Matching Items (9)
Filtering by
- All Subjects: Arm--Movements.
- Creators: Santello, Marco
Description
In order to successfully implement a neural prosthetic system, it is necessary to understand the control of limb movements and the representation of body position in the nervous system. As this development process continues, it is becoming increasingly important to understand the way multiple sensory modalities are used in limb representation. In a previous study, Shi et al. (2013) examined the multimodal basis of limb position in the superior parietal lobule (SPL) as monkeys reached to and held their arm at various target locations in a frontal plane. Visual feedback was withheld in half the trials, though non-visual (i.e. somatic) feedback was available in all trials. Previous analysis showed that some of the neurons were tuned to limb position and that some neurons had their response modulated by the presence or absence of visual feedback. This modulation manifested in decreases in firing rate variability in the vision condition as compared to nonvision. The decreases in firing rate variability, as shown through decreases in both the Fano factor of spike counts and the coefficient of variation of the inter-spike intervals, suggested that changes were taking place in both trial-by-trial and intra-trial variability. I sought to further probe the source of the change in intra-trial variability through spectral analysis. It was hypothesized that the presence of temporal structure in the vision condition would account for a regularity in firing that would have decreased intra-trial variability. While no peaks were apparent in the spectra, differences in spectral power between visual conditions were found. These differences are suggestive of unique temporal spiking patterns at the individual neuron level that may be influential at the population level.
ContributorsDyson, Keith (Author) / Buneo, Christopher A (Thesis advisor) / Helms-Tillery, Stephen I (Committee member) / Santello, Marco (Committee member) / Arizona State University (Publisher)
Created2013
Description
Reaching movements are subject to noise in both the planning and execution phases of movement production. Although the effects of these noise sources in estimating and/or controlling endpoint position have been examined in many studies, the independent effects of limb configuration on endpoint variability have been largely ignored. The present study investigated the effects of arm configuration on the interaction between planning noise and execution noise. Subjects performed reaching movements to three targets located in a frontal plane. At the starting position, subjects matched one of two desired arm configuration 'templates' namely "adducted" and "abducted". These arm configurations were obtained by rotations along the shoulder-hand axis, thereby maintaining endpoint position. Visual feedback of the hand was varied from trial to trial, thereby increasing uncertainty in movement planning and execution. It was hypothesized that 1) pattern of endpoint variability would be dependent on arm configuration and 2) that these differences would be most apparent in conditions without visual feedback. It was found that there were differences in endpoint variability between arm configurations in both visual conditions, but these differences were much larger when visual feedback was withheld. The overall results suggest that patterns of endpoint variability are highly dependent on arm configuration, particularly in the absence of visual feedback. This suggests that in the presence of vision, movement planning in 3D space is performed using coordinates that are largely arm configuration independent (i.e. extrinsic coordinates). In contrast, in the absence of vision, movement planning in 3D space reflects a substantial contribution of intrinsic coordinates.
ContributorsLakshmi Narayanan, Kishor (Author) / Buneo, Christopher (Thesis advisor) / Santello, Marco (Committee member) / Helms Tillery, Stephen (Committee member) / Arizona State University (Publisher)
Created2013
Description
Learning by trial-and-error requires retrospective information that whether a past action resulted in a rewarded outcome. Previous outcome in turn may provide information to guide future behavioral adjustment. But the specific contribution of this information to learning a task and the neural representations during the trial-and-error learning process is not well understood. In this dissertation, such learning is analyzed by means of single unit neural recordings in the rats' motor agranular medial (AGm) and agranular lateral (AGl) while the rats learned to perform a directional choice task. Multichannel chronic recordings using implanted microelectrodes in the rat's brain were essential to this study. Also for fundamental scientific investigations in general and for some applications such as brain machine interface, the recorded neural waveforms need to be analyzed first to identify neural action potentials as basic computing units. Prior to analyzing and modeling the recorded neural signals, this dissertation proposes an advanced spike sorting system, the M-Sorter, to extract the action potentials from raw neural waveforms. The M-Sorter shows better or comparable performance compared with two other popular spike sorters under automatic mode. With the sorted action potentials in place, neuronal activity in the AGm and AGl areas in rats during learning of a directional choice task is examined. Systematic analyses suggest that rat's neural activity in AGm and AGl was modulated by previous trial outcomes during learning. Single unit based neural dynamics during task learning are described in detail in the dissertation. Furthermore, the differences in neural modulation between fast and slow learning rats were compared. The results show that the level of neural modulation of previous trial outcome is different in fast and slow learning rats which may in turn suggest an important role of previous trial outcome encoding in learning.
