Validation of a global live z-score protocol: mechanism, within-subject results, and a randomized controlled study Society for Applied Neuroscience May 5, 2011 – Thessaloniki, Greece Thomas F. Collura, Ph.D., QEEG-D BrainMaster Technologies The Brain Enrichment Center Bedford, Ohio (C) 2011 Thomas F. Collura, Ph.D. &/or E. Festa, Brown University

Acknowledgement Elena Festa, Ph.D. Elena Festa, Ph.D. William Heindel, Ph.D. William Heindel, Ph.D. Department of Cognitive, Linguistic, and Psychological Sciences Department of Cognitive, Linguistic, and Psychological Sciences Brown University, Providence, Rhode Island Brown University, Providence, Rhode Island Alzheimer’s Association, USA Alzheimer’s Association, USA (C) 2011 Thomas F. Collura, Ph.D. &/or E. Festa, Brown University

Validation Principles Controlled Conditions Controlled Conditions Record physiological & behavioral variables Record physiological & behavioral variables Demonstrate physiological change Demonstrate physiological change Demonstrate behavioral change Demonstrate behavioral change Confirm principles of operation Confirm principles of operation (C) 2011 Thomas F. Collura, Ph.D. &/or E. Festa, Brown University

Validation Specifics Metric based upon QEEG parameters Metric based upon QEEG parameters Live feedback of derived computations Live feedback of derived computations Operant learning of brain Operant learning of brain Demonstrable expected EEG changes Demonstrable expected EEG changes Demonstrable clinical / behavioral changes Demonstrable clinical / behavioral changes (C) 2011 Thomas F. Collura, Ph.D. &/or E. Festa, Brown University

Live Z-Score Principles Normalization of QEEG-based parameters Normalization of QEEG-based parameters Resulting change in brain function Resulting change in brain function “Normal” reference database “Normal” reference database Anatomy, Physiology, Logic Anatomy, Physiology, Logic Activation AND Connectivity changes Activation AND Connectivity changes “First Order” Changes – “expected” “First Order” Changes – “expected” Secondary / Compensating Changes Secondary / Compensating Changes (C) 2011 Thomas F. Collura, Ph.D. &/or E. Festa, Brown University

Possible Changes – “Phenotypes” Normalize aberrant process Normalize aberrant process Focal or Global abnormalities Focal or Global abnormalities Depression, Anxiety, Attention Depression, Anxiety, Attention Normalize coping/compensating mech. Normalize coping/compensating mech. Denial, Masking, Hyperconnection (injury) Denial, Masking, Hyperconnection (injury) PTST, chronic pain, chronic anxiety PTST, chronic pain, chronic anxiety Normalize “Peak performance” mechanism Normalize “Peak performance” mechanism “High” SMR, “Fast” Alpha “High” SMR, “Fast” Alpha Hypercoherence, Hypocoherence Hypercoherence, Hypocoherence (C) 2011 Thomas F. Collura, Ph.D. &/or E. Festa, Brown University

Validation Stages Single subject – Within Session Single subject – Within Session Single subject – Across Sessions Single subject – Across Sessions Across subjects – Within Session Across subjects – Within Session Across subjects – Across Sessions Across subjects – Across Sessions Physiological AND Behavioral observations Physiological AND Behavioral observations (C) 2011 Thomas F. Collura, Ph.D. &/or E. Festa, Brown University

Single Subject - Within Session Individual Z-Scores (C) 2011 Thomas F. Collura, Ph.D. &/or E. Festa, Brown University

Single Subject – Within Session Aggregate (All) Z-Scores (C) 2011 Thomas F. Collura, Ph.D. &/or E. Festa, Brown University

Subjective Change “More aware of my pain” “More aware of my pain” (Chronic Pain) (Chronic Pain) Normalization of abnormal alpha Normalization of abnormal alpha Removal of coping mechanism Removal of coping mechanism (C) 2011 Thomas F. Collura, Ph.D. &/or E. Festa, Brown University

Single Subject – Across Sessions (Guan) (C) 2011 Thomas F. Collura, Ph.D. &/or E. Festa, Brown University

Clinical Changes - Guan Reduction of Anxiety Reduction of Anxiety Reduction of Depression Reduction of Depression Improved ability to study Improved ability to study Improved ability to return to work Improved ability to return to work (C) 2011 Thomas F. Collura, Ph.D. &/or E. Festa, Brown University

Single Subject – Across Sessions (Lambos) (C) 2011 Thomas F. Collura, Ph.D. &/or E. Festa, Brown University

