The Midwest Society for The Midwest Society for Behavioral Medicine and Behavioral Medicine and Biofeedback (MSBMB) Biofeedback (MSBMB)

DSM-5 and Biomarkers/PhenotypesDSM-5 and Biomarkers/Phenotypes

Jay Gunkelman, QEEG-DiplomateJay Gunkelman, QEEG-Diplomate CSO, Brain Science InternationalCSO, Brain Science International

Jay@brainsinternational.com

The modern dilemma in psychology: The modern dilemma in psychology:

Diagnosis, when the DSM is being Diagnosis, when the DSM is being abandoned by the author.abandoned by the author.

Top-down changeTop-down change

Reliability but no ValidityReliability but no Validity

The The Research Domain Criteria (RDoC) project project transforms diagnosis by incorporating genetics, transforms diagnosis by incorporating genetics, imaging, cognitive science, and other levels of imaging, cognitive science, and other levels of

information, forming a foundation for a new information, forming a foundation for a new classification system.classification system.

““That is why NIMH will be re-orienting its research That is why NIMH will be re-orienting its research away from DSM categoriesaway from DSM categories. Going forward, we will . Going forward, we will be supporting research projects that look across be supporting research projects that look across current categories – or sub-divide current current categories – or sub-divide current categories – to begin to develop a better system.”categories – to begin to develop a better system.”

“ “RDoC, for now, is a research RDoC, for now, is a research framework, not a clinical tool. This is framework, not a clinical tool. This is a decade-long project that is just a decade-long project that is just beginning. … beginning. … RDoC is nothing less RDoC is nothing less than a plan to transform clinical than a plan to transform clinical practice by bringing a new practice by bringing a new generation of research to inform how generation of research to inform how we diagnose and treat mental we diagnose and treat mental disorders.”disorders.”

The DSM is based on behaviorThe DSM is based on behavior

The linkage from genetics to The linkage from genetics to behavior is indirectbehavior is indirect

The intermediate step between The intermediate step between genetics and behavior is the genetics and behavior is the phenotypephenotype

Behaviorally driven therapy can Behaviorally driven therapy can succeed, but is it optimized?succeed, but is it optimized?

Prior studies using EEG have Prior studies using EEG have documented “clusters” of documented “clusters” of EEG/qEEG features within EEG/qEEG features within psychiatric populations psychiatric populations

John ER, et al. Subtyping of Psychiatric Patients by Cluster Analysis of QEEG. John ER, et al. Subtyping of Psychiatric Patients by Cluster Analysis of QEEG. Brain Topography 1992; 4:321-326). Brain Topography 1992; 4:321-326).

Chabot, R. J., & Serfontein G. (1996). Quantitative electroencephalographic Chabot, R. J., & Serfontein G. (1996). Quantitative electroencephalographic profiles of children with attention deficit disorder. profiles of children with attention deficit disorder. Biological Psychiatry, 40,Biological Psychiatry, 40, 951-963. 951-963.

Prichep LS, Mas F, Hollander E, Liebowitz M, John ER, Almas M, De Caria CM, & Prichep LS, Mas F, Hollander E, Liebowitz M, John ER, Almas M, De Caria CM, & Levine RH. (1993) Quantitative electroencephalographic subtyping of Levine RH. (1993) Quantitative electroencephalographic subtyping of obsessive-compulsive disorder. obsessive-compulsive disorder. Psychiatry Research, 50Psychiatry Research, 50(1), 25-32.(1), 25-32.

Prichep LS, & John ER. (1992). QEEG profiles of psychiatric disorders. Prichep LS, & John ER. (1992). QEEG profiles of psychiatric disorders. Brain Brain Topography, 4Topography, 4(4), 249-257.(4), 249-257.

Suffin SC, & Emory WH. (1995). Neurometric subgroups in attentional and Suffin SC, & Emory WH. (1995). Neurometric subgroups in attentional and affective disorders and their association with pharmacotherapeutic affective disorders and their association with pharmacotherapeutic outcome. outcome. Clinical Electroencephalography, 26, 76-83.Clinical Electroencephalography, 26, 76-83.

The underlying assumption in the The underlying assumption in the DSM is: “diagnosis, thus treatment”DSM is: “diagnosis, thus treatment”

The DSM does The DSM does notnot yield optimal treatment yield optimal treatment efficacy following diagnosis efficacy following diagnosis

Diagnoses have multiple “EEG subtypes”, but Diagnoses have multiple “EEG subtypes”, but they they ARE NOT SPECIFICARE NOT SPECIFIC TO THE DIAGNOSISTO THE DIAGNOSIS

Frontal alpha in ADDFrontal alpha in ADD Frontal alpha in depressionFrontal alpha in depression Frontal alpha in early dementiaFrontal alpha in early dementia Frontal alpha in anxietyFrontal alpha in anxiety Frontal alpha in OCDFrontal alpha in OCD

Phenotypic patterns are Phenotypic patterns are notnot isomorphic with the DSM categoriesisomorphic with the DSM categories

Phenotypes have powerful Phenotypes have powerful

implications for both medication, and implications for both medication, and Neurofeedback.Neurofeedback.