ContributorsYuan, Yu'an (Author) / Si, Jennie (Thesis advisor) / Buneo, Christopher (Committee member) / Santello, Marco (Committee member) / Chae, Junseok (Committee member) / Arizona State University (Publisher)
Created2014
Description
Animals learn to choose a proper action among alternatives according to the circumstance. Through trial-and-error, animals improve their odds by making correct association between their behavioral choices and external stimuli. While there has been an extensive literature on the theory of learning, it is still unclear how individual neurons and a neural network adapt as learning progresses. In this dissertation, single units in the medial and lateral agranular (AGm and AGl) cortices were recorded as rats learned a directional choice task. The task required the rat to make a left/right side lever press if a light cue appeared on the left/right side of the interface panel. Behavior analysis showed that rat's movement parameters during performance of directional choices became stereotyped very quickly (2-3 days) while learning to solve the directional choice problem took weeks to occur. The entire learning process was further broken down to 3 stages, each having similar number of recording sessions (days). Single unit based firing rate analysis revealed that 1) directional rate modulation was observed in both cortices; 2) the averaged mean rate between left and right trials in the neural ensemble each day did not change significantly among the three learning stages; 3) the rate difference between left and right trials of the ensemble did not change significantly either. Besides, for either left or right trials, the trial-to-trial firing variability of single neurons did not change significantly over the three stages. To explore the spatiotemporal neural pattern of the recorded ensemble, support vector machines (SVMs) were constructed each day to decode the direction of choice in single trials. Improved classification accuracy indicated enhanced discriminability between neural patterns of left and right choices as learning progressed. When using a restricted Boltzmann machine (RBM) model to extract features from neural activity patterns, results further supported the idea that neural firing patterns adapted during the three learning stages to facilitate the neural codes of directional choices. Put together, these findings suggest a spatiotemporal neural coding scheme in a rat AGl and AGm neural ensemble that may be responsible for and contributing to learning the directional choice task.
ContributorsMao, Hongwei (Author) / Si, Jennie (Thesis advisor) / Buneo, Christopher (Committee member) / Cao, Yu (Committee member) / Santello, Marco (Committee member) / Arizona State University (Publisher)
Created2014
Description
An accurate sense of upper limb position is crucial to reaching movements where sensory information about upper limb position and target location is combined to specify critical features of the movement plan. This dissertation was dedicated to studying the mechanisms of how the brain estimates the limb position in space and the consequences of misestimation of limb position on movements. Two independent but related studies were performed. The first involved characterizing the neural mechanisms of limb position estimation in the non-human primate brain. Single unit recordings were obtained in area 5 of the posterior parietal cortex in order to examine the role of this area in estimating limb position based on visual and somatic signals (proprioceptive, efference copy). When examined individually, many area 5 neurons were tuned to the position of the limb in the workspace but very few neurons were modulated by visual feedback. At the population level however decoding of limb position was somewhat more accurate when visual feedback was provided. These findings support a role for area 5 in limb position estimation but also suggest that visual signals regarding limb position are only weakly represented in this area, and only at the population level. The second part of this dissertation focused on the consequences of misestimation of limb position for movement production. It is well known that limb movements are inherently variable. This variability could be the result of noise arising at one or more stages of movement production. Here we used biomechanical modeling and simulation techniques to characterize movement variability resulting from noise in estimating limb position ('sensing noise') and in planning required movement vectors ('planning noise'), and compared that to the variability expected due to noise in movement execution. We found that the effects of sensing and planning related noise on movement variability were dependent upon both the planned movement direction and the initial configuration of the arm and were different in many respects from the effects of execution noise.
ContributorsShi, Ying (Author) / Buneo, Christopher A (Thesis advisor) / Helms Tillery, Stephen (Committee member) / Santello, Marco (Committee member) / He, Jiping (Committee member) / Santos, Veronica (Committee member) / Arizona State University (Publisher)
Created2011
Description
Understanding where our bodies are in space is imperative for motor control, particularly for actions such as goal-directed reaching. Multisensory integration is crucial for reducing uncertainty in arm position estimates. This dissertation examines time and frequency-domain correlates of visual-proprioceptive integration during an arm-position maintenance task. Neural recordings were obtained from two different cortical areas as non-human primates performed a center-out reaching task in a virtual reality environment. Following a reach, animals maintained the end-point position of their arm under unimodal (proprioception only) and bimodal (proprioception and vision) conditions. In both areas, time domain and multi-taper spectral analysis methods were used to quantify changes in the spiking, local field potential (LFP), and spike-field coherence during arm-position maintenance.
