Andrew Robert Mayer
The Mind Research Network
Project start date: 2012-02-01
Project end date: 2014-01-31
Sponsored Links Excellgen http://Excellgen.com
Grants awarded to Andrew Robert Mayer
MULTIMODAL IMAGING OF THE SENSORY GATING DEFICIT IN SCHIZOPHRENIA
Andrew Robert Mayer, Research Scientist
The Mind Research Network, Albuquerque, Nm 87106
Abstract: This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Multiple lines of research have consistently documented sensory processing deficits in patients with schizophrenia (SP). One such deficit is poor sensory gating, in which there is an increased electrophysiological response for the second of two rapidly presented stimuli in SP compared to healthy normal volunteers (HNV). This effect is typically reported in terms of a gating ratio comparing the amplitude of the response for both the first (S1) and second (S2) stimulus (S2/S1*100). Poor sensory gating has been characterized as both a deficit in selective attention and/or in the formation of memory traces, and is a useful bio-marker of the cognitive and subsequent social dysfunction that is typically observed in SP. Although animal and invasive human studies have consistently implicated the auditory cortex, prefrontal cortex and hippocampus in mediating the sensory gating response, localized activation in these structures has not always been reported during non-invasive imaging modalities. Moreover, this deficit has been primarily been documented using electrophysiological techniques such as electroencephalography (EEG) and magnetoencephalography (MEG). To date, there has not been a single functional magnetic resonance imaging (FMRI) study that has characterized hemodynamic markers of the gating deficit in schizophrenia using the traditional gating paradigm
Keywords: Ammon Horn; Animals; Auditory Cortex; Auditory area; CRISP; Cognitive; Computer Retrieval of Information on Scientific Projects Database; Cornu Ammonis; Dysfunction; EEG; Electroencephalography; Functional Magnetic Resonance Imaging; Functional disorder; Funding; Grant; Hippocampus; Hippocampus (Brain); Human; Human, General; Institution; Investigators; MRI, Functional; Magnetic Resonance Imaging, Functional; Magnetoencephalography; Man (Taxonomy); Man, Modern; Mediating; Memory; Methods and Techniques; Methods, Other; Multimodal Imaging; Multimodality; NIH; National Institutes of Health; National Institutes of Health (U.S.); Patients; Physiopathology; Prefrontal Cortex; Reporting; Research; Research Personnel; Research Resources; Researchers; Resources; Schizophrenia; Schizophrenic Disorders; Selective inattention; Sensory Process; Source; Stimulus; Structure; Techniques; United States National Institutes of Health; dementia praecox; fMRI; hemodynamics; hippocampal; imaging modality; neural mechanism; neuroimaging; neuromechanism; pathophysiology; response; schizophrenic; selective attention; sensory gating; social; tool; volunteer
Project start date: 2009-07-01
Project end date: 2010-06-30
Budget start date: 1-JUL-2009
Budget end date: 30-JUN-2010
PFA/PA: PAR-07-229
5P20RR021938-02_6574 (2009): $266891
ATTENTIONAL DYSFUNCTION AND RECOVERY IN TRAUMATIC BRAIN INJURY (TBI)
Andrew Robert Mayer, Research Scientist
The Mind Research Network, Albuquerque, Nm 87106
Grant 3R21NS064464-01A1S1 from National Institute Of Neurological Disorders And Stroke
Abstract: Several recent meta-analyses suggest that the semi-acute stage of mild traumatic brain injury (mTBI) is associated with mild cognitive deficits in attention, memory and executive functioning. However, routine clinical imaging (MRI and CT) scans are usually insensitive to both the neuronal pathology underlying these acute cognitive deficits as well as to the subsequent recovery process that occurs in the majority (80-90%) of patients. Our currently funded NIH work investigates attentional deficits that are commonly associated with mTBI both semi-acutely (within 3 weeks of injury) and in the more chronic injury phase (3-5 months) using neuropsychological testing coupled with an extensive magnetic resonance imaging (MRI) battery. Specifically, we are using functional MRI (FMRI), diffusion tensor imaging (DTI) and proton magnetic resonance spectroscopy (1H-MRS) to quantify the cognitive and neurophysiological changes that occur following mTBI. Our preliminary data (16 mTBI patients and 16 matched controls) suggest subtle cognitive deficits, metabolic abnormalities and hemodynamic disturbances during the semi-acute stages of mTBI. However, our