SOME SPECIFIC Q-EEG APPLICATIONS RELATED TO NEUROCOGNITIVE DYSFUNCTIONS Biljana Gjoneska 1, Silvana Markovska-Simoska 1, Tatjana Zorcec 2 1 Division of Neuroinformatics, Bioinformatics Unit, ICEIM, Macedonian Academy of Sciences and Arts, Skopje, R. Macedonia 2 Pediatric Clinic, Faculty of Medicine, University of Skopje, R. Macedonia

NEUROINFORMATICS Development of tools and databases for management and sharing of neuroscience data Q-EEG (Quantitative EEG / Computerized EEG / Brain Mapping ) RECORDING OF MULTICHANNEL EEG SIGNAL PROCESSING AND EXTRACTION OF FEATURES ANALYSIS OF FEATURES COMPARISON OF EEG DATA I. INTRODUCTION

EPILEPSY CEREBROVASCULAR PATHOLOGIES SCHIZOPHRENIA DEPRESSION/MANIA ATTENTION DEFICIT HYPERACTIVITY DISORDER INATTENTIVENESSDISTRACTIBILITYIMPULSIVITYHYPERACTIVITY Q-EEG AS A DIAGNOSTIC TOOL ATTENTION DISORDERS SOME DISORDERS WITH UNDERLYING ORGANIC PATHOLOGY

II. THE CYSTIC FIBROSIS STUDY TIME PERIOD: 1 st of February – 30 th April, 2007 PLACE: Department of Psychophysiology - Pediatric Clinic, Skopje, R.M DEFINITION: Prospective, Randomized and Controlled clinical study PARTICIPANTS Table No. 2 – EXPERIMENTAL GROUP Table No. 1 – CONTROL GROUP TECHNOLOGY DATA RECORDING: DATA RECORDING: Software program BOSLAB DATA PROCESSING: DATA PROCESSING: Software program WINEEG STATISTICAL OPERATIONS: STATISTICAL OPERATIONS: Statistica 5 (T test for small samples) MusiciansNumberMeanMin.Max.RangeVarianceStd. Dev. Age Mature CF PatientsNumberMeanMin.Max.RangeVarianceStd. Dev. Age

THE PROCEDURE PER PARTICIPANT WAS CARRIED OUT WITH THE BIPOLAR EEG ELECTRODES PLACED AT F3-O1 AND F4-O2 AND THEY INCLUDED: - INITIAL EEG ASSESSMENT WITH EC & EO; - ONE NEUROFEEDBACK (NF) ALPHA-INCREASING SESSION; - FINAL EEG ASSESSMENT WITH EC & EO. INVESTIGATED PARAMETER: ALPHA PEAK FREQUENCY (APF) EXPRESSED TROUGH THE FREQUENCY IN WHICH THE AMPLITUDE OF ALPHA RHYTHM IS THE HIGHEST AND OBTAINED AFTER PERFORMING FAST FURIER TRANSFORMATION OVER THE DATAPROCEDURE

RESULTS FOR CF APF VALUE AFTER THE INITIAL SESSION APF VALUE FOR CF PATIENTS: INITIAL VS. FINAL SESSION CONCLUSIONS FOR CF -CF IS LIKELY TO HAVE NEGATIVE PSYCHO-EMOTIONAL IMPACT FROM THE DISORDER -THERE ARE GOOD PERSPECTIVES FOR THE Q-EEG EVALUATION AND NF TREATMENT OF MENTAL PROBLEMS IN CF PATIENTS IN ORDER TO IMPROVE THEIR CAPACITY FOR SELF- MANAGEMENT -FURTHER INVESTIGATIONS SHOULD BE CONDUCTED IN ORDER TO CONFIRM THESE RESULTS

