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- All Subjects: Neurosciences
- Creators: Buneo, Christopher A
- Resource Type: Text
Description
The basal ganglia are four sub-cortical nuclei associated with motor control and reward learning. They are part of numerous larger mostly segregated loops where the basal ganglia receive inputs from specific regions of cortex. Converging on these inputs are dopaminergic neurons that alter their firing based on received and/or predicted rewarding outcomes of a behavior. The basal ganglia's output feeds through the thalamus back to the areas of the cortex where the loop originated. Understanding the dynamic interactions between the various parts of these loops is critical to understanding the basal ganglia's role in motor control and reward based learning. This work developed several experimental techniques that can be applied to further study basal ganglia function. The first technique used micro-volume injections of low concentration muscimol to decrease the firing rates of recorded neurons in a limited area of cortex in rats. Afterwards, an artificial cerebrospinal fluid flush was injected to rapidly eliminate the muscimol's effects. This technique was able to contain the effects of muscimol to approximately a 1 mm radius volume and limited the duration of the drug effect to less than one hour. This technique could be used to temporarily perturb a small portion of the loops involving the basal ganglia and then observe how these effects propagate in other connected regions. The second part applied self-organizing maps (SOM) to find temporal patterns in neural firing rate that are independent of behavior. The distribution of detected patterns frequency on these maps can then be used to determine if changes in neural activity are occurring over time. The final technique focused on the role of the basal ganglia in reward learning. A new conditioning technique was created to increase the occurrence of selected patterns of neural activity without utilizing any external reward or behavior. A pattern of neural activity in the cortex of rats was selected using an SOM. The pattern was then reinforced by being paired with electrical stimulation of the medial forebrain bundle triggering dopamine release in the basal ganglia. Ultimately, this technique proved unsuccessful possibly due to poor selection of the patterns being reinforced.
ContributorsBaldwin, Nathan Aaron (Author) / Helms Tillery, Stephen I (Thesis advisor) / Castaneda, Edward (Committee member) / Buneo, Christopher A (Committee member) / Muthuswamy, Jitendran (Committee member) / Si, Jennie (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
The ability to plan, execute, and control goal oriented reaching and grasping movements is among the most essential functions of the brain. Yet, these movements are inherently variable; a result of the noise pervading the neural signals underlying sensorimotor processing. The specific influences and interactions of these noise processes remain unclear. Thus several studies have been performed to elucidate the role and influence of sensorimotor noise on movement variability. The first study focuses on sensory integration and movement planning across the reaching workspace. An experiment was designed to examine the relative contributions of vision and proprioception to movement planning by measuring the rotation of the initial movement direction induced by a perturbation of the visual feedback prior to movement onset. The results suggest that contribution of vision was relatively consistent across the evaluated workspace depths; however, the influence of vision differed between the vertical and later axes indicate that additional factors beyond vision and proprioception influence movement planning of 3-dimensional movements. If the first study investigated the role of noise in sensorimotor integration, the second and third studies investigate relative influence of sensorimotor noise on reaching performance. Specifically, they evaluate how the characteristics of neural processing that underlie movement planning and execution manifest in movement variability during natural reaching. Subjects performed reaching movements with and without visual feedback throughout the movement and the patterns of endpoint variability were compared across movement directions. The results of these studies suggest a primary role of visual feedback noise in shaping patterns of variability and in determining the relative influence of planning and execution related noise sources. The final work considers a computational approach to characterizing how sensorimotor processes interact to shape movement variability. A model of multi-modal feedback control was developed to simulate the interaction of planning and execution noise on reaching variability. The model predictions suggest that anisotropic properties of feedback noise significantly affect the relative influence of planning and execution noise on patterns of reaching variability.
