Functional NeuroCognitive ImagingTM and Notus NeuroCogsTM: A Novel Use of fMRI in the Assessment of Cognitive Function in Major Neurocognitive Disorder

Epps, Caleb T; Tucker, Braden J; Fong, Alina K.; Allen, Mark D.

doi:10.17756/jnpn.2017-015

Cited by 3 publications

(4 citation statements)

References 54 publications

(69 reference statements)

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“…The normative reference atlas makes it possible to search for and verify biomarkers for specific pathologies [ 44 , 45 ]—that is, reliable patterns of deviation from the norm associated with a specific pathology. Our PCS biomarker development followed a 3-step process: biomarker candidate search, independent samples validation, and multivariate base rate discovery.…”

Section: Discussionmentioning

confidence: 99%

Developing the Standard of Care for Post-Concussion Treatment: Neuroimaging-Guided Rehabilitation of Neurovascular Coupling

Wing¹,

Tucker²,

Fong³

et al. 2017

TONIJ

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Background:Emerging research proposes the imbalance between microvascular supply and metabolic demand as a contributing factor in the pathophysiology of mild traumatic brain injury. Prolonged effects on the dysregulation of neurovascular coupling may explain persistent symptomatic models such as Post-Concussion Syndrome.Objective:Increased knowledge of what we refer to as neurovascular uncoupling provides a template for establishing a new concussion treatment standard in the assessment and therapeutic guidance of concussion.Methods:The degree and localization of neurovascular uncoupling were statistically contextualized against a normative-based atlas in 270 concussed patients. Functional NeuroCognitive ImagingTM was used to establish pre-treatment benchmarks and guide neurotherapy. Conventional and functional neurocognitive imaging-directed measures were used to evaluate post-rehabilitative outcomes.Results:Functional neurocognitive imaging was successful in identifying regions of Neurovascular uncoupling unique to each patient’s brain and concussion profile. Longitudinal objective outcome measures demonstrated timely and lasting improvement of neurovascular coupling functioning in a significant majority of patients.Conclusion:We present practice-based evidence supporting the clinical administration of functional neurocognitive imaging with particular efficacy in the neurorehabilitation of concussion. We advocate the reliability of functional neurocognitive imaging in assessing severity and localization of neurovascular uncoupling, and promote its use in the therapeutic guidance and neurorehabilitation of mild traumatic brain injury. We further support the continual exploration of other potential pathophysiological alterations resulting from concussion.

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Section: Discussionmentioning

confidence: 99%

Developing the Standard of Care for Post-Concussion Treatment: Neuroimaging-Guided Rehabilitation of Neurovascular Coupling

Wing¹,

Tucker²,

Fong³

et al. 2017

TONIJ

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“…EPIC treatment and related imaging components of it have previously been reported in Wing et al [23] and Epps et al [87]. Using functional neurocognitive imaging (fNCI) techniques, areas of deficient neural NVC are targeted for rehabilitation.…”

Section: Enhanced Performance In Cognition (Epic) Treatmentmentioning

confidence: 99%

Neurovascular Coupling: A Unifying Theory for Post-Concussion Syndrome Treatment and Functional Neuroimaging

Ct¹,

Allen²

2017

J Neurol Neurophysiol

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Post-concussion syndrome (PCS) occurs in a significant percentage of concussion patients and is defined as having a history of traumatic brain injury with persistence of three or more symptoms. Standard structural clinical neuroimaging studies show no abnormal findings for the majority of PCS patients as opposed to functional MRI, which often reveals irregularities in the blood-oxygen level dependent (BOLD) signal. This suggests that dysregulation of neurovascular coupling, which causes abnormal BOLD signals, plays a significant role in PCS pathology. However, compared to the pathophysiologic mechanisms occurring in acute concussion, the underlying neuropathophysiology of chronic concussive sequelaeor PCS is less understood, though becoming clearer with emerging research. We present a treatment approach grounded in the physiological theory presented here called Enhanced Performance in Cognition (EPIC), which has shown strong clinical success. Dysregulation of neurovascular coupling (NVC), along with disruptions in cerebrovascular reactivity (CVR) and autonomic nervous system (ANS) dysregulation are the targets of EPIC treatment. Success of the approach itself tentatively supports the hypothesis that these three features figure prominently in the neuropathophysiology of PCS. The aim of this report is to provide a theory of the underlying mechanisms of PCS pathology and its treatment that is in accord with the current corpus of research and explains the recent therapeutic success seen in PCS patient using the EPIC treatment. We propose a novel theory concerning the mechanisms by which NVC dysregulation is normalized. This includes focused, intense and repetitive neurocognitive challenges during post-exercise cognitive boost and the avoidance of intracerebral steal in the setting of restored and re-regulated CVR and ANS. It is intended that both the theory and treatment approach are presented explicitly enough to generate empirical studies with clear hypothetical predictions from the theory as well as clinical innovations with significant relevance to improve current practices.

