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Biomedical subjects

D Burke

Publications and source records attributed to D Burke.

At least 235 records · Page 13Linked to original sources

Voluntary activation of human motor axons in the absence of muscle afferent feedback. The control of the deafferented hand.

The ability to activate human motoneurons supplying individual intrinsic muscles of the hand was examined during acute deafferentation of the muscles. Tungsten microelectrodes were inserted percutaneously into motor fascicles of the ulnar nerve of 5 subjects, which was then blocked distally with local anaesthetic. In 4 subjects unitary action potentials were recorded from 16 motor axons, which were identified with respect to their target muscles. In the complete absence of muscle afferent feedback, subjects could voluntarily recruit motoneurons, grade their discharge and sustain a constant level of activity. Significant facilitation of motor efforts was provided by cutaneous feedback from the digits via the median nerve. During attempted maximal voluntary efforts the mean discharge frequencies of single motor axons were significantly lower than those of normally-innervated motor units. This finding suggests that peripheral afferents have a net facilitatory influence on motoneurons. However, during prolonged (20-30 s) maximal voluntary efforts the deafferented motoneurons did not display the progressive decline in discharge frequency shown by normally-innervated motor units during contractile fatigue, a finding consistent with two possible explanations: disfacilitation or reflex inhibition of the motoneuron pool by peripheral afferents. The results also indicate that the otherwise intact nervous system can perform some simple motor tasks with no proprioceptive input other than knowledge of the motor commands. Other factors may contribute to the poor motor performance reported for patients with severe sensory deficits.

Adult↗

Corticospinal volleys evoked by anodal and cathodal stimulation of the human motor cortex.

1. In fifteen neurologically normal subjects, corticospinal volleys evoked by transcranial stimulation of the motor cortex were recorded from the spinal cord using epidural electrodes in the high-thoracic and low-thoracic regions during surgery to correct scoliosis. 2. Anodal stimulation at the vertex produced complex corticospinal volleys that could be recorded at both sites, with multiple waves analogous to the D and I waves documented in animal experiments. These volleys were of higher amplitude when the cathode was 7 cm lateral to the vertex rather than 7 cm anterior. There were no differences in conduction time between the two recording sites for D and I waves, when these waves could be identified at the low-thoracic site. 3. Anodal stimuli of 150 V commonly produced a descending volley containing a single peak at both recording sites. Modest increases in stimulus intensity to 225-375 V produced a peak 0.8 ms in advance of the wave of lowest threshold in thirteen subjects and, in seven subjects, further increases produced an additional peak 1.7 ms in advance of the first-recruited wave. The early peaks increased in size with stimulus intensity, replacing the first-recruited wave. These results suggest that the site of impulse initiation with electrical stimulation of the motor cortex shifts from superficial cortex to deep structures, approximately 5 and 10-11 cm below the cortex. These sites are probably the internal capsule and the cerebral peduncle. 4. With cathode at the vertex and anode over the 'hand area' the response of lowest threshold occurred at the latency of the anodal D wave but could not be recorded at the low-thoracic site, suggesting that it was generated by the anode over the 'hand area'. Slightly higher intensities induced a 'cathodal D wave' and still higher intensities produced late peaks at latencies of anodal I waves. These cathodal D and I waves involved axons innervating lumbar segments. There was no evidence that cathodal stimulation preferentially produced I waves. Cathodal stimulation at the vertex with the anode 7 cm anteriorly produced similar results: D waves were produced at relatively low intensities, but I waves appeared at relatively high stimulus intensities if at all.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Perceptual responses to microstimulation of single afferents innervating joints, muscles and skin of the human hand.