ContributorsApker, Gregory Allen (Author) / Buneo, Christopher A (Thesis advisor) / Helms Tillery, Stephen (Committee member) / Santello, Marco (Committee member) / Santos, Veronica (Committee member) / Si, Jennie (Committee member) / Arizona State University (Publisher)
Created2012
Description
Sound localization can be difficult in a reverberant environment. Fortunately listeners can utilize various perceptual compensatory mechanisms to increase the reliability of sound localization when provided with ambiguous physical evidence. For example, the directional information of echoes can be perceptually suppressed by the direct sound to achieve a single, fused auditory event in a process called the precedence effect (Litovsky et al., 1999). Visual cues also influence sound localization through a phenomenon known as the ventriloquist effect. It is classically demonstrated by a puppeteer who speaks without visible lip movements while moving the mouth of a puppet synchronously with his/her speech (Gelder and Bertelson, 2003). If the ventriloquist is successful, sound will be “captured” by vision and be perceived to be originating at the location of the puppet. This thesis investigates the influence of vision on the spatial localization of audio-visual stimuli. Participants seated in a sound-attenuated room indicated their perceived locations of either ISI or level-difference stimuli in free field conditions. Two types of stereophonic phantom sound sources, created by modulating the inter-stimulus time interval (ISI) or level difference between two loudspeakers, were used as auditory stimuli. The results showed that the light cues influenced auditory spatial perception to a greater extent for the ISI stimuli than the level difference stimuli. A binaural signal analysis further revealed that the greater visual bias for the ISI phantom sound sources was correlated with the increasingly ambiguous binaural cues of the ISI signals. This finding suggests that when sound localization cues are unreliable, perceptual decisions become increasingly biased towards vision for finding a sound source. These results support the cue saliency theory underlying cross-modal bias and extend this theory to include stereophonic phantom sound sources.
ContributorsMontagne, Christopher (Author) / Zhou, Yi (Thesis advisor) / Buneo, Christopher A (Thesis advisor) / Yost, William A. (Committee member) / Arizona State University (Publisher)
Created2015
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
A direct Magnetic Resonance (MR)-based neural activity mapping technique with high spatial and temporal resolution may accelerate studies of brain functional organization.
The most widely used technique for brain functional imaging is functional Magnetic Resonance Image (fMRI). The spatial resolution of fMRI is high. However, fMRI signals are highly influenced by the vasculature in each voxel and can be affected by capillary orientation and vessel size. Functional MRI analysis may, therefore, produce misleading results when voxels are nearby large vessels. Another problem in fMRI is that hemodynamic responses are slower than the neuronal activity. Therefore, temporal resolution is limited in fMRI. Furthermore, the correlation between neural activity and the hemodynamic response is not fully understood. fMRI can only be considered an indirect method of functional brain imaging.
Another MR-based method of functional brain mapping is neuronal current magnetic resonance imaging (ncMRI), which has been studied over several years. However, the amplitude of these neuronal current signals is an order of magnitude smaller than the physiological noise. Works on ncMRI include simulation, phantom experiments, and studies in tissue including isolated ganglia, optic nerves, and human brains. However, ncMRI development has been hampered due to the extremely small signal amplitude, as well as the presence of confounding signals from hemodynamic changes and other physiological noise.
Magnetic Resonance Electrical Impedance Tomography (MREIT) methods could have the potential for the detection of neuronal activity. In this technique, small external currents are applied to a body during MR scans. This current flow produces a magnetic field as well as an electric field. The altered magnetic flux density along the main magnetic field direction caused by this current flow can be obtained from phase images. When there is neural activity, the conductivity of the neural cell membrane changes and the current paths around the neurons change consequently. Neural spiking activity during external current injection, therefore, causes differential phase accumulation in MR data. Statistical analysis methods can be used to identify neuronal-current-induced magnetic field changes.
The most widely used technique for brain functional imaging is functional Magnetic Resonance Image (fMRI). The spatial resolution of fMRI is high. However, fMRI signals are highly influenced by the vasculature in each voxel and can be affected by capillary orientation and vessel size. Functional MRI analysis may, therefore, produce misleading results when voxels are nearby large vessels. Another problem in fMRI is that hemodynamic responses are slower than the neuronal activity. Therefore, temporal resolution is limited in fMRI. Furthermore, the correlation between neural activity and the hemodynamic response is not fully understood. fMRI can only be considered an indirect method of functional brain imaging.
Another MR-based method of functional brain mapping is neuronal current magnetic resonance imaging (ncMRI), which has been studied over several years. However, the amplitude of these neuronal current signals is an order of magnitude smaller than the physiological noise. Works on ncMRI include simulation, phantom experiments, and studies in tissue including isolated ganglia, optic nerves, and human brains. However, ncMRI development has been hampered due to the extremely small signal amplitude, as well as the presence of confounding signals from hemodynamic changes and other physiological noise.
