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Biomedical subjects

H C Kwan

Publications and source records attributed to H C Kwan.

At least 19 recordsLinked to original sources
PubMed1999

Changes in the complex permittivity during spreading depression in rat cortex.

With recent developments in current density imaging (CDI), it is feasible to utilize this new technique in brain imaging applications. Since CDI's ability to measure changes in current density depends on a concomitant activity-dependent change in the conductivity of the brain tissue, we have examined the changes in complex conductivity during spreading depression (SD) in rodent neocortex using a coaxial probe. SD was chosen because it is often referred to as an animal model of cerebral ischemia and migraine with aura. The conductivity measurements revealed a change with short latency (30-60 s) followed by a change with a longer latency (200-300 s). This change in conductivity with short latency has not been reported before, and we conjecture that it may be the priming or triggering mechanism prior to the main SD episode. A 20% change in conductivity during SD is sufficiently large to be measured by CDI. Therefore, the ability to measure changes in the conductivity, as opposed to metabolic changes, makes CDI a viable approach to the study of ischemia and migraine with aura.

Animals↗
PubMed1996

Characterization of cortical spreading depression by imaging of intrinsic optical signals.

The spatiotemporal progression of cortical spreading depression was investigated by imaging of activity-dependent intrinsic optical signals in rat sensorimotor cortex. In contrast to the traditional conception of a uniformly propagating event, the evolution of the spreading depression was characterized by an asymmetrical propagating wavefront and a non-uniform dispersion of optical signals behind the wavefront. As these optical signals are a reflection of underlying molecular and metabolic processes, the imaging approach to spreading depression might constitute a useful technique for investigating the functional organization as well the pathophysiology of the cerebral cortex.

Animals↗
PubMed1995

Statistical prediction of the optimal site for thalamotomy in parkinsonian tremor.

Stereotactic lesions in the thalamus for treatment of parkinsonian tremor are often made at the location where neurons fire at approximately tremor frequency (tremor cells). Some of these cells show a large amount of activity at tremor frequency and are significantly correlated with electromyographic activity (EMG) during tremor. Our analysis of cellular location identifies a cluster of neurons showing activity characterized both by concentration of power at tremor frequency and by significant correlation with EMG. In a retrospective analysis of results in 15 patients, lesions placed within 2 mm of the center of this cluster were uniformly effective in relieving tremor. Therefore, a small lesion targeting this cluster is effective in treatment of parkinsonian tremor.

Brain Mapping↗
PubMed1994

Single unit analysis of the human ventral thalamic nuclear group. Tremor-related activity in functionally identified cells.

During procedures for parkinsonian tremor, neurons in the thalamic ventral nuclear group show periodic activity at tremor frequency (tremor-frequency activity). The tremor-frequency activity of some cells is significantly correlated with tremor. Cells in this region also display functional properties defined by activity related to somatosensory stimuli and to active movement. Cells with activity related to somatosensory stimulation were termed sensory cells while those with activity related to active movement were termed voluntary cells. Cells with activity related to both somatosensory stimulation and active movement were termed combined cells. Those with activity related to neither somatosensory stimulation nor active movement were termed no-response cells. Combined, voluntary and no-response cells were located in the region of thalamus where a lesion stops tremor and anterior to the region where sensory cells were found. Spectral cross-correlation analysis demonstrated that many combined, voluntary and no-response cells had a peak of activity at tremor frequency which was significantly correlated with electromyogram (EMG). Analysis of the phase of thalamic activity relative to EMG activity indicated that voluntary and combined cell activity usually led EMG during tremor. These results suggest that thalamic cells unresponsive to somatosensory stimulation (voluntary and no-response cells) and those responsive to somatosensory stimulation (combined cells) are involved in the mechanism of parkinsonian tremor. The activity of sensory cells frequently lagged behind tremor while activity of combined cells often led tremor. This finding suggests that the activity of these two cell types, both responding to sensory input, is related to tremor by different mechanisms.

Electromyography↗
PubMed1994

Characteristics of somatotopic organization and spontaneous neuronal activity in the region of the thalamic principal sensory nucleus in patients with spinal cord transection.