current multimodal imaging protocol lacks a direct measure of neuronal functioning, which would provide crucial information regarding potential mechanisms underlying these metabolic and vascular abnormalities. Therefore, this competitive revision (Notice Number NOT-OD-09-058; NIH Announces the Availability of Recovery Act Funds for Competitive Revision Applications) seeks to add magnetoencephalography (MEG) as a direct measure of the synchronous firing of neuronal ensembles (i.e., neuron electrophysiology) to complement our ongoing NIH funded work. Twenty-seven well- characterized mild TBI patients and 15 non-cranial trauma controls will undergo neuropsychological testing and an extensive imaging battery 3 weeks and 3-5 months post injury. Participants will be asked to perform both a spatial orienting and a resting-state task during the collection of FMRI (currently funded work) and MEG (competitive revision) data. Amongst all of the imaging modalities, the combination of information from MEG and FMRI is likely to be the most synergistic due to the increased spatial (FMRI) and temporal (MEG) resolution that each modality provides. This hypothesis will be directly tested by applying novel multivariate statistical techniques (joint independent component analyses; J-ICA) to the acquired data. The utility of J-ICA to capitalize on the unique information present in each individual imaging modality has not been studied, and, more importantly, neither has its ability to tell both when (MEG) and where (FMRI) pathological responses are occurring within the brain following mTBI. The impact and innovation of the current proposal lies on several levels. Foremost, it addresses an important gap in our knowledge regarding the development of standardized protocols that are capable of capturing the dynamic neurological changes that occur after mTBI. While it is unlikely that neuroimaging techniques alone will ever be able to provide an independent objective diagnosis, it is likely that they will provide incremental information important for both differential diagnosis and predictions about future outcome. Second, the addition of MEG ensures we are directly measuring neuronal as well as metabolic (1H-MRS) and vascular (FMRI) responses. This is critical given that frank neuronal dysfunction could potentially drive both the metabolic and vascular abnormalities that we are currently observing in our semi-acutely injured mTBI patients. MEG provides exquisite temporal resolution that will permit an evaluation of when (on the millisecond level) the pathological neuronal response is occurring (M50 versus M100 versus M300). To date, there have only been a few studies that have utilized MEG to study mTBI and have been conducted during the semi-acute stage of injury in an unselected population. Finally, a longitudinal study of mild TBI during both the semi-acute and chronic phase that combines these neuroimaging modalities will provide the foundation for a human recovery model in TBI. Although current animal models exist, these are a poor substitute for the complexities inherent in human cognition. In the United States alone, there are approximately 1.2 million mild traumatic brain injury (mTBI) cases per year that result in an estimated cost of $56 billion dollars. The symptoms of mTBI can range from severe physical and mental disability to subtle problems with attention, concentration, or emotional control. Cognitive difficulties are often present in the first few weeks of injury, but typically remit 3-5 months post injury in the majority (approximately 80-90%) of patients. The first step for understanding these cognitive difficulties is to develop biomarkers that are sensitive to neuronal injury and the subsequent recovery process, which will be critical not only for mTBI, but also for more severe forms of TBI. However, the neuropathology underlying cognitive deficits in the acute or chronic phases of mild TBI is often subtle and difficult to detect with conventional imaging techniques. Our currently funded NIH work with magnetic resonance imaging (MRI) techniques provide preliminary evidence of abnormal metabolic and vascular responses in the semi-acute phase of mTBI, which we have also shown to correlate with cognitive dysfunction. This competitive revision will add a direct measurement of synchronous neuronal firing (magnetoencephalography; MEG) to our currently funded protocol. The fusion of high-resolution spatial (FMRI) and temporal (MEG) information, coupled with behavioral and neuropsychological measures over time, will provide unprecedented insight into the foundation of a mTBI recovery model in humans
