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Major events in the development of the forebrain.

The development of the central nervous system can be divided into a number of phases, each of which is characterized by particular developmental disorders. In recent years, much progress has been made in elucidating the mechanisms by which the forebrain develops and in our understanding of major developmental disorders such as holoprosencephaly and neuronal migration disorders. In this general introduction to this symposium the major stages in the development of the forebrain, its regionalization and the genes involved, and some of the developmental disorders derailing cortical development with subsequent damage to the main cortical fiber connections (pyramidal tract and corpus callosum) are discussed.

Brain↗

Computed tomographic demonstration of cerebral edema in a child with galactosemia.

An eight-day-old male infant with galactosemia presented with signs of increased intracranial pressure and no evidence of intracranial infection or hemorrhage. Computed tomographic scans demonstrated the presence of diffuse cerebral edema. With treatment, the edema gradually resolved, although it persisted longer within the white matter and was associated with transient bilateral pyramidal tract signs.

Brain Edema↗

[Rapid course amyotrophic lateral sclerosis].

The case of a 58-year-old woman is reported, whose illness began with a pain in the left shoulder. Later a spastic palsy developed in the hands, and a flaccid one in the arms and lower limbs. After a treatment for 12 months she died from respiratory failure. The motor nerve cells in the spinal cord, brainstem and cerebral cortex together with the pyramidal tracts had degenerated symmetrically.

Amyotrophic Lateral Sclerosis↗

Excitation of the corticospinal tract by electromagnetic and electrical stimulation of the scalp in the macaque monkey.

1. The responses evoked by non-invasive electromagnetic and surface anodal electrical stimulation of the scalp (scalp stimulation) have been studied in the monkey. Conventional recording and stimulating electrodes, placed in the corticospinal pathway in the hand area of the left motor cortex, left medullary pyramid and the right spinal dorsolateral funiculus (DLF), allowed comparison of the actions of non-invasive stimuli and conventional electrical stimulation. 2. Responses to electromagnetic stimulation (with the coil tangential to the skull) were studied in four anaesthetized monkeys. In each case short-latency descending volleys were recorded in the contralateral DLF at threshold. In two animals later responses were also seen at higher stimulus intensities. Both early and late responses were of corticospinal origin since they could be completely collided by appropriately timed stimulation of the pyramidal tract. The latency of the early response in the DLF indicated that it resulted from direct activation of corticospinal neurones: its latency was the same as the latency of the antidromic action potentials evoked in the motor cortex from the recording site in the DLF. 3. Scalp stimulation, which was also investigated in three of the monkeys, evoked short-latency volleys at threshold and at higher stimulus intensities these were followed by later waves. The short-latency volleys could be collided from the pyramid and, at threshold, had latencies compatible with direct activation of corticospinal neurones. The longer latency volleys were also identified as corticospinal in origin. 4. The latency of the early volley evoked by electromagnetic stimulation remained constant with increasing stimulus intensities. In contrast, with scalp stimulation above threshold the latency of the early volleys decreased considerably, indicating remote activation of the corticospinal pathway below the level of the motor cortex. In two monkeys both collision and latency data suggest activation of the corticospinal pathway as far caudal as the medulla. 5. The majority of fast corticospinal fibres could be excited by scalp stimulation with intensities of 20% of maximum stimulator output. Electromagnetic stimulation at maximum stimulator output elicited a volley of between 70 and 90% of the size of the maximal volley evoked from the pyramidal electrodes. 6. Electromagnetic stimulation was also investigated in one awake monkey during the performance of a precision grip task. Short-latency EMG responses were evoked in hand and forearm muscles. The onsets of these responses were approximately 0.8 ms longer than the responses evoked by electrical stimulation of the pyramid.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

[Modulation of pyramidal responses of the sensomotor cortex after combined stimulation of the lateral hypothalamus and the sensomotor cortex of the rat].