1. We explored the region of the principal sensory nucleus of thalamus (Vc) during stereotactic surgical procedures for treatment of patients with pain after spinal cord transection (n = 23). Receptive fields (RFs) of thalamic single neurons and locations of sensations evoked by stimulation (projected field, PF) were determined by standard methods. The cellular thalamic region where sensations were evoked at < 25 microA was termed the "region of Vc." The region of Vc in spinal patients was subdivided into different areas according to RF and PF locations. Areas that were distant from the representation of the anesthetic part of the body were termed "spinal control" areas, whereas those that were adjacent to or included in the representation of the area of absolute sensory loss were termed "border zone/anesthetic" areas. The region of Vc in movement disorder patients were termed the "control" area. 2. Border zone/anesthetic areas of thalamus often exhibited increased representations of the border of the anesthetic part of the body in comparison with the representation of the same parts of the body in control and spinal control areas. 3. In control and spinal control areas the locations of RFs and PFs were usually well matched. However, in border zone/anesthetic areas of the thalamus there was frequently a mismatch between the location of RFs and PFs (RF/PF mismatch). In border zone/anesthetic areas, RFs were often located on the border of the anesthetic part of the body whereas PFs were referred to anesthetic parts of the body. 4. Analysis of first- and higher-order properties of spontaneous neuronal activity revealed that spike trains could be classified into two groups with distinct patterns of activity. The R group (n = 49) was characterized by independence of sequential interspike intervals (ISIs), a Poisson distribution of ISIs, initially inhibitory or flat autocovariance function (acvf), and low level of high-frequency bursting. The O group (n = 26) was characterized by correlation of sequential ISIs, large sustained postspike facilitation on the acvf, and high prevalence of high-frequency bursting--all consistent with a bursting pattern of activity. A third group of spike trains (n = 17) had an initially inhibitory or flat acvf and a unimodal, positively shifted, ISI distribution that did not meet criteria for a Poisson distribution. 5. Spike trains in the R group were much more common in control and control spinal areas, whereas those in the O group were more common in border zone/anesthetic areas.(ABSTRACT TRUNCATED AT 400 WORDS)

Brain Mapping↗
PubMed1993

Mouse mammary tumor virus infection accelerates mammary carcinogenesis in Wnt-1 transgenic mice by insertional activation of int-2/Fgf-3 and hst/Fgf-4.

Transgenic mice carrying the Wnt-1 protooncogene modified for expression in mammary epithelial cells exhibit hyperplastic mammary glands and stochastically develop mammary carcinomas, suggesting that additional events are necessary for tumorigenesis. To induce such events and to identify the genes involved, we have infected Wnt-1 transgenic mice with mouse mammary tumor virus (MMTV), intending to insertionally activate, and thereby molecularly tag, cooperating protooncogenes. Infection of breeding female Wnt-1 transgenics decreased the average age at which tumors appeared from approximately 4 months to approximately 2.5 months and increased the average number of primary tumors per mouse from 1-2 to > 5. A smaller effect was observed in virgin females, and infection of transgenic males showed no significant effect on tumor latency. More than half of the tumors from the infected breeding group contained one or more newly acquired MMTV proviruses in a pattern suggesting that most cells in tumors arose from a single infected cell. Analyses of provirus-containing tumors for induced or altered expression of int-2/Fgf-3, hst/Fgf-4, int-3, and Wnt-3 showed activation of int-2 in 39% of tumors, hst in 3%, and both int-2 and hst in 3%. DNA analyses with probes for protooncogenes and MMTV confirmed that the activations resulted from proviral insertions. There was no evidence for proviral insertions at the int-3, Wnt-3, or Wnt-1 loci. These findings provide further evidence that fibroblast growth factors Int-2 and Hst can cooperate with Wnt-1, another secreted factor, in mammary tumorigenesis, and they illustrate the capacity of this system to identify cooperating oncogenes.

Animals↗
PubMed1993

Neural networks and Parkinson's disease.

A closed-loop or recurrent neural network was taught to generate output discharges to reproduce the prototypical activations in agonist and antagonist muscles which produce the displacement of a limb about a single joint. By introducing a generalized decrease in the excitability of the pre-output layer in the network, the network made the displacement more slowly and also showed an inability to maintain a repetitive movement. These concepts can be applied to the human nervous system in the understanding of the physical basis of movement and its disorders. It is suggested that a movement represents the output of a closed-loop network, such as the cortical-basal ganglia-thalamic-cortical motor loop, which iterates repetitively to its end point or attractor. The model provides an explanation of how the state of thalamic inhibition seen in Parkinson's disease physically may produce bradykinesia and the inability to maintain a repetitive movement.

Basal Ganglia↗
PubMed1991

Automatic end-expiratory air sampling device for breath hydrogen test in infants.

An automatic electronically operated end-expiratory air sampler has been developed for use in small infants. Upon expiration, which is detected by a hot-wire sensor, a small portion of the end-expiratory air is automatically collected into a syringe mounted on a syringe driver. The sampler obtained 87% of the end-expiratory air sample. Additionally, highly reproducible and consistent results were obtained for the respiratory gases (O2, N2, CO2). The sampler has been applied for studying breath hydrogen excretion to detect lactose malabsorption. It may also be applicable to study other expiratory gases in infants.

