Current Collaborative Projects
Robust Spinal Reflex Conditioning System
Dr. Aiko Thompson, Medical University of South Carolina
The long-term goal of this ongoing collaborative project is to enhance the clinical efficacy and efficiency of spinal reflex operant conditioning protocols and accelerate their translation into clinical use. It combines NCAN’s unique expertise in reflex conditioning technology with the Medical University of South Carolina's (MUSC’s) unique experience in clinical use of this technology and strong capacity to test the suitability of new reflex conditioning systems for use by clinical therapists. The aim of the collaboration is to develop, optimize, and validate a robust general-purpose operant conditioning system suitable for clinical use. NCAN will develop algorithms that support complex protocols (e.g., allowing conditioning during a dynamic behavior such as locomotion), facilitate selection of recording and stimulating sites and parameters for a broad range of responses, configure the accompanying stimulation/recording hardware, and produce associated fully integrated instructions. The system with all of its components will be tested, optimized, and validated through push-pull interactions with MUSC, where it will be used by groups of physical therapy students and the results will be assessed by the data provided and by feedback from the users.
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Reflex Conditioning in Cerebral Palsy
Dr. Kathleen Friel, Burke Neurological Institute
This collaborative project will explore the efficacy of spinal reflex operant conditioning for reducing spasticity and improving motor functions in adults and children with cerebral palsy (CP). These individuals constitute a large and otherwise healthy population that frequently suffers from disabling spasticity. If spinal reflex conditioning proves efficacious in reducing this problem, it would be an important therapeutic advance. We have two collaborative aims:
1. To investigate the efficacy of spinal reflex conditioning for reducing spasticity in adults and children with cerebral palsy. We will determine the impact of H-reflex down-conditioning on the soleus H-reflex over 30 conditioning sessions and over subsequent months. We will also assess the associated effects on locomotor speed, symmetry, kinematics, and EMG; on clinical measures of spasticity; and on participant reports of their functioning in daily life. We will compare the data gathered before the conditioning sessions, with those gathered at the end of conditioning and 3 months later. This initial study will incorporate an appropriate control group who complete a comparable protocol that does not include H-reflex down-conditioning.
2. To evaluate the impact of spinal reflex conditioning on corticospinal function. For the participants studied in Aim 1, we will use transcranial magnetic stimulation (TMS) to detect and map the changes in cortical control over spinal cord motoneuron populations associated with spinal reflex conditioning. These data will be gathered before the conditioning sessions, after their completion, and 3 months later. We hypothesize that H-reflex decrease and functional improvements will be associated with stronger corticospinal control that will be evident as increases in the motor evoked potentials (MEPs) produced by TMS.
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Stroke BCI-Based EEG Rehabilitation
Dr. David Reinkensmeyer, University of California, Irvine
This collaborative project is optimizing and validating pre-movement BCI-based EEG sensorimotor-rhythm (SMR) amplitude training as a new method for enhancing recovery of useful motor function in people with strokes that have impaired hand/arm function. If it is successful, it will provide a new therapy that could complement current therapies and augment recovery of useful motor function. We have two collaborative aims:
1. To confirm and extend our preliminary study indicating that BCI-based training to control pre-movement sensorimotor rhythm (SMR) amplitude can improve finger extension in people with moderate to severe hand impairment due to chronic stroke. Using quantitative clinical measures, we will determine the time course, magnitude, consistency, and persistence of this beneficial impact.
2. To determine whether BCI-based training to increase pre-movement cortico-muscular coupling can enhance functional recovery after stroke. Cortico-muscular coherence reflects functional coupling between cortex and muscles; thus, its increase is likely to be associated with increased cortical control and improved motor function. Using quantitative clinical measures, we will determine the time course, magnitude, consistency, and persistence of any beneficial impact that occurs.
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BCI-Based Aphasia Rehabilitation
Dr. Ellyn Riley, Syracuse University
This recently launched collaborative project addresses the need for new therapeutic methods that can enhance language recovery for people afflicted with aphasia after stroke. Recent studies indicate that errorless learning protocols can improve performance during treatment sessions but not necessarily beyond; retrieval practice may be important for effecting long-term improvement. Previous results and a preliminary study (Riley and McFarland, 2017) suggested that EEG-based BCI technology might be able to combine the virtues of errorless learning and retrieval practice to enhance language recovery. With this as our goal, we have two collaborative aims:
1. To establish that EEG features can predict naming errors and error correction in people with aphasia due to stroke. Encouraged by our initial study (Riley and McFarland, 2017), we will use a new paradigm that asks participants to name famous people; it supports studies in those with or without aphasia. Repeated testing enables evaluation of the consistency of retrieval. We expect to find that EEG features in the alpha (8-12 Hz) and/or beta (18-30 Hz) frequency range can predict errors and error correction.