1. Microneurographic techniques were used to isolate single afferent axons within cutaneous and motor fascicles of the median and ulnar nerves at the wrist in thirteen subjects. Of the sixty-five identified afferents, eleven innervated the interphalangeal and metacarpophalangeal joints, sixteen innervated muscle spindles, three innervated Golgi tendon organs and thirty-five supplied the glabrous skin of the hand. 2. Intrafascicular stimulation through the recording microelectrode, using trains of constant-voltage positive pulses (0.3-0.8 V, 0.1-0.2 ms, 1-100 Hz) or constant-current biphasic pulses (0.4-13.0 microA, 0.2 ms, 1-100 Hz), evoked specific sensations from sites associated with some afferent species but not others. 3. Microstimulation of eight of the eleven joint afferent sites (73%) evoked specific sensations. With four, subjects reported innocuous deep sensations referred to the relevant joint. With the other four, the subjects reported a sensation of joint displacement that partially reflected the responsiveness of the afferents to joint rotation. 4. Microstimulation of fourteen of the sixteen muscle spindle afferent sites (88%) generated no perceptions when the stimuli did not produce overt movement. However, subjects could correctly detect the slight movements generated when the stimuli excited the motor axons to the parent muscle. 5. With seven of the nine rapidly adapting (type RA or FAI) cutaneous afferents (88%) microstimulation evoked sensations of 'flutter-vibration', and with two of eight slowly adapting (type SAI) afferents (25%) it evoked sensations of 'sustained pressure'. Of the eighteen SAII afferents, which were classified as such by their responses to planar skin stretch, the majority (83%) generated no perceptions, confirming previous work, but three evoked sensations of movements or pressure. 6. The present results suggest a relatively secure transmission of joint afferent traffic to perceptual levels, and it is concluded that the human brain may be able to synthesize meaningful information on joint displacement on the basis of impulses in a single joint afferent. This could partly compensate for the low responsiveness of individual joint afferents within the physiological range of joint displacements. Although single muscle spindle afferents can adequately encode joint position and movement, the results suggest that the brain needs the information from more than one muscle spindle afferent to perceive changes in joint angle.

Action Potentials↗

Activation of fusimotor neurones by motor cortical stimulation in human subjects.

1. Neural recordings were made from motor fascicles of the ulnar or radial nerves while the motor cortex was stimulated percutaneously using high-voltage electrical stimuli or transient magnetic pulses to determine whether human muscle spindle endings could be activated by such stimuli and, if so, whether this occurred before the recruitment of alpha-motoneurones. 2. In relaxed subjects, no evidence of muscle spindle activation could be detected in nine recordings of multiunit neural activity and four recordings from single spindle afferents using stimulus levels up to 600 V and 1.5 T. These levels produced a prominent twitch contraction of the intrinsic muscles of the hand and of forearm muscles. Passive stretch of the contracting muscle did not reveal a fusimotor action too weak to be detected under isometric circumstances. 3. With twenty-six single spindle afferents, the stimuli were delivered during a voluntary contraction of the receptor-bearing muscle. This served to 'focus' the effects of the stimulus on the relevant motoneurone pools and increased the probability that fusimotor neurones innervating the endings were active. 4. None of the twenty-six spindle afferents could be activated by stimuli subthreshold for alpha-motoneurones, even when the stimuli were delivered during passive stretch of the contracting muscle. With eighteen afferents, stimuli above threshold for alpha-motoneurones were delivered: twelve remained unaffected but the discharge of six altered. 5. Three afferents were activated at latencies of 35, 39 and 40 ms, respectively 16, 20 and 20 ms after the onset of the EMG potentials in the receptor-bearing muscles. This latency difference is too short to be attributable to activation of gamma-motoneurones: arguments are presented that the increase in spindle discharge could result from activation of beta-motoneurones. 6. The discharge of three afferents increased at latencies of 70, 75 and 85 ms, too early to be due to stretch on the falling phase of the twitch contraction of the receptor-bearing muscle. Responses at these latencies could involve activation of gamma- or beta-motoneurones. 7. These findings in human subjects suggest that transient stimulation of the motor cortex may effectively access fusimotor neurones.

Action Potentials↗

Behavior of human muscle receptors when reliant on proprioceptive feedback during standing.