Keywords: Acquired brain injury; Acute; Address; Affect; Animal Model; Animal Models and Related Studies; Anterior; Articulation; Atrophic; Atrophy; Attention; Attention Concentration; Attentional deficit; Auditory; Auditory Cortex; Auditory area; Behavioral; Bilateral; Blood Vessels; Bone; Bone and Bones; Bones and Bone Tissue; Brain; Brain Injuries; CAT Scan, X-Ray; CAT scan; CT X Ray; CT scan; Cartoons; Cell Communication and Signaling; Cell Signaling; Cephalic; Cerebrospinal Fluid; Chronic; Chronic Phase; Classification; Clinical; Clinical Trial Overviews; Cognition; Cognitive; Cognitive Disturbance; Cognitive Impairment; Cognitive decline; Cognitive deficits; Cognitive function abnormal; Collection; Color; Complement; Complement Proteins; Computed Tomography; Computerized Axial Tomography (Computerized Tomography); Computerized Tomography, X-Ray; Control Groups; Coupled; Cranial; Cues; Data; Data Pooling; Data Poolings; Defect; Detection; Development; Diagnosis; Differential Diagnosis; Diffusion; Diffusion MRI; Diffusion Magnetic Resonance Imaging; Diffusion Weighted MRI; Disturbance in cognition; Dorsal; Dysfunction; EEG; EMI scan; Electroencephalography; Electrophysiology; Electrophysiology (science); Emotional; Encephalon; Encephalons; Ensure; Environment; Evaluation; Event; Exhibits; Exploratory/Developmental Grant for Diagnostic Cancer Imaging; FLR; Failure (biologic function); Feedback; Foundations; Functional Magnetic Resonance Imaging; Functional disorder; Funding; Future; H+ element; Human; Human Figure; Human body; Human, General; Hydrogen Ions; Image; Imaging Procedures; Imaging Techniques; Impaired cognition; Individual; Inferior; Injury; Intermediary Metabolism; Intracellular Communication and Signaling; Ischemia; Joints; Knowledge; LBUL; Lobule; Longitudinal Studies; METBL; MR Imaging; MR Spectroscopy; MR Tomography; MRI; MRI, Functional; MRS; MRSI; Magnetic Resonance Imaging; Magnetic Resonance Imaging Scan; Magnetic Resonance Imaging, Functional; Magnetic Resonance Spectroscopy; Magnetoencephalography; Man (Taxonomy); Man, Modern; Measurement; Measures; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; Medical Imaging, Positron Emission Tomography; Memory; Meta-Analyses; Meta-Analysis; Metabolic; Metabolic Processes; Metabolism; Methods; Methods and Techniques; Methods, Other; Metric; Modality; Modeling; Msec; Multimodal Imaging; Multimodality; NIH; NMR Imaging; NMR Tomography; National Institutes of Health; National Institutes of Health (U.S.); Nature; Nerve Cells; Nerve Unit; Nervous; Nervous System, Brain; Neural Cell; Neurocyte; Neurologic; Neurological; Neuronal Dysfunction; Neuronal Injury; Neurons; Neurophysiology / Electrophysiology; Neuropsychologic Tests; Neuropsychological Tests; Neuroses, Post-Traumatic; Neuroses, Posttraumatic; Nuclear Magnetic Resonance Imaging; Outcome; PET; PET Scan; PET imaging; PETSCAN; PETT; PTSD; Parietal; Parietal Lobe; Parietal Lobe of the Brain; Participant; Pathology; Patients; Patients with traumatic brain injury; Pattern; Performance; Phase; Physiopathology; Population; Positron Emission Tomography Scan; Positron-Emission Tomography; Post-Traumatic Stress Disorders; Process; Protocol; Protocols documentation; Proton Magnetic Resonance Spectroscopic Imaging; Protons; Psyche structure; Publications; R21 Award; Rad.-PET; Reaction Time; Recovery; Recovery of Function; Relative; Relative (related person); Research; Resolution; Response RT; Response Time; Rest; Role; Science of neurophysiology; Scientific Publication; Services; Severities; Signal Transduction; Signal Transduction Systems; Signaling; Site; Staging; Stimulus; Stress Disorders, Post-Traumatic; Stress Disorders, Posttraumatic; Sum; Symptoms; Systematics; TBI Patients; Technics, Imaging; Techniques; Testing; Time; Tomodensitometry; Tomography, Xray Computed; Trauma; Trauma, Brain; Traumatic Brain Injury; Traumatic encephalopathy; United States; United States National Institutes of Health; Work; X-Ray Computed Tomography; Zeugmatography; base; biological signal transduction; biomarker; bone; brain damage; brain lesion (from injury); catscan; cingulate cortex; cognitive dysfunction; cognitive loss; cognitive rehab; cognitive rehabilitation; cognitively impaired; computed axial tomography; computerized axial tomography; computerized tomography; cost; diffusion tensor imaging; disability; electrical