2. Based on the results of the first collaborative aim, we will then design a paradigm that uses these selected EEG features to enhance aphasia therapy. First, subject-specific EEG features that predict naming success will be identified. Next, we will incorporate a brief pulse of transcranial alternating current stimulation (tACS) in naming trials in which the participant-specific EEG features associated with successful naming are not present; tACS frequency and location will be based on the frequency and scalp topography of these EEG features.
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Riley People page
Decoding the Prefrontal Cortex
Dr. Robert Knight, University of California, Berkeley
The long-term goal of this collaborative project is to improve the understanding of prefrontal cortex (PFC) function by combining NCAN’s unique technologies to characterize and modify cortical function with UCB’s sophisticated neuroscientific understanding of the PFC. We will use our new stimulation methods to study the influence of the PFC in goal-directed behavior. The collaborative aims are:
1. To test the hypothesis that interactions between PFC and posterior cortical regions are causally related to categorical perception.
2. To test the hypothesis that electrical stimulation of cortical processes in PFC that underlie categorical perception produces persistent changes on a millimeter scale.
To accomplish these collaborative aims, UCB will study subjects with ECoG recording arrays that cover PFC and also cover auditory and/or visual cortical areas. They will collect ECoG data while the subjects perform auditory and/or visual categorical perception tasks. Through two series of push-pull interactions (one for each collaborative aim), UCB and NCAN will test the hypotheses that interactions between PFC and posterior regions are causally responsible for categorical perception (Aim 1), and that changes to cortical processes in PFC resulting from electrical stimulation are functionally heterogeneous on a millimeter scale (Aim 2).
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Cortical Connectivity by DTI and Stimulation
Dr. Nancy Kanwisher, MIT
Through this Collaborative Project with Dr. Kanwisher at MIT, we will apply the new stimulation device developed in TR&D2 and applied to human subjects in TR&D3 to enable Dr. Kanwisher to study the relationship between connectivity established using electrical stimulation and connectivity derived by diffusion tensor imaging (DTI). We will collect DTI data at Albany Medical College, and will scan a subset of those subjects at the Connectome scanner at MGH in Boston (one of only two in the world and optimized specifically for DTI imaging). This project will drive technology development for ECoG stimulation that induces short-term changes in network activity. The push-pull interactions between NCAN and MIT detailed here will achieve the collaborative aim to correlate the connections defined by electrical stimulation to the connections defined by DTI.
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Collaborative Project: BCIs for training and enhancing the motor imagery ability of disabled people enhance rehabilitation
Dr. Alessandro Vato, Catholic University
Motor imagery (MI) is the mental representation of action without engaging in its actual execution (Decety, 1996; MacIntyre et al., 2018). Preparation for movement or imagining actions generates brain oscillations in the motor cortex known as sensorimotor rhythms (SMRs) (Arroyo et al., 1993) that a standard electroencephalogram (EEG) can record. The ability to voluntarily increase/decrease the SMR oscillations in specific frequency bands (i.e., alpha and beta) can help disabled people to control the movement of external objects, such as a computer cursor (Wolpaw et al., 1991) or a mobile robot (Millan et al., 2004) by using a brain-computer interface (BCI) system. Improving the ability to construct a cognitive simulation process can increase sports performance and rehabilitation (Moran et al., 2012; MacIntyre et al., 2018).
Due to the increasing number of experimental and therapeutic protocols involving MI, understanding the brain network involved, and appropriately measuring and improving MI is of growing interest in basic scientific and translational research fields.The long-term goal of this project is to develop a new family of BCIs designed to train and enhance the MI ability of disabled subjects to support and accelerate the rehabilitation process.
The project's first step will consist of identifying the brain network activated by MI in healthy subjects performing different MI tasks. We will characterize the temporal and spatial distribution of α- and β-band oscillations extracted from standard EEG, high-density electroencephalography (hdEEG), and intracortical EEG (ECoG and SEEG). We will analyze brain signals recorded during motor imagery of both hand movements\gestures and walking in different conditions. Finally, we will compare the MI network with the brain regions recruited during action observation and movement execution to study the covert and overt neural correlates of the action.
