Prefrontal lesions and cutaneous responsiveness of cats: Learned discrimination,delayed-response,orientation-localization,and transfer

Cats with gyrus proreus lesions showed a substantial deficit and then gradual recovery of delayed responding to passively-received cutaneous stimuli. At the same time, the animals performed well in the basic, nondelay cutaneous discrimination task and in a battery of sensory and motor neurological tests. There was an earlier postoperative loss in the nondelay cutaneous discriminative test but evidence suggests that this loss was not due to sensory factors. Other early postoperative changes included hyperactivity and failure to maintain an appropriate ready posture when awaiting stimulation. A particularly interesting early deficit was the initiation, but refusal to complete, one of the two discriminative responses; that this deficit was not a “motor” one was shown by the fact that the same response movement-standing up on hindlegs-was performed vigorously when tactile cues which elicited pursuit were applied to the head. Early postoperative reluctance to perform effortful voluntary movements was also seen in a task that required searching with the forelimb. To further assess cognitive ability, cats were tested in the nondelay cutaneous discrimination with the stimuli applied to new loci, on the hindlimbs. They performed as well as do normals in this test of transfer, which was carried out late, after recovery of delayed responding. The present findings, taken together with those of earlier experiments, suggest that learned cutaneous discriminative behaviors are served not only by somatosensory and motor cortex, but also by regions of frontal cortex that have more complex anatomical and physiological properties. Prefrontal cortex may routinely participate in learned associations between stimuli and responses, but in the present case there was considerable recovery following subtotal ablation of the cortical projection of the mediodorsal thalamic nucleus.     

Dissociation of sensorimotor deficits after rostral versus caudal lesions in the primary motor cortex hand representation

Primary motor cortex (M1) has traditionally been considered a motor structure. Although neurophysiologic studies have demonstrated that M1 is also influenced by somatosensory inputs (cutaneous and proprioceptive), the behavioral significance of these inputs has yet to be fully defined in primates. The present study describes differential sensory-related deficits after small ischemic lesions in either the rostral or caudal subregion of the M1 hand area in a nonhuman primate. Squirrel monkeys retrieved food pellets out of different sized wells drilled into a Plexiglas board. Before the lesion, monkeys retrieved pellets by directing the hand to the well, inserting fingers directly into it, and extracting the pellet. After a lesion to the rostral portion of M1, monkeys frequently failed to direct the hand accurately to the well. Instead, fingers contacted the surface of the board outside the well before entering the well. These aiming errors are consistent with both the large amount of proximal motor outputs and the predominant proprioceptive inputs of rostral M1. Overall, these aiming errors are suggestive of dysfunctional processing of proprioceptive information or the failure to integrate proprioceptive information with motor commands. In contrast, after a lesion to the caudal portion of M1, monkeys frequently examined their palm visually for the presence of the pellet after an attempted retrieval. These errors are consistent with both the large amount of distal motor outputs and the predominant cutaneous inputs of caudal M1. Thus these errors are suggestive of a deficit in processing of cutaneous information or the failure to integrate cutaneous information with motor commands. Rostral and caudal M1 lesions result in different deficits in sensory-dependent motor control that appear to correlate with broad segregation of motor outputs and previously described sensory inputs of M1.     

The specificity of motor neurone regeneration (preferential reinnervation)

The major determinant of functional recovery after lesions in the peripheral nervous system is the accurate regeneration of axons to their original target end-organs. Unfortunately, regenerating motor axons are often misrouted to sensory target end-organs, and sensory axons formerly innervating skin are often misrouted to muscle. As such regeneration is robust, but often inaccurate, a better understanding of how regenerating axons reinnervate terminal pathways would be of fundamental interest to basic and clinical neuroscience. This review will consider the underlying cellular and molecular mechanisms that influence the accuracy of peripheral nerve regeneration, within the context of 'preferential motor reinnervation' (PMR). Much previous work with PMR has utilized the rodent femoral nerve and has shown that regenerating motor axons preferentially, albeit incompletely, reinnervate a distal terminal nerve branch to muscle (quadriceps) vs. skin (saphenous). One interpretation of this body of work has been that Schwann cell tubes have a specific identity that can be recognized by regenerating motor axons and that influences their subsequent behaviour. We disagree with that interpretation, and suggest motor and cutaneous pathways are not inherently different in terms of their ability to support regeneration of motor axons. In fact, recent experiments indicate under certain conditions motor axons will preferentially reinnervate the inappropriate terminal cutaneous pathway instead of the appropriate pathway to muscle. We suggest that it is the relative level of trophic support provided by each nerve branch that determines whether motor axons will remain in that particular branch. Within the context of the femoral nerve model, our results suggest a hierarchy of trophic support for regenerating motor axons with muscle contact being the highest, followed by the length of the terminal nerve branch and/or contact with skin.     

