areas were reached from afferent pathways from the trigeminal ganglion, the trigeminal nuclei and thalamic nuclei from which neurons project their axons upon whisker stimulation. The maximum BOLD responses were obtained for a stimulus frequency of 1 Hz, a stimulus pulse width of 100 μs and for current intensities between 1.5 and 3 mA. The BOLD response was nonlinear as a function of frequency and current intensity. Additionally, modeling BOLD responses in the rat barrel cortex from separate cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO₂) measurements showed good agreement with the shape and amplitude of measured BOLD responses as a function of stimulus frequency and will potentially allow to identify the sources of BOLD nonlinearities. Activation of the rat barrel cortex using trigeminal nerve stimulation will contribute to the interpretation of the BOLD signals from functional magnetic resonance imaging studies.     

Event-related fMRI of auditory and visual oddball tasks

Functional magnetic resonance imaging (fMRI) was used to investigate the spatial distribution of cortical activation in frontal and parietal lobes during auditory and visual oddball tasks in 10 healthy subjects. The purpose of the study was to compare activation within auditory and visual modalities and identify common patterns of activation across these modalities. Each subject was scanned eight times, four times each for the auditory and visual conditions. The tasks consisted of a series of trials presented every 1500 ms of which 4-6% were target trials. Subjects kept a silent count of the number of targets detected during each scan. The data were analyzed by correlating the fMRI signal response of each pixel to a reference hemodynamic response function that modeled expected responses to each target stimulus. The auditory and visual targets produced target-related activation in frontal and parietal cortices with high spatial overlap particularly in the middle frontal gyrus and in the anterior cingulate. Similar convergence zones were detected in parietal cortex. Temporal differences were detected in the onset of the activation in frontal and parietal areas with an earlier onset in parietal areas than in the middle frontal areas. Based on consistent findings with previous event-related oddball tasks, the high degree of spatial overlap in frontal and parietal areas appears to be due to modality independent or amodal processes related to procedural aspects of the tasks that may involve memory updating and non-specific response organization.     

Comparing BOLD fMRI signal changes in the awake and anesthetized rat during electrical forepaw stimulation

The difference between awake curarized and alpha-chloralose anesthetized animals was studied with respect to the BOLD signal response in an fMRI experiment. By studying the activation of the cortex upon electrical forepaw stimulation in the same rat, but following consecutively applied curarization and alpha-chloralose anesthesia protocols, it was possible to compare quantitatively the effect of both immobilization protocols on the fMRI data. The largest BOLD signal change as a result of forepaw stimulation was found in the awake condition, however the activated areas are less specific than those in the anesthetized state leaving it more difficult to interpret.     

Electric stimulation fMRI of the perforant pathway to the rat hippocampus

The hippocampal formation is a brain system that is implicated in learning and memory. The major input to the hippocampus arrives from the entorhinal cortex (EC) to the dentate gyrus (DG) through the perforant path. In the present work, we have investigated the functional properties of this connection by concomitantly applying electrophysiological techniques, deep-brain electric microstimulation and functional magnetic resonance imaging in anesthetized rats. We systematically delivered different current intensities at diverse stimulation frequencies to the perforant path while recording electrophysiological and blood-oxygenation-level-dependent (BOLD) signals. We observed a linear relationship between the current intensity used to stimulate the hippocampal formation and the amplitude and extension of the induced BOLD response. In addition, we found a frequency-dependent spatial pattern of activation. With stimulation protocols and train frequencies used for kindling, the activity strongly spreads ipsilaterally through the hippocampus, DG, subiculum and EC.     

Differential electrical excitation of the auditory nerve

The multichannel cochlear prosthesis requires an electrode stimulus configuration which produces a stimulus field spatially localized to each electrode. In this paper, a three-dimensional discrete resistance model of the cochlea was developed which exhibits electrical response properties similar to those observed during electrical stimulation of the cochlea. The model results suggest that the spatial attenuation of current within the cochlea varies greatly in magnitude, depending on the stimulus configuration. In addition, the model suggests that the spatial attenuation of current in both the auditory nerve fiber endings in the organ of Corti and in the myelinated fibers within the cochlear ground paths is different from the voltage attenuation in the scalar fluids. Therefore the efficacy with which a particular stimulus configuration differentially excites local terminal auditory nerve fiber populations cannot be deduced from scalar voltage measurements which have previously been recorded in the literature. Consequently physiological experiments were performed in the cat to measure the current distributions in the terminal nerve fiber region for monopolar and bipolar stimulation of the scala tympani, and also for stimulation between the scala tympani and the scala vestibuli. The mean length constants measured in the basal turn for these stimuli were found to be 12, 3, and 7.5 mm, respectively.     