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Collaborative Project: Alerting, Orienting, and Executive Control Networks in Children and Adults
Dr. Sudhin Shah, Weill Cornell Medical College
Cognitive impairments are a devastating and persistent sequela following acquired brain injuries. For those with co-occurring impairment of oromotor, oculomotor gross and fine motor function, assessment of emerging and residual cognitive function is extremely challenging. Relatedly, while there are >5.3 million persons, in the US alone, with chronic executive attention and cognitive dysfunction following traumatic brain injury, there are currently no targeted interventions. We are currently conducting a multimodal imaging study, in our lab, aimed at elucidating the biological correlates of executive attention post traumatic brain injury. The aims of this collaborative project are to:
(1) develop a working prototype of a system that displays continuous real-time feedback of alertness/attentional state (a) to people with persistent cognitive impairment, as a cue to aid focus, and (b) to caregivers of people who are unable to communicate due to motoric impairment, as a cue to guide attempts at interaction; and
(2) establish a proof-of-concept that executive attention can be improved by real-time non-invasive electrical stimulation in-phase with known EEG correlates of attention that may form a basis for novel therapeutic interventions in future.
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Collaborative Project: Mechanisms of Amygdala-Mediated Memory Enhancement in Humans
Dr. Cory Inman, University of Utah
Direct electrical stimulation (DES) of the basolateral complex of the amygdala (BLA) can improve declarative memory, reflecting the role of the BLA in modulating memory processes in medial temporal lobe (MTL) regions as a function of emotional arousal. Thus, DES can reveal mechanisms of BLA-mediated memory enhancement relevant to human mental health and disease. DES of the BLA can be used to interrogate the function of memory circuits, especially how neuronal oscillations in the MTL support declarative memory. First, BLA is hypothesized to wield the capacity to prioritize long-term retention of information initially encountered adjacent in time. Second, the BLA preferentially projects to anterior MTL regions and thus is hypothesized to preferentially modulate memory processes in those anatomic regions, processes thought to support memory for non-spatial items more so than memory for spatial locations. Third, although emotional arousal, amygdala activity, MTL activity, and memory performance are typically correlated, we hypothesize that DES will reveal that BLA outputs to other MTL regions cause improved memory performance by directly eliciting pro-memory oscillatory states in those networks. The expected outcomes represent a significant advancement for the basic science of normal memory function and significant movement towards novel therapeutics designed to emulate endogenous mechanisms of memory enhancement.
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Collaborative Project: Exploring Triple-Strategy Protocols in Animals
Dr. Martin Oudega, Northwestern University, Hines VA Hospital, Shirley Ryan AbilityLab
Over the past five years, our group has used our long-term animal methodology to develop and explore paired associative stimulation (PAS), a targeted-plasticity approach in subacute and chronic SCI to inducing beneficial plasticity in the nervous system that strengthens corticospinal-motoneuron synapses. In this collaborative project, we are investigating the benefits of the combination of PAS with NCAN's methods for inducing beneficial plasticity, including its well-established targeted-plasticity reflex operant conditioning (ROC) approach and their new generalized plasticity-inducing strategy, weak epidural electrical stimulation over sensorimotor cortex (electrocortical stimulation (ECS)). Also, we will investigate the potentially benefits of the combination of PAS with neuroplasticity-enhancing approaches including an intracellular small peptide (ISP) that interferes in the axon growth-inhibitory CSPG-PTPsigma signaling pathway, and an injectable nanofiber-hydrogel composite (NHC) that provides biologically active cues to an SCI site thereby promoting angiogenesis and a repair-promoting shift in inflammation. These plasticity-inducing approaches will also be combined with targeted skill-specific treadmill locomotor training. We expect that various combinations of the targeted-plasticity therapies (ROC & PAS), the generalized-plasticity therapy (ECS), pharmaceutical approaches (ISP), bioengineering approaches (NHC), and skill-specific practice (treadmill locomotion) will produce greater and/or faster improvements in motor function than any of these approaches used alone. Use of our subacute and chronic models of SCI will advance the development and translation of combinatorial technology and the understanding needed to create effective multi-strategy protocols that can be applied clinically.