Periodical pyramidal tract (PT) stimulation in freely moving rats has been shown to be accompanied by statistically significant increased functional activity of neuronal populations of the sensorimotor cortex (SMC) manifesting as potentiation of the primary positive phase of the pyramidal-cortical response (PCR). When periodical PT stimulation is combined with the lateral hypothalamus (LH) stimulation of the same periodicity, a statistically significant increase in the magnitude of potentiation of the PCR positive phase compared to that occurring without the LH activation is observed. When the periodical PT stimulation is combined with the LH and SMC stimulation of the same periodicity, the potentiation of the PSR positive phase increases significantly in comparison with the potentiation occurring without the SMC stimulation.

Animals↗

[Myelopathy-hand and cervical spondylotic myelopathy].

The clinical manifestations and MRI characteristics of 58 patients with cervical spondylotic myelopathy were analysed in this study. The results showed that there was myelopathy-hand in 49 patients and none in 9 patients. Two groups were not significantly different in gender, age, course and involved segment, side or level of spinal cord(P > 0.05), but were significantly different in the compression degree of spinal cord(P < 0.01). In the positive group, the degree of myelopathy-hand was positively related to the severity of spastic gait, pyramidal tract sign and spinal cord compression.

Adult↗

Thyrotropin-releasing hormone-immunoreactive projections to the dorsal motor nucleus and the nucleus of the solitary tract of the rat.

Thyrotropin-releasing hormone-immunoreactive nerve terminals heavily innervate the dorsal motor nucleus and nucleus of the solitary tract, whereas cell bodies containing thyrotropin-releasing hormone residue most densely in the hypothalamus and raphe nuclei. By using double-labeling techniques accomplished by retrograde transport of Fluoro-Gold following microinjection into the dorsal motor nucleus/nucleus of the solitary tract combined with immunohistochemistry for thyrotropin-releasing hormone, it was demonstrated that thyrotropin-releasing hormone-immunoreactive neurons projecting to the dorsal motor nucleus/nucleus of the solitary tract reside in the nucleus raphe pallidus, nucleus raphe obscurus, and the parapyramidal region of the ventral medulla, but not in the paraventricular nucleus of the hypothalamus. The parapyramidal region includes an area along the ventral surface of the caudal medulla, lateral to the pyramidal tract and inferior olivary nucleus and ventromedial to the lateral reticular nucleus. Varying the position of the Fluoro-Gold injection site revealed a rostral to caudal topographic organization of these raphe and parapyramidal projections.

Animals↗

Relationship between input and output of cells in motor and somatosensory cortices of the chronic awake rat. A study using glass micropipettes.

Experiments using the same glass microelectrode (6--8 M omega) for recording and stimulating were performed on 12 rats in which 379 cortical cells were studied in 65 penetrations through the motor and somatosensory cortical zones. To avoid anaesthetic effects the rats were chronically implanted with a head system derived from the one developed by Noda et al. (1971). These animals well accepted head fixation and the peripheral receptive fields could thus be easily investigated. In a preliminary experiment the number of pyramidal cells activated by a given stimulus intensity was evaluated. The lowest threshold intensities were always observed in the Vth pyramidal layer, as well as correspondence between cell input and output. The same type of organization, with identical thresholds, existed in the so-called "Motor" and "Somatosensory" cortical zones. Movements could be obtained when stimulating near non-PT cells (600--700 micron below the cortical surface). However, thresholds were higher at this level and it is thought that the movements were due to a spread of the stimulating current to the pyramidal tract cell layer.

Animals↗

The transition from development to motor control function in the corticospinal system.

