Diagnosing TBI, Biomarkers, Electrical NeuroImaging and EEG Networks

Diagnosing TBI, Biomarkers, Electrical NeuroImaging and EEG Networks Robert W. Thatcher, Ph.D. NeuroImaging Laboratory Applied Neuroscience, Inc. St. Petersburg, FL

Tau and CTE are not Valid nor Sensitive nor Necessary to Determine Mild to Severe TBI The New CTE/Tau Definition of TBI Ignores 30 Years of Neuroscience and Thousands of Scientific Publications that are > 95% Accurate in the Detection of TBI without the Necessity of an Autopsy

Essential Steps in Helping Patients with TBI & Neurological/Psychological Problems Symptoms Clinical History Assessment Treatment QEEG DTI MRI fmri PET Neurofeedback HPN tdcs rtms Medication

An EEG Severity Index of Traumatic Brain Injury Robert W. Thatcher, Ph.D. Duane M. North, M.S. Richard T. Curtin, B.A. Rebecca A. Walker, B.S. Carl J. Biver, Ph.D. Juan F. Gomez, B.A. Andres M. Salazar, M.D. Defense and Veterans Head Injury Program (DVHIP) J Neuropsychiatry Clin Neurosci, 13:1, Winter 2001

NEUROIMAGE 7, 352-367 (1998) ARTICLE NO. N1980330 Biophysical Linkage between MRI and EEG Amplitude in Close Head Injury R. W. Thatcher,* 1 C. Biver, R. McAlaster, M. Camacho,* and A. Salazar *Bay Pines VA Medical Center, Bay Pines, FL 33774; and Defense and Veterans Head Injury Program, Washington, DC 20307

Brodmann Areas and Symptoms Frontal Lobe Thinking, Planning, Executive Functions, Motor Execution, Mood Control Parietal Lobe Somatosensory Perception Integration of Visual and Somatospatial Information Temporal Lobe Language Function and Auditory Perception Involved in Long Term Memory and Emotion Occipital Lobe Visual Perception & Spatial Processing Posterior Cingulate Long-term Memory, Attention Anterior Cingulate Gyrus Volitional Movement, Attention, Long Term Memory Parahippocampal Gyrus Short-term Memory, Attention

Electrical Neuroimaging and Cortical Source Localization Horizontal, Sagital & Coronal Views of a Single Slice Cortical Surface Projection Tomographic Slice Display

Electrical Neuroimaging Assessment and Treatment Advantages of Electrical Neuroimaging: 1 - Spatial Resolution 1 cm to 3 cm 2 - Temporal Resolution 1 msec 3 - Imaging of Current Sources 4 - Imaging of Network Connections 5 - Integration with DTI & fmri (Brodmann Areas) 6 - Inexpensive ($10,000 vs $3,000,000) 7 - Dry Electrodes & Wireless Caps 8 - Portable 9 - Integration with Smart Phones & Tablets 10 - Can Assess & Treat in Real-Time

How are Neurons Selected and then Synchronized in Different Functional Modules and Hubs? Answer: Phase Shift followed by Phase Locking

Reinforced with In-Phase Suppressed if Out-of-phase

In-Phase to LFP vs Anti-Phase Switching to the Neocortex In-Phase is Reinforced Out-of-Phase Is Suppressed In-Phase is Reinforced Out-of-Phase Is Suppressed

The Brain Is Organized by Clusters of Neurons called Modules and Hubs

Symptoms are Related to Dysregulation of Nodes and Connections Between Nodes

Loreta Default Brain Network

EEG Phase Reset as a Phase Transition in the Time Domain 90 0 r 1 r 2 ϕ Phase difference at t 1, t 2, t 3, t 4 = 45 0 0 0 Phase difference at t 5, t 6, t 7, t 8 = 10 0 1 st Derivative of Phase-Difference + 0 - Negative 1 st Derivative 1 2 3 4 5 6 7 8 Time Phase difference at t 5, t 6, t 7, t 8 = 135 0 r 2 r 1 ϕ Phase difference at t 1, t 2, t 3, t 4 = 45 0 1st Derivative of Phase-Difference + 0-1 2 3 4 5 6 7 8 Time Positive 1st Derivative

Phase Reset Metrics

Phase Shift Fp1-Fp1 Phase Difference in Degrees Fp1-F3 Fp1-C3 Fp1-P3 Fp1-O1 Fp1-Fp1 1 st Derivative deg/100 msec Phase Shift Duration Fp1-F3 Fp1-C3 Phase Synchrony Interval Fp1-P3 Fp1-O1 1 st Derivative deg/100 msec

