1996 — 1997 |
Hatsopoulos, Nicholas G |
F32Activity Code Description: To provide postdoctoral research training to individuals to broaden their scientific background and extend their potential for research in specified health-related areas. |
Neural Basis of Sequential Motor Learning
The goal of this research is to understand how movement segments are assembled into complex motor sequences. The general hypothesis to be tested t=is that neurons in the supplementary motor area of motor cortex (SMA) are recruited and act as "temporal binders" during the learning and performance of a new movement sequence so that the transitions between movement segments are performed smoothly and without delay. Monkeys will be trained to generate memorized hand movement sequences in the horizontal plane. Simultaneous extracellular unit recordings will be made in SMA and primary motor cortex (MI) during the task performance using single micro- electrodes, micro-wire arrays, and silicon electrode arrays. According to the hypothesis, temporal binding neurons in SMA will be active during particular segment transitions for previously-learned sequences and will increase gradually as novel sequences containing new transitions are learned. In addition, the cross-correlations between successively activated directionally-selective neurons in MI will become stronger at these transitions. Since many forms of learning require the composition of smaller but familiar elements, this research may reveal fundamental mechanisms of learning, particularly of motor-skill learning. In addition, a number of movement disorders such as Parkinson's disease can be characterized as a breakdown in the generation of smooth movement sequence. Therefore, this research could provide insights into the etiology and treatment of such disorders.
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0.966 |
1999 — 2001 |
Hatsopoulos, Nicholas G |
K01Activity Code Description: For support of a scientist, committed to research, in need of both advanced research training and additional experience. |
Motor Components in Motor Skill Learning and Performance
The goal of this project is to understand how neural representations of simple movements are combined to learn and perform complex, motor skills. Learning to perform many complex, sequential movements including play a musical instrument, engaging in a sport, speaking, or writing can be viewed as the process by which already learned movement segments or "primitives" are bound together in novel ways. Multi-channel recordings will be made using a novel 100 electrode array implanted in the primary (MI) and supplementary motor areas (SMA) of monkey cortex while the animals learns to perform sequential movements of the hand and arm. Theoretical work suggests that this binding process may manifest itself as temporal interactions among ensembles of neurons. Temporal interaction patterns such as correlated discharge among MI and SMA neurons will be examined when movement segments are performed together as a functional unit and compared with patterns occurring when the same segments are generated independently or in isolation. A number of movement disorders such as Parkinson's disease can be characterized as a breakdown in the generation of smooth movement sequences. Therefore, this research could provide insights into the etiology and treatment of such disorders.
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0.966 |
2004 — 2011 |
Hatsopoulos, Nicholas G |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. R56Activity Code Description: To provide limited interim research support based on the merit of a pending R01 application while applicant gathers additional data to revise a new or competing renewal application. This grant will underwrite highly meritorious applications that if given the opportunity to revise their application could meet IC recommended standards and would be missed opportunities if not funded. Interim funded ends when the applicant succeeds in obtaining an R01 or other competing award built on the R56 grant. These awards are not renewable. |
Coding of Action by Motor &Premotor Cortical Ensembles
DESCRIPTION (provided by applicant): The objective of this project is to understand what and how movement features are encoded in ensembles of interacting motor cortical neurons. Although previous electrophysiological research has focused on encoding in single motor cortical neurons, very little work has examined whether spatial-temporal patterns of activity emerging from ensembles of interacting neurons encode features of movement planning and execution. To test this hypothesis, high-density electrode arrays will be chronically implanted in primary motor cortex (MI) and dorsal premotor cortex (PMd) from which 100s of single units will be simultaneously recorded while monkeys perform complex visuo-motor tasks with the arm. A continuous random-tracking task and a step random-tracking task are ideally suited to investigate neural encoding because they uncouple the statistical dependencies among many of the relevant motor variables, more thoroughly sample the movement space, and reduce non-stationarities. Forward and reverse correlation, information-theoretic, and decoding methods will be used to analyze the encoding problem as well the information mapping between the two cortical areas. Two specific aims are proposed in this project. First, kinematic and kinetic tuning properties of motor cortical ensembles will be investigated and compared to single neuron tuning functions under different behavioral contexts. The stability of these tuning functions will be examined by applying different external loads to the arm, varying the behavioral mode (freely moving vs. isometric), or changing the posture of the forearm. Second, it will determined whether spatio-temporal patterns within motor cortical ensembles can be elicited by altering the temporal dynamics and predictability of the movement. This work is significant because it will elucidate how groups of interacting cortical neurons control and coordinate complex movements and will provide an important step in understanding how neuronal ensembles in other cortical areas represent other high-level functioning. In addition, this work has direct relevance towards the development of a neuro-motor prosthesis by which paralyzed patients may be able to control external devices by activating their cortex.
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1 |
2009 — 2015 |
Shubin, Neil (co-PI) [⬀] Ross, Callum (co-PI) [⬀] Hale, Melina [⬀] Hatsopoulos, Nicholas Maciver, Malcolm |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Igert: Integrative Training in Motor Control and Movement
This Integrative Graduate Education and Research Traineeship (IGERT) project builds links broadly across Chicago's scientific community to develop an integrative training program for U.S. doctoral students in motor control and movement. To develop an integrative understanding of movement, it is necessary to address both the biology and the engineering of the systems involved and how they work together. Students from graduate programs at the University of Chicago and Northwestern University will obtain the biological and engineering backgrounds required to develop the integrative approach needed to take the field in new directions. Educational tools include a boot camp, a three-quarter common core curriculum, a discussion series, required laboratory rotations, and workshops and seminars at the Field Museum. The program will involve outreach to local Chicago-area schools, with training for students and faculty in the development and conduct of effective outreach. Mentoring of undergraduate students by IGERT graduate trainees will be done in close collaboration with local universities that primarily serve underrepresented minorities in the Chicago area. A trans-institutional website will highlight opportunities and results related to this program's IGERT goals and provide resources for teachers and students. IGERT is an NSF-wide program intended to meet the challenges of educating U.S. Ph.D. scientists and engineers with the interdisciplinary background, deep knowledge in a chosen discipline, and the technical, professional, and personal skills needed for the career demands of the future. The program is intended to catalyze a cultural change in graduate education by establishing innovative new models for graduate education and training in a fertile environment for collaborative research that transcends traditional disciplinary boundaries.