Differential activation of nerve fibers with magnetic stimulation in humans

Background  

Earlier observations in our lab had indicated that large, time-varying magnetic fields could elicit action potentials that travel in only one direction in at least some of the myelinated axons in peripheral nerves. The objective of this study was to collect quantitative evidence for magnetically induced unidirectional action potentials in peripheral nerves of human subjects. A magnetic coil was maneuvered to a location on the upper arm where physical effects consistent with the creation of unidirectional action potentials were observed.     

Functional MRI involving painful stimulation of the ankle and the effect of physiotherapy joint mobilization

We examined whether cerebral activation due to secondary hyperalgesia resulting from intrajoint capsaicin injection could be detected using functional magnetic resonance imaging (fMRI) in alpha-chloralose anesthetized rats. We also examined whether we could detect analgesic changes in the central nervous system response to pain as a result of physiotherapy joint manipulation. Robust activation of areas of the brain known to be associated with the processing of pain, namely the anterior cingulate (bilateral), frontal cortex (bilateral) and sensory motor cortex (contralateral), was found in all animals following injection of 25 microl of capsaicin (128 microg/ml in 7.5% DMSO) into the plantar surface of the rat hindpaw (n = 7) and 75 microL into the ankle joint (n = 13). Significantly greater activation was observed when capsaicin was injected into the plantar surface of the hindpaw compared to the ankle joint. Mechanical allodynia and secondary hyperalgesia following capsaicin injection into the ankle joint also resulted in activation of the same brain regions. Trends toward decreased areas of activation in brain regions associated with pain in animals following physiotherapy joint mobilization were observed.     

Diffusion tensor imaging reveals microstructural alteration of the trigeminal nerve root in classical trigeminal neuralgia without neurovascular compression and correlation with outcome after internal neurolysis

ObjectivesDiffusion tensor imaging (DTI) has been used to detect microstructural alteration and effect of surgical treatment of the trigeminal nerve root (TR) in patients with classical trigeminal neuralgia (CTN) underwent microvascular decompression (MVD). Patients with CTN without neurovascular compression (woNVC) is a special population of TN, however, the pathogenesy of CTN woNVC and the mechanism of internal neurolysis (IN) remain unknown.Materials and methods21 patients with CTN woNVC who underwent IN and 20 healthy controls were included in this study. The differences in the means, kurtosis and skewness of fractional anisotropy (FA) and apparent diffusion coefficient (ADC) between the affected and unaffected nerves in patients and both nerves in controls were investigated by independent t-test and paired t-test respectively. Longitudinal changes of FA and ADC were correlated with outcome of IN via Spearman correlation coefficient.ResultsSignificant differences were found in preoperative mean and kurtosis values for both FA and ADC of the affected side TR, compared to the unaffected side and control group respectively. However, these differences remarkably reduced postoperatively. Further, the Spearman correlation coefficient showed a strong negative correlation between decrease of ADC in the affected side and the surgical outcome in BNI total score.ConclusionThe changes of diffusive property of TR, especially the FA and ADC, provide alternative radiological evidence for evaluating the mechanism of CTN woNVC. The modification of DTI metrics could be an effective factor for providing potential noninvasive biomarkers for determining the prognosis of patients with CTN woNVC underwent IN.     

Comparison of BOLD,diffusion-weighted fMRI and ADC-fMRI for stimulation of the primary visual system with a block paradigm

