BEYNİN İŞLEVLERİYLE ELEKTRİKSEL AKTİVİESİ ARASINDAKİ İLİŞKİLER

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1 BEYNİN İŞLEVLERİYLE ELEKTRİKSEL AKTİVİESİ ARASINDAKİ İLİŞKİLER
“SİNAPS KAVŞAĞINDA PSİKİYATRİ” GÜZ OKULU, 1-5 Eylül 2003, Artvin T. Psikiyatri Derneği Elazığ Şubesi ve İnönü Üniversitesi Prof.Dr. Pekcan Ungan H.Ü. Tıp Fakültesi Biyofizik Anabilim Dalı

2 ElectroEncephaloGraph
~ 1928 ElectroEncephaloGraph E E G Hans Berger ( ) elektroensefalogram

3 EEG nin oluşumu

4 Hücresel deşarj aktivitesi (PSTH) ile Uyarılmış Potansiyeller (EP)
arasındaki korelasyon Uyanık Yavaş dalga uykusu Karmos et al. / Evoked cortical field potential and unit responses in the wakefullness-sleep cycle in cats. In: Koella et al. (eds.): Sleep’86. Stuttgart, Gustav Fisher Verlag, pp: (1988)

5 – + EEG _ + MEG MEG: hücre-içi akımlar EEG: hücre-dışı akımlar
Akım dipolü – EEG _ + +  Tek bir sinir hücresinin elektriksel aktivitesi kafa yüzeyinden kaydedilemez.  Ancak, dipolleri birbirine paralel olacak biçimde histoanatomik düzene sahip çok sayıda hücre senkron biçimde çalışırlarsa belirli ve anlamlı bir EEG ya da MEG aktivitesi kaydedilebilir. MEG

6 EEG MEG

7 senkronizasyon sonucunda oluşan EEG örnekleri
Hücreler-arası senkronizasyon sonucunda oluşan EEG örnekleri Oksipital alfa aktivitesi (10 Hz patlamaları) Normal kişi (göz kapalı) ‘Petit mal’ epileptik deşarjlar (3 Hz diken-dalga) Epileptik hasta (absans nöbeti)

8 Uyanıklık ve uyku safhalarında EEG

9 δ α θ γ β EEG nin spektral bilşenleri delta teta alfa beta gama
Güç (µV2) delta teta alfa beta gama 2 3 5 7 20 30 50 70 1 1 Frekans (Hz)

10 UYARILMIŞ POTANSİYELLER
 Uyarılmış Potansiyeller, zaman içinde birbirini izleyen (değişik latanslı) ve genellikle herbirisi beyindeki bir başka sürece ait olan ardışık dalgalardan oluşurlar.  Dalga latansları, bu dalgaların kaynaklandıkları düzeyler hakkında kabaca bir fikir verirler.  Uyarılar-arası zaman kısaltıldıkça, önce uzun latanslı yanıtlar, daha sonra kısa latanslılar kaybolur. Dalgaların “toparlanma süreleri” (recovery cycle) olarak bilinen bu özellik, bağımsız yanıt bileşenlerinin birbirinden ayrılması için kullanılır. Kısa latanslı: Beyin sapı Orta latanslı: Tegmentum; talamus; birincil korteks 10 ms uyarı Uzun latanslı: İkincil korteks; assosiyasyon alanları 50 ms uyarı İşitsel Uyarılmış Potansiyeller uyarı 500 ms

11 SCD HARİTALARI VE DİPOL KAYNAKLARI SCD milisaniye
P Ungan, S Yagcioglu, C Goksoy: Differences between the N1 waves of the responses to interaural time and intensity disparities: Scalp topography and dipole sources. Clinical Neurophysiology, 112: , 2001

12 EŞDEĞER AKIM DİPOLLERİ
EEG EEG / MEG + MRI

13 brain-oxygenation-level-dependent BOLD-fMRI
functional magnetic resonance imaging fMRI aktivasyon haritası Stimulation (alternating checkerboard) MRI yanıtının dinamiği

