Changes in the excitability of anterior horn cells in a mental rotation task of body parts.

INTRODUCTION/AIMS: Mental rotation (MR), a tool of implicit motor imagery, is the ability to rotate mental representations of two- or three-dimensional objects. Although many reports have described changes in brain activity during MR tasks, it is not clear whether the excitability of anterior horn cells in the spinal cord can be changed. In this study, we examined whether MR tasks of hand images affect the excitability of anterior horn cells using F-wave analysis. METHODS: Right-handed, healthy participants were recruited for this study. F-waves of the right abductor pollicis brevis were recorded after stimulation of the right median nerve at rest, during a non-MR task, and during an MR task. The F-wave persistence and the F/M amplitude ratio were calculated and analyzed. RESULTS: Twenty participants (11 men and 9 women; mean age, 29.2 ± 4.4 years) were initially recruited, and data from the 18 that met the inclusion criteria were analyzed. The F-wave persistence was significantly higher in the MR task than in the resting condition (p = .001) or the non-MR task (p = .012). The F/M amplitude ratio was significantly higher in the MR task than in the resting condition (p = .019). DISCUSSION: The MR task increases the excitability of anterior horn cells corresponding to the same body part. MR tasks may have the potential for improving motor function in patients with reduced excitability of the anterior horn cells, although this methodology must be further verified in a clinical setting.

Tail Nerve Electrical Stimulation and Electro-Acupuncture Can Protect Spinal Motor Neurons and Alleviate Muscle Atrophy after Spinal Cord Transection in Rats.

Spinal cord injury (SCI) often results in death of spinal neurons and atrophy of muscles which they govern. Thus, following SCI, reorganizing the lumbar spinal sensorimotor pathways is crucial to alleviate muscle atrophy. Tail nerve electrical stimulation (TANES) has been shown to activate the central pattern generator (CPG) and improve the locomotion recovery of spinal contused rats. Electroacupuncture (EA) is a traditional Chinese medical practice which has been proven to have a neural protective effect. Here, we examined the effects of TANES and EA on lumbar motor neurons and hindlimb muscle in spinal transected rats, respectively. From the third day postsurgery, rats in the TANES group were treated 5 times a week and those in the EA group were treated once every other day. Four weeks later, both TANES and EA showed a significant impact in promoting survival of lumbar motor neurons and expression of choline acetyltransferase (ChAT) and ameliorating atrophy of hindlimb muscle after SCI. Meanwhile, the expression of neurotrophin-3 (NT-3) in the same spinal cord segment was significantly increased. These findings suggest that TANES and EA can augment the expression of NT-3 in the lumbar spinal cord that appears to protect the motor neurons as well as alleviate muscle atrophy.

Transcranial magnetic stimulation and amyotrophic lateral sclerosis: pathophysiological insights.

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disorder of the motor neurons in the motor cortex, brainstem and spinal cord. A combination of upper and lower motor neuron dysfunction comprises the clinical ALS phenotype. Although the ALS phenotype was first observed by Charcot over 100 years ago, the site of ALS onset and the pathophysiological mechanisms underlying the development of motor neuron degeneration remain to be elucidated. Transcranial magnetic stimulation (TMS) enables non-invasive assessment of the functional integrity of the motor cortex and its corticomotoneuronal projections. To date, TMS studies have established motor cortical and corticospinal dysfunction in ALS, with cortical hyperexcitability being an early feature in sporadic forms of ALS and preceding the clinical onset of familial ALS. Taken together, a central origin of ALS is supported by TMS studies, with an anterograde transsynaptic mechanism implicated in ALS pathogenesis. Of further relevance, TMS techniques reliably distinguish ALS from mimic disorders, despite a compatible peripheral disease burden, thereby suggesting a potential diagnostic utility of TMS in ALS. This review will focus on the mechanisms underlying the generation of TMS measures used in assessment of cortical excitability, the contribution of TMS in enhancing the understanding of ALS pathophysiology and the potential diagnostic utility of TMS techniques in ALS.

Effect of volitional relaxation and motor imagery on F wave and MEP: do these tasks affect excitability of the spinal or cortical motor neurons?

OBJECTIVE: To test if simple motor imagery, like thumb abduction, preferentially influences the excitability of the spinal or cortical motoneurons. METHODS: Ten healthy subjects underwent two separate experiments, each consisting of recording F waves and MEPs from abductor pollicis brevis (APB) in three consecutive sessions: (1) baseline, (2) after immobilizing APB for 3 h, and (3) after brief muscle exercise. During the immobilization, the subjects were instructed to volitionally relax APB in experiment 1 (relaxation task), and mentally simulate thumb abduction without actual movement in experiment 2 (imagery task). RESULTS: Relaxation task suppressed both MEPs and F waves. Motor imagery reduced this suppression, restoring F waves nearly completely (94%) and MEPs only partially (77%). Hence, the rest-induced decline of MEPs in part results from cortical modulation. In contrast, statistical analysis revealed no differences in imagery-induced recovery of motoneuron excitabilities whether assessed by F wave or MEP. Thus, increased excitability of spinal motoneurons responsible for F-wave changes also accounts for recovery of MEPs. CONCLUSIONS: Volitional relaxation depresses the spinal and cortical motoneurons, whereas mental simulation counters rest-induced suppression primarily by restoring spinal excitability. SIGNIFICANCE: The present findings help elucidate physiologic mechanisms underlying motor imagery.