During early postnatal development, corticospinal (CS) system stimulation, electrical or transcranial magnetic, is minimally effective in producing muscle contraction, despite having axon terminals that excite spinal neurons. Later, after stimulation becomes more effective, the cortical motor representation develops, and movements the system controls in maturity are expressed. We determined whether development of temporal facilitation (response enhancement produced by the second of a pair of pyramidal tract stimuli, or a higher stimulus multiple of a train of stimuli) correlated with these changes. Facilitation of the monosynaptic CS response was larger in older kittens and adults than younger kittens. When facilitation was strong, strong motor responses were evoked by pyramidal stimulation with small currents and few pulses. With strong facilitation in older kittens, corticospinal axon varicosities colocalize synaptophysin like adults, suggesting a presynaptic mechanism. With effective facilitation, control signals from the cortex can be sufficiently effective to provoke muscle contraction for guiding movements.

Action Potentials↗

Assessment of spinal cord injury by counting corticospinal and rubrospinal neurons.

This paper describes an objective, quantifiable technique for assaying the degree of severity of spinal cord injury. Twenty-one rats underwent a C7-T1 laminectomy: 12 received a C8 spinal cord clip compression injury with forces of either 2.3, 16.9 or 53.0 g; 4 had cord transection at C8, and 5 had no cord lesion. Postoperative clinical neurological assessment was performed by the inclined plane method. At 4 weeks, the spinal cord-injured rats underwent a T10 transection and insertion of a Gelfoam pledget impregnated with horseradish peroxidase (HRP). HRP was similarly administered to 9 normal rats. Longitudinal sections of the spinal cord encompassing the injury site were stained with Luxol fast blue, and coronal sections from the cerebrum and midbrain were processed for HRP reactivity with tetramethylbenzidine. Labelled corticospinal and rubrospinal neurons were counted in every 6th section to derive a cortical score (CS) and a red nucleus score (RNS) for each animal. The CS reflected the extent of the pathological changes at the site of cord injury and the ln CS decreased linearly with increasing injury severity (P less than 0.0001). In contrast, the RNS was only reduced in animals with severe (53.0 g) cord injuries (P less than 0.0006). The degree of preservation of the dorsal columns including the corticospinal tracts at the injury site correlated with the CS, whereas the RNS was related to the degree of preservation of the lateral columns. Counts of rubrospinal neurons, but not corticospinal neurons, correlated closely (r = 0.96, P less than 0.001) with the inclined plane results, suggesting the importance of non-pyramidal tracts in controlling gross motor function. Thus, counting corticospinal and rubrospinal neurons is an objective, reliable test of the severity of experimental spinal cord injury.

Animals↗

[Response of pericruciate cortex neurons to stimulation of the medial geniculate body].

Electrical responses of 239 pericruciate neurons were studied in anaesthetized and curarized cats after stimulation of the medial geniculate body and medullary pyramids. The medial geniculate body stimulation evoked in the pericruciate neurons predominantly excitatory effects in the form of increase in the mean frequency of spike activity, generation of EPSPs and EPSPs-spike sequences. The latency analysis has shown that medial geniculate neurons have mono- and polysynaptic connections with pericruciate neurons not belonging to the pyramidal tract units.

Animals↗

[Central motor conduction time in diagnosis of spinal processes].

In patients with extra- and intramedullary spinal disorders (32 cases with myelopathy due to cervical spondylosis, 11 with syringomyelia and 17 with spinal tumours) central motor conduction time (CMCT) was studied after transcranial magnetic stimulation of the cortex. Compound muscle action potentials (CMAP) were recorded from abductor digiti minimi muscle (ADM) and anterior tibial muscle (TA) bilaterally. Of 37 patients with extramedullary located cervical lesions CMCT to the ADM was abnormal in 51% (n = 19) and to the TA in 70% (n = 26). In 10 patients with intramedullary cervical lesions abnormal CMCT to the ADM as well as to the TA was observed in 30% (n = 3) each. In extramedullary disorders measurement of CMCT to the TA was more sensitive in detecting impaired central motor conduction, though not significantly. Prolonged CMCT correlated to clinical signs of upper motor neuron involvement and to spinal cord compression. In addition, the method proved useful for detection of subclinical lesions of corticospinal pathways. The different results between intra- and extramedullary affections are explained by the anatomical localisation of pyramidal tract fibers.

