Clinical Significance of Neuronal Oscillations in Children and Adolescents

103-107O R I G I N A L P A P E R

Clinical Significance ofNeuronal Oscillations in

Children and Adolescents

Nada Pop-JordanovaPédiatrie Clinic, Faculty of Medicine, University of Skopje, Macedonia

Original paperSUMMARYIn the assessment and treatment of young patients the complex structure and changes ofneuronal activity during childhood and adolescence must be considered. Consequently, amultidimensional approach, combining psychometric tests with neurometric tools, in particularEEG and QEEG, is important. This paper is devoted to own experience with this approachapplied to pédiatrie patients. Two specific groups of disorders are considered, identified aspsychic (attention deficit hyperaaivity disorder, obsessive compulsive disorder and mentalanorexia) and somatopsychic (dehydration, and lead toxicityj. In addition to standard prop-erties, in analyzing neuronal oscillations, the brain rate parameter is used. It is shown thatindividually adapted integral approach, based on multichannel data for spectrum-weightedfreqtjencies and corresponding arousal levels is crucial. Still, any sophisticated neurometrlcscan not be substitute for clinical competence and experience.Key words: EEG spectrum, brain rate, ADHD, dehydration, anorexia

¡ 1. INTRODUCTION, Having in mind the complex processes of growth and de-velopment, the holistic approach in pedintric research andclinic is needed, including physical, emotional and cognitivedomains. As major indicators of information processing inthe developing human brain, changes in spontaneous neuro-nal oscillations, event related potentials, as well as brain met-abolic activity are very relevant. Of all imaging modalities,EEG and quantitative EEG (QEEG) are the most practical, sim-ple, inexpensive and readily applicable in clinical conditions.! The mental arousal, empirically correlated witb EEG fre-quency bands, may characterize different mental disorders.So, underarousal (UA) is seen in attention deficit, autism, re-tardation, etc., while opposite, overarousal (OA) is present inanxiety, alcoholism, caffeine consumption etc. "Mixed" state(UA or OA) can be seen in attention deficit hyperactivity dis-orders (ADHD), obsessive compulsive disorder (OCD), head-ache etc. which allows dividing these disorders in differentsubgroups (clusters).

The relationship between the EEG and developmentalprocesses from newborn to adult has been extensively stud-ied. The corresponding normative data bases for QEEG fea-tures related to development are established in order to helpthe differential diagnosis of a variety of brain dysfunctions.In multicentric studies it was shown that these features inQEEG are independent of cultural, ethnic or socio-economicbackground (1,2,3.4,5).

In general, in normal children with increasing age thedecrease in slow wave activity and increase in fast wave ac-

tivity is typical finding. The elovalnd slowwave activity in children with ADHD orintellectual disabilities is interpreted bythe delay in brain maturation as well asby the neurotransmitter dysfunction. U issupposed that the intelligence quotient iscorrelated with the degree of EEG matura-tion and thus reflects the active numberof synapses and the degree of differenti-ation of the neuronal controlling system(6).

In the following, some examples fromour clinical practice concerning tbe rele-vance of neuronal oscillations in pédiat-rie disorders (both psychic and somato-psychic) will be presented and discussed.

2. METHODOLOGYThe examined children and adoles-

cents had been diagnosed according bothIGD-10 and DSM-IV. 13efore psychoneuro-logical evaluations, all necessary clinical,biochemical and radiological investiga-tions were undertaken.

As a part of psychological evalua-tions. Ghild Behavior Ghecklist-Achen-bach (CBGL) and Gonnor's rating scaleswere completed by parents. For (he as-sessment of cognitive abilities of cbil-dren we used Wechsler Intellectual Scale(WISG-R), Koch's Block-Design Test. Ge-stalt-Bender Motor Test and Ravens Pro-gressive Matrices. For testing personal-ity characteristics, Kysenck PersonalityQuestionnaire (EPQ), Beck Depression In-ventory, Sarason's General Anxiety Scale(GAS), Profile Emotional Index (PIE) andMinnesota Multiphase Personality Inven-tory (MMPI) were applied.