Clinical Changes - Lambos ADHD / Defiant / Violent ADHD / Defiant / Violent Reduction in violent outbursts Reduction in violent outbursts Improved ability to pay attention Improved ability to pay attention Increased compassion with others Increased compassion with others Ability to transfer to regular class Ability to transfer to regular class (C) 2011 Thomas F. Collura, Ph.D. &/or E. Festa, Brown University

Controlled Study Aging Population Aging Population Normal and Mild Alzheimer’s Normal and Mild Alzheimer’s N=79 N=79 Real NF: 4-channels: Cz C4 P3 P4 Real NF: 4-channels: Cz C4 P3 P4 Percent Z Scores (PZOK): 248 Z-Scores Percent Z Scores (PZOK): 248 Z-Scores Cognitive / Behavioral Measures Cognitive / Behavioral Measures (C) 2011 Thomas F. Collura, Ph.D. &/or E. Festa, Brown University

NFT Study in AD and Aging Train posterior sites to: Train posterior sites to: enhance cortical processing within posterior systems enhance cortical processing within posterior systems relieve burden of anterior systems to moderate deteriorated posterior system relieve burden of anterior systems to moderate deteriorated posterior system Investigate the short-term effects of NFT on neurocognitive measures of attention and sensory integration in healthy elderly and patients with early stage AD Investigate the short-term effects of NFT on neurocognitive measures of attention and sensory integration in healthy elderly and patients with early stage AD Compare performance of true-NFT vs. mock-NFT subjects Compare performance of true-NFT vs. mock-NFT subjects (C) 2011 Thomas F. Collura, Ph.D. &/or E. Festa, Brown University

Experimental Design Healthy elderly and AD patients assigned to either mock or true-NFT group Healthy elderly and AD patients assigned to either mock or true-NFT group Each mock-NFT subject demographically matched to a true-NFT subject Each mock-NFT subject demographically matched to a true-NFT subject 8 NFT sessions 8 NFT sessions 1-2 sessions/week over 4-6 weeks 1-2 sessions/week over 4-6 weeks Assessment battery pre & post NFT Assessment battery pre & post NFT Within 2 weeks of NFT sessions Within 2 weeks of NFT sessions (C) 2011 Thomas F. Collura, Ph.D. &/or E. Festa, Brown University

Healthy Elderly Participants GROUP N (m,f) AGEEDMMSERBANS NFT 20 (5,15) 71.6(8.1)16.0(3.3)28.8(1.1)108.2(12.2) Mock NFT 19 (3,16) 72.2(8.3)16.0(2.6)28.8(1.2)108.5(13.1) MMSE: Mini-Mental State Examination RBANS: Repeatable Battery for the Assessment of Neuropsychological Status (C) 2011 Thomas F. Collura, Ph.D. &/or E. Festa, Brown University

Mild AD Participants GROUP N (m,f) AGEEDMMSERBANS NFT 18 (8,10) 78.0(5.0)14.0(3.1)24.4(1.1)74.7(13.1) Mock NFT 12 (6,6) 77.5(6.4)14.0(2.6)25.4(1.2)79.3(9.7) MMSE: Mini-Mental State Examination RBANS: Repeatable Battery for the Assessment of Neuropsychological Status (C) 2011 Thomas F. Collura, Ph.D. &/or E. Festa, Brown University

NFT sessions NFT sessions Electrode sites: C3, C4, P3, P4 Electrode sites: C3, C4, P3, P4 10 min. % z-score ok training 10 min. % z-score ok training 5 min. baseline (eyes closed) pre & post 5 min. baseline (eyes closed) pre & post Brainwave activity recorded with Atlantis I (4+4) system (BrainMaster Technologies, Inc.) Brainwave activity recorded with Atlantis I (4+4) system (BrainMaster Technologies, Inc.) Real-time z-score neurofeedback training provided by using the Z score DLL (Applied Neuroscience, Inc.) in conjunction with Brainmaster 3.21 software (BrainMaster Technologies, Inc.) Real-time z-score neurofeedback training provided by using the Z score DLL (Applied Neuroscience, Inc.) in conjunction with Brainmaster 3.21 software (BrainMaster Technologies, Inc.) Methods (C) 2011 Thomas F. Collura, Ph.D. &/or E. Festa, Brown University

