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Neuroengineering/Human Neurophysiology Research


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Peter N. Steinmetz, MD, PhD, biosketch
Director, Neuroengineering Program
Principal Investigator, Neuroengineering/Human Neurophysiology Laboratory
Barrow Neurological Institute

 
Peter N. Steinmetz, MD, PhD


Laboratory Focus
Research in the Neuroengineering/Human Neurophysiology Laboratory is aimed at developing quantitative biophysical descriptions of brain structure and function and using those descriptions to:

  • Understand the integrative operation of the central nervous system
  • Manipulate the brain through electrical stimulation and recording The last decade of the twentieth century was the 'Decade of the Brain' that dramatically expanded our knowledge of the nervous system at all levels. 

The largest questions remain, however. Namely, how do these levels fit together so that the brain produces such myriad and interesting behavior? Our research approach is founded in the belief that understanding biophysical details at the level of roughly 1 mm^3 of the cortex—a few cortical columns, encompassing ~10,000 cells—will be crucial to understanding the functional operation of the cortex. This is a regime that lies above single cells and below the limits of resolution of current imaging modalities, such as fMRI. This is roughly the regime influenced by stimulating electrodes, and with the continuing advance of computational power, is also a regime approachable with biophysical modeling.

The laboratory presently has three main research foci:

  • Plasticity of Single-unit Neural Responses in Human Brain
  • Deep Brain Stimulation and Electrodes
  • Single Neuron Recording in Hypothalamic Hamartomas


Plasticity of Single-unit Neural Responses in Human Brain

Some of the more exciting recent developments in neuroscience have been in developing electrical interfaces to the central nervous system, for example, using electrical stimulation to treat neurological disease as well as current attempts to use recordings from chronically implanted electrodes to control robotic and prosthetic devices. A key question has been how well people can learn to control neural responses, both field potentials and single unit activity, and how these can be used to control external devices.

We have an extraordinary opportunity to directly record single-unit neural responses from the medial temporal lobe of awake human patients (who have electrodes implanted for clinical monitoring prior to surgery for otherwise intractable epilepsy).

 
Figure 1: Two neurons firing in the hippocampus of an epilepsy patient



The Barrow Neuroscience Research Center at Barrow Neurological Institute houses world-class research laboratories, and lecture facilities. The 70,000-square-foot facility was built in 1999 to advance the scope of research through technically advanced equipment and a highly specialized research staff. In this work, we are studying how changes in attention modify neural responses in the human brain, as well as how these responses may be manipulated by the will of the human subject.

Deep Brain Stimulation and Electrodes

High frequency electrical stimulation of thalamus and basal ganglia has been used during the past 20 years for the treatment of advanced stages of Parkinson's disease. Its mechanism of action remains uncertain, however, and the choice of target location and stimulation parameters have been determined by empirical algorithms. Both improving existing therapies and deployment for other brain disorders (dystonias, OCD) can benefit greatly from a better understanding of the biophysical mechanisms of this therapy. We are using large scale finite element models to compute stimulation-induced electric fields within deep brain structures.

Combining these models with compartmental neuron models allows us to predict the effects of these electric fields on specific neuronal elements, such as axons and cell bodies. Guided by these predictions, we are also performing simultaneous micro-stimulation and micro-recordings in-vitro to gain insight into how DBS affects neuronal firing.


Single Neuron

 
Figure 2: Microwires and depth electrode used to record single neuron activity

Recording in Hypothalamic Hamartomas Hypothalamic hamartomas are a rare tumor, most often found in children, which cause epileptic seizures. We are working in collaboration with the Barrow Hypothalamic Hamartoma Center to record single neuron activity in these tumors prior to their resection. See Figure 2.


Other research areas include:

  • Biophysics of Neuronal Computation
  • Information Processing Temporal Coding
  • Synchronous Neuronal Firing

Our primary goals in these recordings are to determine if there are separate patterns of firing activity in-situ which correspond to the two separate classes of cells which have been identified in-vitro. Such distinctions may provide clues as to the way these tumors cause seizures throughout the brain, enabling development of improved treatments in the future for this debilitating type of tumor.
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