Depression of the recurrent inhibition of extensor motoneurons by the action of group II afferents.

The influence of varying the muscular afferent fiber input on both the normal firing rate (Fn) and the amount of recurrent inhibition (Fn-Fi) induced by a constant ventral root stimulation was investigated on tonic extensor motoneurons recorded from ventral root filaments in decerebrate cats. The afferent input was varied by graded electrical stimulation of the gastrocnemius nerves and by vibrating the triceps surae muscle (100 mum amplitude). When the input consisted solely of impulses in Ia afferents, as was the case during vibration, the mean recurrent inhibition Fn-Fi was 2.3 times greater than during nerve tetanization at 1.8 times threshold of group I (TI). This strength generally excited all group I and some low-threshold group II afferents. Between 1.8 TI and 8 TI, Fn-Fi decreased by some 50%. The average Fn increased slightly and motoneurons with a phasic discharge pattern were recruited when the stimulus strength was raised so as to excite group II afferents; these cells were never recruited during vibration and nerve tetanization at 1.8 TI. The results indicate the possibility of a disinhibitory action of secondary muscle spindle afferents on extensor motoneurons by reducing the recurrent inhibition.

Corticostriatal cells in comparison with pyramidal tract neurons: contrasting properties in the behaving monkey.

Antidromically identified neurons projecting to the putamen (CPNs) and pyramidal tract neurons (PTNs) were recorded from motor and premotor cortex of a monkey which performed a load-bearing task with the wrist. CPNs appeared as a uniform population with very slowly conducting axons and low spontaneous activity. In contrast to PTNs, they exhibited weak, mostly insignificant correlation with graded steady-state forces, responded to torque perturbations with remarkably long latency, and seemed to discharge much later with active movement. Collateral branching of PTNs to the putamen was found to be infrequent (1%). We suggest that the putamen receives a cortical message that is strikingly different from that sent down the pyramidal tract.

Pyramidal tract neurons in somatosensory cortex: central and peripheral inputs during voluntary movement.

Recordings with pyramidal tract neurons (PTNs) in the primary somatosensory cortex of the monkey show that these neurons have 3 properties in common with PTNs of primary motor cortex: (1) they exhibit discharge prior to the onset of voluntary movement, (2) their discharge frequency varies as a function of strength of muscular contraction, and (3) they show reflex responses to afferent stimuli that occur during movement. These findings support the view that in addition to its widely recognized role in somesthetic perception, somatosensory cortex has a direct role in the control of movement.

Spinal dynorphin immunoreactivity increases bilaterally in a neuropathic pain model.

Increased spinal levels of dynorphin, an endogenous opioid kappa agonist, are seen in models of both chronic and acute hyperalgesia. This study determined the extent and localization of spinal immunoreactive dynorphin following sciatic cryoneurolysis (SCN), a neuropathic pain model produced by a peripheral nerve freeze lesion. SCN results in behaviors associated with neuropathic pain such as autotomy (the gnawing and scratching of the affected limb), touch-evoked and mechanical allodynia, and spontaneous nociceptive behavior. Following SCN, 4 rats that displayed autotomy and 3 rats that did not were randomly chosen for immunohistochemical staining of dynorphin-like immunoreactivity (DLIR). The area of DLIR above a standardized threshold level was quantified in both dorsal horns of each spinal cord section using a computer-assisted image analyzer to express DLIR in pixels. DLIR was observed both ipsilateral and contralateral to the injured peripheral nerve. In addition, the area of DLIR was significantly greater (P = 0.05) in rats that showed autotomy behavior (mean = 52.6 x 10(3) +/- 25.6) compared to rats with no autotomy (mean = 13.8 x 10(3) +/- 4.78). In sharp contrast to the ipsilateral dynorphin increases observed in other neuropathic pain models, we observe a bilateral increase at 21 days following SCN.

Relation of motor cortex neurons to precisely controlled and ballistic movements.

A visual pursuit-tracking paradigm was used for training monkeys to position a handle within a small zone and rotate it by pronation-supination movements. Motor cortex unit discharge was examined in relation to movements carried out in this situation, with particular attention to large ballistic movements as compared to small precisely controlled movements. Intense unit discharge was found to occur with even the smallest movements made to achieve accurate positioning of the handle. Within the group of motor cortex pyramidal tract neurons (PTNs), slowly conducting tonically discharging PTNs showed the most selective relations to these small precisely controlled movements.

Sensory responses in motor cortex neurons during precise motor control.

