Neuroplasticity and Neuromarker Driven Neuromodulation: The Future Path to Normalizing Brain Function

January 2016

Philip A Defina
James P Halper
Jonathan Fellus
Charles J Prestigiacomo
…and others.

ABSTRACT: The purpose of this paper is to present a novel approach to promoting brain neuroplasticity through the application of neuromarker driven neuro- modulation. A tripartite model utilizing structural, electromagnetic, and neurochemical modalities to identify and localize neuromarkers and then to create personalized, tailored interventions are described. It is proposed that neuromarker-guided neuromodulation of brain pathways can promote neuroplasticity for healing, repair and improved neuroconnectivity. A clinical application of this model has already been utilized and reported in preliminary retrospective research in the treatment of severe disorders of consciousness. This model serves as a template for future use of neuromarker driven procedures and complex interventions for brain repair.

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Disrupted Axonal Fiber Connectivity As a Marker of Impaired Consciousness States

June 2013

Project: PVS / MCS
Philip A. Defina
Rafael Rodriguez-RojasRafael
Batista García-Ramó
Yasser Iturria
Maylen Carballo-Barreda
…and others.

ABSTRACT: Background: Persistent vegetative states (PVS) and locked-in syndrome (LIS) are well differentiated disorders of consciousness that can be reached after a localized brain injury in the brainstem. The relations of the lesion topography with the impairment in the whole-brain architecture and functional disconnections are poorly understood. Methods: Two patients (PVS and LIS) and 20 age-matched healthy volunteers were evaluated using diffusion tensor imaging (DTI). Anatomical network was modeled as a graph whose nodes are represented by 71 brain regions. Inter-region connections were quantified through Anatomical Connection Strength (ACS) and Density (ACD). Complex networks properties such as local and global efficiency and vulnerability were studied. Mass univariate testing was performed at every connection using network based statistic approach. Results: LIS patients’ network showed significant differences from controls in the brainstem-thalamus-frontal cortex circuitry, while PVS patients showed a widespread disruption of anatomical connectivity in both hemispheres. Both patients showed a reorganization of network attributes, with decreased global and local efficiency, significantly more pronounced in PVS. Conclusions: Our results suggest that DTI-based network connectivity combined with graph theory is useful to study the long-range effect of confined injuries and the relationship to the degree of consciousness impairment, underlying PVS and LIS.

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The new neuroscience frontier: Promoting neuroplasticity and brain repair in Traumatic Brain Injury

November 2009

The Clinical Neuropsychologist 23(8):1391-9
DOI: 10.1080/13854040903058978
SourcePubMed
Philip A Defina
Jonathan Fellus
Mary Zemyan Polito
John Deluca
…and others.

ABSTRACT: Increased awareness of traumatic brain injury (TBI) in the military, a persistent call for evidence-based treatment, and recent government funding have revealed new research opportunities in neuroscience. This paper describes a relatively new frontier for research: that of the facilitation or enhancement of neuroplasticity and brain repair in TBI using novel treatment protocols. Such protocols, algorithmically introduced, may be tailored to the individual through the matching of neuromarkers with specific interventions. Examples of neuromarkers and interventions employed for the purpose of neuromodulation are reported. Problems with lack of controlled studies and inferring causation in correlational research are noted. Healthy skepticism and open-minded creativity are needed so that we can think in unorthodox ways, create partnerships, harness available knowledge and expertise, and ultimately develop effective treatments.

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