Training Regimen Training Regimen Sessions 1-4 Sessions % of z-scores within 1 STD of normative range 75% of z-scores within 1 STD of normative range Sessions 5-8 Sessions % of z-scores within 1 STD of normative range 80% of z-scores within 1 STD of normative range Audiovisual feedback provided through continuous modulation of the picture contrast of an IMAX nature movie and organ tones when reward criterion sustained for 500 ms Audiovisual feedback provided through continuous modulation of the picture contrast of an IMAX nature movie and organ tones when reward criterion sustained for 500 ms Mock-NFT subjects received feedback in each NFT session based on the recorded brainwave activity across each NFT session of the matched true-NFT subjects Mock-NFT subjects received feedback in each NFT session based on the recorded brainwave activity across each NFT session of the matched true-NFT subjects Methods (C) 2011 Thomas F. Collura, Ph.D. &/or E. Festa, Brown University

Assessment Battery Assessment Battery Several standardized neuropsychological tests of cognitive functions and emotional well-being (RBANS, CAD, GDS) Several standardized neuropsychological tests of cognitive functions and emotional well-being (RBANS, CAD, GDS) Resting brainwave activity 64-channel EEG recording (eyes closed) Resting brainwave activity 64-channel EEG recording (eyes closed) Behavioral and EEG measures of neurocognitive tests assessing specific component attentional processes Behavioral and EEG measures of neurocognitive tests assessing specific component attentional processes Methods (C) 2011 Thomas F. Collura, Ph.D. &/or E. Festa, Brown University

Neurocognitive Measures Alerting, Orienting, & Executive Control Alerting, Orienting, & Executive Control Spatial Orienting/Simon Interference task Spatial Orienting/Simon Interference task Selective Attention & Sensory Integration Selective Attention & Sensory Integration Visual Search task Visual Search task (C) 2011 Thomas F. Collura, Ph.D. &/or E. Festa, Brown University

Visual Search: Selective Attention and Sensory Integration Set Size 1Set Size 3Set Size 5 (C) 2011 Thomas F. Collura, Ph.D. &/or E. Festa, Brown University

Visual Search and Sensory Integration: Healthy Elderly (C) 2011 Thomas F. Collura, Ph.D. &/or E. Festa, Brown University

Visual Search and Sensory Integration: Mild AD (C) 2011 Thomas F. Collura, Ph.D. &/or E. Festa, Brown University

Results: Visual Search Healthy Elderly Healthy Elderly Real NFT decreased RTs for both sensory binding conditions Real NFT decreased RTs for both sensory binding conditions Mock NFT had no effect on RTs for either binding conditions Mock NFT had no effect on RTs for either binding conditions Mild AD Mild AD Real NFT had no effect on RTs for either binding conditions Real NFT had no effect on RTs for either binding conditions Mock NFT had no effect on RTs for either binding conditions Mock NFT had no effect on RTs for either binding conditions (C) 2011 Thomas F. Collura, Ph.D. &/or E. Festa, Brown University

Simon Interference Congruent Covert Orienting/Simon Interference LEFT Incongruent (C) 2011 Thomas F. Collura, Ph.D. &/or E. Festa, Brown University

Orienting Alerting Double Invalid LEFT Valid No Cue LEFT (C) 2011 Thomas F. Collura, Ph.D. &/or E. Festa, Brown University

Effects of NFT on Simon Interference Healthy ElderlyMild AD (C) 2011 Thomas F. Collura, Ph.D. &/or E. Festa, Brown University

Results: Simon Interference Healthy Elderly Healthy Elderly Real NFT had no effect on RTs for either Congruent or Incongruent trials Real NFT had no effect on RTs for either Congruent or Incongruent trials Mock NFT increased RTs for both Congruent and Incongruent trials Mock NFT increased RTs for both Congruent and Incongruent trials Mild AD Mild AD Real NFT had no significant effect on RTs for either Congruent or Incongruent trials Real NFT had no significant effect on RTs for either Congruent or Incongruent trials Mock NFT had no significant effect on RTs for either Congruent or Incongruent trials Mock NFT had no significant effect on RTs for either Congruent or Incongruent trials (C) 2011 Thomas F. Collura, Ph.D. &/or E. Festa, Brown University

Effects of NFT on Spatial Orienting Healthy ElderlyMild AD (C) 2011 Thomas F. Collura, Ph.D. &/or E. Festa, Brown University

Results: Spatial Orienting Healthy Elderly Healthy Elderly Real NFT reduced RTs for both Valid and Invalid Cue trials Real NFT reduced RTs for both Valid and Invalid Cue trials Mock NFT increased RTs for both Valid and Invalid Cue trials Mock NFT increased RTs for both Valid and Invalid Cue trials Mild AD Mild AD Real NFT selectively reduced RTs for Invalid Cue trials Real NFT selectively reduced RTs for Invalid Cue trials Mock NFT had no effect on RTs for either Valid or Invalid Cue trials Mock NFT had no effect on RTs for either Valid or Invalid Cue trials (C) 2011 Thomas F. Collura, Ph.D. &/or E. Festa, Brown University