Postnatal development of a segmental switch enables corticospinal tract transmission to spinal forelimb motor circuits.

Development of skilled movements and the corticospinal tract (CST) begin prenatally and continue postnatally. Because the CST is required for skilled movements in maturity, it is accepted that motor skills cannot occur until the CST develops a mature organization. We recently showed that the CST plays an essential role in postnatal development of interneurons comprising the spinal circuits it engages. We proposed that CST signals are more effectively transmitted to ventral motor circuits after interneuron maturation, thereby enabling expression of CST motor functions, suggesting development of a segmental switch promoting transmission. We tested this by recording CST-evoked focal synaptic potentials, extracellularly, in the cervical enlargement of cats before and after interneuron maturation [postnatal week 5 (PW5) to PW7]. We compared monosynaptic CST amplitude input to segmental circuits with oligosynaptic ventral horn responses, as a measure of CST-evoked segmental response transmission from input to output. The M1 primary motor cortex was unilaterally inactivated between PW5 and PW7 to determine activity dependence. CST interneuron contacts were identified using confocal microscopy. CST terminals contact diverse interneuron classes. CST stimulation strongly activated ventral motor circuits at the ages when both interneurons and CST spinal terminations have developed a mature phenotype, supporting development of segmental transmission of CST signals. CST activity blockade impeded development of effective segmental transmission by the inactivated CST and created a novel path for transmission from the ipsilateral, unaffected, CST. Our findings show that development of segmental CST signal transmission regulates nascent CST motor control functions and provide insight into systems-level mechanisms for protracted motor skill development.

Effect of motion imagery to counter rest-induced suppression of F-wave as a measure of anterior horn cell excitability.

OBJECTIVE: To test if motor imagery prevents the rest-induced suppression of anterior horn cell excitability. METHODS: Ten healthy subjects underwent two separate experiments, each consisting of stimulating the median nerve 100 times and recording F-waves from abductor pollicis brevis (APB) in three consecutive sessions: (1) after muscle exercise to standardize the baseline, (2) after immobilization of APB for 3h and (3) after muscle exercise to check recovery. We instructed the subject to volitionally relax APB in experiment 1 (relaxation task), and to periodically simulate thumb abduction without actual movement in experiment 2 (imagery task). RESULTS: F-wave persistence and amplitude declined after relaxation task and recovered quickly after exercise, but changed little with imagery task. F-wave latencies showed no change when analyzed individually. The frequency distribution of collective F-waves recorded from all subjects remained the same after relaxation task, but showed a shift toward longer latencies after imagery task. CONCLUSIONS: Mental imagery without overt motor output suffices to counter the effect of sustained volitional muscle relaxation, which would, otherwise, cause a reversible reduction in anterior horn cell excitability. SIGNIFICANCE: This finding documents the importance of central drive for spinal excitability, which affects F-wave studies of a paretic muscle.

Intraspinal microstimulation using cylindrical multielectrodes.

A cylindrical multielectrode system specifically designed for intraspinal microstimulation was mechanically and electrically evaluated in the ventral horn of the feline lumbo-sacral spinal cord. Electrode insertions proved to be straight as evaluated from radiographs. Impedances were measured in situ and force recruitment curves from quadriceps muscles were collected over a wide range of stimulus parameters. For a given charge, higher current amplitudes produced greater forces than proportionally longer pulse durations, indicating that charge is not the sole indicator of evoked force in applications utilizing electrical stimulation. Overlap measurements for calculating current-distance constants were collected at a variety of current amplitudes, electrode pair separations, and pair orientations in the spinal grey matter. Forces obtained in the majority of these trials demonstrated an order effect, presumably due to asymmetric neuronal connectivity within the spinal cord. In the cases showing no order effect, the dorso-ventral electrode pair orientation yielded a higher average current-distance constant (278 microA/mm2) than either the medio-lateral or rostro-caudal electrode pair orientations (197 microA/mm2). Specifications of an array of cylindrical multielectrodes for use in future intraspinal microstimulation prostheses were updated.

Mesencephalic projections to the first cervical segment in the cat.