Complete ulnar innervation of the thenar muscles combined with normal sensory fibres in a subject with no peripheral nerve lesion.

A complete ulnar innervation of all thenar muscles, including the opponens, have to our knowledge been described only in patients with severe traumatic lesions of the median nerve. The present study reports a subject with exclusive ulnar innervation of the thenar muscles in the right hand. The patient had no anamnestic or objective signs of peripheral nerve lesions. While his sensory and motor ulnar nerve fibres were normal, electrophysiological examination of the right median nerve showed normal course of the sensory fibres but apparently no motor fibres to the thenar muscles.     

Impact of obstructive apnea syndrome on upper airway respiratory muscles

This article reviews studies of upper airway muscles in humans, with emphasis on muscle fiber structural and electrophysiological changes observed in patients with obstructive sleep apnea syndrome (OSAS). The concept of OSAS as a progressive disease is discussed and also possible causes. These include local nervous lesions in the upper airway, both motor and sensory. Previous muscle biopsy studies have given evidence for motor neuron lesions such as, e.g., the phenomenon of type grouping in histological sections. New data obtained with concentric needle EMG recordings from the palatopharyngeus muscles are also presented. In 10/12 OSAS patients there were typical findings indicating motor neuropathy (reduced EMG activity at maximal voluntary effort, long and polyphasic motor-unit potentials and, in two cases, spontaneous denervation activity), whereas such findings were only present in 3/15 patients with habitual snoring. This supports the hypothesis that progression from habitual snoring to the clinical disease of OSAS could be attributed to peripheral neurogenic lesions.     

The role of the monkey sensory cortex in the recovery from cerebellar injury

Summary The aim of the study was to investigate the contribution of the primary sensory cortex in the compensation of cerebellar deficits during self-paced movements. For this purpose, monkeys were trained on motor tasks which required goal-reaching and independent finger movements. The intermediate and lateral deep cerebellar nuclei and the sensory cortex were lesioned in isolation and in sequence and the course of motor recovery was studied on the test performances. The deep nuclei were lesioned by kainic acid injections, the sensory cortex was removed by ablation. Cerebellar lesions in isolation produced obvious deficits at proximal and distal joints, affecting both slow and fast motor adjustments. Only lesions of the anterior portions of the intermediate and lateral deep nuclear complexes produced deficiencies in voluntary movements. Lesions of the posterior portions produced postural disturbances. The process of recovery following cerebellar lesions was slow and, depending on the nature of the task, was found to be differentially disruptive for motor performances requiring fast and slow motor adjustments. The deficits at distal joints appeared to be more enduring than those at proximal joints. Sensory cortical lesions in isolation produced much less severe and more transient motor deficits. They consisted of hand clumsiness and their recovery was fast and reached higher levels of performance than following cerebellar lesions. When the sensory cortex was removed secondarily to a cerebellar lesion and after recovery from the cerebellar deficits, the initially recovered motor performance became much worse again (decompensation). Removal of the sensory cortex prior to a cerebellar lesion exaggerated the cerebellar deficits and severely limited their recovery. Slow and fast motor performances were completely abolished for three weeks following sequential lesions. Signs of recovery subsequently appeared and stabilized at low levels of performance by five to seven weeks. The effects of combined, sequential cerebellar and sensory cortical lesions were much worse than expected if the effects from the two lesions were merely additive. This indicates that there is some functional interrelationship between the sensory cortex and the cerebellum, which promotes compensation. The somatosensory cortex appears to play a crucial role in the process of recovery from cerebellar motor deficits and it is likely that sensation is an important component in the process of recovery. It is suggested that the sensory cortex exerts its compensatory actions via a structure or structures which receives convergent cerebellar and sensory cortical inputs.     

