[Urokinase therapy in diabetic retinopathy (author's transl)].
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Biomedical subjects
Publications and source records attributed to H Asanuma.
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We have shown (Asanuma et al., 1979c) that the monkey motor cortex receives peripheral somesthetic inputs directly from the thalamus. In the present experiments, we studied the pathways which mediated these inputs by stimulating superficial radial (SR) and deep radial (DR) nerves and recording evoked potentials from the motor and sensory cortices and the following results were obtained: 1. The focus for SR and DR evoked potentials in the sensory cortex was located in a circumscribed small area whereas in the motor cortex, the evoked potentials were distributed in a wide area along the central sulcus including the distal forelimb area. 2. Ablation of the sensory cortex reduced the size, but neither abolished nor changed the latency of the evoked potentials in the motor cortex. 3. Section of dorsal column nearly abolished the evoked potentials in the motor cortex, but only halved their size in the sensory cortex. 4. Section of ventrolateral cervical column including the spinothalamic tract halved the size of evoked potentials in the sensory cortex, but did not change the size in the motor cortex. 5. It is concluded that direct peripheral inputs to the motor cortex are mediated primarily through the dorsal column system whereas the peripheral inputs to the sensory cortex are mediated through both dorsal column and spinothalamic tract.
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The possibility that the motor cortex receives peripheral input directly from the thalamus was examined using the evoked potential method and the following results were obtained. Potentials in the motor cortex evoked by stimulation of superficial radial (SR) or group II deep radial (DR) nerve were neither abolished nor delayed by ablation of the sensory cortex. Potentials in the motor cortex evoked by stimulation of group II DR nerve were most severely reduced by interruption of the spinocervcial tract. Potentials evoked by stimulation of SR nerve were more severely reduced in the sensory cortex than in the motor cortex by section of the dorsal funiculus or cooling of the cuneate nucleus. The size of evoked potentials in the motor cortex increased rapidly when stimulus intensity to DR nerve exceeded the threshold to group II fibers. The results suggest that some inputs from the SR and group II DR nerves reach the motor cortex without a relay through the sensory cortex.
Cells in the thalamus projecting to the distal forelimb regions of the motor cortex, area 3a, and the sensory cortex were identified with horseradish peroxidase (HRP). These cortical areas were defined by mapping evoked potentials from superficial and deep radial nerve stimulation. Following injections into the motor cortex, the labelled cells were distributed throughout a large region (greater than 2 mm wide) in the ventral portion of the ventral lateral nucleus (VL). The border area between VL and the ventral posterolateral nucleus (VPL) also contained labelled cells. The region containing labelled cells following injections into area 3a was in the rostral, dorsal VPL, and overlapped with the region containing cells labelled by injections into the motor cortex. Cells labelled by injections into the sensory cortex were near the center of VPL distinctly separated from those labelled after injections into either area 3a or the motor cortex.
The locations and receptive fields of thalamic neurons projecting to the motor cortex were examined and the following results were obtained. (1) Neurons located at the border area between nucleus ventralis lateralis (VL) and nucleus ventralis posterolateralis (VPL) could be activated antidromically from the motor cortex. (2) These neurons received topographically organized somesthetic inputs arising from skin and deep receptors. (3) The receptive fields of neurons in the small area of the motor cortex where these thalamic neurons projected could be examined in 8 instances. In 6 instances, the cortical neurons and the thalamic projection neurons were activated by exactly the same stimuli in the periphery. (4) Removal of the sensory cortex did not significantly change the characteristics of afferent inputs from the periphery to the motor cortex. (5) It is concluded that the motor cortex receives somesthetic inputs directly from the thalamus. The functional role of these inputs was discussed in relation to the known cortical reflexes.
The branching pattern of individual pyramidal tract (PT) neurons of the monkey motor cortex was studied by activating these neurons antidromically from within the cervical motor nuclei and also from other regions of the spinal cord. 1. Fifty-four neurons were activated from motor nuclei in the cervical cord. Twenty-eight of these were activated from one segment and six (11%) were activated from motor nuclei of different segments. The remaining 20 neurons were activated from motor nuclei and also from unspecified region(s) of the gray matter. 2. Another 156 neurons were activated from unspecified regions(s) of cervical gray matter which could have been motor nuclei or outside the nuclei, and 64 of these were activated from more than one segment. 3. The branching patterns of PT neurons sending axons directly to motor nuclei innervating distal forelimb muscles suggested that they branch less than the rest of PT neurons.
The projection of individual pyramidal tract (PT) neurons from the hindlimb area in the precentral gyrus of the cerebral cortex to the lumbar spinal cord was studied in the monkey by systematically searching for sites within identified regions of the spinal gray from which the PT neurons could be antidromically activated by local stimulation. All investigated neurons belonged to the fast conducting fraction of PT neurons. The following results were obtained. 1. Each PT neuron could be activated from more than one region of the spinal gray matter, including identified spinal motor nuclei and areas dorsomedial to these nuclei, but do not the intermediate nucleus or regions dorsal to it. "Passage areas" and "termination areas" were defined. 2. Half of the PT neurons with termination areas within motor nuclei had these areas in more than one nucleus. There were thus strong suggestions for synaptic contacts of some PT neurons with motoneurons of more than one muscle. 3. Four groups of three or four neurons were recorded simultaneously by the same cortical electrode. Comparisons of passage and termination areas within groups revealed both similarities and differences in projections of neighboring neurons. Every neuron was activated from some region(s) where others of the group were not. Common passage areas, or passage and termination areas, for two or three neurons of a group within at least one motor nucleus were found for all groups. Termination areas in the same motor nucleus have been found for the majority of the neurons of only one group. These common projection areas are compatible with, but not prove, that group of adjacent PT neurons has common target cells in the spinal cord.