In both areas, individual neurons were classified based on the spectrum of their spiking patterns. A large proportion of cells in the SPL that exhibited sensory condition-specific oscillatory spiking in the beta (13-30Hz) frequency band. Cells in the IPL typically had a more diverse mix of oscillatory and refractory spiking patterns during the task in response to changing sensory condition. Contrary to the assumptions made in many modelling studies, none of the cells exhibited Poisson-spiking statistics in SPL or IPL.
Evoked LFPs in both areas exhibited greater effects of target location than visual condition, though the evoked responses in the preferred reach direction were generally suppressed in the bimodal condition relative to the unimodal condition. Significant effects of target location on evoked responses were observed during the movement period of the task well.
In the frequency domain, LFP power in both cortical areas was enhanced in the beta band during the position estimation epoch of the task, indicating that LFP beta oscillations may be important for maintaining the ongoing state. This was particularly evident at the population level, with clear increase in alpha and beta power. Differences in spectral power between conditions also became apparent at the population level, with power during bimodal trials being suppressed relative to unimodal. The spike-field coherence showed confounding results in both the SPL and IPL, with no clear correlation between incidence of beta oscillations and significant beta coherence.
In both areas, individual neurons were classified based on the spectrum of their spiking patterns. A large proportion of cells in the SPL that exhibited sensory condition-specific oscillatory spiking in the beta (13-30Hz) frequency band. Cells in the IPL typically had a more diverse mix of oscillatory and refractory spiking patterns during the task in response to changing sensory condition. Contrary to the assumptions made in many modelling studies, none of the cells exhibited Poisson-spiking statistics in SPL or IPL.
Evoked LFPs in both areas exhibited greater effects of target location than visual condition, though the evoked responses in the preferred reach direction were generally suppressed in the bimodal condition relative to the unimodal condition. Significant effects of target location on evoked responses were observed during the movement period of the task well.
In the frequency domain, LFP power in both cortical areas was enhanced in the beta band during the position estimation epoch of the task, indicating that LFP beta oscillations may be important for maintaining the ongoing state. This was particularly evident at the population level, with clear increase in alpha and beta power. Differences in spectral power between conditions also became apparent at the population level, with power during bimodal trials being suppressed relative to unimodal. The spike-field coherence showed confounding results in both the SPL and IPL, with no clear correlation between incidence of beta oscillations and significant beta coherence.
ContributorsVanGilder, Paul (Author) / Buneo, Christopher A (Thesis advisor) / Helms-Tillery, Stephen (Committee member) / Santello, Marco (Committee member) / Muthuswamy, Jit (Committee member) / Foldes, Stephen (Committee member) / Arizona State University (Publisher)
Created2017
Description
Rasopathies are a family of developmental syndromes that exhibit craniofacial abnormalities, cognitive disabilities, developmental delay and increased risk of cancer. However, little is known about the pathogenesis of developmental defects in the nervous system. Frequently, gain-of-function mutations in the Ras/Raf/MEK/ERK cascade (aka ERK/MAPK) are associated with the observed pathogenesis. My research focuses on defining the relationship between increased ERK/MAPK signaling and its effects on the nervous system, specifically in the context of motor learning. Motor function depends on several neuroanatomically distinct regions, especially the spinal cord, cerebellum, striatum, and cerebral cortex. We tested whether hyperactivation of ERK/MAPK specifically in the cortex was sufficient to drive changes in motor function. We used a series of genetically modified mouse models and cre-lox technology to hyperactivate ERK/MAPK in the cerebral cortex. Nex:Cre/NeuroD6:Cre was employed to express a constitutively active MEK mutation throughout all layers of the cerebral cortex from an early stage of development. RBP4:Cre, caMEK only exhibited hyper activation in cortical glutamatergic neurons responsible for cortical output (neurons in layer V of the cerebral cortex). First, the two mouse strains were tested in an open field paradigm to assess global locomotor abilities and overall fitness for fine motor tasks. Next, a skilled motor reaching task was used to evaluate motor learning capabilities. The results show that Nex:Cre/NeuroD6:Cre, caMEK mutants do not learn the motor reaching task, although they performed normally on the open field task. Preliminary results suggest RBP4:Cre, caMEK mutants exhibit normal locomotor capabilities and a partial lack of learning. The difference in motor learning capabilities might be explained by the extent of altered connectivity in different regions of the corticospinal tract. Once we have identified the neuropathological effects of various layers in the cortex we will be able to determine whether therapeutic interventions are sufficient to reverse these learning defects.
