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Direct recording of the output of the motor cortex produced by transcranial magnetic stimulation in a patient with cerebral cortex atrophy.

OBJECTIVE: To examine the descending motor activity evoked by transcranial magnetic stimulation (TMS) in a chronic alcoholic patient with a slight atrophy of the peri-central cortex and compare with that observed in neurologically intact subjects. METHODS: EMGs from the first dorsal interosseous (FDI) muscle, and descending activity from an electrode implanted in the high cervical epidural space for relief of pain were recorded after TMS of the hand area of motor cortex. A figure-of-8 coil was used to induce either a posterior-anterior (PA) or a latero-medial (LM) flow across the central sulcus. RESULTS: In intact subjects, LM stimulation evoked the earliest volley, which we termed a D wave. This was followed by later, presumed I waves at intervals of about 1.5 ms. At a stimulus intensity of 120% resting threshold (RMT), up to 5 I waves were seen. PA stimulation rarely evoked D waves at intensities up to 120% RMT, but 3 or 4 I waves were visible in all subjects. The patient had an increased resting threshold, and the descending volleys were dominated by a D wave. I waves were unclear, with two possible small peaks at 5.5 and 7.2 ms. CONCLUSIONS: The lack of I waves in the patient was probably due to an impairment of interneuronal circuitry in the context of the brain damage related to chronic alcohol abuse, and is consistent with a trans-synaptic origin of the I waves in humans. The intact D wave is consistent with the assumption that the D wave represents direct stimulation of the axons of intact corticospinal neurones in the subcortical white matter. The patient's increased RMT reflects the fact that usually multiple descending volleys are needed to discharge resting spinal motoneurones.

Alcoholism↗

Effects of reversible cold block of face primary somatosensory cortex on orofacial movements and related face primary motor cortex neuronal activity.

Our previous studies have revealed that face primary somatosensory cortex (SI) as well as face primary motor cortex (MI) play important roles in the control of orofacial movements in awake monkeys, and that both face MI and face SI neurons may have an orofacial mechanoreceptive field and show activity related to orofacial movements. Since it is possible that the movement-related activity of face MI neurons could reflect movement-generated orofacial afferent inputs projecting to face MI via face SI, the present study used reversible cold block-induced inactivation of the monkey's face SI to determine if face MI neuronal activity related to a trained tongue-protrusion task, chewing or swallowing was dependent on the functional integrity of the ipsilateral face SI and if inactivation of face SI affects orofacial movements. The effects of face SI cold block were tested on chewing, swallowing and/or task-related activity of 73 face MI neurons. Both task and chewing and/or swallowing-related activity of most face MI neurons was independent of the functional integrity of the ipsilateral face SI since SI cold block affected the movement-related activity in approximately 25% of the neurons. Similarly, unilateral cold block of SI had very limited effects on the performance of the task and chewing, and no effect on the performance of swallowing. These findings suggest that movement-induced reafferentation via face SI may not be a significant factor in accounting for the activity of the majority of ipsilateral face MI neurons related to trained movements, chewing and swallowing.

Animals↗

Local field potential oscillations in primate cerebellar cortex: synchronization with cerebral cortex during active and passive expectancy.

Many brain regions, such as the cerebellum, primary somatosensory cortex (SI), and primary motor cortex (MI), interact to produce coordinated actions. Synchronization of local field potentials (LFPs) in sensorimotor cerebral areas has been related to motor performance, often through 10- to 25-Hz oscillatory LFPs. The macaque cerebellar paramedian lobule (PM) also shows 10- to 25-Hz LFP oscillations, which are modulated in a stimulus-response lever press task to get reward (active condition), but also, albeit differently, in a similarly timed stimulus-reward relation (passive condition). This study focuses on simultaneous LFP activity in primate SI or MI and the PM cerebellum during the active (left- or right-hand lever presses) and passive conditions. Results show a similar modulation pattern of 10- to 25-Hz oscillations in the cerebellum, MI, and SI during the active condition (left or right hand), decreasing after stimulus onset, returning, and again decreasing after movement onset. In the passive condition, when the monkey did not move but got reward, all 3 areas show an oscillatory profile where oscillations increase after stimulus onset and last until reward, denoting a role for these oscillations in passive expectancy. However, synchronization between cerebellar LFPs and SI LFPs is higher during the active condition than during the passive condition, and highest for the interested hand. This greater PM-SI synchronization, when the monkey had to press the lever, could represent a form of cerebro-cerebellar communication, perhaps to serve somatosensory processing to accomplish the task; PM-MI synchronization was less selective for the hand used and might carry a more general type of information.