Precentral neurons whose activity changed with precisely controlled small supination-pronation movements almost invariably showed sensory responses to small perturbations which pronated or supinated the forearm in conscious monkeys. Conversely, most units failing to show changes with small movements but being recruited with large ballistic movements were unaffected by these kinesthetic inputs. Moreover, perturbations which yielded intense short-latency unit responses when delivered during postural stability usually failed to modify unit activity when delivered during a ballistic movement. It is suggested that sensory feedback continuously modulates motor cortex neuron discharge during accurate positioning and precise fine movement, whereas during ballistic movements such modulation is greatly attenuated.

Intrathecal catheterization alone reduces autotomy after sciatic cryoneurolysis in the rat.

There is substantial evidence that sciatic cryoneurolysis (SCN, freeze lesion of the sciatic nerve) is a neuropathic pain model in the rat. During characterization of this model, SCN was performed 4 days after either a sham operation or the insertion of an indwelling intrathecal catheter preparatory to selective spinal drug administration. Body weight and autotomy scores were recorded for the next 22 days until sacrifice. The catheter group experienced significant weight loss (7.5%) by 4 days but rapidly regained to parity with the sham group. Autotomy scores and the frequency of severe autotomy (score > 3) were less at day 22 in the catheter group as compared with the sham-control group (p < 0.005, p < 0.03, respectively). Intrathecal catheterization itself effects the degree of behavioral response to neurogenic pain and thus, should be controlled for in studies using nociceptive animal models.

Relationships among trihalomethane formation potential, organic carbon and lake enrichment.

Trihalomethanes (THMs) are potential carcinogens formed from the reaction of the disinfectant chlorine with organic matter in the source water. This study of Kansas drinking water supply lakes evaluates the relationship among THM formation potential (THMFP), organic carbon and lake trophic state (LTS). THMFP was positively correlated to organic carbon. Total THMFP and total organic carbon were positively correlated to LTS, an estimator of lake enrichment, when very turbid lakes were omitted. These very turbid lakes (due to high suspended solids concentrations) had higher than expected THMFP, based on LTS, and higher organic carbon concentrations. THM data measured in the treated drinking water were positively correlated to THMFP, total organic carbon and LTS. The levels of organic carbon that contribute to THMs are a result of lake and watershed factors related to increasing levels of enrichment and suspended sediments. These factors are controllable by appropriate management practices.

Thalamic deep brain stimulation improves eyeblink conditioning deficits in essential tremor.

Several lines of evidence point to a disturbance of olivo-cerebellar pathways in essential tremor (ET). For example, subjects with ET exhibit deficits in eyeblink conditioning, a form of associative learning which is known to depend on the integrity of olivo-cerebellar circuits. Deep brain stimulation (DBS) of the ventrolateral thalamus is an established therapy for ET. If tremor in ET is related to the same pathology of the olivo-cerebellar system as impaired eyeblink conditioning, one may expect modulation of eyeblink conditioning by DBS. Delay eyeblink conditioning was assessed in 11 ET subjects treated with DBS (ET-DBS subjects) who were studied on two consecutive days with DBS switched off (day 1) and on (day 2). For comparison, 11 age-matched ET subjects without DBS (ET subjects) and 11 age-matched healthy controls were studied. On day 1, eyeblink conditioning was diminished in ET-DBS subjects and in ET subjects compared with controls. When DBS was switched on ET-DBS subjects exhibited conditioning rates within the range of controls on day 2, while ET subjects improved only minimally. Improved eyeblink conditioning in ET-DBS subjects suggests that thalamic DBS counteracts a functional disturbance of olivo-cerebellar circuits which is thought to be responsible for eyeblink conditioning deficits in ET. Modulation of cerebello-thalamic and/or thalamo-cortico-cerebellar pathways by DBS may play a role.

Electrophysiological proof of diffusion-weighted imaging-derived depiction of the deep-seated pyramidal tract in human.

In the living human brain the pyramidal tract (PT) can be displayed with magnetic resonance diffusion-weighted imaging (DWI). Although this imaging technique is already being used for planning and performing neurosurgical procedures in the PT vicinity, there is a lack of verification of DWI accuracy in other areas outside the directly subcortical PT parts. Before definitive electrode placement into the subthalamic nucleus (STN) in patients with Parkinson disease (PD) for chronic stimulation, the stimulation effect on PD symptoms and the side-effects, namely PT activation at the level of the internal capsule (IC), are electrophysiologically tested. To analyze DWI accuracy by matching the stereotactic coordinates of the electrophysiologically proven IC position with these of the DWI-derived IC display, DWI was added to the routine MRI work-up in the stereotactic frame prior to functional surgery in 6 patients. In all of the 10 displayed fiber tracts, concordant findings for imaging and macrostimulation were made. The authors proved for the first time that DWI correctly depicts the deep seated, principle motor pathways in the living human brain. Due to methodical limitations of this study the accuracy of the proven IC display is limited to 3 mm which has proven to be sufficient for the planning and performance of neurosurgical procedures in the vicinity of large fiber tracts.