14 Gall’in frenolojik yaklaşımı bir bakıma doğru, bir bakıma yanlıştı.
37 mental & moral özellik: • düzen dikkatlilik süreklilik savaşkanlık mükemmeliyet arkadaşlık yıkıcılık yapıcılık kendine saygı hesaplama renk ağırlık lisan Franz Joseph Gall ( )

15 serebral lokalizasyonism
Pierre Paul Broca (1860 larda) Carl Wernicke (1870 lerde) Broca’nın “Tan” isimli bir afazik hastasının otopsi ile çıkarılmış beyni

16 Penfield’in homonculus’u Gustav Fritsch Eduard Hitzig
(hayvanlarda, motor korteks stimülasyonu) Feodor Krause (insan hastalarda, motor korteks stimülasyonu) David Ferrier ( ) Penfield’in homonculus’u

17 Beynin fonksiyonları Hissetme (duyular) Koku, görme, işitme, tad-koku, dokunma, ağrı Denge ve harekete ilişkin süreçler kas, tendon ve iskelet bileşenlerinden gelen bilgilerin değerlendirilmesi Temel içgüdüler ve duygular açlık, cinsel istek, hiddet, nefret, korku, sahiplenme, vb. Temel davranışsal repertuvar Refleksler, temel ve öğrenilmiş hareket şablonları, oyun, ortamı araştırma, vb. Kognitif yetenekler Dikkat, ilişki kurma, bellek ve öğrenme, tanıma, soyutlama, yaratıcılık, tercih, vb.

18 Uyarılmış potansiyeller - fonksiyon ilişkisine
örnekler

19 Endojen yanıtlar üzerinde ‘öncü’ (priming) etkisi
Ardışık yüz görüntüsü çiftleri ile uyarılan potansiyeller Unprimed: yabancı yüzden sonra tanıdık yüz; Primed same: tanıdık yüzden sonra aynı resim; Primed different: tanıdık yüzden sonra, aynı kişinin değişik bir resmi. Fig. 2. ERPs at inferior and posterior temporal electrodes (TP , TP , P , P , PO , PO ). It can be seen that repetition does not affect the N170, but starts to influence ERPs from |200 ms onwards, and this effect is most prominent at more anterior and inferior locations (e.g. TP ). Two faces (prime and target faces) are shown in succession. Instruction: instantly press left (or right) button if target is familiar and press right (or left) button if target is unfamiliar. Unprimed: unfamiliar prime, followed by familiar target. Primed same: familiar prime, followed by the same picture. Prime different: familiar prime, followed by a different picture of the same person. 500 ms S .R . Schweinberger et al.: Event-related brain potential evidence for a response of inferior temporal cortex to familiar face repetitions. Cognitive Brain Research 14: 398–409 (2002).

20 Kısa süreli bellek taraması ve N1 amplitüdü
Fig. 1. Sample segment of the stimulus sequence for the 5-item MEMORY and NUMBER tasks. In the MEMORY task, the appropriate button press depended on whether the probe was in-set or out-of-set. In the NUMBER task, the appropriate button press depended on whether the probe digit was odd or even. In this example, a correct button press is indicated to an in-set probe in the MEMORY task or to an even number in the NUMBER task. Fig. 2. Behavioral measures (means and standard errors) for all subjects for accuracy (above) and RT (below) as a function of set size for MEMORYand NUMBER tasks. Fig. 3. Grand averaged evoked potentials for probes (above) and for presentation set items (below) at the Cz site. Stimulus onset is indicated by the vertical dashed lines and the average includes a 120 ms prestimulus period and an 840 ms poststimulus period. Components are labeled by polarity and approximate latency after stimulus onset. 2 3 EM Conley et al.: The N100 auditory cortical evoked potential indexes scanning of auditory short-term memory. Clin. Neurophysiol. 110: (1999)