Magnetic Resonance Electrical Impedance Tomography (MREIT) methods could have the potential for the detection of neuronal activity. In this technique, small external currents are applied to a body during MR scans. This current flow produces a magnetic field as well as an electric field. The altered magnetic flux density along the main magnetic field direction caused by this current flow can be obtained from phase images. When there is neural activity, the conductivity of the neural cell membrane changes and the current paths around the neurons change consequently. Neural spiking activity during external current injection, therefore, causes differential phase accumulation in MR data. Statistical analysis methods can be used to identify neuronal-current-induced magnetic field changes.
ContributorsFu, Fanrui (Author) / Sadleir, Rosalind (Thesis advisor) / Kodibagkar, Vikram (Committee member) / Kleim, Jeffrey (Committee member) / Muthuswamy, Jitendran (Committee member) / Helms Tillery, Stephen (Committee member) / Arizona State University (Publisher)
Created2019
Description
There is a critical need for creating an implantable microscale neural interface that can chronically monitor neural activity and oxygenation. These are key aspects for understating the development of impaired neural circuits and their functions. A technology with such capability would foster new insights in the studies of brain diseases and disorders. The propose is that MR-PISTOL (Proton imaging of Siloxane to Map Tissue Oxygenation Levels) imaging technique can be used for direct measurements of oxygen partial pressure at microelectrode-tissue interface. The strategy consists of coating microelectrodes with soft-silicone, a ultra-soft conductive PDMS (polydimethylsiloxane), as a carrier for liquid siloxanes MR-PISTOL contrast agents. This work presents a proof-of-concept of an injection molding technique for batch fabricate microelectrodes with such coating. Also, reports stability studies of soft-silicone loaded with liquid polydimethylsiloxane (PDMSO) in rodent brains. A batch of thirty coated carbon electrodes was achieved using candy molds. Coating uniformity was evaluated in twelve probes. They were randomly chosen and imaged with a custom image setup that allows 90o rotation of the probes. The total average coating thickness before and after rotation were 0.397 millimeters with standard deviation of 0.070 millimeters and 0.442 millimeters with standard deviation of 0.062 millimeters. Therefore, data confirms that this technique yields uniform coating. Stability of fabricated coated carbon electrodes unloaded (n= 3) and loaded with PDMSO (n= 3) was assessed. 3D X-ray imaging using Zeiss Xradia 520 machine was chosen for studying coatings mechanical stability in ex-vivo rat brain. Transmission electron microscopy (TEM) and scanning electron microscope (SEM) with an energy dispersive x-ray microanalysis (EDS) detector were used to investigate their chemical stability in in vivo mouse brain. Initial EDS analysis from TEM and SEM of acute (6 hours) and chronic (2 weeks) brain slices suggest that PDMSO does not leach into brain. More experiments should be done to confirm and endorse this finding. The mechanical study shows that coating loaded with PDMSO delaminated during insertion. This was not observed with electrodes used in the chemical stability studies. Further experiments need to be done to identify possible causes of mechanical failures.
Contributorsde Mesquita Teixeira, Livia (Author) / Muthuswamy, Jitendran (Thesis advisor, Committee member) / Kodibagkar, Vikram (Thesis advisor, Committee member) / Sridharan, Arati (Committee member) / Arizona State University (Publisher)
Created2018
Description
Prosthetic users abandon devices due to difficulties performing tasks without proper graded or interpretable feedback. The inability to adequately detect and correct error of the device leads to failure and frustration. In advanced prostheses, peripheral nerve stimulation can be used to deliver sensations, but standard schemes used in sensorized prosthetic systems induce percepts inconsistent with natural sensations, providing limited benefit. Recent uses of time varying stimulation strategies appear to produce more practical sensations, but without a clear path to pursue improvements. This dissertation examines the use of physiologically based stimulation strategies to elicit sensations that are more readily interpretable. A psychophysical experiment designed to investigate sensitivities to the discrimination of perturbation direction within precision grip suggests that perception is biomechanically referenced: increased sensitivities along the ulnar-radial axis align with potential anisotropic deformation of the finger pad, indicating somatosensation uses internal information rather than environmental. Contact-site and direction dependent deformation of the finger pad activates complimentary fast adapting and slow adapting mechanoreceptors, exhibiting parallel activity of the two associate temporal patterns: static and dynamic. The spectrum of temporal activity seen in somatosensory cortex can be explained by a combined representation of these distinct response dynamics, a phenomenon referred in this dissertation to “biphasic representation.” In a reach-to-precision-grasp task, neurons in somatosensory cortex were found to possess biphasic firing patterns in their responses to texture, orientation, and movement. Sensitivities seem to align with variable deformation and mechanoreceptor activity: movement and smooth texture responses align with potential fast adapting activation, non-movement and coarse texture responses align with potential increased slow adapting activation, and responses to orientation are conceptually consistent with coding of tangential load. Using evidence of biphasic representations’ association with perceptual priorities, gamma band phase locking is used to compare responses to peripheral nerve stimulation patterns and mechanical stimulation. Vibrotactile and punctate mechanical stimuli are used to represent the practical and impractical percepts commonly observed in peripheral nerve stimulation feedback. Standard patterns of constant parameters closely mimic impractical vibrotactile stimulation while biphasic patterns better mimic punctate stimulation and provide a platform to investigate intragrip dynamics representing contextual activation.