potential; excitotoxicity; executive control; executive function; experiment; experimental research; experimental study; fMRI; failure; frontal cortex; frontal eye fields; frontal lobe; functional recovery; gray matter; hemodynamics; imaging; imaging modality; improved; injured; innovate; innovation; innovative; insight; long-term study; mental; millisecond; model organism; neural; neuroimaging; neuron injury; neuronal; neuropathology; neurophysiology; neuropsychological; novel; parietal cortex; pathophysiology; psychomotor reaction time; public health relevance; relating to nervous system; research study; response; social role; spatiotemporal; spinal fluid; substantia grisea; traumatic brain damage; traumatic neurosis; vascular
Relevance: In the United States alone, there are approximately 1.2 million mild traumatic brain injury (mTBI) cases per year that result in an estimated cost of $56 billion dollars. The symptoms of mTBI can range from severe physical and mental disability to subtle problems with attention, concentration, or emotional control. Cognitive difficulties are often present in the first few weeks of injury, but typically remit 3-5 months post injury in the majority (approximately 80-90%) of patients. The first step for understanding these cognitive difficulties is to develop biomarkers that are sensitive to neuronal injury and the subsequent recovery process, which will be critical not only for mTBI, but also for more severe forms of TBI. However, the neuropathology underlying cognitive deficits in the acute or chronic phases of mild TBI is often subtle and difficult to detect with conventional imaging techniques. Our currently funded NIH work with magnetic resonance imaging (MRI) techniques provide preliminary evidence of abnormal metabolic and vascular responses in the semi-acute phase of mTBI, which we have also shown to correlate with cognitive dysfunction. This competitive revision will add a direct measurement of synchronous neuronal firing (magnetoencephalography; MEG) to our currently funded protocol. The fusion of high-resolution spatial (FMRI) and temporal (MEG) information, coupled with behavioral and neuropsychological measures over time, will provide unprecedented insight into the foundation of a mTBI recovery model in humans
Project start date: 2009-03-01
Project end date: 2011-08-31
Budget start date: 30-SEP-2009
Budget end date: 31-AUG-2011
PFA/PA: PA-06-181
3R21NS064464-01A1S1 (2009): $507037
Neurochemistry Of Pain: Measuring Glutamatergic Brain Activity In Response To P
Andrew Robert Mayer
The Mind Institute
msc11 6040
albuquerque, Nm 87131
Grant 1R03DA024212-01A1 from National Institute On Drug Abuse IRG: ZDA1
Abstract: It is estimated that about 50 million people in the United States suffer from persistent, serious pain. Response to pain involves both peripheral and central mechanisms with several systems, neurotransmitters and receptors playing a role in pain transmission and response. The neural structures supporting the perception of pain as experience of an unpleasant stimulus strongly overlap with those that support the experience of negative emotion and those areas proposed to be involved in a final common pathway for initiation of drug seeking behaviors in addiction. How acute pain in response to an injury or disease transitions to a chronic pain syndrome, and the underlying neurobiology of pain are still poorly understood. This project proposes to extend previous findings using functional Magnetic Resonance Spectroscopy (fMRS) in pain by linking changes in neural activation to changes in concentration of the neurotransmitter glutamate and one of it´s intermediates, glutamine, in response to pain. We hypothesize 1) that painful stimuli administered to healthy humans will increase central neuronal activity and glutamatergic neurotransmission in regions of the brain associated with pain perception, 2) Glutamine levels measured with 1H-MRS will reflect relative levels of activity and glutamatergic transmission and 3) Pain thresholds will be negatively correlated with reports of negative emotion and somatic complaints, while glutamate and glutamine responses to a painful stimulus will be positively correlated with these same measures. The ability to measure such activation and neurotransmitter increases will provide a novel surrogate marker for categorizing pain syndromes. Such investigations of the underlying central neurochemical responses to pain and the development of a technique to precisely measure these responses will have implications extending beyond a better understanding of pain and improving pain treatment and may even impact on the important related issue of addiction to analgesics