QEEG was performed with Mit-sar (Russia) instrumentation. Gomputermethods of analysis of the electric neu-ronal oscillations are diagnostically veryuseful, disclosing different EEG features.Moreover, with QEEG and to])ographicbrain maps, it is often possible to observeattributes of brain functions that cannotbe seen in the raw EEG signal. In podi-atric practice QEEG is used in the evalu-ation of many disorders such as: AIDHD.learning disabilities, epilepsy, drug ad-diction, FTSD, autism, schizophrenia,bipolar disorders, OGD, general anxiety,speech problems etc.

One specific parameter, related to

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Clinical Significance of Neuronal Oscillations in Children and Adolescents

both EEG and QEEG, is the brainrate (/J. defined as the EEG spec-trum weighted frequency (7,8,9). Itcan be easily calculated from thestandard spectrum data:

L L

Lwhere the index i denotes the

frequency band [for delta i ~ 1, fortheta Í = 2, etc.) and V, is the corre-sponding mean electric potential orpower. Following the standard live-band classification, one h a s / , = 2,6, 10, 14 and 18 respectively.

The used neurofeedback equip-ment was Biograpb/Procomp Ver-sion 2.1 [Thought Technology, Can-ada). Opérant conditioning training[biofeedback) showed very satisfac-tory results in many psychophysio-logical disorders in pédiatrie prac-tice. EEG biofeedback (neurofeed-back, NF) refers to a specific opérant condition-ing paradigm where individual learns to changefrequency, amplitude or synchronization of brainwaves. Practically, all neurofeedback interventionscan be reduced to the need of mastering flexibilityin shifting EEG spectrum, empirically related to thegeneral mental activation, i.e. mental arousal [whichis somehow coupled witb metabolic activity). There-fore, the introduced brain-rate/,, could be employedas a complementary biofeedback parameter, charac-terizing the whole EEG spectrum [as distinct frome.g. theta/beta ratio) [11,12,13,14,15,16).

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a=I 19,78 Hz,

FIGURE 2. QEEG for an ADHD patient Subtype 3-(increased beta) Note thepeak frequencies at 19.78 ond 19.29 Hz

FIGURE 1. QEEG for an ADHD patient Subtype l-(increased delta-thela) Notecharacteristic peak frequency at 2.90 Hz

3. RESULTS3.1. Attention Deficit Hyperactivity Disorder

The pattern of neuronal oscillations plays animportant role in the evaluation and treatment ofchildren and adolescents with ADHD. These pa-tients are characterized with QEEG abnormalities inup to 80%. In this population, frontal/polar regionsare most likely to show deviations from normal de-velopment, with disturbed thalamocortical and sep-tal-hippocampal pathways (10). Reviewing the EEGstudies of children with ADHD it can be concludedthat most of them have generalized or Intermittent

spectrum shift. It is the reason thatwe introduced the brain rate calcu-lation [/,,) in addition to theta/betaratio in the assessment procedureand as a neurofeedback parameter.

In our country, the incidenceof ADHD is about 2% (12.Î5). Se-lection of ADHD patients (N = 50)in this study is made by diagnosticIGD-10 criteria. The spectrogramanalysis is based on four QEEG sub-types of ADHD [17,18). The resuUsshowed abnormal increase in delta-theta frequency range centrally orfrontally (Subtype 1) in 30% of chil-dren (Figure 1), abnormal increaseof beta activity frontally [Subtype3) in 25% (Figure 2), and abnormalincrease of alpha activity posterioror central (Subtype 4) in 45% (Fig-ure 3).