1. This study investigated the muscle-spindle discharge from the pretibial flexor muscles of standing human subjects while they performed maneuvers that altered their reliance on proprioceptive feedback to control balance. Single-unit recordings were made from 100 identified muscle afferents, 81 from muscle-spindle endings and 19 from Golgi tendon organs. 2. With 49 spindle endings the subjects stood on a horizontal platform and with 32, on a platform tilted in dorsiflexion (4 degrees) to ensure that the pretibial muscles were active to maintain balance. When standing freely on a horizontal platform without support or vision, there was little or no electromyographic (EMG) activity in the pretibial muscles, and spindle discharge rates were low (55% active; mean rate for all 49 endings, 4.1 Hz). When standing similarly on the tilted platform, 69% of the spindle afferents were active, and the mean discharge rate was 5.4 Hz. The greater number of actively discharging spindle afferents and the preservation of mean discharge rate despite muscle shortening indicates that the pretibial muscles are subjected to increased fusimotor drive when they are tonically active to maintain balance. 3. The effects of small degrees of body sway induced voluntarily or by an external stimulus were studied with 41 afferents (29 spindles; 12 tendon organs). Activation of the pretibial muscles to compensate for backward sway was accompanied by a spindle discharge that usually exceeded the discharge produced by comparable passive movement. This indicates that the pretibial muscles are subjected to increased fusimotor drive when they are phasically active to maintain balance. 4. To vary the reliance placed on the feedback from proprioceptive inputs, the subjects abruptly opened and shut their eyes, took and released support, or tilted their heads. There were no detectable changes in afferent activity unless the maneuver produced a change in EMG activity in the pretibial muscles and/or body sway. Thirty afferents (26 of 46 spindles; 4 of 7 tendon organs) underwent a change in discharge rate associated with a transient change in posture, as recorded by the force platform, or a change in EMG activity in the receptor-bearing muscle. The discharge pattern of 23 afferents did not show any clear change with these maneuvers. 5. It is concluded that maneuvers that increase the reliance on proprioceptive feedback when subjects are standing quietly do not significantly alter the fusimotor drive to the pretibial muscles in the absence of muscle contraction.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Reflex activation of muscle spindles in human pretibial muscles during standing.

1. Experiments were performed in standing subjects to determine whether low-threshold cutaneous and muscle afferents from mechanoreceptors in the human foot reflexly influence fusimotor neurons innervating pretibial flexor muscles. Recordings were made from 30 identified muscle-spindle afferents, four tendon-organ afferents, and one alpha-motor axon innervating the pretibial flexor muscles. The subjects stood without support or vision on a force platform while trains of electrical stimuli (5 stimuli, 300 Hz) were delivered at nonpainful intensities to the sural nerve or to the posterior tibial nerve at the ankle. 2. Seventeen of the 30 spindle endings had no background discharge, and none was activated by the sural or posterior tibial stimuli. Five silent afferents were given a background discharge by sustained pressure on the relevant tendon, but with two the discharge was dominated by a tremor rhythm obscuring any reflex response to the stimuli. Based on peristimulus time histograms (PSTHs), the sural stimuli then produced increases in discharge of two of the remaining three endings at latencies of 84 and 90 ms. These effects could not be explained by muscle stretch and are presumed to have been fusimotor mediated. 3. When the subjects stood freely without support or vision, 13 muscle-spindle endings had a background discharge, but with three endings tremor developed at the ankle and dominated the spindle discharge. Sural stimuli affected the discharge of five of nine endings unaffected by tremor. With three of these endings, there were changes in discharge that could be explained by muscle stretch.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

High performance isoelectric focusing using capillary electrophoresis instrumentation.

High performance isoelectric focusing in capillaries provides rapid, high resolution separation of proteins based on their isoelectric points. Results can be obtained in a matter of minutes with little or no sample preparation. The technique requires the use of coated capillaries to reduce electroendosmosis so that stable, focused zones can be attained. Once focused, protein zones may be mobilized by the addition of salt to the catholyte or anolyte buffer. On-tube UV monitoring enables direct detection of sample components during mobilization with mass sensitivity equal to that of silver staining. The linear relationship between mobilization time and isoelectric point allows the technique to be used for estimation of protein pI. Demonstrated applications include separation of proteins in biological fluids with possible clinical applications, and characterization of biopharmaceutical proteins and monoclonal antibodies.

Capillary Action↗

Deficits of thermal sensation in patients with unilateral cerebral lesions.