Project start date: 2007-09-27
Project end date: 2008-08-31
1R03DA024212-01A1 (2007): $247826
Multimodal Imaging Of The Sensory Gating Deficit In Chronic Cocaine Abusers
Andrew Robert Mayer
The Mind Institute
msc11 6040
albuquerque, Nm 87131
Grant 1R03DA022435-01A2 from National Institute On Drug Abuse IRG: ZDA1
Abstract: Cocaine dependence is a debilitating disease affecting millions of Americans and current treatment regimens are ineffective on nearly 90% of patients. Deficits in higher-order attention and memory processes (i.e., executive dysfunction, reduced working memory capacity and difficulties with attentional switching) are common amongst this group and likely contribute to relapse. However, even more basic deficits, including the failure to inhibit repeated sensory stimuli (i.e., sensory gating), are present. These gating deficits may be more severe in abusers with co-morbid psychiatric profiles such as a proneness to experience paranoia or users with more basic attentional disorders. Both of these sub-groups are associated with increased drug dependence and likelihood of relapse. A paradigm that is capable of identifying these sub-groups of users with associated co-morbidity issues would increase our knowledge on the neurobiology of addiction and could be used as a bio-marker for determining the efficacy of alternative treatment regimens, both of which are directly relevant to NIDA´s overall mission statement. Therefore, we propose to use multimodal neuroimaging, including functional magnetic resonance imaging (FMRI), electroencephalography (EEG) and magnetoencephalography (MEG), and novel data fusion techniques to investigate basic inhibitory processes (i.e., sensory gating) in 12 healthy normal volunteers and 24 chronic cocaine abusers. Neuropsychological and psychological data will also be collected and correlated with performance on the gating task, with emphasis on clinical measures of attentional dysfunction and cocaine induced paranoia. The proposed task will be a variant of the traditional gating paradigm as participants will be exposed to pairs of identical tones and non-identical tones in addition to clicks. MEG and EEG data will be collected simultaneously, and FMRI data will be collected within 24 hours of the electrophysiological data. The specific aims of this project are 1) a more comprehensive understanding of the neurobiology of addiction by characterizing the neural networks (mesocorticolimbic pathway) underlying inhibitory processes to repeated and novel stimuli in chronic cocaine abusers, 2) to determine if basic failures in inhibition are indicative of faster relapse rates, and 3) to determine if basic inhibitory deficits are related to clinical characteristics (i.e., cocaine induced paranoia and attentional deficits) that are more prominent in certain sub-populations of abusers who might carry dual-diagnoses. This proposal is innovative and unique because it is one of the first attempts to utilize several different imaging modalities (FMRI/MEG/EEG) to investigate the neurobiology of addiction in a group where failures in inhibition have been shown to contribute to likelihood of relapse. Moreover, the use of multimodal neuroimaging and subsequent novel data fusion techniques will resolve a long-standing question in the gating literature, namely "where" and "when" the gating deficit occurs. Our long-term goal (planned R01 submission) is to evaluate the multi-modal imaging data as a predictor of treatment success, and to use task performance to identify a sub-group of patients where alternative treatment interventions should be considered. The minimal cognitive demands of this task also make it ideal for studying cocaine dependence in animals so that novel models of addiction can be developed and pharmacologically tested. Cocaine abuse continues to be a major health problem in the United States with approximately 1.8 million current users. Chronic cocaine abuse and dependence are associated with major medical, neurological, neuropsychiatric, social and interpersonal complications for the individual, their support network and society at whole. This grant will utilize neuroimaging techniques to increase our understanding of the neurobiology of addiction and to determine whether these techniques may be a more sensitive measure and predictor of relapse amongst certain sub-groups of cocaine users