Initially, the neurofeedbacktraining to increase the SMR EEGrhythm (11-13 Hz) and, at the same

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104 vol l 7 no 2 JUNE 2009 ORIGINAL PAPER

Clinical Significance of Neuronal Oscillations in Children and Adolescents

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time, to inhibit the activity in the tbe-ta range (4-8 Hz) was performed. Afterthat, specific trainingadapted to the pa-tient subtype is applied. The treatmentcomprised 40 sessions, each 60-minuteduration, and one per week.1 Table 1 shows the decrease of theamplitude of theta waves, the increaseof the amplitude of beta waves, as wellas tbe changes of theta/beta ratio ob-tained with NF training. In addition,changes in brain-rate as a spectrumshift indicator are displayed.

In comparison to the considerablechange in theta/beta ratio, the improve-ment indicated by brain rate appearedto be more realistic and comparable toclinical outcome. Results from WISC-R showed that verbal and manipula-tive intelligence scores became slight-ly higher after NF training, whichcorresponded to the improvement ofschool marks for 10-20 percent. Con-nor's rating scales for children chockedby mothers and teachers before treat-ment amounted 87 ± 2.3 (mean scores),which confirmed attention deficit, im-pulsivity, social inadaptability and hy-peractivity. This figure decreased after the treat-pient for about 30%.i A recent multidisciplinary research showedcorrelation of ADD spectral changes with food aller-gies and heavy metals toxicity (19). Some our resultsrelated to the toxicity of lead emission and ADDsymptoms are discussed in chapter .

tion based on inhibitors ol" selectiveserotonin reuptake.

Psyciionietric tests (Actual Anx-iety Questionnaire, MMPI] showedhigh scores for anxiety, connectedwith obsession thoughts that patientstried to neutralize by compulsive acts.The anxiety was also confirmed by themean brain-rate values in Cz, amount-ing in EO 6.82, while in HlC 7.52, indi-cating inner arousai.

The QEEG spectrum (Figure 4) ischacterised by tbe overact ivated fron-tal cortex in beta range (which is sim-ilar to ADHD Subtype 3). It is inter-esting to notify that our results (show-ing beta excess) differ from results ofPricbep et all., 1992 witb two mainsubtypes of OCD (excess of tbeta and

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L QEEG spectra of a patient with OCD compared n il h

ParameterBeta brain waves

Theta brain waves

Theta/beta ratio

Brain rate

before NF (mV)

4.86 ± 1.6

20.95 ± 1.38

4.7 ± 1.38

7.86 ± 0.S6

after NF (mV)

8.0:

15.29

2.08.22

t 1.38

± 1.38

± 1.6

± 0.63

t-test

5.23

8.47

4.56.6

Significance

p< 0.01

p< 0.01

p< 0.01

P< 0.01

TABLE 1. Changes of biofeedback parameters before and after training

! 3.2. Obsessive Compulsive DisorderOCD sample comprised six adolescents, mean

age 15.17 ± 2.96 (five boys, one girl). The patientswere previously treated without success by medica-

excess of alpba).The neurofeedback training in this group

did not give significant improvement. Much bet-ter results have been obtained by EDR and HRVbiofeedback.

3.3. Mental anorexiaWe treated 60 patients with mental anorexia,

20% of which have been hospitalized. Mean age was13.15 ± 1.99 years (75% girls). The specifics in oursample is lower age that in the literature (we hadchildren even of 7 years witb anorexia) and rela-

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Clinical Significance of Neuronal Oscillations in Children and Adolescents

tively high percent of males (we had 14boys, mean age 12.5 years).

Psychometric evaluations showedhigh anxiety scores (GASC- mean 33 ±1.6 from max score 35), as well as highpsychopathologic scores (p< 0.01), lowextroversion (p<0.01), and low L scores(p< 0.05) on Eyzenck Personality Ques-tionnaire. Tested with MMPI. most pa-tients presented four pick profile Hs-Pd-Pt-Sc related to high anxiety, obses-sion, hypersensitivity. and accentuatedbodily narcissism (9,16,20).

