Hon C. Kwan

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.

Abnormal single-unit activity recorded in the somatosensory thalamus of a quadriplegic patient with central pain

We have performed single unit analysis of the activity of cells located in the ventral nuclear group of thalamus in a patient with dysesthetic pain below the level of a clinically complete traumatic spinal cord transection at C5. Cells located in the parasagittal plane 14 mm lateral to the midline responded to tactile stimulation in small facial and intraoral receptive fields, which were characteristic of patients without somatosensory abnormality [30]. In this patient the 16 mm lateral parasagittal plane contained cells with receptive fields located on the occiput and neck instead of the upper extremity as would normally be expected. Cells with receptive fields on the neck and occiput had not previously been observed in recordings from single units (n = 531) responding to somatosensory stimulation [30]. Thus, on the basis of their location in a region of thalamus which normally represents parts of the body below the level of the spinal cord transection and their unusual receptive fields adjacent to these same parts of the body, we propose that the cells in the 16 mm lateral plane have lost their normal afferent input. Analysis of the autopower spectra of spike trains indicates that cells in the 16 mm lateral plane exhibited a higher mean firing rate and greater tendency to fire in bursts than cells in the 14 mm lateral plane (P less than 0.005). Finally, electrical stimulation at the recording sites in the 16 mm lateral plane evoked a burning sensation in the occiput, neck and upper extremity. These results suggest that regions of thalamus which have lost their normal somatosensory input contain neurons which exhibit abnormal spontaneous and evoked activity and that electrical stimulation of these regions can produce the sensation of burning dysesthesia.

Evolutionary autonomous agents and the nature of apraxia

BackgroundEvolutionary autonomous agents are robots or robot simulations whose controller is a dynamical neural network and whose evolution occurs autonomously under the guidance of a fitness function without the detailed or explicit direction of an external programmer. They are embodied agents with a simple neural network controller and as such they provide the optimal forum by which sensorimotor interactions in a specified environment can be studied without the computational assumptions inherent in standard neuroscience.MethodsEvolutionary autonomous agents were evolved that were able to perform identical movements under two different contexts, one which represented an automatic movement and one which had a symbolic context. In an attempt to model the automatic-voluntary dissociation frequently seen in ideomotor apraxia, lesions were introduced into the neural network controllers resulting in a behavioral dissociation with loss of the ability to perform the movement which had a symbolic context and preservation of the simpler, automatic movement.ResultsAnalysis of the changes in the hierarchical organization of the networks in the apractic EAAs demonstrated consistent changes in the network dynamics across all agents with loss of longer duration time scales in the network dynamics.ConclusionThe concepts of determinate motor programs and perceptual representations that are implicit in the present day understanding of ideomotor apraxia are assumptions inherent in the computational understanding of brain function. The strength of the present study using EAAs to model one aspect of ideomotor apraxia is the absence of these assumptions and a grounding of all sensorimotor interactions in an embodied, autonomous agent. The consistency of the hierarchical changes in the network dynamics across all apractic agents demonstrates that this technique is tenable and will be a valuable adjunct to a computational formalism in the understanding of the physical basis of neurological disorders.

Stretch reflex modulation during a cyclic elbow movement

Small torque pulses were delivered to the forearm in order to test the stretch reflex of the brachialis and triceps arm muscles in 11 normal subjects performing a cyclic movement about the elbow in the horizontal plane. The flexion-extension movement was paced by a metronome and performed under various loading conditions. Reflexes for each muscle were tested either in each 50 msec segment of the 2 sec cycle period, or in a smaller number of selected phases. A late reflex, appearing at a latency of about 60 msec (measured from the onset of the torque increment), was modulated extensively during the movement cycle. The amplitude of the late reflex increased markedly at the onset of a muscle contraction. In many of the subjects reflex responsiveness began to increase as early as 200 msec prior to the onset of voluntary muscle activity. Peak reflex responses were elicited by stimuli delivered 100-150 msec prior to the peak rate of increase of dynamic load (composed of inertial, viscous and elastic forces). The increase in responsiveness was followed by a drop which was generally coincident in time with the peak rate of increase of the load opposing muscle contraction. The modulation of the late reflex is appropriately timed for reflex-generated tension to help counteract dynamic loads, intrinsic to the movement.