ContributorsRoose, Cassandra Ann (Author) / Newbern, Jason M. (Thesis director) / Olive, Foster (Committee member) / Bjorklund, Reed (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
The RAS/MAPK (RAS/Mitogen Activated Protein Kinase) pathway is a highly conserved, canonical signaling cascade that is highly involved in cellular growth and proliferation as well as cell migration. As such, it plays an important role in development, specifically in development of the nervous system. Activation of ERK is indispensable for the differentiation of Embryonic Stem Cells (ESC) into neuronal precursors (Li z et al, 2006). ERK signaling has also shown to mediate Schwann cell myelination of the peripheral nervous system (PNS) as well as oligodendrocyte proliferation (Newbern et al, 2011). The class of developmental disorders that result in the dysregulation of RAS signaling are known as RASopathies. The molecular and cell-specific consequences of these various pathway mutations remain to be elucidated. While there is evidence for altered DNA transcription in RASopathies, there is little work examining the effects of the RASopathy-linked mutations on protein translation and post-translational modifications in vivo. RASopathies have phenotypic and molecular similarities to other disorders such as Fragile X Syndrome (FXS) and Tuberous Sclerosis (TSC) that show evidence of aberrant protein synthesis and affect related pathways. There are also well-defined downstream RAS pathway elements involved in translation. Additionally, aberrant corticospinal axon outgrowth has been observed in disease models of RASopathies (Xing et al, 2016). For these reasons, this present study examines a subset of proteins involved in translation and translational regulation in the context of RASopathy disease states. Results indicate that in both of the tested RASopathy model systems, there is altered mTOR expression. Additionally the loss of function model showed a decrease in rps6 activation. This data supports a role for the selective dysregulation of translational control elements in RASopathy models. This data also indicates that the primary candidate mechanism for control of altered translation in these modes is through the altered expression of mTOR.
ContributorsHilbert, Alexander Robert (Author) / Newbern, Jason (Thesis director) / Olive, M. Foster (Committee member) / Bjorklund, Reed (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
Description
Our ability to estimate the position of our body parts in space, a fundamentally proprioceptive process, is crucial for interacting with the environment and movement control. For proprioception to support these actions, the Central Nervous System has to rely on a stored internal representation of the body parts in space. However, relatively little is known about this internal representation of arm position. To this end, I developed a method to map proprioceptive estimates of hand location across a 2-d workspace. In this task, I moved each subject's hand to a target location while the subject's eyes were closed. After returning the hand, subjects opened their eyes to verbally report the location of where their fingertip had been. Then, I reconstructed and analyzed the spatial structure of the pattern of estimation errors. In the first couple of experiments I probed the structure and stability of the pattern of errors by manipulating the hand used and tactile feedback provided when the hand was at each target location. I found that the resulting pattern of errors was systematically stable across conditions for each subject, subject-specific, and not uniform across the workspace. These findings suggest that the observed structure of pattern of errors has been constructed through experience, which has resulted in a systematically stable internal representation of arm location. Moreover, this representation is continuously being calibrated across the workspace. In the next two experiments, I aimed to probe the calibration of this structure. To this end, I used two different perturbation paradigms: 1) a virtual reality visuomotor adaptation to induce a local perturbation, 2) and a standard prism adaptation paradigm to induce a global perturbation. I found that the magnitude of the errors significantly increased to a similar extent after each perturbation. This small effect indicates that proprioception is recalibrated to a similar extent regardless of how the perturbation is introduced, suggesting that sensory and motor changes may be two independent processes arising from the perturbation. Moreover, I propose that the internal representation of arm location might be constructed with a global solution and not capable of local changes.
ContributorsRincon Gonzalez, Liliana (Author) / Helms Tillery, Stephen I (Thesis advisor) / Buneo, Christopher A (Thesis advisor) / Santello, Marco (Committee member) / Santos, Veronica (Committee member) / Kleim, Jeffrey (Committee member) / Arizona State University (Publisher)
Created2012