Short-latency projections to the cat's cerebral cortex from skin and muscle afferents in the contralateral forelimb

1. The potentials evoked in the first sensorimotor area on stimulation of muscle and skin nerves in the contralateral forelimb were recorded in preparations with either the dorsal funiculus (DF) or the spinocervical tract (SCT) interrupted.2. The short-latency, surface-positive potentials in these preparations are mediated by the remaining path, either the DF or SCT.3. Cutaneous afferents project through both paths to two discrete areas which correspond to the classical sensory and motor cortices (Fig. 10 A and B). The projection areas are not identical: the DF path seems to activate most effectively the sensory cortex; and the SCT path, most effectively the motor cortex.4. The potentials evoked from cutaneous nerves have a similar latency in the two areas. On stimulation of the superficial radial nerve the latency was about 4.5 msec in preparations with intact DF, and about 5.3 msec in preparations with intact SCT.5. High threshold muscle afferents project to the same areas as the cutaneous afferents.6. Group I muscle afferents project, exclusively through the DF path, to an area distinct from the two cutaneous projection areas (Fig. 10C). It occupies a caudal part of the motor cortex and an intermediate zone between the sensory and motor cortices.7. The projection areas are compared with the recent cytoarchitectonic map of Hassler & Muhs-Clement (1964) (Fig. 10D).8. It is suggested that the afferent projections to the motor cortex and the intermediate zone are used in the integration of movements elicited from the cortex. The general similarity in the organization of afferent paths to the motor cortex and the cerebellum is pointed out.     

The organization of primary afferent depolarization in the isolated spinal cord of the frog

1. The organization of primary afferent depolarization (PAD) produced by excitation of peripheral sensory and motor nerves was studied in the frog cord isolated with hind limb nerves.2. Dorsal root potentials from sensory fibres (DR-DRPs) were evoked on stimulation of most sensory nerves, but were largest from cutaneous, joint and flexor muscle afferents. With single shock stimulation the largest cutaneous and joint afferent fibres gave DR-DRPs, but potentials from muscle nerves resulted from activation of sensory fibres with thresholds to electrical stimulation higher than 1.2-1.5 times the threshold of the most excitable fibres in the nerve. This suggests that PAD from muscle afferents is probably due to excitation of extrafusal receptors.3. Dorsal root potentials produced by antidromic activation of motor fibres (VR-DRPs) were larger from extensor muscles and smaller or absent from flexor muscles. The VR-DRPs were produced by activation of the lowest threshold motor fibres.4. Three types of interactions were found between test and conditioning DRPs from the same or different nerves. With maximal responses occlusion was usually pronounced. At submaximal levels linear summation occurred. Near threshold the conditioning stimulus frequently resulted in a large facilitation of the test DRP. All three types of interactions were found with two DR-DRPs, two VR-DRPs or one DR-DRP and one VR-DRP.5. The excitability of sensory nerve terminals from most peripheral nerves was increased during the DR-DRP. The magnitude of the excitability increase varied roughly with the magnitude of the DR-DRP evoked by the conditioning stimulus.6. There was a marked excitability increase of cutaneous and extensor muscle afferent terminals during the VR-DRP. Flexor muscle afferent terminals often showed no excitability changes to ventral root stimulation. In those experiments where afferent terminals from flexor muscles did show an excitability increase, the effects were smaller than those of cutaneous and extensor terminals.7. The VR-DRPs appear to reflect activity of a negative feed-back loop from extensor motoneurones on to sensory fibres from cutaneous and extensor muscles. This system may have a role in modulating the ballistic movement of the frog. DR-DRPs, on the contrary, are widespread in origin and distribution. PAD from sensory fibres may function to sharpen contrast between incoming afferent information.     

Ipsilesional trajectory control is related to contralesional arm paralysis after left hemisphere damage

We have recently shown ipsilateral dynamic deficits in trajectory control are present in left hemisphere damaged (LHD) patients with paresis, as evidenced by impaired modulation of torque amplitude as response amplitude increases. The purpose of the current study is to determine if these ipsilateral deficits are more common with contralateral hemiparesis and greater damage to the motor system, as evidenced by structural imaging. Three groups of right-handed subjects (healthy controls, LHD stroke patients with and without upper extremity paresis) performed single-joint elbow movements of varying amplitudes with their left arm in the left hemispace. Only the paretic group demonstrated dynamic deficits characterized by decreased modulation of peak torque (reflected by peak acceleration changes) as response amplitude increased. These results could not be attributed to lesion volume or peak velocity as neither variable differed across the groups. However, the paretic group had damage to a larger number of areas within the motor system than the non-paretic group suggesting that such damage increases the probability of ipsilesional deficits in dynamic control for modulating torque amplitude after left hemisphere damage.     