The blood oxygen level-dependent (BOLD) effect is extensively used for functional MRI (fMRI) but presents some limitations. Diffusion-weighted fMRI (DfMRI) has been proposed as a method more tightly linked to neuronal activity. This work proposes a protocol of DfMRI acquired for several b-values and diffusion directions that is compared to gradient-echo BOLD (GE-BOLD) and to repeated spin-echo BOLD (SE-BOLD, acquisitions performed with b = 0 s/mm²), which was also used to ensure the reproducibility of the response.A block stimulation paradigm of the primary visual system (V1) was performed in 12 healthy subjects with checkerboard alternations (2 Hz frequency). DfMRI was performed at 3 T with 5 b-values (b = 1500, 1000, 500, 250, 0 s/mm²) with TR/TE = 1004/93 ms, Δ/δ = 45.4 ms/30 ms, and 6 spatial directions for diffusion measures. GE-BOLD was performed with a similar block stimulation design timing. Apparent Diffusion Coefficient (ADC)-fMRI was computed with all b-values used. An identical Z-score level was used for all fMRI modalities for the comparison of volumes of activation. ADC-fMRI and SE-BOLD fMRI activation locations were compared in a voxel-based analysis to a cytoarchitectural probability map of V1.SE-BOLD activation volumes represented only 55% of the GE-BOLD activation volumes (P < 0.0001). DfMRI activation volumes averaged for all b-values acquired represented only 12% of GE-BOLD (P < 0.0001) and only 22% of SE-BOLD activation volumes (P < 0.005). Compared to SE-BOLD-fMRI, ADC-fMRI activations showed fewer pixels outside of V1 and a higher average probability of belonging to V1.DfMRI and ADC-fMRI acquisition at 3 T could be easily post-processed with common neuro-imaging software. DfMRI and ADC-fMRI activation volumes were significantly smaller than those obtained with SE-BOLD. ADC-fMRI activations were more precisely localized in V1 than those of SE-BOLD-fMRI. This validated the increased capability of ADC-fMRI compared to BOLD to enhance the precision of localizing an fMRI activation in the cyto-architectural zone V1, thereby justifying the use of ADC-fMRI for neuro-scientific studies.     

Effects of vagal nerve stimulation on laryngeal function

Functional electrical stimulation is a developing methodology that shows significant potential in the management of peripheral neuromuscular deficits. Potential applications in the head and neck area, including control of bilateral vocal fold paralysis and spasmodic dysphonia, have recently been explored. Despite promising early results, very little is known about the mechanisms of action or the long-term effects of electrical stimulation on human laryngeal function. Recent development of implantable vagal nerve stimulators as a method to control intractable seizures in individuals who have not responded to medication provides a unique opportunity to study its effect on the normal human larynx. Laryngeal and vocal function testing was studied on five individuals who had undergone vagal nerve stimulator implants for intractable seizures. Consistent abduction/adduction of the left vocal fold was achieved at 20 and 40 Hz, respectively. Higher levels of electrical stimulation produced hemispasm of the larynx. Results were consistent with studies in the literature of recurrent laryngeal nerve stimulation in animal and human models. The vagus nerve provides relatively easy access for implantation of electrodes to provide electrical stimulation to the muscles of the larynx. Vagal nerve stimulation may prove efficacious in the treatment of movement disorders of the larynx; further study is needed.     

Exit jet particle velocity in the in vivo canine laryngeal model with variable nerve stimulation

This study extends previous work on exit jet particle velocity in the in vivo canine model of phonation by measuring air particle velocity at multiple locations in the midline of the glottis and across multiple levels of recurrent laryngeal nerve (RLN) and superior laryngeal nerve (SLN) stimulation. In a second experiment, exit jet particle velocity was measured at midline and offmidline positions with constant levels of RLN and SLN stimulation. In this study, peak particle velocity was higher at the anterior commissure than at the posterior commissure in the midline of the glottis, and peak particle velocity was higher at the midline than at offmidline positions. In addition, increasing levels of RLN stimulation resulted in increasing peak particle velocity; however, increasing levels of SLN stimulation failed to produce a uniform effect on peak particle velocity.     

Use of focused ultrasound for stimulation of nerve structures

Pulsed focused ultrasound can stimulate the receptor and conductive nerve structures of humans and animals as well as the neurons of the central nervous system of invertebrates. The possibility of a wide practical use of this method in medicine and physiology is considered. For example, the stimulating ability of focused ultrasound is applied to the diagnosis of neurological diseases, to the study of skin and tissue sensitivity in man, to the diagnosis of hearing disorders, and to the introduction of auditory information to the deaf with certain forms of hearing pathology. The factors that affect focused ultrasound as a stimulus for the irritation of nerve structures are discussed.     

Vibration responses of the organ of Corti and the tectorial membrane to electrical stimulation

Coupling of somatic electromechanical force from the outer hair cells (OHCs) into the organ of Corti is investigated by measuring transverse vibration patterns of the organ of Cori and tectorial membrane (TM) in response to intracochlear electrical stimulation. Measurement places at the organ of Corti extend from the inner sulcus cells to Hensen's cells and at the lower (and upper) surface of the TM from the inner sulcus to the OHC region. These locations are in the neighborhood of where electromechanical force is coupled into (1) the mechanoelectrical transducers of the stereocilia and (2) fluids of the organ of Corti. Experiments are conducted in the first, second, and third cochlear turns of an in vitro preparation of the adult guinea pig cochlea. Vibration measurements are made at functionally relevant stimulus frequencies (0.48-68 kHz) and response amplitudes (<15 nm). The experiments provide phase relations between the different structures, which, dependent on frequency range and longitudinal cochlear position, include in-phase transverse motions of the TM, counterphasic transverse motions between the inner hair cell and OHCs, as well as traveling-wave motion of Hensen's cells in the radial direction. Mechanics of sound processing in the cochlea are discussed based on these phase relationships.     