Animals↗

Involvement of NMDA and non-NMDA receptors in the neuronal responses of the primary motor cortex to input from the supplementary motor area and somatosensory cortex: studies of task-performing monkeys.

The involvement of N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptors in mediating the excitatory responses of neurons in the primary motor cortex (MI) to electrical stimulation of the supplementary motor area (SMA) and the somatosensory cortex (SI) was examined in monkeys performing a trained motor task. During the task, a total of 109 MI neurons were identified and classified as movement related (91), motor set related (7), or mixed (11). Subsequently, the influence of receptor antagonists on the stimulus-evoked and task-related activities of these neurons was examined. The selective NMDA antagonist D-2-amino-5-phosphonovaleric acid (APV) and the selective non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) were applied iontophoretically through multibarreled micropipettes. One barrel was used for extracellular unit recording. The excitatory response evoked by SI stimulation was suppressed by CNQX in the vast majority (83%) of the motor task related neurons, and only 10% were suppressed by APV. On the other hand, the response evoked by SMA stimulation was suppressed by APV in 56% of the neurons and by CNQX in 54%. APV and CNQX had parallel effects on the stimulus-evoked responses and the task-related neuronal activity. These results indicate that NMDA and non-NMDA receptors are both involved in mediating the excitatory responses of MI neurons to input from the SMA and SI. On the other hand, the data suggest a greater contribution of non-NMDA receptors in response to SI input and greater involvement of NMDA receptors in mediating the response to SMA input, especially among set-related MI neurons.

2-Amino-5-phosphonovalerate↗

The effects of localized inactivation of somatosensory cortex, area 2, on the cat motor cortex.

Direct corticocortical afferents to the primary motor cortex (MI) originate in area 2 and area 3a of the primary somatosensory cortex (SI). The functional and morphological characteristics of the two pathways indicate that they relay different sensory signals to MI. The role of area 2 in relaying peripheral information to the cat MI was studied using electrophysiological techniques. Neurons that responded to stimulation of peripheral receptive fields on the contralateral forepaw were identified in MI by extracellular recordings. In area 2 of SI, neurons with the same receptive field modality and location as those in MI were also identified. Field potentials to electrical stimulation of the peripheral receptive field were recorded at the somatotopically matched sites in both MI and SI. Neuronal activity at the recording site in area 2 was blocked by injection of lidocaine, a local anesthetic. Changes in MI and area 2 responses were monitored before and after inactivation of area 2. Neuronal activity near the injection site was abolished, and evoked potentials (EPs) in area 2 were considerably diminished immediately following the injection. In MI, spontaneous activity levels were altered at some sites, but overall these changes were not significant. MI EPs recorded in response to peripheral stimulation were altered, and various patterns of change were noted in the early and late phases of the EPs. Changes often occurred in only one phase of the response. In some EPs, both early and late phases changed, but the direction and magnitude of change in one phase were not always linked to such changes in the other phase. Both increases and decreases in the amplitude and the area of each phase were observed. The morphological characteristics of the projection were reviewed and related to the findings in the study. It is proposed that inherent features of the pathway may account for the variable patterns of change that were observed.

Animals↗

[Quantitative characteristics of the cortex area 4y associative projections to subfields of the sensomotor and parietal cerebral cortex in cat].

The ipsilateral association connections of the motor cortex area 4y after its local electrolytic lesion in the cat were studied using Nauta-Gigax method. Relative quantitative distribution of the efferent association fibers projecting from area 4y to the somatosensory regions I and II, motor and parietal cortex, was determined. It was shown that the major projections from area 4y are directed to area 2pri (secondary somatosensory zone) and to area 5ab. Sparse degenerating fibers were found in the areas 1, 2, 3a and 3b of the primary somatosensory cortical zone. No efferent fibers were traced projecting from area 4y to the areas 4fu, 4sfu, 6aa, 6ab and 6ifu. It is suggested that the morphological basis of the motor reactions implemented by area 4y is formed not by fundal (4fu, 4sfu, 6ifu) or premotor (6aa, 6ab) subfields, but by the areas 2pri and 5ab which are involved to a maximum degree.

Animals↗

DNA damage and p21(WAF1/CIP1/SDI1) in experimental injury of the rat adrenal cortex and trauma-associated damage of the human adrenal cortex.