Wright, C, & Gunkelman J. (1998). QEEG evaluation doubles the rate of clinical Wright, C, & Gunkelman J. (1998). QEEG evaluation doubles the rate of clinical success. success. Abstracts of the 6th Annual Conference, Abstracts of the 6th Annual Conference, Society for the Study of Society for the Study of Neuronal Regulation, Austin, TX.Neuronal Regulation, Austin, TX.

Suffin SC, & Emory WH. (1995). Neurometric subgroups in attentional and Suffin SC, & Emory WH. (1995). Neurometric subgroups in attentional and affective disorders and their association with pharmacotherapeutic affective disorders and their association with pharmacotherapeutic outcome. outcome. Clinical Electroencephalography, 26, 76-83.Clinical Electroencephalography, 26, 76-83.

Johnstone, J., Gunkelman, J.,& Lunt, J.. (2005). Clinical database development: Johnstone, J., Gunkelman, J.,& Lunt, J.. (2005). Clinical database development: Characterization of EEG Phenotypes. Characterization of EEG Phenotypes. Clinical EEG and Neuroscience, 2Clinical EEG and Neuroscience, 2, 99-, 99-107.107.

Phenotypes have led to enhanced Phenotypes have led to enhanced outcomes clinicallyoutcomes clinically

S. Suffin and H. Emory (attentional and affective, S. Suffin and H. Emory (attentional and affective, medication)medication)

L. Prichep (OCD, medication)L. Prichep (OCD, medication)

Chabot, et al. (ADD/ADHD, medication)Chabot, et al. (ADD/ADHD, medication)

C. Wright (ADD/ADHD, Neurofeedback)C. Wright (ADD/ADHD, Neurofeedback)

M.I.N.D. (U.C. Davis, Autism)M.I.N.D. (U.C. Davis, Autism)

Databases for EEG are starting to include the genetic Databases for EEG are starting to include the genetic component (Brain Resource Company, Australia)component (Brain Resource Company, Australia)

Some EEG patterns have Some EEG patterns have strongstrong genetics linksgenetics links

Low voltage EEGLow voltage EEG Enoch, MA, et al. (2002). The relationship between two intermediate phenotypes for , et al. (2002). The relationship between two intermediate phenotypes for

alcoholism: Low voltage alpha EEG and low P300 ERP amplitude. alcoholism: Low voltage alpha EEG and low P300 ERP amplitude. Journal of Studies on Journal of Studies on Alcohol, 63Alcohol, 63(5), 509-17.(5), 509-17.

Porjesz B, et al. (2002). Linkage disequilibrium between the beta frequency of the Porjesz B, et al. (2002). Linkage disequilibrium between the beta frequency of the human EEG and a GABAA receptor gene locus. Proceedings of the National Academy human EEG and a GABAA receptor gene locus. Proceedings of the National Academy of Sciences of the United States of America; 99(6): 3729-3733.of Sciences of the United States of America; 99(6): 3729-3733.

Gunkelman J. (2001). Low voltage or absolute power. Journal of Neurotherapy; 5:1-2.Gunkelman J. (2001). Low voltage or absolute power. Journal of Neurotherapy; 5:1-2.

Epileptiform burstsEpileptiform bursts Kaneko S., Iwasa H., & Okada M. (2002). Genetic identifiers of epilepsy. Kaneko S., Iwasa H., & Okada M. (2002). Genetic identifiers of epilepsy. Epilepsia, 43 Epilepsia, 43

((Suppl 9), 16-20.Suppl 9), 16-20.

Huag K, et al. (2003) Mutations in CLCN2 encoding a voltage-gated chloride channel Huag K, et al. (2003) Mutations in CLCN2 encoding a voltage-gated chloride channel are associated with idiopathic generalized epilepsies. Nature Genetics; 33:527-532.are associated with idiopathic generalized epilepsies. Nature Genetics; 33:527-532.

A limited set of phenotypic divergence A limited set of phenotypic divergence patterns can characterize the bulk of the patterns can characterize the bulk of the

variance of the EEGvariance of the EEG

These EEG phenotypes predict effective These EEG phenotypes predict effective therapy therapy

(medication and NF)(medication and NF)

The following table is not a substitute for professional evaluation and The following table is not a substitute for professional evaluation and consultationconsultation

EpileptiformEpileptiform Transient spike/wave, sharp waves, paroxysmal EEG Transient spike/wave, sharp waves, paroxysmal EEG

Anticonvulsant medicationAnticonvulsant medicationInhibit low and high frequencies over affected regions, reward SCP and/or SMR.Inhibit low and high frequencies over affected regions, reward SCP and/or SMR.