Using a quantitative psychophysical test, the thresholds for detection of heat and cold were determined at both wrists in 16 hemiparetic patients with unilateral cerebral lesions and 1 patient with a unilateral frontal lesion but no hemiparesis. These data were compared with normal values for the absolute thermal thresholds and the symmetry of thermal thresholds in 25 age-matched control subjects. Significant elevation of thermal thresholds was found in all patients with clinically detectable deficits of nociceptive or thermal sensations. Thresholds were also elevated in 3 of 10 hemiparetic patients with no clinical evidence of impairment of nociceptive or thermal sensations. Deficits were found in patients with superficial cortical lesions as well as in those with extensive lesions involving deep structures, including thalamus. In patients with superficial lesions, the elevation of thermal threshold was slight (less than 1 degree C) and there was often little or no sensory deficit to clinical testing. In patients with very high thermal thresholds (greater than 6 degrees C), the lesions involved deep structures and there were clinically obvious deficits of thermal and nociceptive sensations.

Adolescent↗

The cortical distribution of muscle and cutaneous afferent projections from the human foot.

Somatosensory evoked potentials to electrical stimulation of muscle and cutaneous afferents from the foot were recorded in normal human subjects using multiple channels centred on the vertex and referenced to the contralateral earlobe. Low-threshold muscle afferents were selectively activated by an insulated microelectrode inserted percutaneously at the motor point of abductor hallucis. Low-threshold cutaneous and joint afferents of the hallux or second toe were stimulated with ring electrodes. The posterior tibial and sural nerves were stimulated at the ankle through surface electrodes. The cerebral distribution of the initial cortical response (N33-P40) to stimulation of muscle afferents largely paralleled that to stimulation of its parent nerve, the posterior tibial nerve (which contains afferents of muscle, cutaneous and joint origin). They were maximal slightly posterior and ipsilateral to the vertex. The cutaneous-joint afferent projection from the hallux paralleled that from the sural nerve and both were less lateralized than the tibial and abductor hallucis projections.

Adult↗

Cyclopean tilt aftereffects can be induced monocularly: is there a purely binocular process?

A series of experiments have been reported by Wolfe and Held which they have taken as evidence for the existence of more than one binocular process in human vision, specifically a simple binocular process (OR-gate) and a purely binocular process (AND-gate). In one of their studies, it was shown that tilt aftereffects induced with cyclopean stimuli produced measurable effects only when testing was binocular, which suggested that cyclopean adaptation affects only the AND-gate mechanism. If the two alleged mechanisms (AND or OR) are independent, monocular adaptation with luminance contrast stimuli should produce aftereffects which can only be measured with luminance contrast test stimuli. Cyclopean test displays would probe only the unadapted AND-mechanism. Results to the contrary are reported, casting doubt upon the functional independence, perhaps even the existence, of the so-called purely binocular process.

Adaptation, Ocular↗

Changes in excitability of human cutaneous afferents following prolonged high-frequency stimulation.

Prolonged high-frequency stimulation of cutaneous nerves can result in paraesthesiae that begin 20 to 30 s after the end of the train and last for 5 to 10 min. In the present experiments the effects of such stimulation on the excitability of human cutaneous afferents and on their refractory and supernormal periods were measured to determine whether these changes could explain the postactivation paraesthesiae. Attention was focused on the axons of lowest threshold (1.0-1.5 T) in the compound sensory action potential evoked by stimulating the digital nerves of the index or middle fingers. Repetitive activation produced two opposing effects on the excitability of low-threshold cutaneous afferents. Following stimulus trains of short duration (1-5 min) the dominant effect was a long-lasting decrease in excitability, such that the amplitude of a test afferent volley was always less than before stimulation. With these trains, no subject experienced paraesthesiae. For 10 min after stimulus trains lasting longer than 7 to 12 min the dominant effect was an increase in excitability such that the amplitude of the test volley was greater than before stimulation. Within this interval, following such trains, subjects experienced paraesthesiae. The extent and duration of supernormality induced by a supramaximal conditioning stimulus were greatly increased by stimulation for 1 min. Following stimulation for 10 min, the degree of supernormality of the enhanced test volley was much the same as before stimulation, but was inappropriately high for the size of the test volley. The sum total of the excitability change and the change in supernormality resulted in a larger potential after stimulation, whether the train lasted 1 min or 10 min. It is concluded that the postactivation changes in axonal excitability could predispose the most excitable axons to generate ectopic impulses and, thereby, to produce paraesthesiae.

Axons↗

The effects of voluntary contraction on the H reflex of human limb muscles.