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Two receiving areas in the pericruciate cortex are known for inputs from group I muscle afferents of forelimb nerves. One focus is near the postcruciate dimple of area 3a, and the other in the lateral sigmoid gyrus of the motor cortex (area 4gamma). The cortico-cortical projection of area 3a to 4gamma, and the relay by this projection of group I muscle afferent input to the motor cortex were investigated in cats. The following results were obtained. 1. Seventy-four neurons within area 3a were antidromically activated by intracortical microstimulation of the motor cortex. 2. Although excitation evoked by stimulation of group I muscle afferents could be demonstrated for only a few (8 of 48) cortico-cortical neurons in extracellular recordings, due to the methodological limitations discussed, this input evoked EPSPs in 8 of 9 cortico-cortical neurons recorded intracellularly. Therefore, it is likely that the majority of neurons projecting from area 3a to the motor cortex have an excitatory synaptic input from group I afferents. 3. Neurons projecting from area 3a to the motor cortex were most commonly found in cortical layer III, although some were found in layer V. 4. Five of nine pyramidal tract neurons of area 3a had a strong excitatory synaptic input from group I muscle afferents. 5. A new type of pyramidal tract neuron was found which has cortico-cortical axon collaterals connecting the two cytoarchitectonic regions. These various neurons may be part of a feedback system from muscle afferents to the motor cortex.
The results suggest : (1) that PT neurons sending axons to motor nuclei innervating distal forelimb muscles branch less than other PT neurons; (2) that a group of PT neurons located close together may influence various species of motoneurons, but that this influence is the strongest on motoneurons of one species; (3) that individual PT neurons terminate only on a small fraction of a given motoneuron group.
The effective spread of stimulating current for pyramidal tract (PT) cells and fibers was studied using a method of cancelling the shock artifacts and the following results were obtained: 1. The excitability of PT axon collaterals was as high as that of PT cells. 2. These axon collaterals extended as far as 1.0 mm horizontally from the PT cells. 3. The low threshold area for activation of a given PT cell was as wide as 3--4 mm2 on the surface of the cortex. 4. Intracortical microstimulation (ICMS) delivered to the PT cell layer produced direct (D) and indirect (I) descending volleys in the pyramidal tract, but ICMS to the superficial layer (III) produced only I-waves. 5. These I-waves grew significantly larger after 15--20 msec from the start of the train of stimuli. 6. It is concluded that either surface stimulation, or short train of ICMS is inadequate for delineating fine localization of motor function within the cortex. Longer train (30--40 msec) with high frequency pulses (300--400 cy/sec) can produce muscle contraction with much smaller currents, increasing the accuracy of measuring the localization of motor function.
Branching patterns of single corticospinal (CS) neurons were studied in the cat by activating these neurons antidromically from various regions of the spinal cord. 1. One hundred and ninety-three neurons were activated antidromically by microstimulation in the gray substance of the cervical cord and the majority of them were found in the forelimb area of the pericruciate cortex. 2. Branches to the lower levels of the spinal cord were found for 30% of the neurons projecting to the cervical gray matter. 3. The remaining 70% sent axons only to the cervical gray matter and some of them sent multiple branches to several segments in the cervical cord. 4. Only a few CS neurons located outside of the forelimb area could be activated from the cervical cord, but all of them also sent branches to the lower levels of the spinal cord. Neurons projecting to both the cervical cord and the lower levels were intermingled in the cortex with those projecting only to the cervical cord. 5. CS neurons activated from a given area of the cervical cord were often clustered together in a small area of the cortex, although some of these CS neurons sent their other branches to other parts of the spinal cord and neurons projecting to other parts were also intermingled among them. 6. The functional significance of multiple axonal branching of CS neurons is discussed in relation to cortical motor functions.
The functional organization of projections from the cerebellar subcortical nuclei to the motor cortex through the nucleus ventralis lateralis (VL) of the thalamus was studied using tungsten microelectrodes for stimulation and recordings in acute and chronic cats. The following results were obtained. (1) Microstimulation of a small area of the ventral thalamus produced contraction of a single limb muscle as well as movements of whiskers. (2) The stimulus parameters for producing low threshold contraction of limb muscles were different from those for face muscles. The decrease of the frequency gradualy increased the threshold values for face muscles whereas the decrease abruptly increased the threshold for limb muscles. The optimum duration of the train for the lowest thresholds was longer for face muscles. (3) Stimulation of cerebellar nuclei (interpositus and lateralis) produced contraction of limb muscles. The stimulus parameters for the minimum threshold were similar to those for producing contraction of limb muscles from the ventral thalamus. (4) The peripheral receptive fields of neurons located around the low threshold sites in the thalamus were diffuse, i.e. they were driven insecurely by twisting the joints or pressure to the deep structures, but could not be driven by touch or light pressure on a circumscribed area of the body. (5) Chronic ablation of the motor cortex did not abolish the muscle contractions produced by thalamic stimulation, excluding the possibility that the effects were produced by stimulation of the branches of the pyramidal tract fibers reaching the ventral thalamus. (6) Chronic section of the brachium conjunctivum abolished or changed the characteristics of the contractions produced by thalamic stimulation indicating that the previous effects were produced by stimulation of cerebellar efferent fibers reaching the thalamus. (7) From these results it was concluded that the efferent impulses originating from the cerebellar nuclei can produce contraction of a particular muscle through activation of the red nucleus. These impulses are, at the same time, transmitted to a small group of neurons in the VL and then forwarded to the neurons in the motor cortex. (8) The functional significance of the VL projection system has been discussed in relation to the efferent zones within the motor cortex.
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