Effects of NFT on Alerting Healthy ElderlyMild AD (C) 2011 Thomas F. Collura, Ph.D. &/or E. Festa, Brown University

Results: Alerting Healthy Elderly Healthy Elderly Real NFT had no effect on RTs for either Double or No Cue trials Real NFT had no effect on RTs for either Double or No Cue trials Mock NFT selectively increased RTs for No Cue Cue trials Mock NFT selectively increased RTs for No Cue Cue trials Mild AD Mild AD Real NFT reduced RTs for both Double and No Cue Trials Real NFT reduced RTs for both Double and No Cue Trials Mock NFT increased RTs for both Double and No Cue Trials Mock NFT increased RTs for both Double and No Cue Trials (C) 2011 Thomas F. Collura, Ph.D. &/or E. Festa, Brown University

Summary: Real NFT Healthy Elderly Healthy Elderly No effect on cross-cortical sensory integration, but enhanced selective attention in the visual search task No effect on cross-cortical sensory integration, but enhanced selective attention in the visual search task Generalized enhancement of response times in spatial orienting Generalized enhancement of response times in spatial orienting No effect on either alerting measures or response inhibition in Simon interference No effect on either alerting measures or response inhibition in Simon interference Mild AD Mild AD No effect on either cross-cortical sensory integration or selective attention measures in the visual search task No effect on either cross-cortical sensory integration or selective attention measures in the visual search task Selective improvement in disengagement in spatial orienting Selective improvement in disengagement in spatial orienting Enhanced phasic and tonic alerting Enhanced phasic and tonic alerting No effect on response inhibition in Simon interference No effect on response inhibition in Simon interference (C) 2011 Thomas F. Collura, Ph.D. &/or E. Festa, Brown University

Summary: Mock NFT Healthy Elderly Healthy Elderly No effect on cross-cortical sensory integration or selective attention in the visual search task No effect on cross-cortical sensory integration or selective attention in the visual search task Generalized slowing of response times for spatial orienting, alerting and Simon interference measures Generalized slowing of response times for spatial orienting, alerting and Simon interference measures Mild AD Mild AD No effect on cross-cortical sensory integration or selective attention in the visual search task No effect on cross-cortical sensory integration or selective attention in the visual search task No effect on response times for spatial orienting or Simon interference measures No effect on response times for spatial orienting or Simon interference measures Generalized slowing of response times for the alerting measures Generalized slowing of response times for the alerting measures (C) 2011 Thomas F. Collura, Ph.D. &/or E. Festa, Brown University

Non-Memory Impairments in AD Attention Attention Cognitive operations involved in the detection and selection of sensory information Cognitive operations involved in the detection and selection of sensory information Automatic (stimulus-driven) Automatic (stimulus-driven) Voluntary (controlled, goal-directed) Voluntary (controlled, goal-directed) Different attentional processes mediated by distinct neural subsystems Different attentional processes mediated by distinct neural subsystems Sensory Integration Sensory Integration The “Binding Problem” The “Binding Problem” Moment-by-moment ability to combine distinct sensory inputs related to a single object into a coherent, unified representation Moment-by-moment ability to combine distinct sensory inputs related to a single object into a coherent, unified representation Dependent upon effective interactions across cortical areas Dependent upon effective interactions across cortical areas (C) 2011 Thomas F. Collura, Ph.D. &/or E. Festa, Brown University

Non-Memory Impairments in AD (and Aging) Posterior Cortical Processing Systems Posterior Cortical Processing Systems Alerting (cortical tonus) Alerting (cortical tonus) Orienting Orienting Sensory Integration Sensory Integration Inefficient cortical processing in Aging Inefficient cortical processing in Aging Corticocortical disconnectivity in AD Corticocortical disconnectivity in AD Anterior Executive Control Processes Anterior Executive Control Processes Changes in frontal cortex with age and AD results in less efficient controlled attentional processes Changes in frontal cortex with age and AD results in less efficient controlled attentional processes Greater demands placed on anterior executive processes to moderate deterioration in posterior attentional and sensory systems Greater demands placed on anterior executive processes to moderate deterioration in posterior attentional and sensory systems (C) 2011 Thomas F. Collura, Ph.D. &/or E. Festa, Brown University