21 Bellek yükü (set-size) arttıkça, N1 amplitüdü azalıyor
Fig. 5. Grand averaged evoked potentials to probes for the MEMORY and NUMBER tasks at Cz. The portion of the average shown includes only the prestimulus period and the time of occurrence of the N100 and P200 components. Means and standard errors for peak amplitudes of N100 pooled over electrodes are plotted as a function of set size on the graphs to the right. Note the amplitude decrement of N100 as a function of set size in the MEMORY task but not in the NUMBER task. P200 amplitude increased slightly as a function of set size in both tasks. Fig. 6. Grand averaged evoked potentials for in-set and out-of-set probes are shown as a function of set size in the MEMORY task at Cz. The portion of the average shown includes only the prestimulus period and the time of occurrence of the N100 and P200 components. Means and standard errors for peak amplitudes of N100 pooled over electrodes are plotted as a function of set size on graphs to the right. N100 amplitude changed linearly with set size for in-set but not out-of-set probes. 5 6 EM Conley et al.: The N100 auditory cortical evoked potential indexes scanning of auditory short-term memory. Clin. Neurophysiol. 110: (1999)

22 P3 Tekrarlananı tanıma etkisi Ekzojen / Endojen bileşenler + 2 µV
400 ms Fig. 1. The ERP repetition/recognition effect displayed for the left (P3) and right (P4) parietal electrodes. Correctly recognized repeated words (hits) elicit a more positive ERP from approximately ms after the onset of their presentation when compared to correctly rejected new words. Tekrarlandığı için sayılan sözcükler Yeni olduğu için sayılmayan sözcükler E. Düzel: When, where, what: the electromagnetic contribution to the WWW of brain activity during recognition. Acta Psychologica 105: (2000).

23 MMN (Mismatch Negativity)
Fark-potansiyel (aykırı-standart) yanıtlar aykırı standart zaman Standart uyaranlar Aykırı uyaranlar

24 Bebeklerde MMN Cheour et al.: Development of language-specific phoneme representations in the infant brain. Nat Neurosci 1998;1:

25 Dikkatin ERP ler üzerindeki etkisi
-2 -4 2 4 6 8 P3 N2 MMN µV P2 P1 standart uyaran aykırı uyaran (dikkat yok) aykırı uyaran (dikkat) N1 100 200 300 400 500 600 ms

26 P300 (P3) ‘3-uyaran’ paradigması: P3a: anterior-santral
Bir standart uyaran, İki aykırı uyaran: a) hedef uyaran b) hedef olmayan uyaran ‘Kolay’: Hedef standarttan kolayca ayrılabiliyor. ‘Zor’ : Hedef standarttan kolayca ayrılamıyor. P3a: anterior-santral P3b: parieto-santral P3a P3b MD Comerchero, J Polich: P3a and P3b from typical auditory and visual stimuli Clin. Neurophysiol. 110: 24–30 (1999)

27 (erken ve geç bileşenler)
Novelty-P3 (erken ve geç bileşenler) nP3 dalgası, iki bileşenden oluşuyor: P3erken: parietal/santral; dikkate bağlı olarak değişmiyor. P3geç: frontal/santral; uyarıya dikkat edildiği zaman daha büyük kaydediliyor. P3a Fig. 1. (a) Distribution over the scalp of the 30 electrodes used in the EEG recordings. (b) Event-related brain potentials (ERPs) at midline electrodes elicited to standard and novel stimuli, and the corresponding difference waves. These revealed the nP3 response, which had two different phases of respective peak latencies at 235 and 335 ms. Gray shadows show the latency intervals used in nP3 analysis, i.e., 185–285 ms for its early phase (dark gray) and 285–385 ms for its late phase (light gray). (c) Scalp potential and current density distributions of the two phases of the nP3. Scalp potential maps show that the late phase of the nP3 was more anteriorly distributed than the earlier phase. Scalp current density analyses revealed positive currents over central, bilateral and left frontotemporal areas during the early nP3a, and over superior parietal, bilateral temporoparietal and frontal areas during the late nP3. E Yago et al .: Spatiotemporal dynamics of the auditory novelty-P3 event-related brain potential Cognit. Brain Res. 16: 383–390 (2003)