Theoretical evaluation of peripheral nerve stimulation during MRI with an implanted spinal fusion stimulator

This study examines the requirements for nerve excitation near a spinal fusion implant during magnetic resonance imaging. The implant is the Spinal Fusion SpF^® device manufactured by Electro Biology Inc. The electric field induced within the biological medium was calculated using a three-dimensional finite difference model (described in a separate paper by Beuchler et al. from the University of Utah). Magnetic thresholds were obtained for excitation of myelinated nerve fibers that are near the implant. Minimum (rheobase) thresholds were determined for long duration dB/dt pulses, as well as strength-duration time constants (from which thresholds at other durations could be determined) for various geometries between the implant and a myelinated nerve fiber. The lowest thresholds occur when a large (20-μm diameter) fiber is situated near the bare tip of a wire from the implant, and a long duration (2 ms) stimulus is provided for which dB/dt is constant and monophasic. Magnetic thresholds for shorter durations of dB/dt are higher in accordance with a strength-duration law. In a magnetic field having a time derivative of 10 T/s that is uniform over the torso, nerve excitation is possible under worst-case conditions only for nerve fibers that are within 0.14 mm of the bare wire tip of the implant. With 20 T/s, excitation is possible only within 1 mm of the wire tip.     

LMI-based robust adaptive synchronization of FitzHugh-Nagumo neurons with unknown parameters under uncertain external electrical stimulation

This Letter addresses a nonlinear robust adaptive control that utilizes linear matrix inequalities for asymptotic synchronization of two coupled chaotic FitzHugh-Nagumo neurons under unknown parameters and uncertain stimulation current amplitudes and phase shifts. Synchronization of chaotic neurons using the proposed control method through numerical simulation is demonstrated.     

Event-related functional MR imaging of visual cortex stimulation at high temporal resolution using a standard 1.5 T imager

The authors report the technical feasibility of measuring event-related changes in blood oxygenation for studying brain function in humans at high temporal resolution. Measurements were performed on a conventional wholebody 1.5 T clinical scanner with a nonactive-shielded standard gradient system of 1 ms rise time for a maximum gradient strength of 10 mT/m. The radiofrequency (RF) transmitting and receiving MR unit consists of a commercially available circular polarized head coil. Magnet shimming with all first-order coils was performed to the volunteer's head resulting in a magnetic field homogeneity of about 0.1–0.2 ppm. The measuring sequence used was a modified 3D, first-order flow rephased, FLASH sequence with reduced bandwidth = 40 Hz/pixel, TR = 80 ms, TE = 56 ms, flip angle = 40–50°, matrix = 64 × 128, field-of-view = 200–250 mm², slice thickness = 4 mm, NEX = 1, 128 partitions, and a total single scan time of about 10 min. In this sequence the 3D gradient table was removed and the 3D partition-loop acts as a time-loop for sequential measurement of 128 or 32 consecutive images at the same slice position. This means that event-related functional MRI could be performed with an interscan delay of 80 ms for a series of 128 sequential images or with an interscan delay of 320 ms for a simultaneous measurement of four slices with a series of 32 sequential images for each slice. We used a TTL signal given by the gradient board at the beginning of every line-loop in the measuring sequence and a self-made “TTL-Divider-Box” for the event triggering. This box was used to count and scale down the TTL signals by a factor of 128 and to trigger after every 128th TTL signal a single white flash-light, which was seen by the volunteer in the dark room of the scanner with a period of 10.24 s. As a consequence, the resulting event-related scan data coincide at each line of the series of 128 sequential images, which were repeated in 128 × 80 ms or 32 × 320 ms for the single- or four-slice experiment, respectively. Visual cortex response magnitude measured was about 5–7% with an approximate Gaussian shape and a rise time from stimulus onset to maximum of about 3–4 s, and a fall time to the baseline of about 5–6 s after end of stimulus. The reported data demonstrate the feasibility of functional MRI studies at high temporal resolution (up to 80 ms) using conventional MR equipment and measuring sequence.