14.45 15.45 16.22 14.45 15.45 16.22 LEFT Anterior - Posterior 24 cm 2.59 3.49 4.45 5.50 6.49 7.52 8.40 9.56 10.44 11.46 12.52 13.51 14.45 15.45 16.22 AGEs (0.44 16.22 Years) 1.61 0.44 70 65 60 55 50 45 40 70 65 RIGHT Anterior - Posterior 24 cm 60 55 50 AGEs (0.44 16.22 Years) milliseconds milliseconds 45 40 13.51 0.44 1.61 2.59 3.49 4.45 5.50 6.49 7.52 8.40 9.56 10.44 11.46 12.52 LEFT Posterior - Anterior 24 cm 2.59 3.49 4.45 5.50 6.49 7.52 8.40 9.56 10.44 11.46 12.52 13.51 14.45 15.45 16.22 AGEs (0.44 16.22 Years) 1.61 0.44 70 65 60 55 50 45 40 Development of Phase Shift Duration 6 cm 6 cm 6 cm 12 cm 18 cm 24 cm 70 65 RIGHT Posterior - Anterior 24 cm 60 55 50 AGEs (0.44 16.22 Years) milliseconds milliseconds 6 cm 13.51 0.44 1.61 2.59 3.49 4.45 45 40 6 cm 5.50 6.49 7.52 8.40 9.56 10.44 11.46 12.52

13.51 14.45 15.45 16.22 13.51 14.45 15.45 16.22 Development of Phase Synchrony Interval LEFT Anterior - Posterior 6 cm 4.45 5.50 6.49 7.52 8.40 9.56 10.44 11.46 12.52 13.51 14.45 15.45 16.22 AGEs (0.44 16.22 Years) 6 cm 12 cm 18 cm 24 cm 3.49 2.59 1.61 450 400 350 300 250 200 150 100 450 400 RIGHT Anterior - Posterior 6 cm 350 300 250 AGEs (0.44 16.22 Years) 0.44 milliseconds milliseconds 200 150 100 0.44 1.61 2.59 3.49 4.45 5.50 6.49 7.52 8.40 9.56 10.44 11.46 12.52 LEFT Posterior - Anterior 6 cm 4.45 5.50 6.49 7.52 8.40 9.56 10.44 11.46 12.52 13.51 14.45 15.45 16.22 AGEs (0.44 16.22 Years) 3.49 2.59 1.61 450 400 350 300 250 200 150 100 24 cm 24 cm 450 400 RIGHT Posterior - Anterior 6 cm 350 300 250 AGEs (0.44 16.22 Years) 0.44 milliseconds milliseconds 200 0.44 1.61 2.59 3.49 4.45 24 cm 150 100 24 cm 5.50 6.49 7.52 8.40 9.56 10.44 11.46 12.52

Published in NeuroImage, 42(4): 1639-1653, 2008. INTELLIGENCE AND EEG PHASE RESET: A TWO COMPARTMENTAL MODEL OF PHASE SHIFT AND LOCK Thatcher, R. W. 1,2, North, D. M. 1, and Biver, C. J. 1 EEG and NeuroImaging Laboratory, Applied Neuroscience Research Institute. St. Petersburg, FL 1 and Department of Neurology, University of South Florida College of Medicine, Tampa, FL 2

Regressions & Correlations of Phase Shift Duration Short Distances (6 cm) IQ = 78 + 13.78 x (msec) IQ = 70 +11.85 x (msec) IQ = 75 + 24.45 x (msec) IQ = 68 + 34.40 x (msec) r =.876 @ p<.01 r =.954 @ p<.0001 r =.868 @ p<.01 r =.874 @ p<.01 Regressions & Correlations of Phase Locking Interval Short Distances (6 cm) IQ = 143-3.11 x (msec) IQ = 142-3.36 x (msec) IQ = 132-4.57 x (msec) IQ = 140-20.08 x (msec) r = -.875 @ p<.01 r = -.930 @ p<.001 r = -.895 @ p<.01 r = -.985 @ p<.0001

Pyramidal Cell Model of EEG Phase Reset and Full Scale I.Q. High Phase Lock Duration (LD) LFP Full Scale I.Q. Distant EPSP Loop Connections LD Low 150 250 350 Local IPSP Connections SD Average EPSP Duration Average Φ = Θ LFP Θ Pr ef LD SD High Full Scale I.Q. Time (msec) Phase Shift Duration (SD) Low 40 50 60 Time (msec)

This is a preprint of an article to be published in Frontiers in Physiology (2014) 3-DIMENSIONAL PHASE RESET OF BRODMANN AREAS OF THE DEFAULT NETWORK Thatcher, R.W. North, D.M. and Biver, C. J. EEG and NeuroImaging Laboratory, Applied Neuroscience, Inc., St. Petersburg, Fl

DTI Shows Six Major Modules and Hubs

Correlations Between EEG Neuroimaging and Diffusion Spectral Imaging (DTI)