The effects of a voluntary contraction on the H reflexes of various muscles were quantified to determine whether the reflex responses were sufficiently reproducible to be used in diagnostic studies. During a voluntary contraction, H reflexes could be recorded reliably from tibialis anterior and abductor pollicis brevis, but accurate identification of the onset of the H wave from the on-going background EMG required duplicate averages of multiple responses. During a contraction the H reflex could be obtained at lower stimulus intensities in the forearm flexor muscles than when relaxed, and a more clear separation of the H wave from the M wave was possible. The background contraction abolished the attenuation of reflex amplitude with increasing stimulus repetition rates, such that repetition rates of up to 4 Hz could be used without significant loss of reflex amplitude. There were only small and usually insignificant differences in the latency of the H reflex or its variability when elicited with the forearm muscles relaxed and when flexor carpi radialis was contracting steadily. The reflex latencies of abductor pollicis brevis, tibialis anterior and soleus were compared with F wave latencies for these muscles. The minimal F wave latencies were shorter than the H reflex latencies for abductor pollicis brevis (mean 2.2 ms) and tibialis anterior (mean 1.0 ms) but not for soleus. Comparison of the spread of F wave latencies (F max-F min) suggests that, for soleus, F waves are recorded only from the faster conducting motor units in the pool, presumably those less readily recruited in the H reflex. It was calculated that the distribution of motor conduction velocities responsible for the F waves of abductor pollicis brevis was 8.8 m.s-1. This value underestimates the likely distribution of motor conduction velocities for the thenar muscle by as much as 50%, consistent with the view that F waves rarely occur in slowly conducting motor units, the units of lowest threshold in reflex studies. It is concluded that, for many motoneuron pools, the H reflex and the F wave appear preferentially in different motoneurons, low and high threshold, respectively, and that reflex studies can provide information not available from somatosensory evoked potentials or F wave studies.

Adult↗

Paraesthesiae and hypaesthesia following prolonged high-frequency stimulation of cutaneous afferents.

The activity of cutaneous afferents was recorded in human subjects using microelectrodes inserted into individual fascicles of the median nerve at the wrist before and after a 10 min train of electrical stimuli at 200 Hz delivered to the appropriate digital nerve (via ring electrodes) or to individual afferent axons (via the microelectrode). Changes in neural activity produced by the stimulation were correlated with the time course of paraesthesiae and with changes in the ability to detect cutaneous stimuli. From approximately 20 s after the end of the stimulus train, there was a progressive increase in neural activity, and individual afferents became spontaneously active and discharged in high-frequency bursts. At this time the subjects began to experience paraesthesiae. Repetitive stimulation proximal to a complete digital nerve block induced paraesthesiae that were felt distal to the block in the insensate digit, indicating that they did not arise from the unmyelinated terminal segment of the axon or from a stimulus-induced disorder of receptor function. Recordings of the compound action potential evoked by submaximal test stimuli were made after the 10 min stimulus train and revealed evidence of an early transient increase in excitability superimposed on a long-lasting decrease in excitability, reaching a nadir approximately 30-40 min after the end of the repetitive stimulation. In parallel recordings, there was no detectable change in the cutaneous afferent volley evoked by mechanical stimulation, paraesthesiae, can be attributed directly to a disturbance in peripheral afferent fibres, while the poststimulation negative symptoms such as hypaesthesia arise from stimulation-induced refractoriness at central synaptic relays.

Adult↗

Conduction velocities of muscle and cutaneous afferents in the upper and lower limbs of human subjects.

In the cat and monkey the fastest axons in the peripheral nerve are group I afferents from muscle, but there are no definitive data on conduction velocity for these afferents in human subjects. Knowledge of the relative conduction velocities of muscle and cutaneous afferents is important for the interpretation of reflex studies, evoked potentials and other aspects of motor control. To rectify this deficiency, the conduction velocities of the fastest muscle and cutaneous afferents were determined for the median, ulnar and tibial nerves of normal subjects. Low-threshold muscle afferents innervating abductor pollicis brevis, abductor digiti minimi and abductor hallucis were stimulated selectively through a microelectrode inserted percutaneously at the motor point. Low-threshold cutaneous afferents were stimulated with ring electrodes around the proximal phalanx of digits II or V for the upper limb and digit II for the lower limb. Compound action potentials were recorded with bipolar near-nerve electrodes at two sites in the proximal limb segment and conduction velocities of the fastest afferents in the neural volley calculated. The mean conduction velocities of the muscle and cutaneous afferents were, respectively, 74.7 +/- 6.5 m.s-1 and 80.3 +/- 6.7 m.s-1 for the median nerve, 67.5 +/- 10.2 m.s-1 and 67.5 +/- 10.5 m.s-1 for the ulnar nerve, and 54.7 +/- 3.4 m.s-1 and 52.8 +/- 3.2 m.s-1 for the tibial nerve. For upper and lower limb nerves the conduction velocities of low-threshold muscle and cutaneous afferents were not significantly different when measured over the same proximal segment.