28 Spontan EEG - fonksiyon ilişkisine
örnekler

29 Alfa ve gamma aktiviteleri, affektif görsel uyarılar tarafından module edilirler.
hoş nötr Fig. 4. Baseline corrected grand mean spherical spline topographical distributions of the alpha (8±12 Hz) and g-40 (30±50 Hz) frequency band for the 3 affective categories. Note: different scales for the alpha and gamma band. nahoş M Müller at al.: M Processing of affective pictures modulates right-hemispheric gamma band EEG activity. Clin. Neurophysiol. 110: (1999)

30 Bellek performansı ve EEG
Normalized percent power (O1) Fig. 12. Normalized percent power for good (bold line) and bad memory performers (dotted line) during memorizing words at O1 [84] . The ongoing EEG was analysed for 4 min and arbitrarily segmented in epochs of 4 s in order to achieve a frequency resolution of 0.25 Hz. Significant results of t-tests between good and bad memory performers are marked by one asterisk for the 5%-level or two vertically arranged asterisks for the 1%-level . Good memory performers show significantly more upper alpha but less theta power. Similar results were found for all recording sites and even during resting sessions with eyes open and closed. Sözcükleri hatırlama görevi sırasında İyi (sürekli çizgi) ve kötü (kesikli çizgi) bellek performansı gösterenler. W Klimesch: EEG alpha and theta oscillations reflect cognitive and memory performance: a review and analysis. Brain Res. Rev. 29: 169–195 (1999).

31 Sözcükleri ve yüzleri tanıma görevi sırasında EEG gücünde değişmeler
theta ERS (5-8 Hz) words faces Sözcükleri ve yüzleri tanıma görevi sırasında EEG gücünde değişmeler % ERD % ERD alpha ERD lower (8-10 Hz) higher (10-13 Hz) % ERD sözcükler dolu daireler: gerçekten yeni; boş daireler : gerçekten eski. Figure 1. Change in electroencephalogram ~EEG! power over time in the theta frequency range for new and old stimuli averaged across all electrode sites. Power is represented as a percentage change from the mean EEG power in the 21,250 to 0-ms baseline period. Error bars represent the 95% confidence intervals of the mean. Key: filled circles true new; empty circles true old. Figure 2. Change in electroencephalogram ~EEG! power over time in the upper and lower alpha frequency ranges for new and old stimuli averaged across all electrode sites. Power is represented as a percentage change from the mean EEG power in the 21,250 to 0-ms baseline period. Error bars represent the 95% confidence intervals of the mean. Key: filled circles true new; empty circles true old. time (ms) time (ms) yüzler time (ms) time (ms) AP Burgess, JH Gruzelier: Short duration power changes in the EEG during recognition memory for words and faces. Psychophysiology 37: 596–606 (2000).

32 EMG ile kortikal EEG arasında koherens
Fig. 3. Topographic distribution of the coherence estimate between EEG and EMG using the different derivation methods. The grouped average of 5 subjects is shown. The upper limit of the coherence estimate is 0.03 for the linked earlobe reference and 0.05 for the common average reference or CSD. The significance limit (0.01) is applied as the lower limit. The average image of four frequency bins (3.9 Hz) is used. For the linked earlobe and common average reference, the coherence estimate shows the peak at the left central and medial frontal areas. For CSD, the coherence peak is localized over the left central area. T Mima and M Hallett: Electroencephalographic analysis of cortico-muscular coherence: reference effect, volume conduction and generator mechanism. Clin. Neurophysiol. 110: (1999).

33 Hazırlık Potansiyelleri (Bereitschaftspotential)
basit karmaşık seconds movement onset İstemli hareketlerde, hareketten çok önce başlayan bir negatif kayma BASİT KARMAŞIK RQ Cui et al.: High resolution DC-EEG mapping of the Bereitschaftspotential preceding simple or complex bimanual sequential finger movement. Exp. Brain Res. 134:49–57 (2000).

