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

Acknowledgement Elena Festa, Ph.D. William Heindel, Ph.D. Department of Cognitive, Linguistic, and Psychological Sciences Brown University, Providence, Rhode Island Alzheimer’s Association, USA

Validation Principles Controlled Conditions Record physiological & behavioral variables Demonstrate physiological change Demonstrate behavioral change Confirm principles of operation

Validation Specifics Metric based upon QEEG parameters Live feedback of derived computations Operant learning of brain Demonstrable expected EEG changes Demonstrable clinical / behavioral changes

Live Z-Score Principles Normalization of QEEG-based parameters Resulting change in brain function “Normal” reference database Anatomy, Physiology, Logic Activation AND Connectivity changes “First Order” Changes – “expected” Secondary / Compensating Changes

Possible Changes – “Phenotypes” Normalize aberrant process Focal or Global abnormalities Depression , Anxiety, Attention Normalize coping/compensating mech. Denial, Masking, Hyperconnection (injury) PTST, chronic pain, chronic anxiety Normalize “Peak performance” mechanism “High” SMR, “Fast” Alpha Hypercoherence, Hypocoherence

Validation Stages Single subject – Within Session Single subject – Across Sessions Across subjects – Within Session Across subjects – Across Sessions Physiological AND Behavioral observations

Single Subject - Within Session Individual Z-Scores

Single Subject – Within Session Aggregate (All) Z-Scores

Subjective Change “More aware of my pain” (Chronic Pain) Normalization of abnormal alpha Removal of coping mechanism

Single Subject – Across Sessions (Guan)

Clinical Changes - Guan Reduction of Anxiety Reduction of Depression Improved ability to study Improved ability to return to work

Single Subject – Across Sessions (Lambos)

Clinical Changes - Lambos ADHD / Defiant / Violent Reduction in violent outbursts Improved ability to pay attention Increased compassion with others Ability to transfer to regular class

Controlled Study Aging Population Normal and Mild Alzheimer’s N=79 Real NF: 4-channels: Cz C4 P3 P4 Percent Z Scores (PZOK): 248 Z-Scores Cognitive / Behavioral Measures

NFT Study in AD and Aging Train posterior sites to: enhance cortical processing within posterior systems 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 Compare performance of true-NFT vs. mock-NFT subjects

Experimental Design Healthy elderly and AD patients assigned to either mock or true-NFT group Each mock-NFT subject demographically matched to a true-NFT subject 8 NFT sessions 1-2 sessions/week over 4-6 weeks Assessment battery pre & post NFT Within 2 weeks of NFT sessions

Healthy Elderly Participants GROUP N (m,f) AGE ED MMSE RBANS 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) (2.6) (1.2) 108.5 (13.1) MMSE: Mini-Mental State Examination RBANS: Repeatable Battery for the Assessment of Neuropsychological Status

Mild AD Participants GROUP N (m,f) AGE ED MMSE RBANS 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) (2.6) 25.4 (1.2) 79.3 (9.7) MMSE: Mini-Mental State Examination RBANS: Repeatable Battery for the Assessment of Neuropsychological Status

Methods NFT sessions Electrode sites: C3, C4, P3, P4 10 min. % z-score ok training 5 min. baseline (eyes closed) pre & post 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.)

Methods Training Regimen Sessions 1-4 Sessions 5-8 75% of z-scores within 1 STD of normative range Sessions 5-8 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 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 Assessment Battery Several standardized neuropsychological tests of cognitive functions and emotional well-being (RBANS, CAD, GDS) Resting brainwave activity 64-channel EEG recording (eyes closed) Behavioral and EEG measures of neurocognitive tests assessing specific component attentional processes

Neurocognitive Measures Alerting, Orienting, & Executive Control Spatial Orienting/Simon Interference task Selective Attention & Sensory Integration Visual Search task

Visual Search: Selective Attention and Sensory Integration Set Size 1 Set Size 3 Set Size 5

Visual Search and Sensory Integration: Healthy Elderly

Visual Search and Sensory Integration: Mild AD

Results: Visual Search Healthy Elderly Real NFT decreased RTs for both sensory binding conditions Mock NFT had no effect on RTs for either binding conditions Mild AD Real NFT had no effect on RTs for either binding conditions

Covert Orienting/Simon Interference LEFT Congruent LEFT Incongruent

Orienting LEFT Valid LEFT Invalid Alerting LEFT No Cue LEFT Double

Effects of NFT on Simon Interference Healthy Elderly Mild AD

Results: Simon Interference Healthy Elderly Real NFT had no effect on RTs for either Congruent or Incongruent trials Mock NFT increased RTs for both Congruent and Incongruent trials Mild AD 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

Effects of NFT on Spatial Orienting Healthy Elderly Mild AD

Results: Spatial Orienting Healthy Elderly Real NFT reduced RTs for both Valid and Invalid Cue trials Mock NFT increased RTs for both Valid and Invalid Cue trials Mild AD Real NFT selectively reduced RTs for Invalid Cue trials Mock NFT had no effect on RTs for either Valid or Invalid Cue trials

Effects of NFT on Alerting Healthy Elderly Mild AD

Results: Alerting Healthy Elderly Mild AD Real NFT had no effect on RTs for either Double or No Cue trials Mock NFT selectively increased RTs for No Cue Cue trials Mild AD Real NFT reduced RTs for both Double and No Cue Trials Mock NFT increased RTs for both Double and No Cue Trials

Summary: Real NFT Healthy Elderly Mild AD No effect on cross-cortical sensory integration, but enhanced selective attention in the visual search task Generalized enhancement of response times in spatial orienting No effect on either alerting measures or response inhibition in Simon interference Mild AD No effect on either cross-cortical sensory integration or selective attention measures in the visual search task Selective improvement in disengagement in spatial orienting Enhanced phasic and tonic alerting No effect on response inhibition in Simon interference

Summary: Mock NFT Healthy Elderly Mild AD 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 Mild AD No effect on response times for spatial orienting or Simon interference measures Generalized slowing of response times for the alerting measures

Non-Memory Impairments in AD Attention Cognitive operations involved in the detection and selection of sensory information Automatic (stimulus-driven) Voluntary (controlled, goal-directed) Different attentional processes mediated by distinct neural subsystems Sensory Integration The “Binding Problem” 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 The measures that improve with Real NFT are different across the groups. The most compelling data is from the search task with the healthy elderly real NFT group.  They show enhanced selective attention across both sensory binding conditions.  Real NFT improves attentional disengagement and alerting measures in the mild AD NFT group. Mock NFT either has no effect or elicits generalized slowing for both groups. I have other data I haven't analyzed yet from different tasks (an audiovisual semantic integration task, a stroop real world object task, a different covert orienting and alerting task)--

Non-Memory Impairments in AD (and Aging) Posterior Cortical Processing Systems Alerting (cortical tonus) Orienting Sensory Integration Inefficient cortical processing in Aging Corticocortical disconnectivity in AD Anterior Executive Control 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