The PMRF Lab conducts animal and human-subjects research in the broad fields of neurophysiology, neurological rehabilitation, and neural engineering.

We are particularly interested in the ways that brainstem-spinal neural circuits integrate pain and movement-related information after stroke and spinal cord injury; understanding basic principles of neural plasticity and communication between functionally and spatially distinct regions of the brainstem and spinal cord; and using technology to exploit the adaptive capacity of the central nervous system to improve therapeutic outcomes.

Pre-clinical/animal
model research

In this line of research, we study neural plasticity and communication between spinal circuits that process pain and movement-related information. This research relies heavily on recurrent neural-computer interfaces (rNCI), also known as closed-loop or bi-directional neural-computer interfaces. rNCI are an emerging technology that uses biophysical signals recorded from one region of the nervous system to trigger electrical, optical, or chemical stimulation in another region. We are translating advances in our understanding of spinal plasticity into multi-modal therapies to restore natural patterns of neural transmission after spinal cord injury. 

  • Neural plasticity
  • Neural-computer interfaces
  • Electrophysiology
  • Neuropathic pain
  • Movement impairments
  • Neuromodulation
  • Biophysics

Clinical/human-subjects
research

In this line of research, we study relationships between the neural control of movement and pain perception in humans. Specifically, we study how the brainstem differentially regulates the relative amount of transmission in (or, put another way, the excitability of) spinal motor and pain networks using a class of neurotransmitter known as the monoamines (serotonin, norepinephrine). We also study neural plasticity in these same brainstem-spinal circuits. This research is particularly relevant to understanding the causes of movement impairments after stroke and to developing new strategies for neurorehabilitation.  

  • Neuropharmacology
  • Clinical electrophysiology
  • Electromyography
  • Robotics/mechatronics
  • Motor rehabilitation
  • Sensorimotor integration
  • Conditioned pain modulation

Examples of current research studies

Intraspinal functional connectivity and neural plasticity 

Perception and action are central to our ability to interact with and learn from the world around us. Yet, we are only beginning to appreciate how the nervous system makes staggeringly complex tasks and decisions seem routine. In this line of research, we study the spinal cord’s role in these processes. The spinal cord is the first stop in the CNS for sensory feedback coming from the body (perception) and the last stop in the CNS for sending motor commands out to muscles (action). Therefore, it presents a unique opportunity for studying communication within sensory and motor networks and how these networks learn and adapt. 

Currently, we are studying whether seemingly spontaneous patterns of neural activity in spinal networks may actually represent (at least in part) a ‘memory’ or ‘replay’ of past experiences and a default state of readiness to execute behaviors – even when unconscious. We are also studying intraspinal local field potentials, a type of biophysical signal that reflects the aggregate neural activity of a large population of simultaneously active neurons. Specifically, we want to understand whether these signals convey meaningful information between functionally and spatially different neural structures, in effect representing a different language that networks of neurons could use to communicate (in addition to direct synaptic information transfer from one neuron to another). These studies are primarily conducted in vivo in rats using electrophysiological recordings of hundreds to thousands of neurons in the spinal cord, as well as recordings from peripheral nerves and muscles.

Intraspinal microstimulation for multi-modal rehabilitation

Spinal cord injury (SCI) often results in motor impairments and neuropathic pain. These conditions are related to changes in neural transmission in regions of the spinal cord that control motor output and sensory processing. Generally, there is too little neural transmission in spinal motor pathways below the lesion, whereas there is excessive, inappropriate neural transmission in pain pathways below the lesion.

We have previously developed a recurrent neural computer interface that allows us to deliver small amounts of electrical current inside the spinal cord within a few milliseconds of detecting specific, functionally related neural activity in other regions. This so-called ‘closed loop’ intraspinal microstimulation approach allows us to restore natural patterns of neural transmission in sensorimotor pathways that span an SCI by artificially connecting neurons that can still be activated voluntarily with those that are weakened or cannot be activated voluntarily due to the lesion. Once the appropriate patterns of neural activity have been (re)introduced, they can be reinforced over time by taking advantage of a fundamental type of neural learning called spike-timing-dependent plasticity, in which the strength of neural connections can be increased or decreased when one neuron repeatedly contributes to the firing of another. We have shown that this approach can lead to long-term improvements in elbow, wrist, and digit control in chronic cervical SCI. 

Currently, we are exploring the extent to which intraspinal microstimulation for motor rehabilitation can also be designed to reduce pathologically increased transmission in spinal pain pathways below an SCI. These studies are conducted in vivo in rats using a combination of neural-computer interfaces, targeted neuropharmacology, and physical rehabilitation.

Rehabilitative neuroplasticity in brainstem-spinal neural pathways

If a person is trying to escape from a frightening or stressful situation, like running away from a bear while on a hike, they will likely find that they’re able to run much faster than when they’re just on a daily jog. And if they stub their toe along the way, they probably won’t notice the pain. On the other hand, if a person is falling asleep in class after a long night and was asked to do as many pushups as possible, they’d likely not be at peak performance. But their toe would absolutely kill when they stood up and stubbed it on their desk. 

You can thank a region of the brainstem known as the ponto-medullary reticular formation (PMRF) for both of these phenomena. Neural pathways descending from the PMRF to the spinal cord release a type of neurotransmitter that dramatically increases motor-related neural transmission while it simultaneously reduces pain-related transmission. Our research suggests that neural transmission from the PMRF to the spinal cord also becomes pathologically increased after a stroke, and appears to be a key contributor to many common post-stroke movement impairments. 

Currently, we are studying interrelationships between the neural control of movement and pain perception to further our understanding of how altered transmission from the PMRF to the spinal cord contributes to movement and sensory impairments. We are also attempting to reduce pathologically increased transmission in these same pathways by using non-invasive electrical stimulation to drive restorative neuroplasticity. These studies are conducted in individuals with and without chronic hemiparetic stroke using a combination of non-invasive electrical stimulation, mechatronic devices/robotics, electromyography, and targeted neuropharmacology.