The Organization and Evolution of Dorsal Stream Multisensory Motor Pathways in Primates

In Prosimian primates, New World monkeys, and Old World monkeys microstimulation with half second trains of electrical pulses identifies separate zones in posterior parietal cortex (PPC) where reaching, defensive, grasping, and other complex movements can be evoked. Each functional zone receives a different pattern of visual and somatosensory inputs, and projects preferentially to functionally matched parts of motor and premotor cortex. As PPC is a relatively small portion of cortex in most mammals, including the close relatives of primates, we suggest that a larger, more significant PPC emerged with the first primates as a region where several ethologically relevant behaviors could be initiated by sensory and intrinsic signals, and mediated via connections with premotor and motor cortex. While several classes of PPC modules appear to be retained by all primates, elaboration and differentiation of these modules likely occurred in some primates, especially humans

The role of cholinergic and serotonergic neocortical projections in controlling skilled movement in rats : evaluation of a model of dementia

vii, 166 leaves : ill. ; 28 cm.The ascending cholinergic and serotonergic projections are central to cortical activation and normal behavior. The objective of this thesis was to determine whether unilaterally damaging both of these systems would disrupt the production of skilled movements on the contralateral side of the body. Rats received unilateral damage to either the ascending cholinergic, or serotonergic, or both projections. The respective lesions reduced neocortical leveles of acetylcholine and serotonin as assessed by acetylcholinesterase reactivity and immunohistochemical staining for serotonin. Subjects were assessed on a battery of sensorimotor tasks sensitive to neocortical integrity. The cholinergic lesion produced mild deficits on some taks but damage to both together did not abolish skilled movement. The impairments are decreased in relation to the severe effects of bilateral lesions. The results show that the sensorimotor cortex remains functional following deafferentation of both cholinergic and serotonergic afferents

Modeling middle cerebral artery stroke in rats : an examination of the skilled reaching impairments

xiii, 345 leaves : ill. ; 29 cm. + 1 CD-ROMMiddle cerebral artery (MCA) stroke can produce chronic incapacitating motor impairments. Understanding the neural basis of the motor syndromes is complicated by the diversity of neural structures damaged but the problem can be addressed in laboratory rats by inducing selective infarcts. Nevertheless, the motor syndromes that ensue from stroke in rats remain poorly understood and undermine its potential as a model for clinical stroke. The objective of the present thesis was to document the skilled reaching impairments from neocortical and subcortical MCA infarcts in rats. In addition, the integrity of the motor system components spared by the infarct was assessed neurophysiologically and neuroanatomically. Characteristic reaching impairments emerged from each infarct but there were also some overlapping features that might be explained by neural dysfunction extending beyond the boundaries of the infarct. The present studies showed that the laboratory rat is an ideal animal model for studying stroke, which should be of interest to both clinical and research scientists studying stroke

Low-frequency cortical activity is a neuromodulatory target that tracks recovery after stroke.

Recent work has highlighted the importance of transient low-frequency oscillatory (LFO; <4 Hz) activity in the healthy primary motor cortex during skilled upper-limb tasks. These brief bouts of oscillatory activity may establish the timing or sequencing of motor actions. Here, we show that LFOs track motor recovery post-stroke and can be a physiological target for neuromodulation. In rodents, we found that reach-related LFOs, as measured in both the local field potential and the related spiking activity, were diminished after stroke and that spontaneous recovery was closely correlated with their restoration in the perilesional cortex. Sensorimotor LFOs were also diminished in a human subject with chronic disability after stroke in contrast to two non-stroke subjects who demonstrated robust LFOs. Therapeutic delivery of electrical stimulation time-locked to the expected onset of LFOs was found to significantly improve skilled reaching in stroke animals. Together, our results suggest that restoration or modulation of cortical oscillatory dynamics is important for the recovery of upper-limb function and that they may serve as a novel target for clinical neuromodulation

