Update on the Theory and Practice of Infra-Low Frequency ... · • Update on the results of...
Transcript of Update on the Theory and Practice of Infra-Low Frequency ... · • Update on the results of...
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Update on the Theory and Practice of Infra-Low Frequency Neurofeedback
Clinical Summit, Los Angeles, May-June 2019Siegfried Othmer
Copyright, The EEG Institute, 2019
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Agenda for Day One: Past and Present
• Update on the results of research on ILF NF• Review of the Theoretical Understanding of ILF NF
– The basis for moving forward on protocol development • The present challenge: Synchrony training
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We have data!
• Analysis of our collective CPT data • Analysis of EEG Institute CPT data • Results of pilot study on 251 ADHD children and
adolescents• Results of a study on frontal lesions in traumatic brain
injury• Controlled study of ILF NF with HRV as control
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QIK CPT Data Analysis for the Network
Last year we showed comprehensive data from over a decade:• Segregated by age category: 6-10; 10-20; 20-70+ • Segregated by time: 2006-end 2013; 2014-2017• This yielded ‘improvement factors’ on the order of 2 for the
discrete errors• This did not yield a good sense of the clinical significance
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Performance comparison, post-2013 with pre-2014
The significant improvements are high-lighted
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6-9 years
# Errors at the Median decline from 30 to 15
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How meaningful are the changes observed in the discrete error distribution?
We can use our norming data to assign a mental age to the median score for each distribution We can then express the training-induced changes in terms of equivalent mental age The median score is the best choice to characterize the distribution as a whole
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Improvements in terms of equivalent mental age
6
6.2
7.3
6.6
10
8.5
8
7.6
0 2 4 6 8 10 12
COMMISSION ERRORS
OMISSION ERRORS
REACTION TIME
VARIABILITY
Improvements in Implicit Mental Age: All Categories, 6-9 age range
Post-training Pre-training
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Improvements in terms of equivalent mental age
9
10.3
12.1
10.4
17
13.8
12.6
11.8
0 2 4 6 8 10 12 14 16 18
COMMISSION ERRORS
OMISSION ERRORS
REACTION TIME
VARIABILITY
Improvement in Implicit Mental Age:All Categories: Age Range: 10-19
Post-training Pre-training
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Improvements in terms of equivalent mental age
13
11.7
12
11.9
19.3
17.2
12.9
13.4
0 5 10 15 20 25
COMMISSION ERRORS
OMISSION ERRORS
REACTION TIME
VARIABILITY
Improvement in Implicit Mental Age:Total Age Range
Post-training Pre-training
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Improvements in terms of equivalent mental age
15.5
18.5
14.5
13.8
27
30
16.5
16.8
0 5 10 15 20 25 30 35
COMMISSION ERRORS
OMISSION ERRORS
REACTION TIME
VARIABILITY
Improvement in Implicit Mental Age:Total Age Range: EEG Institute
Post-training Pre-training
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Analysis of EEG Institute CPT data by John Putman
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EEG Institute CPT data; analysis by John Putman
0
20
40
60
80
100
120
140
160
1 4 7 10 13 16 19 22 25 28 31 34 37 40 43 46 49 52 55 58 61 64 67 70 73 76 79 82 85 88 91 94 97 100
103
106
109
112
115
118
121
124
127
130
133
136
139
142
145
148
151
154
Accuracy, pre-score < 100 (N = 155)
Accu pre Accu post
8 significant declines in score in first 20 sessions: ~5%
Improvement in mean standard score from 81.9 – 99.0
Improvement in mean percentile score from 12th to 47th
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EEG Institute CPT data; analysis by John Putman
0
20
40
60
80
100
120
140
1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43 45 47 49 51 53 55 57 59 61 63 65 67 69 71 73 75 77 79 81 83 85 87 89 91
Performance pre-score <100 (N=91)
Perf pre Perf post
8 significant declines in score in first twenty sessions: 9%
Improvement in mean standard score from 89.4 – 99.0
Improvement in percentile score from 24th to 47th
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Om Pre Post N=271 10.3 5.3N=92 22.9 9.0
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Commission Errors
02468
1012141618
Mn pre Mn post
Mean Commission ErrorsN= 271
Pre-training 16.4Post-20 sessions 9.3Improvement factor 1.8
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Therapeutic effect of Infra-Low-Frequency Neurofeedback (ILF NF) training on
Children and Adolescents with Attention Deficit Disorder