Breath Tests↗
PubMed1990

Single unit analysis of the human ventral thalamic nuclear group. Activity correlated with movement.

During neurosurgical operations for the relief of movement disorders, single thalamic neurons (n = 107) were identified with activity which was related to verbally cued active movements (movement-related cells). The activity of each neuron was examined during different contralateral movements in order to determine the movement which was associated with the most consistent and pronounced change in firing rate (the optimal response). The optimal response was determined by analysis of histograms of neuronal activity which were constructed by using the onset of EMG activity to synchronize successive repetitions of the active movement. Movement-related cells exhibited optimal responses associated with such movements as making a fist, extension or flexion of the wrist, flexing or extending the elbow, pointing with the entire upper extremity, extending the tongue and lifting the leg. Most movement-related cells recorded in a single parasagittal plane in an individual patient had optimal responses related to movements involving the same part of the body. Movement-related cells were classified into those that were activated in response to somatosensory stimulation (combined cells, n = 20) and those which were not (voluntary cells, n = 87). Combined cells were activated in advance of EMG activity during active movement and so could be distinguished from cells responding only to sensory stimulation (sensory cells). Movement-related cells (combined and voluntary cell types) were located anterior to sensory cells and tended to show a mediolateral somatotopic organization parallel to that of sensory cells with cutaneous receptive fields. Combined cells responded to somatosensory stimulation of the same part of the body as that involved in the active movement related to the optimal response of the cell. Combined cells responding to passive movements of a joint always had their optimal response during active movement about the same joint. The activity of combined cells during parkinsonian tremor may clarify the role of sensory feedback in tremor.

Electric Stimulation↗
PubMed1990

Neural network control of simple limb movements.

It is possible to embed the control and computation of a simple single-joint movement at different speeds by a small non-linear network of neuron-like elements. The network "learns" by appropriate adjustment of the strengths of interconnection, or synaptic weights, between the neuron-like elements. The learning of a few movement trajectories is generalized to the learning of a family of unlearned trajectories. These observations are in support of our hypothesis that relaxation of a network from an initial state to a final equilibrium state is both causal and computational to movement generation and control.

Electromyography↗
PubMed1990

Thalamic single-unit activity occurring in patients with hemidystonia.

Lesions of the ventrolateral complex of the human thalamus may relieve abnormal movements in patients with dystonia. We have now recorded the thalamic single-unit activity and the electromyographic (EMG) activity in the upper extremity during the physiologic localization which is required prior to thalamotomy for hemidystonia. The activity of thalamic single units was correlated with the EMG signal by spectral methods. Results of this analysis indicate that a group of thalamic cells show a concentration of activity, occurring at the same frequency as the EMG activity during dystonia. In many cases, there was statistically significant correlation between thalamic and EMG signals at the frequency of dystonia. The activity of these cells may be involved in the generation of dystonic movements.

Dominance, Cerebral↗
PubMed1989

Characteristics of the bursting pattern of action potentials that occurs in the thalamus of patients with central pain.

Neurons in the somatosensory thalamus of patients with central pain following spinal cord injury fire in bursts of action potentials more frequently than do similar neurons in patients without pain. Furthermore, the characteristic firing pattern within these bursts is similar to that which is shown to be associated with the occurrence of calcium spikes in intracellular studies of thalamic nuclei. This finding may have significant implications for the etiology and treatment of central pain states.

Action Potentials↗
PubMed1989

Detection of feedback in the central nervous system using system identification techniques.

An analysis method to detect the presence of feedback between biological signals, particularly those associated with the central nervous system, is presented. The technique is based on recent results in the system identification literature involving the concept of a feedback free process. It may be applied to volume conducted signals such as EEG and EMG, as well as to neuronal spike trains through the use of a data transformation procedure. The utility of the technique is then demonstrated in a study of the relationship between Parkinsonian tremor and certain tremor cells found in the thalamus of Parkinsonian patients, using data collected during thalamotomies. The results obtained suggest that feedback mechanisms may be an important factor contributing to Parkinsonian tremor.

Biofeedback, Psychology↗
PubMed1988

Single-unit analysis of the human ventral thalamic nuclear group: somatosensory responses.