Generally low magnitudes (fast or slow) Generally low magnitudes (fast or slow) Metabolic support (LVS), nutraceuticals Metabolic support (LVS), nutraceuticals Reward alpha activity posteriorly. (Penniston protocol for LVF)Reward alpha activity posteriorly. (Penniston protocol for LVF)

Faster alpha variants, not low voltageFaster alpha variants, not low voltage Alpha frequency greater than 12 Hz over posterior cortex. Alpha frequency greater than 12 Hz over posterior cortex.

GABA related medication (slightly slows the EEG frequencies)GABA related medication (slightly slows the EEG frequencies) Reward 9-10Hz alpha at Pz, shift alpha frequency lower with alpha/theta protocolReward 9-10Hz alpha at Pz, shift alpha frequency lower with alpha/theta protocol

Spindling excessive beta Spindling excessive beta High frequency beta with a spindle morphology, often with an anterior emphasis.High frequency beta with a spindle morphology, often with an anterior emphasis. AnticonvulsantsAnticonvulsants Inhibit beta frequencies, wide band inhibit, possibly Penniston if alpha levels are depressed.Inhibit beta frequencies, wide band inhibit, possibly Penniston if alpha levels are depressed.

Persistent alpha with eyes openPersistent alpha with eyes open Lack of appreciable alpha blocking with eye opening, generally this is slower alpha Lack of appreciable alpha blocking with eye opening, generally this is slower alpha

SNRI or amphetamine SNRI or amphetamine Reward beta frequencies, inhibit alpha. Reward higher frequency alpha.Reward beta frequencies, inhibit alpha. Reward higher frequency alpha.

Diffuse slow activity, with or without low frequency alpha.Diffuse slow activity, with or without low frequency alpha. Increased delta and theta (1-7 Hz) with or without slow posterior dominant rhythm StimulantIncreased delta and theta (1-7 Hz) with or without slow posterior dominant rhythm Stimulant

Inhibit midline frontocentral activity below 10 Hz., add reward anterior beta frequencies for increased Inhibit midline frontocentral activity below 10 Hz., add reward anterior beta frequencies for increased effecteffect

Focal abnormalities, not epileptiform.Focal abnormalities, not epileptiform. Focal slow activity or focal lack of activity. Focal slow activity or focal lack of activity. Inhibit slow activity (<10 Hz) and reward higher frequencies(> 12 Hz).Inhibit slow activity (<10 Hz) and reward higher frequencies(> 12 Hz).

Mixed fast and slowMixed fast and slow Increased activity below 8 Hz., lack of alpha, increased beta frequency activity Combine across Increased activity below 8 Hz., lack of alpha, increased beta frequency activity Combine across

classes, e.g. stimulant + anticonvulsant classes, e.g. stimulant + anticonvulsant Inhibit slow frequencies, reward SMR. Inhibit slow frequencies, reward SMR.

Frontally dominant excess theta or alpha frequency activityFrontally dominant excess theta or alpha frequency activity Antidepressant, stimulant Antidepressant, stimulant Inhibit midline frontocentral activity below 10 Hz., add reward anterior beta frequencies for increased Inhibit midline frontocentral activity below 10 Hz., add reward anterior beta frequencies for increased

effecteffect

Frontal asymmetriesFrontal asymmetries Variable asymmetry L>R or R>L, primarily at F3, F4. Variable asymmetry L>R or R>L, primarily at F3, F4. Antidepressant Antidepressant Reward F3 beta, inhibit F3 theta and alpha frequencies.Reward F3 beta, inhibit F3 theta and alpha frequencies.

Excess temporal lobe alphaExcess temporal lobe alpha Increased alpha activity generated in temporal lobe Increased alpha activity generated in temporal lobe Stimulant Stimulant Inhibit 9-12 Hz activity over affected temporal region(s), + inhibit frontal slow activity.Inhibit 9-12 Hz activity over affected temporal region(s), + inhibit frontal slow activity.

Slow variantSlow variant

Epileptiform (myoclonus)Epileptiform (myoclonus)

Beta spindleBeta spindle

Failure of alpha blockingFailure of alpha blockingFp1

Fp2

F3

F4

C3

C4

P3

P4

O1

O2

F7

F8

T3

T4

T5

T6

Fz

Cz

Pz

20

50 µV

50 µV

50 µV

50 µV

50 µV

50 µV

50 µV

50 µV

50 µV

50 µV

50 µV

50 µV

50 µV

50 µV

50 µV

50 µV

50 µV

50 µV

50 µV

50 µV

Addiction outcomes are about more than Addiction outcomes are about more than sobriety… a dry drunk is not “cured”… we sobriety… a dry drunk is not “cured”… we

look for “optimal function” when the look for “optimal function” when the “brain works better”.“brain works better”.

Big data meets EEG/qEEG

Beta spindles: N=390 Beta spindles: N=390 (with 49 ADHD)(with 49 ADHD)

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