In vivo models are needed to study the reactions of tissues to DNA damage, such as the induction of the cyclin-dependent kinase inhibitor p21, indicating potential repair of the damage, versus apoptosis, indicating the elimination of the damaged cells. Damage to DNA occurs in tissues during shock, sepsis, and other critical medical conditions. Previous studies have found evidence of damage to the cortex of adrenal glands from organ donors who had undergone severe trauma prior to death. The present experiment studied rats under experimental interventions of clinical relevance to patients with conditions that put them at risk for damage to the adrenal glands. These interventions comprised ischaemia and reperfusion injury, sepsis following caecal ligation and puncture, acute pancreatitis, and administration of chemical agents (zymosan and acrylonitrile). All the interventions caused an increase in p21 mRNA as assessed by northern blotting and in situ hybridization. Increased nuclear p21 protein was shown by immunohistochemistry. All the interventions caused damage to DNA, as shown by labelling of available 3' termini of single-strand breaks with terminal transferase. The number of cells undergoing apoptosis, visualized by ligation of a hairpin oligonucleotide probe to double-strand breaks in DNA, was much lower. In rat adrenal glands, apoptotic cells were infrequent under all the conditions studied. They were more abundant in human organ donor adrenal glands that were previously shown to have extensive DNA damage accompanied by induction of p21. The similarity of the effects of a wide variety of surgical interventions and chemical agents suggest a common pathophysiological mechanism which is not specific to the initiating injury. Experimental injury of the rat adrenal cortex provides a model for investigating the role of organ DNA damage and of mediators of the response to DNA damage, such as p21.

Adrenal Cortex↗

Environmental complexity has different effects on the structure of neurons in the prefrontal cortex versus the parietal cortex or nucleus accumbens.

Complex housing has been used widely as a model of experience-dependent change. Animals housed in complex environments typically show synaptogenesis throughout the sensory and motor cortex as well as the striatum and hippocampus, and thus it is generally assumed that such changes are likely to be found throughout the cerebrum. The purpose of the present study was to determine whether persistent alterations of dendritic morphology would be found in two regions that had previously not been examined, namely, the medial prefrontal region (Cg3) and nucleus accumbens (NAcc). The results show that housing female rats in complex environments for 3.5 months increased dendritic arborization on medium spiny neurons in the NAcc and on pyramidal cells in the somatosensory cortex (Par 1), but not in Cg3. Environmental complexity increased spine density in all three areas, however. The failure to find increased dendritic length or branching in Cg3 was unexpected. Thus, the data suggest that complex housing may not engage prefrontal neurons in the same manner as neurons in sensory or motor areas. It appears that complex housing may not produce generalized changes in cerebral morphology. The data further suggest that it is prudent to measure both dendritic length and spine density in studies of experience-dependent effects on synaptic plasticity.

Animals↗

Differential relation of discharge in primary motor cortex and premotor cortex to movements versus actively maintained postures during a reaching task.

The activity of cells in primary motor cortex (MI) and dorsal premotor cortex (PMd) were compared during reaching movements in a reaction-time (RT) task, without prior instructions, which required precise control of limb posture before and after movement. MI neurons typically showed strong, directionally tuned activity prior to and during movement as well as large gradations of tonic activity while holding the limb over different targets. The directionality of their movement- and posture-related activity was generally similar. Proximal-arm muscles behaved similarly. This is consistent with a role for MI in the moment-to-moment control of motor output, including both movement and actively maintained postures, and suggests a common functional relation for MI cells to both aspects of motor behavior. In contrast, PMd cells were generally more phasic, frequently emitting only strong bursts of activity confined mainly to the behavioral reaction time before movement onset. PMd tonic activity during different postures was generally weaker than in MI, and showed a much more variable relation with their movement-related directional tuning. These results imply that the major contribution of PMd to this RT task occurred prior to the onset of movement itself, consistent with a role for PMd in the selection and planning of visually guided movements. Furthermore, the nature of the relative contribution of PMd to movement versus actively maintained postures appears to be fundamentally different from that in MI. Finally, there was a continuous gradient of changes in responses across the rostrocaudal extent of the precentral gyrus, with no abrupt transition in response properties between PMd and MI.

Animals↗

Adrenal cortex adenylate cyclase. Specific binding sites for 5'-guanylyl-imidodiphosphate in partially purified plasma membranes from bovine adrenal cortex.