Changes of steady state activity in motor cortex consistent with the length-tension relation of muscle.

Steady state activity of motor cortex (MI) neurons and muscles was examined in relation to joint position. Two monkeys performed either isometric or load-bearing isotonic contractions, at different joint positions and during variation of steady torque. In either condition, MI steady state firing rate were found to be related to the amount of muscular excitation necessary to adjust muscle tension to length at any given position and load. The results obtained from 526 neurons (including pyramidal tract neurons) demonstrate for 206 neurons a correlate of the length-tension relation of muscle in the motor cortex.

Reflex responses of gamma motoneurones to vibration of the muscle they innervate.

1. High frequency vibration was applied to the tendon of the non-contracting triceps surae muscle while recording the background discharges of single gamma fibres only small nerve bundles were cut, leaving most of the nerve supply to the triceps intact. 2. 22% out of a total of sixty-three gamma efferents were tonically inhibited by vibration. The inhibition appeared between 25 and 50mum peak-to-peak amplitude of vibration and increased to a plateau for amplitudes of about 100mum. The dependence of the tonic vibration reflex of alpha-efferents on the amplitude of vibration was found to be similar. Increasing the frequency of vibration from 150 to 300 Hz increased the degree of inhibition. 3. 33% of the fusimotor neurones investigated responded to muscle vibration with an increase in discharge rate. The threshold amplitudes of this reflex ranged from 20 to 50mum. Some features of the reflex, in particular the parallel post-vibratory facilitation found in alpha and gamma efferents, pointed to a polysynaptic pathway organized in an alpha-gamma linkage. 4. All gamma efferents inhibited by vibration showed inhibitory responses to antidromic stimulation of the parent ventral root, and most of them were inhibited by ramp stretch of the triceps. The gamma motoneurones facilitated by vibration, however, were excited by muscle stretch and were less susceptible to antidromic inhibition, some lacking it completely. 5. Cutting the nerves to triceps abolished the inhibitory as well as the excitatory responses of gamma efferents to muscle vibration. Both fusimotor reflexes were preserved after spinal section and subsequent administration of L-DOPA. 6. It is concluded that both of the fusimotor reflex effects of vibration are caused by excitation of primary spindle endings within the triceps. The inhibition of fusimotor neurones is thought to be mediated by Renshaw cells activated during vibration. The significance of positive feed-back on to gamma motoneurones as a result of autogenetic facilitation by Ia afferents is discussed in connexion with stability in the stretch reflex loop.

Transcortical reflexes and servo control of movement.

Sherrington proposed that the major role of proprioceptors is in processing afferent inputs generated by the active movements of the animal itself, and noted that the reflex effects of proprioceptive inputs are "mild." Current experimental results are consistent with the view that the major role of both segmental and transcortical proprioceptive reflexes is in small active movements and active postural stability, with muscle afferent inputs reducing "...errors of muscle length produced by fluctuating levels of motor discharge..." as stated by Goodwin and coworkers in 1978. Exteroceptive reflexes generate intense muscular responses and are of critical importance in prompt reprogramming essential for effective responses to environmental stimuli. Within the motor cortex (MI) there is a caudal region (MI/c) which receives exteroceptive cutaneous inputs and a rostral region (MI/r) which receives proprioceptive inputs. Transcortical reflexes mediated via pyramidal tract neurons (PTNs) of MI/r have properties which are analogous to segmental proprioceptive reflexes: changes of muscle length elicit PTN discharges which oppose the length change and so act to maintain stability. Furthermore, MI/r PTNs which are recruited earliest for small active movements are most sensitive to proprioceptive inputs. Data are not yet available concerning transcortical reflexes via MI/c during voluntary movement, but it is speculated that the cutaneous reflexes via MI/c might be functionally analogous to segmental cutaneous reflexes. Short-latency reflex responses also occur in postcentral (PoC) PTNs, and in this report we present results concerning the properties of PoC PTNs during active and passive movement. Caudal (area 2-5) PoC PTNs were similar to MI PTNs in that they often discharged prior to electromyogram (EMG) activity with active movement, and had different discharge frequencies with different steady state loads, but were unlike most MI PTNs in having the same changes of discharge with active and passive movement. Our finding of PoC discharge prior to movement onset, confirming that of Soso and Fetz in 1980, is discussed in connection with the concept of corollary discharge.