Activity in ventral premotor cortex is modulated by vision of own hand in action

Parietal and premotor cortices of the macaque monkey contain distinct populations of neurons which, in addition to their motor discharge, are also activated by visual stimulation. Among these visuomotor neurons, a population of grasping neurons located in the anterior intraparietal area (AIP) shows discharge modulation when the own hand is visible during object grasping. Given the dense connections between AIP and inferior frontal regions, we aimed at investigating whether two hand-related frontal areas, ventral premotor area F5 and primary motor cortex (area F1), contain neurons with similar properties. Two macaques were involved in a grasping task executed in various light/dark conditions in which the to-be-grasped object was kept visible by a dim retro-illumination. Approximately 62% of F5 and 55% of F1 motor neurons showed light/dark modulations. To better isolate the effect of hand-related visual input, we introduced two further conditions characterized by kinematic features similar to the dark condition. The scene was briefly illuminated (i) during hand preshaping (pre-touch flash, PT-flash) and (ii) at hand-object contact (touch flash, T-flash). Approximately 48% of F5 and 44% of F1 motor neurons showed a flash-related modulation. Considering flash-modulated neurons in the two flash conditions, ∼40% from F5 and ∼52% from F1 showed stronger activity in PT- than T-flash (PT-flash-dominant), whereas ∼60% from F5 and ∼48% from F1 showed stronger activity in T- than PT-flash (T-flash-dominant). Furthermore, F5, but not F1, flash-dominant neurons were characterized by a higher peak and mean discharge in the preferred flash condition as compared to light and dark conditions. Still considering F5, the distribution of the time of peak discharge was similar in light and preferred flash conditions. This study shows that the frontal cortex contains neurons, previously classified as motor neurons, which are sensitive to the observation of meaningful phases of the own grasping action. We conclude by discussing the possible functional role of these populations

The pedunculopontine tegmental nucleus and the nucleus basalis magnocellularis: Do both have a role in sustained attention?

It is well established that nucleus basalis magnocellularis (NbM) lesions impair performance on tests of sustained attention. Previous work from this laboratory has also demonstrated that pedunculopontine tegmental nucleus (PPTg) lesioned rats make more omissions on a test of sustained attention, suggesting that it might also play a role in mediating this function. However, the results of the PPTg study were open to alternative interpretation. We aimed to resolve this by conducting a detailed analysis of the effects of damage to each brain region in the same sustained attention task used in our previous work. Rats were trained in the task before surgery and post-surgical testing examined performance in response to unpredictable light signals of 1500 ms and 4000 ms duration. Data for PPTg lesioned rats were compared to control rats, and rats with 192 IgG saporin infusions centred on the NbM. In addition to operant data, video data of rats' performance during the task were also analysed

Gene Expression Changes in the Motor Cortex Mediating Motor Skill Learning

The primary motor cortex (M1) supports motor skill learning, yet little is known about the genes that contribute to motor cortical plasticity. Such knowledge could identify candidate molecules whose targeting might enable a new understanding of motor cortical functions, and provide new drug targets for the treatment of diseases which impair motor function, such as ischemic stroke. Here, we assess changes in the motor-cortical transcriptome across different stages of motor skill acquisition. Adult rats were trained on a gradually acquired appetitive reach and grasp task that required different strategies for successful pellet retrieval, or a sham version of the task in which the rats received pellet reward without needing to develop the reach and grasp skill. Tissue was harvested from the forelimb motor-cortical area either before training commenced, prior to the initial rise in task performance, or at peak performance. Differential classes of gene expression were observed at the time point immediately preceding motor task improvement. Functional clustering revealed that gene expression changes were related to the synapse, development, intracellular signaling, and the fibroblast growth factor (FGF) family, with many modulated genes known to regulate synaptic plasticity, synaptogenesis, and cytoskeletal dynamics. The modulated expression of synaptic genes likely reflects ongoing network reorganization from commencement of training till the point of task improvement, suggesting that motor performance improves only after sufficient modifications in the cortical circuitry have accumulated. The regulated FGF-related genes may together contribute to M1 remodeling through their roles in synaptic growth and maturation.McGovern Institute for Brain Research at MITNational Institutes of Health (U.S.) ((NIH grant 1-RC1-NS068103-01)National Institutes of Health (U.S.) (NIH grant R01-MH084966)Roberto Rocca Education Program (Fellowship)Massachusetts Institute of Technology. Undergraduate Research Opportunities Program (Fellowship)Italy. Ministero dell'istruzione, dell'università e della ricerca (MIUR grant RBIN04H5AS)Italy. Ministero dell'istruzione, dell'università e della ricerca (MIUR grant RBLA03FLJC)Italy. Ministero dell'istruzione, dell'università e della ricerca (FIRB n. RBAP10L8TY