Project start date: 2007-08-06
Project end date: 2009-07-31
1R03DA022435-01A2 (2007): $256974
ATTENTIONAL DYSFUNCTION AND RECOVERY IN TRAUMATIC BRAIN INJURY (TBI)
Andrew Robert Mayer, Research Scientist
The Mind Research Network, Albuquerque, Nm 87106
Grant 5R21NS064464-02 from National Institute Of Neurological Disorders And Stroke
Abstract: A recent meta-analysis involving 1463 cases (39 different studies) of mild traumatic brain injury (TBI) indicated that cognitive dysfunction was typically present in the semi-acute phase of injury (effect size d = .54) but that no neuropsychological deficits were observable at three months post-injury. Of all cognitive deficits following mild TBI, difficulties with attention and distractibility are one of the most commonly reported, and observed, symptoms. However, the neuropathology underlying attentional dysfunction in the first few weeks of injury and the subsequent recovery process are currently understudied using newer neuroimaging techniques. The current application proposes to use neuropsychological testing and two laboratory measures (orienting and selective attention tasks) to quantify this attentional deficit, and functional magnetic resonance imaging (FMRI), diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS) to quantify the underlying neuronal changes that occur as a function of time in mild TBI. Specifically, 27 mild TBI patients and 15 non-cranial trauma controls will undergo neuropsychological testing and an extensive imaging battery 3 weeks and 3-5 months post injury. During the FMRI session, participants will be asked to perform a spatial orienting task and a task that requires them to process conflicting information from two sensory modalities (Numeric Stroop). To date, the vast majority of TBI neuroimaging studies have employed only a single imaging modality (MRS or FMRI or DTI), have selected patients without controlling for time post-injury or severity of injury, and have not studied patients longitudinally. Thus, the impact and innovation of the current proposal therefore lies on several levels. Foremost, it addresses an important gap in our current knowledge regarding the development of standardized protocols that are capable of capturing the dynamic neurological changes that occur after a mild TBI. Routine clinical imaging modalities (MRI and CT scans) are usually insensitive to both the neuronal pathology underlying acute cognitive deficits as well as to the subsequent recovery process that occurs in the majority (80-90%) of patients. Second, each of the selected imaging modalities contains different information about the functioning of different classes of neuronal tissues (i.e., FMRI = indirect measure of gray matter functioning and vasculature; DTI = measure of white matter integrity; MRS = direct measure of neuronal and axonal health). The combination of information from these three different imaging techniques is likely to be synergistic and exceed the sum of each individual modality alone. We will directly test this hypothesis by applying novel multivariate statistical techniques (joint independent component analyses; J-ICA) to the acquired imaging data. Finally, a longitudinal study of mild TBI during both the semi-acute and chronic phase using these neuroimaging modalities will provide the foundation for a human recovery model in TBI. While it is unlikely that neuroimaging techniques alone will ever be able to provide an independent objective diagnosis, it is likely that they will provide incremental information that will be important for both differential diagnosis and predictions about future outcome. Importantly, the realization of the above will be critical for eventually identifying the minority of mild TBI patients at risk for developing future complications so that intervention can occur acutely, when there is a better chance of success. In the United States alone, there are approximately 1.2 million mild traumatic brain injury (TBI) cases per year that result in an estimated cost of $56 billion dollars. The symptoms of mild TBI can range from severe physical and mental disability to subtle problems with attention, concentration, or emotional control. Cognitive difficulties are often present in the first few weeks of injury, but typically remit 3-5 months post injury in the majority (approximately 80-90%) of patients. The first step for understanding these cognitive difficulties is to develop