Specific binding sites for 5'-guanylyl-imidodiphosphate [Gpp(NG)p] have been identified in a partially purified plasma membrane fraction from bovine adrenal cortex. The apparent affinity of Gpp(nh)p at 30 degrees C was 12muM-1 and the concentration of binding sites was 100 pmoles per mg of protein. Binding of Gpp(NH)p is inhibited by Mn2+ greater than Mg2+ greater than Ca2+ and enhanced by low concentrations of the chelators ethylenediamino-tetraacetic acid (EDTA) and ethylene glycolbis-(beta-aminoethylether))-N,N'-tetraacetic acid (EGTA). High concentrations of EDTA are inhibitory and at 2.5 mM EDTA binding of Gpp(NH)p is only 10% of that observed in the absence of the chelator. The bound labeled GTP analogue exchanged only slowly with the unlabeled nucleotide after a steady state has been reached. EDTA also releases the bound labeled Gpp(NH)p from its binding sites. The slow dissociation of Gpp(NH)p can explain the persistent activation of adenylate cyclase observed after pretreatment of bovine adrenal cortex plasma membranes with Gpp(NH)p and subsequent washing. It is suggested that at least parts of these binding sites are identical to the sites identified earlier as regulatory sites for angiotensin high-affinity receptors (Glossmann et. al., 1974a) and for ACTH-stimulated cyclase Glossmann and Gips, 1974).

Adenylyl Cyclases↗

Activity of neurons of the cat motor cortex during differentiation between reactions of right and left paw placement on a support developed in response to stimulation of the parietal cortex of the different hemispheres.

Differentiation was developed in cats between reactions of the placement of the right and left paw on a support in response to stimulation of the ipsilateral (right or left, respectively) parietal cortex (PC) in the region of field 5. The shortest-latency primary responses of the neurons of the MC do not vary in relation to whether stimulation of the PC does or does not elicit the conditioned motor reaction of the limb. Stimulation of the PC as a conditional signal triggering the cPR elicits, in addition to the primary responses, the generation of excitatory reactions of neurons of the MC in the interval from 20 to 200 msec and longer; if the motor reaction is not triggered or if a reaction of the limb ipsilateral to the motor cortex is triggered, an inhibitory pause is generated in the indicated time interval.

Animals↗

Thalamic and temporal cortex input to medial prefrontal cortex in rhesus monkeys.

To determine the source of thalamic input to the medial aspect of the prefrontal cortex, we injected retrograde tracers (wheat germ agglutinin conjugated to horseradish peroxidase, nuclear yellow, and/or bisbenzimide) into seven medial prefrontal sites and anterograde tracers (tritiated amino acids) into six thalamic sites, in a total of nine rhesus monkeys. The results indicated that ventral precallosal and subcallosal areas 14 and 25, and the ventral, subcallosal part of area 32, all receive projections from the mediodorsal portion of the magnocellular division of the medial dorsal nucleus (MDmc). The dorsal, precallosal part of area 32 receives projections mainly from the dorsal portion of the parvocellular division of the medial dorsal nucleus (MDpc), which also provides some input to area 14. Polar area 10 receives input from both MDpc and the densocellular division of the medial dorsal nucleus (MDdc), as does supracallosal area 24. Area 24 receives additional input from the anterior medial nucleus and midline nuclei. All medial prefrontal cortical areas were also found to receive projections from a number of cortical regions within the temporal lobe, such as the temporal pole, superior temporal gyrus, and parahippocampal gyrus. Areas 24, 25, and 32 receive, in addition, input from the entorhinal cortex. Combining these results with prior anatomical and behavioral data, we conclude that medial temporal areas that are important for object recognition memory send information directly both to dorsal medial prefrontal areas 24 and 32 and to ventral medial prefrontal areas 14 and 25. Only the latter two areas have additional access to this information via projections from the mediodorsal part of MDmc.

Animals↗

Neuronal activity in dorsomedial frontal cortex and prefrontal cortex reflecting irrelevant stimulus dimensions.

Previous studies of the dorsomedial frontal cortex (DMF) and the prefrontal cortex (PF) have shown that, when monkeys respond to nonspatial features of a discriminative stimulus (e.g., color) and the stimulus appears at a place unrelated to the movement target, neurons nevertheless encode stimulus location. This observation could support the idea that these neurons always encode stimulus location, regardless of its relevance to an instrumentally conditioned behavior. Past studies, however, leave open the possibility that activity observed during one operant task might reflect the contingencies of a different task, performed at different times. To test these alternatives, we examined the activity of DMF and PF neurons in two rhesus monkeys conditioned to perform an operant eye-movement task in which only the color and shape of visual stimuli served as salient discriminative features. Each of eight stimuli was associated with a response to a different eye-movement target. The location of these stimuli varied from trial to trial but was of no behavioral relevance, and the monkeys did not perform any operant task in which stimulus location controlled behavior. A substantial minority of neurons in both DMF and PF nevertheless encoded stimulus location, which indicates that this property does not depend on its relevance in an instrumentally conditioned behavior.