The QEEG analysis (Figure 5)showed significant excess of beta ac-tivity in frontal region (again similar toADHD Subtype 3).

Biofeedback training comprised FIGURE 5.combination of EDR and EEG modali-

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FIGURE 6. Correlation of theta/beta ratio with fb

ties. With EDR we obtained significant rising ofthe skin resistance (p<0.01) related to lowering thesympathetic activity and Ihe psychological stress.To achieve further relaxation, within the same ses-sion alpha neurofeedback training in frontal regionwas applied. Minimum 10 sessions were needed forobtaining clinical improvement, expressed in de-creasing anxiety and obsessive thoughts related tothe weight.

3.4. Severe dehydration in infancyThe sample comprised 40 children, aged 8.82 ±

1.33 years, with a history of severe dehydration inthe early infancy caused by diarrhea. The results ofKoch's Block-Design Test, Gesta it-Bender Motor Testand Rey's Test showed lower intellectual capacity,slower visual-motor maturation and some emotionalproblems, compared with the control group. Mini-mal changes in EEG recording were noticed in 93%of children during hyperventilation. In 7,5% focal

spike-waves changes were fonnd, sug-gesting antiepileptic medication (15,22).

As an indicator of prefrontal func-tioning, the Contingent Negative Vari-ability (GNV) electroexpectrogrammeshowed decreased amplitude and de-layed reaction time (p< 0.05) in com-parison to the control group of healthychildren of the same age (Table 2).

It may be inferred that the severedehydration in childhood may havedetrimental psychoneural effects onthe developing brain.

3.5. Exposure to lead emissionA randomly selected group of 100

children living in a highly pollutedpart of the Macedonian city Veles wasexamined. Consequently, a sample of31 children with blood lead level over16.51 /xg/dl (norm < 10 Mg/dl) was se-

EXP cycles

Max. CNV amplitude

Min. Reaction time

Examined group (40children)

0.68.9/JV

303 msec.

Control group {38children)

3.513.8/iV

245 msec.

TABLE 2: Contingent Negative Variability (CNV)

lected (mean age - 13.62 ± 0.6). Mnltimodal assess-ment with Thought Technology equipment (EEG,EMG, BVP, Skin Conductance, Temperature andRespiration), as well as cognitive psychological tests[Raven matrices and Bender-Gestalt) on selectedchildren have been performed (23).

Negative correlations of blood lead level withIQ (r =-0.28) and positive with Iheta/beta ratio [r =0.47) in tested children were found. Simultaneously,the strong negative correlation (r =-0.80) betweentheta/beta and/,, is confirmed (Figure 6).

The described relations correspond to ADD char-

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Clinical Significance of Neuronal Oscillations in Children and Adolescents

acteristics oí exposed children (24,25,25,26,27,28).

4. CONCLUSIONAlong with multitude psychometric tests, the

neurometric tools describing neuronal oscillations,in particular EEG and QEEG are quite important inpédiatrie diagnostics and therapy. These techniquesmay be efficiently used to assess mental disordersincluding ADHD. OCD and anorexia, as well asmental effects of some somatic disorders, as are de-hydration and toxicity.

Neurometric results sbould be complementedwith other clinical assessment, since the same EEGpatterns may be found in different disorders (e.g. in-creased frontal beta activity in ADHD Subtype 3,OCD or mental anorexia).

Individually adapted integral approach in bothdiagnostics and therapy is important, based on mul-tichanel data for spectrum-weighted frequencies(brain rate] and corresponding arousal levels.I Finally, QEEG can not be a substitute for con-

ventional EEG, and even less for clinical compe-tence. A multidimensional approach, combiningpsychotherapy, pbarmacotherapy and neurotherapy(including biofeedback modalities) is needed, sup-ported by parents and teachers.

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Corresponding author: Prof Nada Pop-Jordanova, MD, PhD. PédiatrieClinic. Faculty of Medicine, University of Skopje, Macedonia. E-mail:

npopjordanova@gmail.com

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