Cutaneous sensibility and peripheral nerve function in patients with unmedicated essential hypertension

Sensorimotor deficits in patients with essential hypertension may be due to impaired nerve function. Cutaneous sensory thresholds, median nerve sensory and motor conduction velocities, and median nerve sensory action potential amplitudes were assessed in 30 patients with unmedicated essential hypertension and 29 normotensives. Cutaneous sensory thresholds were higher and sensory action potential amplitudes smaller in hypertensives than normotensives whereas sensory and motor nerve conduction velocities did not differ between groups. These data suggest that hypertension may reduce the number of active sensory nerve fibers without affecting myelination. Sensory action potential amplitudes were inversely related to cutaneous sensory thresholds, suggesting that subclinical axonal neuropathy of sensory afferents may help account for perceptual deficits that characterize hypertension.     

脑磁图在大脑感觉运动功能区占位性病变患者中的应用

目的：探讨脑磁图（MEG）在大脑皮层感觉、运动功能区占位性病变患者中的应用价值.方法：对81例大脑皮层感觉和（或）运动功能区及其附近占位性病变患者,应用151信道全头型MEG系统,通过电流刺激正中神经和胫神经确定上、下肢体感皮层的位置,运动皮层分别通过双手食指按压键盘引起的MEG反应来定位.术前将磁源性影像（MSI）通过神经影像导航进行三维重建,了解相应功能区与病变的解剖关系,设计手术入路.感觉功能区病变患者和运动功能区不能确定的患者术中通过电刺激正中神经（或胫神经内踝）使用皮层电极于拟定的中央沟前后的皮层记录体感诱发电位（CSEP）,依据中央沟前后皮层记录到的CSEP具有极性反转的特征来确定中央沟.其中8例患者通过对指运动行功能磁共振（fMRI）检查,在术中唤醒状态下通过电刺激大脑皮层确定运动功能区.结果：81例患者全部定位出感觉功能区,75例患者定位出运动功能区,6例患者因功能障碍或配合差运动功能区不能定位.术后1例患者病变对侧肢体运动障碍加重,其余80例患者无感觉、运动功能损害.结论：术前行MEG功能区定位有助于医生选择合适的手术入路和避免术中损伤脑功能区皮质,最大限度地保护神经功能,减少手术伤残率,提高手术疗效.     

Responses of cat motor cortex neurons to cortico-cortical and somatosensory inputs

Summary Intracellular techniques were used to investigate a cortico-cortical path from sensory cortex to motor cortex of cats. Cortico-cortical epsps were evoked in motor cortex neurons by microstimulation of area 3a. Epsps with latencies between 1.2 and 2.4 ms were identified as monosynaptic. These short latency cortico-cortical effects were recorded in layers II through VI of the motor cortex. Neurons with monosynaptic cortico-cortical epsps also received excitatory inputs from forelimb nerves, usually from both muscle and cutaneous afferent fibers. The epsps evoked from forelimb nerves in motor cortex neurons were preceded by neural activity in somatosensory cortex. Time delays between arrival of inputs in sensory cortex and in motor cortex were compared to the latencies of cortico-cortical epsps in the same motor cortex neurons. It was apparent that the timing was appropriate for the identified cortico-cortical path to have relayed some sensory inputs to motor cortex.Supported by the Medical Research Council of Canada (MT-7373, DG-186), the Harry Botterell Foundation for the Neurological Sciences, the Ontario Ministry of Health, and the Faculty of Medicine, Queen's UniversityRecipient of a Medical Research Council of Canada Studentship.Recipient of a Medical Research Council of Canada Fellowship     