Action Potentials↗

Depolarization of brain cortex slices and synaptosomes by lithium. Determination of K+-equilibrium potential in cortex slices.

K+-equilibrium potential was determined in brain cortex slices of rat by measuring 86Rb+ distribution between the extra- and intracellular space. The ratio of internal to external Rb+ concentration was 39 +/- 1.8, corresponding to a resting membrane potential of 93.8 mV. Li+ (1-126 mM) decreased the membrane potential in both cortex slices and synaptosomes in a concentration-dependent manner. The presence of 1 mM Li+ was enough to cause a slight but distinct depolarization. During incubation in Li+-containing medium slices took up K+; however, for depolarization the presence of extracellular Li+ seemed to be necessary.

Animals↗

The physiological identification of pyramidal tract neurons within transplants in the rostral cortex taken from the occipital cortex during development.

Axons from neurons in the occipital cortex transiently extend to the pyramidal tract (PT) during the early postnatal development of rats. Normally, these axons are eliminated by the end of the third postnatal week. However, if a portion of fetal occipital cortex is transplanted to the parietofrontal region in newborn hosts then some neurons in the transplant will extend pyramidal tract axons and maintain them. Intracortical microstimulation and electrophysiological recording techniques were used to identify the physiological characteristics of the transplanted pyramidal tract cells and to determine if motor effects could be elicited from the occipital transplant. Microstimulation of the transplant did not reliably evoke movement but the low density and disarray of PT cells within the transplant might account for this. Recording from within the transplant revealed that the overall cell activity was depressed. We were able to identify neurons within the transplant which responded antidromically to stimulation of the pyramidal tract, indicating that their axons have the capacity to conduct impulses and are therefore likely to have developed some viable connections. The functional significance of such projections remains uncertain.

Animals↗

Thalamic projections to the anterior suprasylvian and posterior sigmoid cortex: an HRP study of the "vestibular areas" of the cerebral cortex in the cat.

We have confirmed electrophysiologically the existence of an oligosynaptic vestibular projection to the cortex surrounding the rostral end of the anterior suprasylvian sulcus ( ASsS ). However, we failed to confirm a similar projection to area 3a in the posterior sigmoid gyrus. We studied the thalamic projections to each of these cortical regions by injecting small amounts of HRP in the cortex and looking for neurons retrogradely labeled throughout the thalamus. The exact location of the cortical injections was assessed cytoarchitectonically. The heaviest neuronal labeling after injections in the banks of ASsS was obtained in Po (including in this complex GMmc ). A moderate number of projections was found from VPi, VPm and VPl (the labeling in the latter being particularly prominent in a case injected in the lower bank of ASsS ), and also from VL. Occasional labeled neurons were found in the rostro-ventral part of LP. After injections in area 3a in the posterior sigmoid gyrus, which affected to a minor degree either area 3b or 4, many labeled cells appeared in the rostral and dorsal part of VPl, and in the central and lateral parts of VL. Fewer labeled cells were found in VPi, Po and LP. In most cases some occasional labeled cell was observed also in the intralaminar nuclei and in Vm.

Afferent Pathways↗

Dorsolateral prefrontal cortex and anterior cingulate cortex white matter alterations in late-life depression.

BACKGROUND: The dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) are critical for mood regulation. Alterations in the white matter connections of these regions may impair their role in mood regulation and increase the risk of developing depression. This study used diffusion tensor imaging to examine for white matter microstructural abnormalities of these regions and of central white matter structures in late-life depression. METHODS: One hundred six elderly depressed subjects and eighty-four elderly nondepressed subjects underwent clinical assessment and diffusion tensor imaging. The apparent diffusion coefficient (ADC) and fractional anisotropy (FA) were measured in regions of interest placed in the white matter of the DLPFC, ACC, corpus callosum, and internal capsule. Differences between groups were assessed, controlling for age, sex, and total cerebral volume. RESULTS: After controlling for covariates, depressed subjects had significantly lower FA values in white matter of the right ACC, bilateral superior frontal gyri, and left middle frontal gyrus. There were no significant differences in ADC values. CONCLUSIONS: Lower FA, representing lower tissue organization, is observed in depressed elders in the DLPFC and right ACC. These findings support the hypothesis that altered connectivity between brain regions contributes to the risk of depression.

Aged↗