Adult↗

Magnetic resonance imaging in motor neuron disease.

Magnetic resonance imaging (MRI) of the brain was evaluated in 20 patients with motor neuron disease (MND) and in a control group of 11 healthy people. Bilateral increased signal areas of various sizes in the centrum semiovale, corona radiata, internal capsule, pedunculi of midbrain, pons, medulla and even in the frontal lobe, topographically related with the corticospinal tract, were found in 8 out of 20 patients. Three out of 4 patients with progressive bulbar paralysis and 5 out of 11 cases of amyotrophic lateral sclerosis had abnormal MRI. Such MRI abnormalities have neither been found in patients with progressive muscular atrophy nor in controls, suggesting that they may be the hallmark of pyramidal tract degeneration in motor neuron disease.

Adult↗

[Mirror movements observed in patients skilled in playing the piano--symptomatological study].

We investigated mirror movements observed in two patients skilled in playing the piano and compared these symptoms with those reported in patients associated with frontal lobe, corpus callosum or cervical cord lesion. We found the following common features in our two patients: 1) mirror movements were observed during skilled finger movements such as playing the piano, 2) these were observed in distal parts of the bilateral upper extremities, 3) contralateral imitative associated movements were seen concomitantly, 4) frontal lobe symptoms and callosal disconnection syndrome were not seen, 5) both patients recalled having mirror movements in their infancy, and one had family history. These characteristics of mirror movements in our patients were similar to those in patients associated with cervical cord lesion, but were different from those in patients associated with frontal lobe or corpus callosum lesion. It is suggested that abnormal pathways in the pyramidal tract or cervical cord lesion elicited mirror movements in our patients.

Adult↗

Direct and indirect corticospinal control of arm and hand motoneurons in the squirrel monkey (Saimiri sciureus).

Anatomic evidence suggests that direct corticomotoneuronal (CM) projections to hand motoneurons in the New World squirrel monkey (Saimiri sciureus) are weak or absent, but electrophysiological evidence is lacking. The nature of the corticospinal linkage to these motoneurons was therefore investigated first with the use of transcranial magnetic stimulation (TMS) of the motor cortex under ketamine sedation in five monkeys. TMS produced early responses in hand muscle electromyogram, but thresholds were high (compared with macaque monkey) and the onset latency was variable. Second, stimulation of the pyramidal tract (PT) was carried out with the use of chronically implanted electrodes in ketamine-sedated monkeys; this produced more robust responses that were markedly facilitated by repetitive stimulation, with little decrease in latency on the third compared with the first shock. Finally, postsynaptic potentials were recorded intracellularly from 93 arm and hand motoneurons in five monkeys under general chloralose anesthesia. After a single PT stimulus, the most common response was a small, slowly rising excitatory postsynaptic potential (EPSP), either alone (35 of 93 motoneurons) or followed by an inhibitory postsynaptic potential (39 of 93). The segmental delay of the early EPSPs was within the monosynaptic range (mean 0.85 ms); however, the rise time of these EPSPs was slow (mean 1.3 ms) and their amplitude was small (mean 0.74 mV). These values are significantly slower and smaller than EPSPs in a comparable sample of Old World macaque monkey motoneurons. The results show that CM connections do exist in the squirrel monkey but that they are weak and possibly located on the remote dendrites of the motoneurons. The findings are consistent with earlier anatomic studies. Repetitive PT stimulation produced large, late EPSPs in some motoneurons, suggesting that, in this species, there are relatively strong nonmonosynaptic pathways linking the corticospinal tract to hand motoneurons.

Animals↗

Synaptic inputs of feline rubrospinal neurons from the parietal association cortex, pretectum and medial lemniscus, and their lesion-induced sprouting.