ContributorsTanner, Justin Cody (Author) / Helms Tillery, Stephen I (Thesis advisor) / Santos, Veronica J (Committee member) / Santello, Marco (Committee member) / Greger, Bradley (Committee member) / Buneo, Christopher A (Committee member) / Arizona State University (Publisher)
Created2017
Description
Compressed sensing magnetic resonance spectroscopic imaging (MRSI) is a noninvasive and in vivo potential diagnostic technique for cancer imaging. This technique undersamples the distribution of specific cancer biomarkers within an MR image as well as changes in the temporal dimension and subsequently reconstructs the missing data. This technique has been shown to retain a high level of fidelity even with an acceleration factor of 5. Currently there exist several different scanner types that each have their separate analytical methods in MATLAB. A graphical user interface (GUI) was created to facilitate a single computing platform for these different scanner types in order to improve the ease and efficiency with which researchers and clinicians interact with this technique. A GUI was successfully created for both prospective and retrospective MRSI data analysis. This GUI retained the original high fidelity of the reconstruction technique and gave the user the ability to load data, load reference images, display intensity maps, display spectra mosaics, generate a mask, display the mask, display kspace and save the corresponding spectra, reconstruction, and mask files. Parallelization of the reconstruction algorithm was explored but implementation was ultimately unsuccessful. Future work could consist of integrating this parallelization method, adding intensity overlay functionality and improving aesthetics.
ContributorsLammers, Luke Michael (Author) / Kodibagkar, Vikram (Thesis director) / Hu, Harry (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Multisensory integration is the process by which information from different sensory modalities is integrated by the nervous system. This process is important not only from a basic science perspective but also for translational reasons, e.g., for the development of closed-loop neural prosthetic systems. A mixed virtual reality platform was developed to study the neural mechanisms of multisensory integration for the upper limb during motor planning. The platform allows for selection of different arms and manipulation of the locations of physical and virtual target cues in the environment. The system was tested with two non-human primates (NHP) trained to reach to multiple virtual targets. Arm kinematic data as well as neural spiking data from primary motor (M1) and dorsal premotor cortex (PMd) were collected. The task involved manipulating visual information about initial arm position by rendering the virtual avatar arm in either its actual position (veridical (V) condition) or in a different shifted (e.g., small vs large shifts) position (perturbed (P) condition) prior to movement. Tactile feedback was modulated in blocks by placing or removing the physical start cue on the table (tactile (T), and no-tactile (NT) conditions, respectively). Behaviorally, errors in initial movement direction were larger when the physical start cue was absent. Slightly larger directional errors were found in the P condition compared to the V condition for some movement directions. Both effects were consistent with the idea that erroneous or reduced information about initial hand location led to movement direction-dependent reach planning errors. Neural correlates of these behavioral effects were probed using population decoding techniques. For small shifts in the visual position of the arm, no differences in decoding accuracy between the T and NT conditions were observed in either M1 or PMd. However, for larger visual shifts, decoding accuracy decreased in the NT condition, but only in PMd. Thus, activity in PMd, but not M1, may reflect the uncertainty in reach planning that results when sensory cues regarding initial hand position are erroneous or absent.
ContributorsPhataraphruk, Preyaporn Kris (Author) / Buneo, Christopher A (Thesis advisor) / Zhou, Yi (Committee member) / Helms Tillery, Steve (Committee member) / Greger, Bradley (Committee member) / Santello, Marco (Committee member) / Arizona State University (Publisher)
Created2023