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Collaborations

Biomarkers of Traumatic Brain Injury and Concussion

The objective of these studies is to develop objective measures of brain health that are sensitive to mild Traumatic Brain Injury (mTBI or concussion). Concussion often results in increased cerebral cortical baseline activity which results in changes in central information processing. Protocols used for this study target detection of changes in neural transmission mediated by both GABAergic and NMDA receptor systems, and by neuron-glial interactions. The figure below exemplifies a multi-parametric approach of assessments of concussed vs. non-concussed individuals. Using this multi-parametric method, we currently have a 99% confidence level (via Hotelling's t-square statistic) in differentiating these two groups.

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Pharmacological Screening / Drug Testing

CM technology is currently being used in multiple studies to evaluate the efficacy of pharmacological interventions in several different neurological disorders. Previous studies have demonstrated sensitivity of the method to drug effects. In one study (Folger et al, 2008), we investigated the effects of a low dosage of dextromethorphan (60 mg of DXM; over-the counter cough syrup), an NMDAR antagonist, to observe if it had an impact on an individual’s performance. The significance of that study was that while the drug had no significant effect on discriminative measures that are predominantly mediated by peripheral factors, the adaptation metrics were significantly impacted. Over a 3 hour time course, the low dose of cough syrup caused the adaptation metrics to deviate from normative values and returned to baseline. Thus, this demonstrated that the adaptation metric is a sensitive reflection of central information processing, and the sensitivity far exceeds any metrics that can be obtained by modern medical imaging techniques.

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Biomarkers of Aging and Alzheimer's Disease

The major goal of the work proposed is to utilize a novel method for quantitative sensory testing of tactile information processing to characterize an aging subject population. The method is driven by a conceptual model derived from neurophysiological observations of the dynamic changes that are evoked in SI cortex when stimuli that promote cortical regional interactions are presented to the skin. These sensory testing methods are atypical of the sensory testing methods that have dominated the literature for the past several decades primarily because they are designed from the perspective of generating measurable percepts that are most influenced by cortical-cortical interactions.

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Studies in alcohol and substance abuse

Chronic alcoholism leads to down-regulation of a patient's GABAergic system and/or up-regulation of the patient's glutaminergic neurotransmission. In other words, in the case of the GABA system, chronic alcohol abuse will (since alcohol works as a GABA agonist) necessitate the administration of a GABA agonist. In the case of glutaminergic neurotransmission, chronic alcohol abuse will lead to an up-regulation of the NMDA receptor system (since alcohol is also an NMDA receptor antagonist).

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Information Processing in Autism

There is substantial evidence that in autism cerebral cortical information processing is abnormal in the "high-order" areas that underlie language and social interaction skills, and also in the "lower-order areas" which accomplish the initial processing of thalamocortical afferent activity evoked by sensory stimulation. Abnormalities in the response of primary sensory cortex in autism have been convincingly demonstrated using psychophysical testing procedures and neurophysiological recording methods. For example, autism subjects routinely exhibit hyperarousal to sensory input, and a decreased ability to select among competing sensory inputs. Furthermore, the regions of cortex devoted to stimulus-driven sensory processing display excessive responsivity in individuals with autism, and exhibit little-to-no specificity in their response to either the location or modality of a sensory stimulus.

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Studies in Chronic Pain

Pain is associated with a wide range of injury and disease, and is often the disease itself. Millions suffer from acute or chronic pain every year and the effects of pain exact a tremendous cost in the US, with estimates in the neighborhood of $5-600 billion annually in terms of both direct health care costs and the indirect costs due to lost productivity. One of the central issues in pain is understanding the source of the pain and the mechanisms responsible for it. There are currently no objective, standardized, quantitative methods for measuring the degree to which an individual’s CNS has been altered by their pain. Better diagnostic tools can lead to better and more effective treatments. Currently, we are studying several types of chronic pain in collaboration with the Center for Neurosensory Disorders at the University of North Carolina. The figure below exemplifies the impact that one type of pain (VVS: Vulvar Vestibulitus Syndrome; female pelvic pain) has on the individual’s brain health. Also note that there are significant differences in the results obtained between these subjects and control subjects in tests performed on the finger tips – a body site remote to the location of the pain. This is because the tests are designed to objectively assess cortical information processing.

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Malingering studies

Malingering is the intentional production of false or grossly exaggerated physical or psychological symptoms, motivated by external incentives such as avoiding military duty, avoiding work, obtaining financial compensation, evading criminal prosecution, or obtaining drugs. In other words, people try to cheat on many types of examinations in order to look like they have a neurological problem when they do not or when they want to elude detection of a neurological problem. Malingering is expensive, in that fraud, that broadly includes malingering, in that it is estimated to cost the insurance industry $150 billion annually (or ~ $1800 per family in the US). The obvious way for someone to cheat on a test is just to perform poorly. However, most of the CM diagnostics are designed such that individuals who have neurological deficits actually outperform healthy individuals. To paraphrase, illusory conditions will confound the results of healthy individuals, but will only confound unhealthy individuals to a certain degree, or not at all. We are currently in the initial stages of conducting malingering studies, to investigate if healthy individuals are able to knowingly simulate (i.e.., fake) neurological deficits.

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