biomarkers that are sensitive to neuronal injury and the subsequent recovery process. This will be critical not only for mild TBI, but also for more severe forms of TBI as well. However, the identification of the pathology underlying cognitive deficits in the acute or chronic phases of mild TBI is often subtle, and hard to detect with conventional imaging techniques such as CT or MRI. This suggests that the diagnostic utility and predictive validity of more research-based neuroimaging techniques, such as functional magnetic resonance imaging (FMRI), diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS) needs to be explored. The use of multiple neuroimaging techniques is crucial because different modalities measure different signals (e.g., hemodynamic, metabolic or electrophysiological) that originate from different tissue sources in the brain (e.g., white versus gray matter), which will be important for identifying the diffuse injuries that may occur following head trauma. It is likely that the underlying acute pathology is multifaceted and involves both white and gray matter, suggesting that sampling several different domains of neuronal integrity is a necessary first step to understanding the acute cognitive deficits as well as the subsequent normal recovery process. Moreover, these bio- markers may be useful for distinguishing the small percentage of mild TBI patients who continue to have cognitive problems due to the injury
Keywords: Acquired brain injury; Acute; Address; Affect; Age; Agitation; Animal Model; Animal Models and Related Studies; Anisotropy; Anterior; Area; Articulation; Attention; Attention Concentration; Attentional deficit; Auditory; BOLD response; Bilateral; Blood flow; Body Tissues; Brain; Brain Injuries; CAT Scan, X-Ray; CAT scan; CT X Ray; CT scan; Cell Communication and Signaling; Cell Signaling; Cephalic; Chronic; Chronic Phase; Cingulate Gyrus; Clinical; Clinical Trial Overviews; Cognitive; Cognitive Disturbance; Cognitive Impairment; Cognitive decline; Cognitive deficits; Cognitive function abnormal; Complex; Computed Tomography; Computerized Axial Tomography (Computerized Tomography); Computerized Tomography, X-Ray; Conflict; Conflict (Psychology); Control Groups; Corpus callosum splenium; Cranial; Craniocerebral Trauma; Creatine; Cues; Data; Data Pooling; Data Poolings; Delayed Memory; Development; Diagnosis; Diagnostic; Differential Diagnosis; Diffuse; Diffusion; Diffusion MRI; Diffusion Magnetic Resonance Imaging; Diffusion Weighted MRI; Disease; Disorder; Disturbance in cognition; Down-Regulation; Down-Regulation (Physiology); Downregulation; Dysfunction; EMI scan; Emotional; Employee Strikes; Encephalon; Encephalons; Excitement, Psychomotor; Exhibits; FLR; Failure (biologic function); Foundations; Frequencies (time pattern); Frequency; Functional Imaging; Functional Magnetic Resonance Imaging; Functional disorder; Future; Gender; Glutamates; Glycine, N-(aminoiminomethyl)-N-methyl-; Gray; Gray unit of radiation dose; Group Processes; Gyrus Cinguli; H+ element; Head Injuries; Head Trauma; Health; Human; Human, General; Hydrogen Ions; Image; Imaging Procedures; Imaging Techniques; Impaired cognition; Individual; Inferior; Injuries, Craniocerebral; Injury; Intermediary Metabolism; Intervention; Intervention Strategies; Intracellular Communication and Signaling; Joints; Knowledge; L-Glutamate; LBUL; Laboratories; Lobule; Longitudinal Studies; METBL; MR Imaging; MR Spectroscopy; MR Tomography; MRI; MRI, Functional; MRS; MRSI; Magnetic Resonance Imaging; Magnetic Resonance Imaging Scan; Magnetic Resonance Imaging, Functional; Magnetic Resonance Spectroscopy; Man (Taxonomy); Man, Modern; Maps; Measurable; Measurement; Measures; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; Memory; Memory, Delayed; Meta-Analyses; Meta-Analysis; Metabolic; Metabolic Processes; Metabolism; Methods and Techniques; Methods, Other; Minority; Modality; Modeling; Motor; Multimodal Imaging; Multimodality; N-acetyl aspartate; N-acetyl-L-aspartate; N-acetylaspartate; NMR Imaging; NMR Tomography; Nature; Nerve Cells; Nerve Unit; Nervous; Nervous System, Brain; Neural Cell; Neurocyte; Neurologic; Neurological; Neuronal Injury; Neurons; Neuropsychologic Tests; Neuropsychological Tests; Nuclear Magnetic Resonance Imaging; Occupational; Outcome; Parietal; Participant; Pathology; Patients; Patients with traumatic brain injury; Performance; Phase; Physiologic Imaging; Physiopathology; Population; Post-Concussion Symptoms; Post-Concussion