The Quest for Functional Biomarkers in the Prefrontal Cortex Using Functional Near-Infrared Spectroscopy (fNIRS)

Abstract The prefrontal cortex (PFC) has been recognized as one of the most crucial brain regions responsible for cognitive control, thoughts, and actions. Advanced functional imaging has provided tools needed for the sensitive assessment of functional brain activities and also functional abnormalities in various brain regions. Functional near-infrared spectroscopy (fNIRS) is a highly promising neuroimaging modality that provides an efficient way to continuously monitor changes in blood oxygenation in the brain. Functional biomarkers validated and measured from fNIRS data have provided reliable and predictive information on various brain functional disorders. However, selecting optimum biomarkers from a set of hemodynamic features can be extremely challenging. Here, we focus on functional biomarkers driven from fNIRS data and advanced multivariate analysis used to extract those biomarkers. We introduce hemodynamic activation in the left and right prefrontal cortex and the oxygenation variability (OV) index, which is based on variability in oxygen saturation at frequencies attributed to cerebral autoregulation. The OV index has been calculated for toddlers of the age 18–36 months with varying levels of language development in order to compare it with other behavioral measurement. Furthermore, we discuss how multivariate machine learning techniques can be used in order to drive functional biomarkers in the human PFC which can be used as an aid in diagnosis of brain dysfunction such as traumatic brain injury (TBI).

[1]  Isabelle Guyon,et al.  An Introduction to Variable and Feature Selection , 2003, J. Mach. Learn. Res..

[2]  Hellmuth Obrig,et al.  NIRS in clinical neurology — a ‘promising’ tool? , 2014, NeuroImage.

[3]  Jonathan D. Cohen,et al.  A Developmental Functional MRI Study of Prefrontal Activation during Performance of a Go-No-Go Task , 1997, Journal of Cognitive Neuroscience.

[4]  E. Wegman,et al.  A machine learning approach to identify functional biomarkers in human prefrontal cortex for individuals with traumatic brain injury using functional near‐infrared spectroscopy , 2016, Brain and behavior.

[5]  B. Ambridge,et al.  The structure of working memory from 4 to 15 years of age. , 2004, Developmental psychology.

[6]  T. Hatta,et al.  Oxyhemoglobin changes during cognitive rehabilitation after traumatic brain injury using near infrared spectroscopy. , 2013, Neurologia medico-chirurgica.

[7]  E. Courchesne,et al.  Brain growth across the life span in autism: Age-specific changes in anatomical pathology , 2011, Brain Research.

[8]  Katherine E. Prater,et al.  Functional connectivity tracks clinical deterioration in Alzheimer's disease , 2012, Neurobiology of Aging.

[9]  R. Barkley Behavioral inhibition, sustained attention, and executive functions: constructing a unifying theory of ADHD. , 1997, Psychological bulletin.

[10]  K. R. Ridderinkhof,et al.  Neurocognitive mechanisms of cognitive control: The role of prefrontal cortex in action selection, response inhibition, performance monitoring, and reward-based learning , 2004, Brain and Cognition.

[11]  Andrew T. Drysdale,et al.  Resting-state connectivity biomarkers define neurophysiological subtypes of depression , 2016, Nature Medicine.

[12]  G. Gioia,et al.  Ecological Assessment of Executive Function in Traumatic Brain Injury , 2004, Developmental neuropsychology.

[13]  B. Onaral,et al.  FUNCTIONAL NEAR-INFRARED SPECTROSCOPY–BASED ASSESSMENT OF ATTENTION IMPAIRMENTS AFTER TRAUMATIC BRAIN INJURY , 2011 .

[14]  Aron K Barbey,et al.  The frontopolar cortex mediates event knowledge complexity: a parametric functional MRI study , 2009, Neuroreport.

[15]  D. DeMets,et al.  Biomarkers and surrogate endpoints: Preferred definitions and conceptual framework , 2001, Clinical pharmacology and therapeutics.

[16]  Catherine Limperopoulos,et al.  Identification of Pressure Passive Cerebral Perfusion and Its Mediators after Infant Cardiac Surgery , 2005, Pediatric Research.

[17]  A. Villringer,et al.  Non-invasive optical spectroscopy and imaging of human brain function , 1997, Trends in Neurosciences.

[18]  Victor Chernomordik,et al.  Prefrontal cortex hemodynamics and age: a pilot study using functional near infrared spectroscopy in children , 2014, Front. Neurosci..