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“…An example of this process is outlined in Figure 1. Also, for an example of the assessment of activation patterns in individual patients compared to the normative atlas in all six fNCI exams as studied by Epps et al [24] (Figures 2 and 3). In order to provide additional reference values for patient analyses below, healthy control subjects were individually evaluated against the group normative data matrix (i.e., a z-score was computed from each healthy control data point).…”

Section: Functional Verbal Fluency Test (Fvft)mentioning

confidence: 99%

“…As the individual biomarker's false positive rates would compound one another, increasing the potential overall false positive rate, if all five biomarkers were used simultaneously, multivariate base rate analysis was performed and a base rate cutoff matrix was constructed. We adopted a method proposed by Iverson et al [24] where diagnostic values were derived simultaneously from multiple domain scores using multivariate base rate analysis. A uniform cutoff of +/-2 SD (2 nd percentile) was used for the initial false positive rate assessments of each of the five biomarkers.…”

Section: Multivariate Base Rate Discoverymentioning

confidence: 99%

Discovery of Therapy-targeting Biomarkers for Post-Concussion Syndrome using Functional Neurocognitive Imaging

Epps¹,

Allen²

2018

Brain Disord Ther

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Background: Post-concussion syndrome (PCS) occurs in a significant percentage of concussion patients. Functional MRI reveals irregular blood-oxygen level dependent signals in PCS patients. PCS biomarkers with functional predictive values have yet to be discovered and validated. Therefore, this study describes five PCS biomarkers and includes a description of their therapeutic application.Methods: A neurocognitive imaging protocol was developed and a group of healthy control patients was used to generate a normative reference atlas. Biomarker candidate search was performed using an initial sample of PCS patients. Sample validation was applied to each biomarker using a new sample of PCS patients to assess sensitivities/ specificities. A multivariate base rate analysis was performed using 132 new patients and a base rate cutoff matrix was constructed. An example of the biomarker's therapeutic application in a PCS patient is described. Results:The five functional biomarkers included: Frontal Attentional System hypoactivation, Subcortical System hypoactivation, Visual System hyperactivation, Verbal System hypoactivation, and Frontal/Parietal System hyperactivation. Individual biomarker sensitivities and specificities are reported. Collectively, using the base rate cutoff matrix, a threshold using 3/5 biomarkers below the 10 th percentile as the cutoff resulted in a suitable sensitivity (88%) and specificity (99%). The uses of these biomarkers were crucial in guiding the successful treatment of Patient A. Conclusion:We report the discovery of five functional PCS biomarkers. We show an example of the therapeutic application of the five biomarkers in the successful treatment of PCS. These neuroimaging biomarkers serve to advance diagnostic capabilities and subsequent PCS rehabilitation efforts.

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Functional NeuroCognitive ImagingTM and Notus NeuroCogsTM: A Novel Use of fMRI in the Assessment of Cognitive Function in Major Neurocognitive Disorder

Cited by 3 publications

References 54 publications

Developing the Standard of Care for Post-Concussion Treatment: Neuroimaging-Guided Rehabilitation of Neurovascular Coupling

Developing the Standard of Care for Post-Concussion Treatment: Neuroimaging-Guided Rehabilitation of Neurovascular Coupling

Neurovascular Coupling: A Unifying Theory for Post-Concussion Syndrome Treatment and Functional Neuroimaging

Discovery of Therapy-targeting Biomarkers for Post-Concussion Syndrome using Functional Neurocognitive Imaging

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