Immunopathologic studies of cutaneous lupus erythematosus

The studies, as outlined above, strongly suggest that there may be several pathophysiologic mechanisms resulting in the development of cutaneous lupus lesions. It appears that all lupus lesions are associated predominantly with a T-cell infiltrate. Based upon the studies of the neonatal lupus infants, it has been hypothesized that the U1RNP and Ro(SS-A) autoantibodies of maternal origin play a direct pathologic role in the genesis of the annular polycyclic SCLE lesions and this may be mediated by antibody-dependent cellular cytotoxicity mechanisms in which the antibody binds to the respective antigen present on the keratinocyte plasma membrane and the effector cells are T cells derived from the infants. Other studies, using direct immunofluorescence techniques, have demonstrated an association of cutaneous lupus lesions occurring in the presence of immunoglobulin and complement at the dermal/epidermal junction (positive lupus band test) in which the neoantigen of the complement membrane attack complex (C5b-C9) is detected. These data have been interpreted as indicating that immunoglobulin and complement, perhaps in the form of immune complexes, may play a role in the pathogenesis of some cutaneous lupus lesions. Additional studies have determined that there is a substantial number of lupus patients with cutaneous disease, without antinuclear antibodies, who fail to demonstrate the deposition of immunoglobulin and complement at the dermal/epidermal junction. Furthermore, other studies have indicated that ultraviolet light is capable of inducing lesions in lupus patients that histologically are identical to those of cutaneous lupus erythematosus but that failed to demonstrate the deposition of the immunoglobulin and complement components. Since discoid lupus lesions demonstrate a preponderance of T cells, it has been proposed that some of these lesions are the direct result of a T-cell cytotoxic event. However, the nature of the autoantigens responsible for this putative T cell-mediated cytotoxic response is unknown at the present time. The role of ultraviolet light in the genesis of the cutaneous lupus lesions appears to involve, within the epidermis, the generation of autoantigen macromolecules which then react with autoantibodies or specific T cells of the lupus host.     

Movement-related cerebellar activation in the absence of sensory input.

Movement-related cerebellar activation may be due to sensory or motor processing. Ordinarily, sensory and motor processing are obligatorily linked, but in patients who have severe pansensory neuropathies with normal muscle strength, motor activity occurs in isolation. In the present study, positron emission tomography and functional magnetic resonance imaging in such patients showed no cerebellar activation with passive movement, whereas there was prominent movement-related cerebellar activation despite absence of proprioceptive or visual input. The results indicate that motor processing occurs within the cerebellum and do not support the recently advanced view that the cerebellum is primarily a sensory organ.     

Quantification of excitatory receptive fields of complex neurones in cat striate cortex

To use sensory information from the skin to guide motor behaviour the central nervous system must transform sensory coordinates into movement coordinates. As yet, the basic principles of this crucial neural computation are unclear. One motor system suitable as a model for the study of such transformations is the spinal withdrawal reflex system. The spatial organization of the cutaneous input to these reflexes has been characterized, and we now introduce a novel method of motion analysis permitting a quantitative analysis of the spatial input-output relationship in this motor system. For each muscle studied, a mirror-image relationship was found between the spatial distribution of reflex gain for cutaneous input and the pattern of cutaneous unloading ensuing on contraction. Thus, there is an imprint of the movement pattern on this motor system permitting effective sensorimotor transformation. This imprint may indicate the presence of a learning process which utilizes the sensory feedback ensuing on muscle contraction.     

Spatial hemineglect in humans

The paper reviews the main findings of studies of hemispatial neglect after acquired brain lesions in people. The behavioral consequences of experimentally induced lesions in animals and electrophysiological studies, which shed light on the nature of the disorder, are briefly considered. Neglect is behaviorally defined as a deficit in processing or responding to sensory stimuli in the contralateral hemispace, a part of the own body, the part of an imagined scene, or may include the failure to act with the contralesional limbs despite intact motor functions. Neglect in humans is frequently encountered after right parieto-temporal lesions and leads to a multicomponent syndrome of sensory, motor and representational deficits. Relevant findings relating to neglect, extinction and unawareness are reviewed and include the following topics: etiological and anatomical basis, recovery; allocentric, egocentric, object-centered and representational neglect; motor neglect and directional hypokinesia; elementary sensorimotor and associated disorders; subdivisions of space and frames of reference; extinction versus neglect; covert processing of information; unawareness of deficits; human and animal models; effects of sensory stimulation and rehabilitation techniques.     