[19]  S. Tsujimoto The Prefrontal Cortex: Functional Neural Development During Early Childhood , 2008, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[20]  Nick C. Fox,et al.  Biomarkers for Alzheimer's disease therapeutic trials , 2011, Progress in Neurobiology.

[21]  W. Strik,et al.  Loss of functional hemispheric asymmetry in Alzheimer's dementia assessed with near-infrared spectroscopy. , 1997 .

[22]  Nicholas B. Allen,et al.  The emergence of depression in adolescence: Development of the prefrontal cortex and the representation of reward , 2008, Neuroscience & Biobehavioral Reviews.

[23]  N PETRILOWITSCH,et al.  [The development of memory]. , 1956, Archiv fur Psychiatrie und Nervenkrankheiten, vereinigt mit Zeitschrift fur die gesamte Neurologie und Psychiatrie.

[24]  Andrew J Saykin,et al.  Executive dysfunction following traumatic brain injury: neural substrates and treatment strategies. , 2002, NeuroRehabilitation.

[25]  B. Levine,et al.  Transfer function analysis of dynamic cerebral autoregulation in humans. , 1998, American journal of physiology. Heart and circulatory physiology.

[26]  K. Semendeferi,et al.  Human prefrontal cortex: evolution, development, and pathology. , 2012, Progress in brain research.

[27]  E. Miller,et al.  An integrative theory of prefrontal cortex function. , 2001, Annual review of neuroscience.

[28]  F. Murillo-Cabezas,et al.  Invasive and noninvasive assessment of cerebral oxygenation in patients with severe traumatic brain injury , 2010, Intensive Care Medicine.

[29]  Gary H. Glover,et al.  A quantitative comparison of NIRS and fMRI across multiple cognitive tasks , 2011, NeuroImage.

[30]  F. Irani,et al.  Functional Near Infrared Spectroscopy (fNIRS): An Emerging Neuroimaging Technology with Important Applications for the Study of Brain Disorders , 2007, The Clinical neuropsychologist.

[31]  Atsushi Maki,et al.  Non-invasive assessment of language dominance with near-infrared spectroscopic mapping , 1998, Neuroscience Letters.

[32]  Laleh Najafizadeh,et al.  Normative database of judgment of complexity task with functional near infrared spectroscopy—Application for TBI , 2012, NeuroImage.

[33]  Yagesh Bhambhani,et al.  Reliability of near-infrared spectroscopy measures of cerebral oxygenation and blood volume during handgrip exercise in nondisabled and traumatic brain-injured subjects. , 2006, Journal of rehabilitation research and development.

[34]  Alain Ptito,et al.  Functional abnormalities in symptomatic concussed athletes: an fMRI study , 2004, NeuroImage.

[35]  P. Ellen Grant,et al.  Developmental neural networks in children performing a Categorical N-Back Task , 2006, NeuroImage.

[36]  S. Arridge,et al.  Estimation of optical pathlength through tissue from direct time of flight measurement , 1988 .

[37]  Kai Zhang,et al.  Default mode network in concussed individuals in response to the YMCA physical stress test. , 2012, Journal of neurotrauma.

[38]  Jinglong Wu,et al.  Network-Based Biomarkers in Alzheimer’s Disease: Review and Future Directions , 2014, Front. Aging Neurosci..

[39]  Richard A. Mason,et al.  Prefrontal activation during verbal fluency tests in schizophrenia—a near-infrared spectroscopy (NIRS) study , 2005, Schizophrenia Research.

[40]  B. Onaral,et al.  Verbal working memory impairments following traumatic brain injury: an fNIRS investigation , 2014, Brain Imaging and Behavior.

[41]  L. Rabin,et al.  Mild traumatic brain injury and its sequelae: Characterisation of divided attention deficits , 2009, Neuropsychological rehabilitation.

[42]  A. Diamond Normal development of prefrontal cortex from birth to young adulthood: Cognitive functions, anatomy, and biochemistry. , 2002 .

[43]  A. Gandjbakhche,et al.  Prefrontal Hemodynamics in Toddlers at Rest: A Pilot Study of Developmental Variability , 2017, Front. Neurosci..

[44]  Elizabeth Redcay,et al.  Deviant Functional Magnetic Resonance Imaging Patterns of Brain Activity to Speech in 2–3-Year-Old Children with Autism Spectrum Disorder , 2008, Biological Psychiatry.