Adult↗

Dominant effects of tubulin overexpression in Saccharomyces cerevisiae.

The consequences of altering the levels of alpha- and beta-tubulin in Saccharomyces cerevisiae were examined by constructing fusions of the structural genes encoding the tubulins to strong galactose-inducible promoters. Overexpression of beta-tubulin (TUB2) was lethal: cells arrested in the G2 stage of the cell cycle exhibited an increased frequency of chromosome loss, were devoid of microtubules, and accumulated beta-tubulin in a novel structure. Overexpression of the major alpha-tubulin gene (TUB1) was not lethal and did not affect chromosome segregation. The rate of alpha-tubulin mRNA and protein synthesis was increased, but the protein did not accumulate. Overexpression of both alpha- and beta-tubulin together resulted in arrested cell division, and cells accumulated excess tubules that contained both alpha- and beta-tubulin. Transient overexpression of both tubulins resulted in a high frequency of chromosome loss. These data suggest that strong selective pressure exists to prevent excess accumulation of microtubules or beta-tubulin and suggest a model by which this goal may be achieved by selective degradation of unassembled alpha-tubulin. Furthermore, the phenotype of beta-tubulin overexpression is similar to the phenotype of a beta-tubulin deficiency. These results add to a number of recent studies demonstrating that mutant phenotypes generated by overexpression can be informative about the function of the gene product.

Cell Cycle↗

Maintenance of visual fixation using a reaction-time task.

The VEP to pattern reversal was recorded in eight healthy subjects who were instructed to fixate on a central LED in the stimulating screen. The LED could be extinguished at irregular intervals approximately once every 10 s and the subjects were then required to re-light it as rapidly as possible in a reaction-time task. In the first series of recordings subjects were reminded verbally to maintain visual fixation throughout the averaging sequences. When the reaction-time paradigm was used to maintain visual fixation, the VEP was slightly less variable in latency but otherwise identical to that recorded when the subjects maintained visual fixation on a constantly illuminated LED. In a separate series of 8 consecutive averaging runs, subjects were given the reaction-time task but no verbal reminders. VEP parameters differed from those in the first series when verbal reminders had been given. There was no correlation between VEP parameters and the reaction time or its variability in individual subjects or in the group. The reaction-time task is a satisfactory means for ensuring accurate visual fixation but does not obviate the need to provide subjects with verbal encouragement to maintain full attention.

Evoked Potentials, Visual↗

Changes in muscle and cutaneous cerebral potentials during standing.

The cerebral potentials produced by electrical stimulation of mechanoreceptive afferents from the foot were recorded in the sitting and standing postures to determine whether transmission to cortex was altered by the postural change. The latencies of the early components of the cerebral potentials produced by muscle afferents (posterior tibial nerve) and cutaneous afferents (sural nerve) did not change with posture. Standing was associated with an approximately 25-35% decline in amplitude of the earliest components of the posterior tibial cerebral potential (N38-P40, P40-N50) for a stimulus intensity associated with a submaximal afferent volley. The amplitude of the equivalent N38-P40 and P40-N50 components produced by sural afferents also declined during quiet stance. In most experiments the subcortical component (P32-N38) was not reduced by stance so that the amplitude attenuation probably occurs in part at cortical level. Qualitatively similar changes in the cerebral potentials were documented for a range of stimulus intensities, including those which evoked a maximal initial component in the nerve volley. For a similar reduction in the initial (N38-P40) component of the cerebral potential, voluntary plantar flexion in the sitting position produced less attenuation in subsequent components than did standing. Thus, attenuation of the cerebral potential during standing may involve specific posture-related factors in addition to those related to volition.

Afferent Pathways↗