Synaptic inputs of rubrospinal (RN) neurons from the cerebral cortex, pretectal area (PRT), and medial lemniscus (ML) were investigated electrophysiologically in the cat. Stimulation of the ipsilateral parietal association cortex (PASC) and secondary sensory area (SII) produced slow-rising about 3 msec rise time monosynaptic EPSPs which were, in some cases, followed by hyperpolarizations, similar to the sensorimotor cortex (SM)-induced PSPs previously observed. Stimulation of the contralateral cerebral cortex never produced detectable PSPs. Topographical arrangement of PASC-rubral projection was found. Stimulation of the lateral part of PASC induced EPSPs predominantly in RN cells innervating the cervicothoracic spinal segments, while stimulation of the medial part of PASC produced EPSPs predominantly in RN cells innervating the lumbosacral cord. Furthermore, PASC-induced EPSPs were more frequently recorded at the rostral half of RN than at the caudal half. Monosynaptic EPSPs and multisynaptic IPSPs were induced by stimulation of the ipsilateral PRT and ML. PRT- and ML-induced EPSPs had times-to-peak of 1.0 +/- 0.4 msec (mean +/- S.D.) and 1.6 +/- 0.5 msec, respectively, which were intermediate to those of the cerebral peduncle (CP)- and nucleus interpositus of the cerebellum (IP)-induced EPSPs. Furthermore, sensitivity of amplitudes of PRT-induced EPSPs to membrane hyperpolarization was intermediate to those of CP- and IP-EPSPs, and that of ML-induced EPSPs was lower than that of IP-EPSPs. Therefore, it is likely that synapses of PRT and ML fibers are formed between the distal dendrites where CP-rubral synapses terminate and soma where IP-rubral synapses terminate. PASC-induced EPSPs after chronic IP and SM lesions had a new fast-rising component and the effectiveness of ML stimulation to induce the unit spike of RN cells was clearly increased in IP and SM lesioned cats. It was suggested that PASC-rubral fibers sprouted and formed new synapses at the proximal portions of soma-dendritic membranes of RN cells after IP and SM destructions. Collateral fibers to RN cells of the pyramidal tract were also shown to sprout new synapses following IP and ML lesions.

Animals↗

The site of motor corticospinal fibres in the internal capsule of man. A computerised tomographic study of restricted lesions.

The distribution of the motor impairment was correlated to the site and extension of the lesion of 18 patients with restricted lesions of the internal capsule, detectable with computerised tomography (CT). In three cases the lesion was located in the anterior limb of the internal capsule and the patients did not suffer any motor defect. Among the 15 patients with lesions in the posterior limb, 13 presented a distribution of the motor weakness consistent with a location of the corticobulbar fibres in the genu and corticospinal fibres in the anterior half of the posterior limb. Our CT study confirms the classical view on the location of the pyramidal tract in the internal capsule of man, but also evidences the possibility of individual variations.

Adult↗

Corticospinal direct response to transcranial magnetic stimulation in humans.

The corticospinal motor evoked potential (MEP) response to transcranial magnetic stimulation of the motor cortex was investigated in comparison with the direct (D) response to electrical stimulation of the exposed motor cortex from the spinal epidural space in 7 neurologically normal patients during brain tumor surgery. The D response during operation was obtained by transcranial magnetic stimulation of the scalp over the areas of the cerebral motor cortex, the hand or arm areas. The magnetic induced D response showed a conduction velocity of 50.5-72.7 m/sec and was resistant to anesthesia and unaffected by muscle relaxants and tolerant to high frequency (500 Hz) paired magnetic stimulus, and the latencies of magnetic MEPs corresponded to those with direct electrical stimulation. Thus, recordings of the D response by transcranial magnetic stimulation are useful for not only identifying the location of the motor cortex during intracranial surgery but also for non-invasive recording of pyramidal tract activity during extracranial surgery under general anesthesia.

Aged↗