Dr. Adam Alfred1, Andrea Blunck2, Dr. Bernhard Wandernoth3 and Dr. Horst Schneider3
1Praxis für Kinder- und Jugendpsychiatrie, München und Prien2EEG Info, Schweiz3BEE Medic GmbH, Singen
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Presented at the 63rd Annual Meeting of the German Society for Clinical Neurophysiology and Functional
Imaging (DGKN)March 28-30, 2019 in Freiburg, Germany
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Study Objectives
• Goal was to see whether neurofeedback is practical in a large psychiatry practice with high patient turnover
• This was not an efficacy study, or even a clinical effectiveness study– Neither was still in question among the participants
• Practicality was to be established comprehensively, in the context of financial constraints, scheduling constraints, and pharmacological as well as other therapeutic alternatives
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• Praxis für Kinder- und Jugendpsychiatrie Dr. Alfred, München• Praxis für Kinder- und Jugendpsychiatrie und Psychotherapie Thilo Palloks, München• Privat- und Neurofeedback Praxis Klaus Werner Heuschen, München• Praxiszentrum Chiemsee, Praxisgemeinschaft Palloks/Dr. Alfred/Heuschen, Prien
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Multi-center observational study
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Multi-center observational study
• 25 NFB-trained Therapists • Using 16 Cygnet systems
• 251 Patients with clinically validated diagnosis of ADHD• 196 tested with QIKtest pre-post• 43 cases have pre-post symptom data
• Age 7 – 21 years• Survey period: 2016 - 2017
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Results – Continuous Performance Test (CPT)
N= 196 Pre (T0) Post (T2) Diff. p
�̅�𝑥 Reaction Time (RT) 457 ± 88 ms 436 ± 85 ms -21 ms <.0001*1
�̅�𝑥 Variability of RT (VAR) 122 ± 31 ms 104 ± 30 ms -18 ms <.0001*1
�̅�𝑥 Omission Errors (OM) 9.6 ± 15.1 5.0 ± 9.3 -4.6 <.0001*2
�̅�𝑥 Commission Errors (COM) 19.1 ± 17.2 9.0 ± 9.0 -10.1 <.0001*2
*1 Student’s t-test*2 Wilcoxon signed rank test
Comparison of four parameters of Attention and Impulse Control before and after NFB
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Results of CPT expressed in terms of Equivalent Mental Age
8.5
8.9
10
10.2
15
10.3
12.8
12.3
0 2 4 6 8 10 12 14 16
CO
OM
VAR
RT
Improvements in Equivalent Mental Age
Post-training Pre-training
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Results – Symptom Tracking
• After the NFB intervention 97% of the patients had an improvement in symptoms that once were perceived as stressful.
• Only 3% of the patients claimed no noticeable improvement of the symptoms.
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Results – Symptom Tracking• After the NFB therapy, patients (n= 43) rated the
severity of various ADHD-specific symptoms• These were found to be significantly reduced!• Example (the three cardinal symptoms for ADHD):
Severity of Symptoms �̅�𝑥 p
InattentionT2 5.4 ± 2.2
.000T0 8.3 ± 1.4
HyperactivityT2 4.6 ± 2.5
.012T0 8.1 ± 1.2
ImpulsivityT2 6.1 ± 2.5
.018T0 7.4 ± 1.8
7.4
8.1
8.3
6.1
4.6
5.4
0 1 2 3 4 5 6 7 8 9 10
IMPULSIVITY
HYPERACTIVITY
INATTENTION
Severity of the core AD(H)D symptoms
Post (T2) Pre (T0)
Statistics by Wilcoxon signed rank test
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Appraisal
• There were only two dropouts from the study over its duration (< 1%)
• 87% of parents and teachers surveyed expressed satisfaction with the outcome– Taking costs in time and money, as well as the availability of
alternative treatments, into account• Management appraisal:
– “Parents are satisfied; therapists are happy; the accountants are satisfied; and the management burden is light.”
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Pilot study on veterans with TBI/PTSD
• Principal Investigator: Judy Carlson in Hawaii• Four cases of concussion involved in pilot study• All declared fully disabled by the VA:
– PTSD, headaches, sleep issues, attention, quality of life • PTSD scale, military version, declined below clinically
significant values in all four cases in twenty sessions – Average decline in score > 40 points – 10 point improvement is regarded as clinically significant
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Neurofeedback in patients with frontal brain lesions: a randomized, controlled double-blind trial
Annaheim C, Hug K, Messerli M, Simon Y, Stumm C, Hund-Georgiadis M,
REHAB Basel, Basel, SwitzerlandResults:
After 20 sessions of either NF or sham-NF, the NF-group showed a trend towards a larger improvement in the Frontal Assessment Battery and the phasic alertness task. In a subgroup of patients with predominantly frontal brain lesions, these improvements were significantly higher in the NF-group than the sham group.