QEEG & ADHD DIFFERENTIATION BETWEEN ADHD AND HEALTHY SUBJECTS DIFFERENTIATION BETWEEN ADHD AND OTHER PATHOLOGIES SENSITIVE AND SPECIFIC TOOL TO SUBTYPE ADHD KROPOTOV AND MUELLER DESCRIBED DISTINCT EEG CLUSTERS OF ADHD CHILDREN KROPOTOV AND MUELLER DESCRIBED DISTINCT EEG CLUSTERS OF ADHD CHILDREN - β OVER-ACTIVATED ACTIVITY IN FRONTO-CENTRAL OR PARIETAL CORTEX (~ 30%) - SLOW α EXCESS IN: SENSORY-MOTOR CORTEX; IN POSTERIOR TEMPOTRAL AND/OR TEMPORAL CORTEX; OVER WHOLE CORTEX (~30%) - INCREASED θ IN FRONTO-CENTRAL AND FRONTO-MIDLINE CORTEX, AS WELL AS INCREASED θ/β RATIO IN SOME DERIVATIONS (~40%) ADHD SUBTYPES 2007 ZORCEC, POP-JORDANOVA, MUELLER 2007 ZORCEC, POP-JORDANOVA, MUELLER CONFIRMED EXISTENCE OF MORE SPECIFIC EEG CLUSTERS OF ADHD CHILDREN OF ADHD CHILDREN

III. THE ADHD STUDY SUBJECTS: SUBJECTS: 20 children diagnosed with ADHD INCLUSION CRITERIA: INCLUSION CRITERIA: ADHD diagnosis (according to icd-10); Schoolage children (7-12 years); IQ > 90; Free of any medications, Absence of comorbidities; Informed consent from the parents TECHNOLOGY RECORDING APARATURE: RECORDING APARATURE: Standardized 21 Mitsar EEG MONTAGE: MONTAGE: International 10/20 system REFERENTIAL MONTAGE: REFERENTIAL MONTAGE: Linked earlobes ELECTRODE IMPEDANCE: ELECTRODE IMPEDANCE: < 5 kΩ DIGITIZATION RATE: DIGITIZATION RATE: 512 samples per minute BAND-PASS FILTER: BAND-PASS FILTER: 1-50 Hz

SLOW α EXCESS SUBTYPE MOST OF THE CHILDREN (~45%) IMPAIRMENT IS IN THE LIMBIC SYSTEM. GENERATOR IS THE MIDDLE FRONTAL CORTEX AND ANTERIOR CINGULAR GYRUS. IMPAIRMENT IS IN THE LIMBIC SYSTEM. GENERATOR IS THE MIDDLE FRONTAL CORTEX AND ANTERIOR CINGULAR GYRUS. THIS INFLUENCES EXECUTIVE FUNCTIONS WHICH ARE THE HIGHEST COGNITIVE PROCESS. BEHAVIOURALLY, CHILDREN HAVE EMOTIONAL PROBLEMS. RESULTS AND CONCLUSIONS FOR ADHD HIGH β ACTIVITY IN FRONTO-CENTRAL / PARIETAL CORTEX ~ 20% BELONG TO THIS SUBTYPE AND HAVE UNIDENTIFIED IMPAIRMENT “TYPICAL” ADHD BEHAVIOR WITH EASY AND FAST BLOCKADES IN THEIR EFFICIENCY INCREASED θ AMPLITUDE IN FRONTO-CENTRAL CORTEX ~ 30% BELONG TO THIS SUBTYPE IMPAIRMENT IS IN THE CORTEX-BASAL GANGLIA-THALAMUS-CORTEX LOOP. “TYPICAL” ADD BEHAVIOR

IV. THE ELF-EMF META-ANALYSIS SOURCES FOR INVESTIATION: ONLINE DIGITAL ARCHIVES (PUBMED, SCIRUS, WORLD HEALTH, ORGANIZATION); REFERENCED ARTICLES; INTERNATIONAL EMF PROJECTS (COST 281, EMF-NET, REFLEX, WHO-EMF) NAME OF THE STUDY NoAge RangeMean AgeM/F Ratio (1) “Frequency-specific responses in the human brain caused by electromagnetic fields” (1) /8 (2) “Influence of an alternating 3Hz magnetic field with an induction of 1 militesla on chosen parameters of the human occipital EEG” (2) /26 (3) “Preliminary analysis of the effects of DTX mobile phone emissions on the human EEG” (3) 10/// (4) “Alterations in human EEG activity caused by extremely low frequency electromagnetic fields” (4) /9 (5) “Mobile phone 'talk mode' signal delays EEG- determined sleep onset” (5) 1018–2822/ RELEVANT STUDIES: DEMOGRAPHIC PARAMETERS