1. We have studied the functional and somatotopic properties of 531 single mechanoreceptive thalamic neurons in humans undergoing stereotactic surgery for the control of movement disorders and pain. The majority of these somatosensory cells had small receptive fields (RFs) and were activated in a reproducible manner by mechanical stimuli applied to the skin or deep tissues. These neurons, which we termed "lemniscal," could be further classified into those responding to stimulation of cutaneous (76% of lemniscal sensory cells) or deep (24%) structures. 2. The incidence of neurons having cutaneous or mucosal RFs in the perioral region, thumb, and fingers (66%) was much higher than that of neurons having RFs elsewhere on the body. Most of the deep cells were activated by movements of and/or mechanical stimuli delivered to muscles or tendons controlling the elbow, wrist, and fingers. 3. Sequences of cells spanning several millimeters in the parasagittal plane often exhibited overlapping RFs. However, RFs changed markedly for cells separated by the same distances in the mediolateral direction. This suggests that the cutaneous somatotopic representation of each region of the body is organized into relatively thin sheets of cells oriented in the parasagittal plane. 4. By comparing neuronal RFs in different parasagittal planes in thalamus of individual patients we have identified a mediolateral representation of body surface following the sequence from: intraoral structures, face, thumb through fifth finger to palm, with forearm and leg laterally. 5. Along many trajectories in the parasagittal plane the sequence of cells with overlapping RFs was interrupted by another sequence of cells with RFs corresponding to a different body region. The RFs of the intervening sequence characteristically represented body regions known to be located more medially in thalamus (see 3 above). These findings could be explained if the lamellae postulated above were laterally convex. 6. Cells responding to deep stimulation (deep cells) could be further classified into those responding to joint movement (63%), deep pressure (15%), or both (22%). Deep cells were found usually at the anterior-dorsal border and sometimes at the posterior border of the region containing cells responding to cutaneous stimuli. Although there was some overlap in the RFs, deep cells representing wrist were found medial to those representing elbow, and both of these were found medial to cells representing leg.(ABSTRACT TRUNCATED AT 400 WORDS)

Brain Mapping↗
PubMed1988

Methods for microstimulation and recording of single neurons and evoked potentials in the human central nervous system.

An apparatus and technique are described for microstimulation and recording of both slow wave and single neuron (single unit) activities during functional stereotaxic procedures. This method facilitates microstimulation and evoked potential and single unit analysis which, in combination, provide optimum definition of stereotaxic targets in the treatment of functional disorders of the human central nervous system.

Brain↗
PubMed1988

Single unit analysis of the human ventral thalamic nuclear group: correlation of thalamic "tremor cells" with the 3-6 Hz component of parkinsonian tremor.

Although cells firing at tremor frequency, called "tremor cells" (Guiot et al., 1962), have often been recorded in the thalamus of parkinsonian patients, the extent of correlation between these spike trains and tremor has rarely been assessed quantitatively. This paper describes spectral cross-correlation functions calculated between the activity of "tremor cells" and electromyogram (EMG) signals recorded from several muscles in the contralateral arm. The power occurring in the spike train at tremor frequency was described in absolute terms by the spike autopower, and in relation to the average for all spectral components by the spike autopower signal-to-noise ratio (spike autopower SNR). The probability of significant cross-correlation between the thalamic spike train and EMG at tremor frequency was assessed by the coherence at tremor frequency. Autopower spectra of the activity of many of these cells exhibited a concentration of power at tremor frequency, indicated by spike autopower SNRs as high as 18. Of the EMG signals studied, signals recorded from finger flexors were most often significantly correlated at tremor frequency. Significant correlation between the thalamic spike train and finger flexor EMG activity was found in 34% of cells analyzed. Tremor frequency coherence was significantly correlated with tremor frequency spike autopower (r = 0.46, p less than 0.0001) and spike autopower SNR (r = 0.533, p less than 0.0001). The proportion of cells with a spike autopower SNR greater than 2 that were significantly correlated with finger flexor EMG activity was greater than that of cells with a spike autopower SNR of less than 2 (p less than 0.001; chi-square). Therefore, cells exhibiting a large amount of power at tremor frequency were those best correlated with EMG activity during tremor. Some of these cells may be involved in the generation of tremor.

Action Potentials↗
PubMed1987

Interaction between neurons in precentral cortical zones controlling different joints.

The relationship of the strength of interaction between precentral cortical neurons and their distance of separation during active reaching movements was studied in adult primates. Chronic unit recording experiments with two independent microelectrodes were performed in the left precentral forearm area of monkeys trained to execute reaching movements with the right arm in response to a visual cue. Neurons were identified by the joint actions produced by intracortical microstimulation. Cross-correlation analysis was employed to assess the strength of interaction between units. Unit pairs which exhibited the highest strength were recorded by the same electrode. For unit pairs derived from separate electrodes, the incidence and strength of interaction fell as the separation between the units was increased. Neurons identified by intracortical microstimulation as controlling the same or contiguous joints tended to interact with each other with much higher probability than did those neurons identified as controlling non-contiguous joints. When the direction of flow of information was assessed, these was a preferential flow from neurons controlling proximal joints to those controlling distal ones. These results are consistent with recent findings of tight kinematic coupling between contiguous joints and the observation of proximal-to-distal sequence of activation at the neuronal and electromyogram levels during voluntary movement.

Animals↗