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Frontal Assessment
Battery
Improvement demonstrated with a large effect size of 2.7
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Task of Attentional
Performance
Improvement demonstrated with a large effect size of 1.0
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Controlled study of effect of Neurofeedback at Infra-Low Frequencies on Infra-Slow Oscillations of Brain Potentials
Vera A. Grin-Yatsenko, Sergey A. Evdokimov, Olga Kara, Mark Gregory, and Juri D. Kropotov
• Comparison of ILF NF against Heart Rate Variability training • 17 participantsResults:• Significant increase in spectral power in upper ILF regime in training
group—as distinct from control group, where power decreased • Positive changes in functional status reported for both groups• Positive change in CPT performance in NF group
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Power increase in ILF BF group vs decrease in control group
What’s expected? We saw power increase in upper ILF range in depression study.
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CPT Scores
Neurofeedback cohort Heart Rate Variability cohortPre-training Post-training Pre-training Post-training
Commission Errors: 16 1 5 4Omission Errors: 60 20 14 25
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Review of Theoretical Model
• We are training on the dynamics of Default Mode activity• ...in interaction with the Salience Network • …predominantly in the ILF regime• …because the core regulatory functions are organized with
a view toward persistence, toward stasis • We are a predator species, organized to live out of resting
states
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The hemispheric divide
• The dominant cerebral architectural feature in mammalian species is the hemispheric divide
• Functional organization across that divide is one of our greatest challenges
• Hence brain instabilities are our greatest clinical challenge– Macro-instabilities– Subtlety of coordination---autonomic regulation
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The front-back axis
• Coordinating input and output functions ranks as the second greatest challenge for the brain
• This is the primary burden of the Default Mode Network – In collaboration with the Salience Network
• Clinically, this may be the primary issue in our most challenging population—victims of early trauma
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Resting state networks
From “The Restless Brain,” by Marcus Raichle
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Default Mode Network (Mantini)
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Access point for: Access point for:
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Significant correlations in DN
Buckner (2008)This diagram supports the centrality of T4 as the common site in most of our placements
T4T3
P4
P3
From 2012 Summit:
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Legend
• LTC RTC Left / Right Temporal Cortex• dMPFC dorso-Medial Pre-Frontal Cortex• vMPFC ventro-Medial Pre-Frontal Cortex• IPL Inferior Parietal Lobule• PCC Posterior Cingulate Cortex • Rsp Retrosplenial Cortex • PHC Para-Hippocampal Cortex• LHC RHC Left / Right Hippocampal Formation
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Peaks in connectivity gradient…
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The principal hubs of the Default Mode Network
Pasqual-Marqui (2015)Mantini
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Functional Correlation Strengths
according to Buckner, et al (2008)
Principal linkages shown
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Adding subsidiary linkages
Note predominance of right-side linkages
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All Relevant Linkages:
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Reflections on History • There was a two-year period in which Sue was using inter-
hemispheric placements almost exclusively• Primarily:
– T3 - T4– P3 - P4– Fp1 - Fp2
• Father to the thought: Can we combine the calming protocol with the inter-hemispheric placements?
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Placement:{T3-P3} – {T4-P4}
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Placement:{T3-T4} – {P3-P4}
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Visualizing the Temporo-parietal protocol
• One can think of this protocol as combining the two posterior lateralized protocols
• One can equally well think of it as combining the two primary inter-hemispheric protocols
• Neither perspective has preference over the other• The protocol covers both bases….
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If this works in the posterior region, how do we involve
the frontal hub?
Pasqual-Marqui
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The Three New Protocols:
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The objectives and the driving principlesObjectives:• Improved calming with the posterior placement• Improved regulation of the front-back axis Underlying principles: seeking balance and symmetry• Preservation of lateral symmetry in protocol placement• Serving both core objectives simultaneously:
– Calming and Stabilizing – Add activating as a core objective
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Our present challenge: Synchrony training
• Alpha band synchrony– Our first approach to front-back coordination– Following David Kaiser
• synchrony or comodulation?
• ILF synchrony– The preferred approach to front-back coordination
• Gamma band synchrony
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A brain suffering from neglect shows a loss of front-back coordination, i.e. comodulation, in the upper ILF range (from fMRI measurements)
From David Kaiser