Relation of size and activity of motor cortex pyramidal tract neurons during skilled movements in the monkey.

Activity of motor cortex pyramidal tract neurons (PTNs) was recorded in monkeys making large (20 degrees), high velocity and small (1 to 2 degrees), low velocity pronation-supination arm movements in a visual pursuit-tracking paradigm. Antidromic response latencies (ADLs) or PTNs were examined in relation to PTN modulation with the large and small movements to test the hypothesis that PTNs would exhibit a "size principle" analogous to that of spinal cord motoneurons. It was found that smaller PTNs (i.e., those having longer ADLs) discharged just as strongly with small, slow movements as with large, fast movements, while about one-third of the larger PTNs (even those selected for a significant relation to small movement) discharged more intensely with the large movement. Another analysis dealing with PTNs in a selected set of penetrations in an area focal for pronation-supination showed that PTNs with longer ADLs (greater than 1 msec) were more likely to reach maximum frequency with small, slow movement. There was, however, much overlap in the behavior of small and large PTNs, and while there was a statistically significant relation between size and movement-related activity of PTNs, there did not seem to be a "size principle" in the strict sense that this term has been used with reference to spinal cord motoneurons.

Static firing rates of premotor and primary motor cortical neurons associated with torque and joint position.

Single cell activity was studied in the postarcuate premotor area (PMA) and primary motor cortex (MI) of two monkeys performing a load-bearing task with the contralateral hand. Steady-state discharge rates were examined in relation to positional maintenance of the wrist which was held in one of three given positions against graded torques directed towards flexion or extension. Significant and monotonic relationships between tonic firing rate and static torque were found in 41% of 477 MI cells and in only 26% of 470 units studied in PMA. However, for specific cell groups in the PMA the proportion of load-related neurons reached that of the MI samples; this was true for pyramidal tract neurons (PTNs) and for 'non-PTNs' if recorded in their vicinity. The most interesting difference pertains to the range of load over which cells in both areas modulated activity. MI neurons showed steepest change of firing rates over a limited range of small torques around zero external load; the population average displayed a sigmoidal relationship. Proportionally more PMA neurons increased their activity over the entire range of torques examined or showed the highest increase with stronger torques; the population average best fitted a quadratic function. The mean firing rate-torque slope of the PMA population was significantly smaller than that of MI. Many cells in either area were related to both torque and joint position and displayed correlates of length-tension properties of muscle. Change of position sensitivity with torque was found to parallel the rate-torque characteristics in individual neurons. Mean position sensitivity of PMA neurons increased with increasing torques in the 'preferred' direction. In contrast, greatest position sensitivity of the MI population occurred over the range of low torques, which means a clear quantitative dissociation from the muscular activities. The results suggest differential roles of MI and PMA in the control of 'fine' versus 'gross' muscular forces. Undoubtedly, some PMA cell elements (possibly certain output neurons) are involved in aspects of postural control of EMG adjustment to load and joint position.

Inhibition of extensor gamma motoneurons by anatagonistic primary and secondary spindle afferents.

About 2/3 of the gamma efferents isolated from the medial gastrocnemius nerve were inhibited by longitudinal high-frequency vibration applied to the tendons of the non-contracting pretibial flexors (decerebrate cats). The inhibition appeared at 15-25 mum amplitude of vibration and increased up to maximum at nearly 100 mum. Increasing the frequency of vibration from 100 to 300 Hz increased the inhibition. The reflex effects elicited by muscle vibration corresponded well in incidence and magnitude with those evoked by tetanization of the deep peroneal nerve at group I stimulus strength. The reflex disappeared when the nerve supply of the vibrated muscles was cut. The sensitivity of some pretibial proprioceptors to vibration was also tested. It is concluded that primary spindle endings of the pretibial flexors inhibit the extensor gamma motoneurons. Some findings hint at a spinal pathway involving Ia inhibitory interneurons. In addition, an inhibitory action of pretibial group II afferents, probably secondary spindle endings, on extensor gamma efferents was demonstrated. The described fusimotor inhibition by antagonistic muscle spindle afferents is a further example of alpha-gamma-linkage.