Measurements of human forearm viscoelasticity

In human subjects, stiffness of the relaxed elbow was measured by three methods, using a forearm manipulandum coupled to a.d.c. torque motor. Elbow stiffness calculated from frequency response characteristics increased as the driving amplitude decreased. Step displacements of the forearm produced restoring torques linearly related to the displacement. The stiffness was very similar to that calculated from natural frequencies at amplitudes above 0.1 rad. Thirdly, elbow stiffness was estimated from brief test pulses, 120 ms in duration, by mathematically simulating the torque-displacement functions. Stiffness values in the limited linear range (under +/- 0.1 rad) were higher than in the linear range of the first two methods. A major component of elbow stiffness appears to decay within 1 s. The coefficients of viscosity determined from the simulation were, however, very similar to those calculated from the frequency response. Test pulse simulation was then used to determine joint impedance for different, actively maintained elbow angles. Joint stiffness and viscosity increased with progressive elbow flexion.

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.

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.

Cross correlation studies in primate motor cortex: synaptic interaction and shared input

Awake, unrestrained monkeys were trained to reach out with the forelimb and touch a button. Extracellular spike trains were recorded from pairs of neurons in contralateral precentral cortex with the same or separate microelectrodes. The neurons were located in the same or different functional columns as defined by intracortical microstimulation and passive sensory stimulation. Cross correlation analysis showed patterns consistent with synaptic excitation and/or inhibition between members of the cell pairs during the voluntary movement. The strength of correlation was inversely related to distance between columns, with the strongest correlations found between cells within the same column. Inhibitory correlations were virtually restricted to cell pairs within a single column. Temporal analysis showed that direct synaptic interaction and shared input patterns could be clearly distinguished in this physiologic setting. Spatial analysis indicated that shared input was concentrated among columns in the same and adjacent joint controlling zones as well as within a single column. No directional preference of shared input was present, a finding which was consistent with the observed nested organization of the forelimb area.

Activity of primate precentral neurons during voluntary movements triggered by visual signals.

Awake, intact monkeys were trained to perform discrete flexion or extension movements of the hand about the wrist in response to visual signals. The object of the movement was to align a cursor, coupled to a manipulandum, on a target line. Cursor and target lines are displayed on a video monitor placed in front of the monkey. The target line was stepped to the right or left, randomly with regard to direction and timing, with each step implying an instruction for the monkey to make a voluntary movement for alignment. Single unit recording was made in the forelimb area of contralateral precentral cortex. Neurons were classified by their responses to passive sensory stimulation and the effects of local intracortical microstimulation into two populations; wrist flexion-extension (F-E) neurons, and all other forelimb neurons (non-wrist (F-E)). A significantly higher proportion of wrist (F-E) neurons as compared to non-wrist (F-E) neurons were task-related. Moreover the wrist (F-E) neurons exhibited exclusively reciprocal responses to the oppositely directed visual signals, whereas the non-wrist (F-E) neurons showed both reciprocal and bidirectional responses. No significant differences in mean latencies of responses, either in respect to the visual signals or to movement onset, were observed between the two populations of neurons. However the range of latencies in both instances was greater in the non-wrist (F-E) populations. The wrist (F-E) population showed significantly less response variability than the non-wrist (F-E) population with regard to response latencies to visual signals and movement onsets, and the degree of correlation between duration of response and reaction time.

Distribution of responses to visual cues for movement in precentral cortex of awake primates

Unit recordings were made from areas 4 and 6 monkeys after they were trained to align a cursor over a vertical target line on a video screen by control of a manipulandum with wrist flexion or extension movement. The appearance of the cursor and line on the screen was the visual cue for movement. Responses were observed 150 (+/- 40) msec after cue presentation. The responses were found only in the forelimb area of precentral cortex, which was most immediately involved in the control of the task, and the majority of them were uncorrelated with either the specific details of the visual cue, or with the direction of the subsequent wrist movement.