Mesencephalic neurons projecting to the upper cervical spinal cord were examined by mapping the distributions of labeled cells after injecting fluorescent tracers or wheat-germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) into the C1 segment. Injections into the central or deep regions of the ventral horn produced retrograde labeling in cells of several mesencephalic regions. The majority of cells were found contralaterally in the superior colliculus and red nucleus, and ipsilaterally in and around the interstitial nucleus of Cajal (INC), in the cuneiform region, and in the fields of Forel. Smaller numbers of cells were located in the periaqueductal gray matter, nucleus annularis, and magnocellular nucleus of the posterior commissure. Dorsomedial injections in the ventral horn near the ventral commissure labeled only a subset of these projections, including cells in the mesencephalic reticular formation adjacent to the INC and in the nucleus annularis. Dorsolateral injections labeled some cells in the superior colliculus and were particularly effective at labeling cells in the red nucleus. These results suggest that at least ten different cell groups project to the ventral horn of the first cervical segment. Most, but not all, groups originate from regions implicated previously in the control of eye or head movements.

Responses of cat C1 spinal cord dorsal and ventral horn neurons to noxious and non-noxious stimulation of the head and face.

Previous anatomical studies have shown that trigeminal and cervical afferent nerve fibers project to the upper cervical segments of the spinal cord. To determine the response properties of neurons in the upper cervical spinal cord, we studied the response of C1 dorsal and ventral horn cells to electrical and graded mechanical stimulation of the face, head and neck in anesthetized cats. Neurons were classified as low-threshold-mechanoreceptive (LTM), wide-dynamic-range (WDR), nociceptive-specific (NS) or unresponsive, based on their responsiveness to graded mechanical stimulation. Extracellular single unit recordings were obtained from 118 neurons excited by cervical (24), trigeminal (39) or both cervical and trigeminal (55) stimulation and from 24 neurons unresponsive to peripheral stimulation. Based on neuronal mechanical response properties, 52.2% of the responsive neurons were classified as LTM, 35.9% as WDR and 11.9% as NS. WDR neurons exhibited more convergence and had larger receptive fields than either NS or LTM neurons. WDR and NS neurons had longer first spike latencies than LTM neurons at all tested sites. Only WDR neurons were found to project to the contralateral caudal thalamus. Within C1, LTM neurons were located primarily in laminae III and IV, WDR neurons in lamina V and NS neurons in laminae VII and VIII. These data suggest that some neurons in the first cervical segment of the spinal cord receive convergent input from trigeminal and cervical pathways and may be involved in mediating orofacial and cranial pain.

Evidence of rhythmic inhibitory synaptic influences in hindlimb motoneurons during fictive locomotion in the thalamic cat.

Intracellular recordings of various motoneurons of proximal hindlimb muscles were performed on thalamic paralyzed cats, during fictive locomotion that was either spontaneous or evoked by stimulation of the subthalamic region. In motoneurons innervating sartorius (medialis and lateralis), vasti (intermedius, medialis and lateralis) and anterior biceps-semimembranous, one depolarization occurred in each locomotor cycle, alternating with a phase of repolarization that was synchronous with the activation of the antagonistic muscle nerve. This latter phase could be decreased or reversed by intracellular injection of chloride ions or current, revealing the presence of inhibitory inputs onto motoneurons. The pattern of membrane potential variations was more complex in motoneurons of rectus femoris and posterior biceps-semitendinosus muscles, but phases of chloride dependent inhibition were nevertheless identified, mainly during the sartorius nerve activation in the case of rectus femoris, and during the vasti and anterior biceps-semimembranosus nerve activations in the case of posterior biceps-semitendinosus. These inhibitory influences were shown to be controlled by the level of activity in exteroceptive afferents. The characteristics of the excitatory and inhibitory inputs to the hindlimb motoneurons identified here are discussed in relation with the organization of the central pattern generator for locomotion.

Site of anti-nociceptive action of a new benzomorphan derivative ID-1229.

The site of anti-nociceptive action of a new benzomorphan derivative ID-1229, 2-[3-(p-fluorobenzoyl)-1-propyl]-5 alpha, 9 alpha-dimethyl-2'-hydroxyl-6, 7-benzomorphan was investigated using electrophysiological methods. In rabbits, ID-1229 (0.1-0.5 mg/kg) caused slowing in the EEG, and depressed the evoked potentials recorded from the sensory cortex and the Nucleus ventralis posterolateralis of the thalamus elicited by sciatic stimulation. A small dose (1 mg/kg) of ID-1229 decreased the bradykinin-induced unitary discharges of lamina V neuron of the spinal dorsal horn in intact rabbits but not in spinal rabbits. These results suggest that ID-1229 inhibits the sensory transmission of bradykinin-induced pain at the dorsal horn of the spinal cord, through its facilitatory action on the descending inhibitory system from the supra-spinal structure.