Parietal cortex and movement I. Movement selection and reaching

 Recording studies in the parietal cortex have demonstrated single-unit activity in relation to sensory stimulation and during movement. We have performed three experiments to assess the effect of selective parietal lesions on sensory motor transformations. Animals were trained on two reaching tasks: reaching in the light to visual targets and reaching in the dark to targets defined by arm position. The third task assessed non-standard, non-spatial stimulus response mapping; in the conditional motor task animals were trained to either pull or turn a joystick on presentation of either a red or a blue square. We made two different lesions in the parietal cortex in two groups of monkeys. Three animals received bilateral lesions of areas 5, 7b and MIP, which have direct connections with the premotor and motor cortices. The three other animals subsequently received bilateral lesions in areas 7a, 7ab and LIP. Both groups were still able to select between movements arbitrarily associated with non-spatial cues in the conditional motor task. Removal of areas 7a, 7ab and LIP caused marked inaccuracy in reaching in the light to visual targets but had no effect on reaching in the dark. Removal of areas 5, 7b and MIP caused misreaching in the dark but had little effect on reaching in the light. The results suggest that the two divisions of the parietal cortex organize limb movements in distinct spatial coordinate systems. Area 7a/7ab/LIP is essential for spatial coordination of visual motor transformations. Area 5/7b/MIP is essential for the spatial coordination of arm movements in relation to proprioceptive and efference copy information. Neither part of the parietal lobe appears to be important for the non-standard, non-spatial transformations of response selection. Received: 5 June 1996 / Accepted: 12 February 1997     

Attenuation of negative pain affect produced by unilateral spinal nerve injury in the rat following anterior cingulate cortex activation

The affective and the sensory dimensions of pain processing can be differentiated in humans through the use of questionnaires and verbal communication. It is difficult to dissociate these two components of pain processing in rodents, and an understanding of the underlying mechanisms for each component is unclear. The quantification of a novel behavioral response to a repeated noxious cutaneous stimulus together with a measurement of tactile allodynia in nerve-injured rats might be used to differentially explore the sensory and affective components of pain processing in the rat. The present study utilized electrical stimulation of the anterior cingulate cortex, a structure implicated in affective pain processing but not sensory processing, in nerve-injured rats (L5 spinal nerve ligation) and found that the aversive quality of noxious cutaneous hindpaw stimulation was attenuated. There were no effects on sensory processing, because anterior cingulate cortex stimulation did not produce an anti-allodynic effect in L5 spinal nerve ligation animals. Furthermore, anterior cingulate cortex stimulation in animals with bilateral ventrolateral periaqueductal gray area lesions did not affect tactile sensitivity in L5 spinal nerve ligation rats, indicating that an endogenous pain suppression system was not likely activated by anterior cingulate cortex stimulation. However, bilateral ventrolateral periaqueductal gray area lesions in L5 spinal nerve ligation rats blocked the effect produced by anterior cingulate cortex stimulation in the place escape/avoidance paradigm. Specifically, these animals avoided noxious stimulation of the allodynic paw significantly more than anterior cingulate cortex-stimulated, sham or incomplete ventrolateral periaqueductal gray area-lesioned, L5 spinal nerve ligation animals. These findings provide the first quantified report that the activation of the anterior cingulate cortex reduced the aversive quality of repeated noxious tactile stimulation in nerve-injured animals without interfering with normal sensory processing. This effect might require the presence of an intact ventrolateral periaqueductal gray area. It is concluded that the selective manipulation of the anterior cingulate cortex has different effects on pain affect and sensory processing in a rodent model of neuropathic pain.     

Innervation of the avian tonus latissimus dorsi anterior muscle

The motor and cutaneous nerves associated with the pigeon's anterior latissimus dorsi tonus muscle are described. The motor nerve is traced from its origin within the brachialis longus superior nerve of the brachial plexus to within the epimysium of the muscle by means of serial cross sections. The nerve fibers differ in mean diameter at various sites along the nerve. They originate as small fibers within the plexus, become larger as they emerge and then gradually decrease in diameter as they approach the muscle. The number of nerve fibers remains relatively constant until the nerve divides into more than two branches, at which time the number increases. The cutaneous nerve passing through the anterior latissimus dorsi is described and is assumed not to play any role in the innervation, either sensory or motor, of the fibers in this muscle.