Medial View

LORETA Coherence

LORETA Absolute Phase

Essentials of Operant Conditioning 1 - There must be a real & valid neural event to be reinforced 2 - The Reinforcement must be distinct and clear 3 - The interval of time between the spontaneous emitted event & the reinforcement can not be too short, approx. < 250 msec? or too long approx. > 20 sec 4 - The Schedule of Reinforcement is Important with two General Types Continuous vs Partial Reinforcement - Continuous is good at the beginning but not as resistent to extinction as is Partial Reinforcement

Goal is Better Clinical Outcome & Fewer Sessions 80 60 Conventional Non-QEEG Guided NF 40 20 0 QEEG Guided NF Link Symptoms to Functional Systems in Brain 1960 2000 Future

Some Relevant Items and Questions Fact: The EEG is Produced Exclusively by Summated Synaptic Potentials Question - How does EEG Biofeedback Change Synaptic Potentials? Answer - Synapses are Changed by Neuromodulators (dopamine, seratonin, acetylcholing, etc.) by Operant Conditioning Question - How does NPH & Other Priming Techniques Work? Answer Whole Brain Phase Reset Eric Kandel In Search of Memory Norton & Co., 2006 Nobel Prize 2000 Gyorgy Buzsaki Rhythms of the Brain, Oxford Univ. Press, 2006

EEG Neurofeedback

A General Theory of EEG Operant Conditioning and Z Score Biofeedback Definitions 1 - Duration of Spontaneous EEG Event (E) = Neural State Interval (I) 2 - Contiguity Window ( C) = Time period preceding and following a E 3 - Reward Signal (S) = Feedback signal time locked to E 4 - Reward Strength ( R) = Value of the reward if N successes occur in an interval of time, e.g., toys, candy, cookies, money, etc. Category Duration of Spontaneous EEG Event (E) Contiguity Window (C) Reward Signal (S) Reward Strength (R) Measurement Neural State Interval (I) (msec) Time preceding/following E (msec sec) Feedback signal time locked to E (msec) Ordinal or Nominal measure

Seamless QEEG and Neurofeedback Approximately 50 60 minutes for a Single Session in Three Steps from Clinical Interview to QEEG to Neurotherapy Step #2 30 min. Record EEG, Edit EEG & Symptom Check List Match Step #1 10 min. Clinician Step #3 20 min. Interview Symptom Check List Neurofeedback

Neuroimaging Neurofeedback Symptom Check List Click Symptoms or Neuropsychological Diagnoses or Dod/VA List or Networks & Severity List of Matching Brodmann Areas List of Symptoms Anatomical Hypotheses

Progress Charts to be Monitored by a Clinician During Neurofeedback

Non-Invasive Treatment of TBI and Other Clinical Disorders 1 - EEG Neurofeedback uses Operant Conditioning to Reinforce Increased Stability and Efficiency of Information Processing in Nodes and Connections Between Nodes of Networks 2 - High Performance Neurofeedback and Magnetic and Electrical Simulation Reset Phase Relations and Prime the Brain To Self-Modify or Change by Neurofeedback

Neuroimaging Neurofeedback US Army Fort Campbell- Warrior Resilience Program Amplifier A/D Conv Computer Feedback Display-Sound Video & Sound Control Variable & Threshold Z Score DLL Coherence & Phase Current Sources Symptom Check List

Examples of Surface EEG Changes After EEG Neurofeedback Pre-Treatment Post 10 Treatments TBI Subject #1 TBI Subject #2

Examples of Electrical Neuroimaging After Neurofeedback Pre-Treatment Post 10 Treatments S #1 S #2

CHANGES IN DELTA PHASE SHIFT DURATION AFTER 12 MINUTES OF TRAINING

CHANGES IN THETA PHASE SHIFT DURATION AFTER 12 MINUTES OF TRAINING

Inferior Frontal GM (green), Lateral Orbital Gyrus (yellow) and Cingulate (red), overlaid on 3D rendering of Mr. Krynski s MRI scan. From Christos Davatzikos, Ph.D. Professor of Radiology, Univ. of Penn.

Volumes of several brain structures were well below average. Volumetric measurements were first normalized for total brain volume, in order to account for head size variations and to obtain more accurate estimates of focal abnormalities. A z-score of -2.5 (as the one in several brain regions) would be found in less than 0.25% of the normal population. From Christos Davatzikos, Ph.D. Professor of Radiology, Univ of Penn.

This plot indicates a loss of approximately 24% over 58 years in the normative population. Mr. Krynski s loss of 23.6% would therefore correspond to brain loss that would occur by approximately 57 years of normal aging i.e. the volume of his left inferior frontal GM would be expected to be seen at age 98, based on the evolume of his right inferior GM. From Christos Davatzikos, Ph.D. Professor of Radiology, Univ of Penn

LORETA Delta Frequency 3 Hz QEEG Consistent with DTI and Volumetric MRI

QEEG Consistent with DTI and Volumetric MRI LORETA Theta Frequency 6 Hz

BrainSurfer and Brain-Computer-Interface (BCI) Technology

Select a Network, Frequency and Metric