Study EMF production Explored Frequency Protocol 1 Artificial: Helmholtz Coils 1.5 Hz & 10Hz EEG recording during presentation of the EMF for 2 sec, followed by an inter-stimu­lus period of 5 sec. for a total of 50 trials. 2 Artificial: Helmholtz Coils 3 Hz 5 min. field-off EEG, 20 min EEG under stimulation, 5 min. field-off EEG 3 Artificial: Helmholtz Coils 2 Hz 5 min. control period, then 2 trains separated by a 1 min. con­trol pe­riod. At the end again 5 min. control period 4 Artificial: Helmholtz Coils 50, 16.66, 13, 10, 8.33 & 4Hz 2 min. EEG under stimulation, 1 min. field-off EEG 5 Natural: Mobile Phone Device 2 & 8Hz. EEG recording whilst exposure to talk, lis­ten, standby and sham (nil signal) randomly, for 30 min. In the next 90 min is a sleep opportunity. RELEVANT STUDIES: EXPERIMENTAL SETUP AND PROTOCOL

(2) Significant differences were found between sham and real exposure for the relative spectral amplitudes of θ and β band and θ/β ratio. Namely, θ/β ratio becomes almost 6% higher over the left occiput after turning on the field. (2) In each subject, the magnetic field altered ongoing brain activity at the frequency of stimulation from one or more electrodes. The effect was more likely at 10 Hz compared with 1.5 Hz. Namely, significant increase in 10 Hz (α) EEG power was registered. (1) (3) Significant increases and decreases in EEG power spectral density at various brainwave frequencies in the γ band (3) (4) The results indicate that there was a significant increase in α1, α2, and β1 at the frontal brain region, and a significant decrease in α2 band in parietal and occipital region (4) (5) Post-exposure, sleep latency after talk mode was markedly & significantly delayed beyond listen & sham modes. This condition effect over time was also quite evident in 1-4 Hz EEG frontal power which is frequency range particularly sensitive to sleep onset. Namely, EEG δ-power increased significantly in the second 10 min period after listed and sham exposures, the third period after standby exposure, but no period after talk exposure. (5) RESULTS FOR ELF-EMF META-ANALYSIS ALL STUDIES DEMONSTRATE CHANGES

Q-EEG INTERDIGITATED WITH NEUROPSYCHOLOGICAL AND EDUCATIONAL DATABASES CAN: - DEFINE MORE PRECISELY THE NATURE OF BRAIN’S INTEGRITY - OUTLINE (OTHERWISE UNTRACEABLE) SPECIFIC PATTERNS FOR CERTAIN POPULATION PERSPECTIVES OF Q-EEG BRAIN-RATE PARADIGM: BRAIN-RATE PARADIGM: DEFINED AS A MEAN FREQUENCY OF BRAIN OSCILLATIONS WEIGHTED OVER THE ALL BANDS OF THE EEG POTENTIAL (OR POWER) SPECTRUM. i - denotes the frequency band Vi - is the corresponding mean amplitude of the electric potential (or power). (Pop-Jordanova & Pop-Jordanov, 2005),

V. BRAIN-RATE EXPLORATIONS SUBJECTS: 40 Healthy individuals; 27.7 mean age ( ); 17 M / 23 F; METHODOLOGY: Raw EEG in four conditions with Mitsar/WinEEG acquisition software: Eyes closed (EC); Eyes opened (EO); Visual continuous performance task (VCPT); Emotional continuous performance task (ECPT). Brain-rate evaluation is the final procedure. BRAIN RATE RESULTS BRAIN RATE MEAN VALUES t-val.p EC vs. EO / / / EC vs. VCPT EC vs. ECPT

15 SPATIAL DISTRIBUTION OF BRAIN-RATE VALUES

16 CONCLUSIONS FOR BRAIN-RATE BRAIN-RATE CAN SERVE AS A SIMPLE COMPLEMENTARY INDICATOR OF MENTAL AROUSAL LEVEL I.E. MENTAL ACTIVATION/DEACTIVATION. SIGNIFICANTLY GREATER VALUES OF BRAIN-RATE IN EC VS. EO/VCPT/ECPT CONDITIONS ARE OBTAINED. THIS IS A RESULT OF INTERNALLY DIRECTED ATTENTION, ALSO REFFERED BY COOPER, CROFT, DOMINEY, BURGESS & GRUZELIER, MAXIMUM VALUES OF FB ARE OBTAINED IN C3 AND C4, WHILE THE MINIMUM IN CZ POINT.