Syndrome; Post-Concussive Symptoms; Post-Concussive Syndrome; Prefrontal Cortex; Process; Protocol; Protocols documentation; Protons; Psyche structure; Psychomotor Agitation; Psychomotor Hyperactivity; Psychomotor Restlessness; Reaction Time; Recovery; Recovery of Function; Recruitment Activity; Regression Analyses; Regression Analysis; Regression Diagnostics; Relative; Relative (related person); Reporting; Research; Research Resources; Residual; Residual state; Resources; Response RT; Response Time; Restlessness; Risk; Sample Size; Sampling; Science of neurophysiology; Selective inattention; Sensory; Services; Severities; Signal Transduction; Signal Transduction Systems; Signaling; Source; Staging; Statistical Regression; Stimulus; Strikes; Strikes, Employee; Structure; Structure of cingulate gyrus; Sum; Symptoms; Syndrome; TBI Patients; Technics, Imaging; Techniques; Testing; Time; Tissues; Tomodensitometry; Tomography, Xray Computed; Trail Making Test; Trauma; Trauma, Brain; Traumatic Brain Injury; Traumatic encephalopathy; United States; Up-Regulation; Up-Regulation (Physiology); Upregulation; Work; X-Ray Computed Tomography; Zeugmatography; base; behavior measurement; behavioral measure; behavioral measurement; biological signal transduction; biomarker; blood oxygenation level dependent response; brain damage; brain lesion (from injury); catscan; cingulate gyrus; cognitive dysfunction; cognitive loss; cognitive rehab; cognitive rehabilitation; cognitively impaired; computed axial tomography; computerized axial tomography; computerized tomography; cost; diffusion tensor imaging; disability; disease/disorder; experience; fMRI; failure; functional recovery; gray matter; hemodynamics; imaging; imaging modality; improved; in vivo; indexing; injured; innovate; innovation; innovative; interventional strategy; long-term study; mental; model organism; myoinositol; neural; neural mechanism; neuroimaging; neuromechanism; neuron injury; neuronal; neuropathology; neurophysiology; neuropsychological; novel; ocular motor; ocularmotor; oculomotor; pathophysiology; psychomotor reaction time; public health relevance; recruit; relating to nervous system; response; selective attention; social group process; standardize measure; substantia alba; substantia grisea; success; tool; traumatic brain damage; white matter
Relevance: In the United States alone, there are approximately 1.2 million mild traumatic brain injury (TBI) cases per year that result in an estimated cost of $56 billion dollars. The symptoms of mild TBI can range from severe physical and mental disability to subtle problems with attention, concentration, or emotional control. Cognitive difficulties are often present in the first few weeks of injury, but typically remit 3-5 months post injury in the majority (approximately 80-90%) of patients. The first step for understanding these cognitive difficulties is to develop biomarkers that are sensitive to neuronal injury and the subsequent recovery process. This will be critical not only for mild TBI, but also for more severe forms of TBI as well. However, the identification of the pathology underlying cognitive deficits in the acute or chronic phases of mild TBI is often subtle, and hard to detect with conventional imaging techniques such as CT or MRI. This suggests that the diagnostic utility and predictive validity of more research-based neuroimaging techniques, such as functional magnetic resonance imaging (FMRI), diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS) needs to be explored. The use of multiple neuroimaging techniques is crucial because different modalities measure different signals (e.g., hemodynamic, metabolic or electrophysiological) that originate from different tissue sources in the brain (e.g., white versus gray matter), which will be important for identifying the diffuse injuries that may occur following head trauma. It is likely that the underlying acute pathology is multifaceted and involves both white and gray matter, suggesting that sampling several different domains of neuronal integrity is a necessary first step to understanding the acute cognitive deficits as well as the subsequent normal recovery process. Moreover, these bio- markers may be useful for distinguishing the small percentage of mild TBI patients who continue to have cognitive problems due to the injury
Project start date: 2009-03-01
Project end date: 2011-02-28
Budget start date: 1-MAR-2010
Budget end date: 28-FEB-2011
PFA/PA: PA-06-181
5R21NS064464-02 (2010): $196027