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0.915 |
2012 — 2020 |
Hatsopoulos, Nicholas G Ross, Callum F (co-PI) [⬀] |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Coding of Action by Motor & Premotor Cortical Ensembles
Abstract The goal of this project is to understand how spatio-temporal patterns of activity across motor cortex initiate different types of voluntary movements. Large distributed ensembles of motor cortical neurons begin modulating their firing rates prior to voluntary movement and are thought to causally generate these movements. However, it is still unresolved why movement is not initiated when similar modulations in single unit motor cortical activity occur during movement planning, imagery, and visual observation of action. The amplitude of local field potential (LFP) oscillations in the beta frequency (15-40 Hz) range is known to attenuate prior to movement onset and is considered a mesoscopic signature of corticospinal excitability. We have recently discovered a sequential pattern of LFP beta attenuation and single unit modulation timing in primary motor cortex that is spatially organized prior to reaching movement onset but not during movement preparation. Our working hypothesis is that such a propagating sequential pattern is necessary to initiate movement. In this project, we will test and extend this hypothesis by demonstrating that such propagating patterns generalize to movement initiation of different behaviors including 2D reaching under different conditions, more complex 3D reach-to-grasp, and tongue protrusion and occur in premotor cortex. We will first demonstrate that propagating sequences in beta attenuation and single unit modulation timing occur during initiation of each of these behaviors along different portions of the somatotopic map of primary motor and premotor cortices. Second, we will provide a causal link between these propagating patterns and movement initiation by applying subthreshold, spatio-temporal patterns of electrical stimulation. We will demonstrate that movement initiation is delayed when patterned stimulation travels against the natural propagating sequence but not when it mimics the natural propagating pattern. Third, we will provide a mechanistic explanation of how these propagating sequences lead to muscle activation that supports movement initiation using patterned stimulus-triggered muscle activity and muscle decoding. To accomplish these aims, four high-density electrode arrays will be chronically implanted in the either the upper limb or orofacial areas of primary motor and premotor cortices from which 100s of single units and LFPs will be simultaneously recorded. A two-link exoskeletal robot and a motion tracking system using a set of fourteen infrared cameras will monitor the kinematics of the arm and hand. A strain gauge will measure tongue force and kinematics of the tongue will be tracked with a novel 3D x-ray fluoroscopy system. Indwelling EMG electrodes will also measure activity from arm, hand, and tongue muscles. A set of classical and novel computational methods will be employed to characterize the spatio-temporal dynamics of motor cortical activity during movement initiation.
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1 |
2018 — 2021 |
Brunel, Nicolas Hatsopoulos, Nicholas G Maclean, Jason Neil (co-PI) [⬀] |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Large-Scale, Neuronal Ensemble Recordings in Motor Cortex of the Behaving Marmoset
Abstract This project seeks to characterize the spatio-temporal organization of motor cortical (M1) activity at multiple spatial scales associated with upper limb movements of unrestrained marmoset monkeys performing ethological behaviors. The project has two goals: 1) To statistically evaluate the nature and stability of single neuron and ensemble-level motor representations in M1 at the columnar and areal spatial scales, and 2) To use our experimental data to develop a network model of a 3D patch of M1 capable of generating experimentally testable predictions about the movement representations in M1. We will combine two complementary technologies for large-scale neural recording: 1) wireless, high density multi-electrode arrays and 2) calcium fluorescence imaging - while common marmoset monkeys (Callithrix jacchus) perform naturalistic foraging behaviors. Advances in microelectrode array technology have permitted simultaneous electrophysiological recordings from hundreds of neurons in behaving animals. However, given the large inter- electrode distance (>=400 microns), much of the microcircuit activity at the subcolumnar level is unresolved. In contrast, calcium fluorescence imaging provides the opportunity to densely and simultaneously record the spiking activity of hundreds of neurons within a single cortical column. This dense, large-scale imaging allows for the resolution of neurons immediately adjacent to one another which increases the likelihood that they are synaptically connected. We will use a miniature fluorescence microscope attached to the skull which allows for head-free, unconstrained movements of the arm and hand. Moreover, by adding a prism lens to the microscope, we will be able to image neurons across lamina from layer 2/3 through layer 5. Using both technologies, we will characterize single neuron encoding properties, network dynamics, and functional connectivity within and between cortical columns. By bridging spatial scales, we will be able to interpolate between the cortical microcircuit level and the level of a whole cortical area. We will also investigate how the spatio-temporal organization of movement coding changes with motor skill acquisition. A unique and important feature of this project will be the use of natural and unconstrained foraging tasks that involve prey capture which will not require operant conditioning and will provide richer behaviors in order to build more accurate encoding models. We will also build large-scale network simulations of a patch of motor cortex constrained by the recorded data to understand how connectivity relates to tuning properties of single neurons. The model will then allow us to investigate what synaptic rules result in the observed changes in spatiotemporal patterning associated with motor learning. Ultimately, the principles of network dynamics, computation, and encoding deduced from the motor cortex may apply more generally to other neocortical areas. This research may also have applied relevance to brain-machine interface technology.
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1 |