34 Değişik kognitif görevler sırasındaki EEG değişiklikleri
Anderson and Sijercic (1996) Referans görev Gevşeme Mektup yazma bir arkadaşa, seslendirmeksizin, kafadan mektup yazmak Matematik işlem yapma çok kolay olmayan bir çarpma problemini çözmek Görsel sayma hayal edilen bir kara tahtaya, sırayla rakamlar yazıldığını düşünmek Geometrik bir şekli hayali olarak döndürmek belirli bir 3 boyutlu kapalı şeklin bir eksen etrafında döndüğnü hayal etmek. Bir sınıflandırıcı (sinirsel ağ) kullanmak suretiyle, herbir EEG aktivitesinin hangi göreve ait olduğu, belirli doğruluk düzeylerinde saptanabilmektedir. Learning to control brain activity: A review of the production and control of EEG components for driving brain–computer interface (BCI) systems E.A. Curran, M.J. Stokes / Brain and Cognition 51 (2003) 326–

35 ERD / ERS Bir kişi, beyninin elektriksel aktivitesini kontrol edebilir
(brain/computer interface -BCI-) Bir hareketi yaptığını düşünmek Roma grubu (Babiloni et al., 1999) Hayal edilen el ve ayak hareketleri sırasında 8–30Hz bandında EEG değişiklikleri (signal space projection - SSP- technique) Graz grubu (Pfürtscheller et al., 2000) Planlanan veya hayal edilen el ve ayak hareketleri sırasında α ve β bantlarında ERD/ERS Bir hareketi ya da hareket içermeyen bir kognitif görevi yaptığını düşünmek Oxford/London grubu (Penny & Roberts, 1999) El hareketlerinin hayal edilmesi ve mental aritmetik sırasında 8–30Hz bandında EEG değişiklikleri (görsel geri-besleme ile BCI) Operant koşullama ve EEG eğitimi New York grubu (Wolpaw et al., 1991; Vaughan et al., 1996) Santral µ aktivitesinde (8–12 Hz band) değişme Tübingen grubu (Birmbauer et al., 1999) ERD / ERS EA Curran, MJ Stokes: Learning to control brain activity: A review of the production and control of EEG components for driving brain–computer interface (BCI) systems. Brain and Cognition 51: 326– (2003).

36 Olaya ilişkin desenkronizasyon / senkronizasyon (ERD/ERS)
Bir parmağın hareket ettirilmesi G Pfurtscheller, FH Lopes da Silva: Event-related EEG/MEG synchronization and desynchronization: basic principlesClinical Neurophysiology 110: (1999)

37 Beta senkronizasyonu Beta power; grand average
A. Stancak, G. Pfurtscheller: Event-related desynchronisation of central beta-rhythms during brisk and slow self-paced finger movements of dominant and nondominant hand. Cognit. Brain Res. 4: 171–183 (1996).

38 BCI Farklı ekstremitelerin hareketi, farklı frekans bantlarında,
farklı ERD/ERS paternleri oluşturuyorlar. BCI G Pfurtscheller et al.: Foot and hand area mu rhythms. Int. J. Psychophysiol. 26: (1997)

39 Kürsör hareketini kontrol eden mu ritmi
genliği ile, kürsörün yukarıya/aşağıya hareketi arasındaki ilintinin (r2) skalp topografisi. C3 elektrodu için, hareketin yönü ile EEG arasındaki ilintinin (r2) spektrumu (EEG nin frekansına göre değişimi) Fig. 1. Topographical and spectral specificity of EEG control in one subject. Top: Scalp topography of r2 for the mu rhythm frequency band that control cursor movement online. (The nose is at the top.) Control is focused over the left sensorimotor cortex. Bottom: r2 spectrum for electrode C3 (i.e. over the midpoint of the left central sulcus), which controlled cursor movement online. Control is focused in the mu rhythm frequency band. The relationship between target position(i.e. top or bottom) and the EEG measure that controlled cursor movement (e.g. mu rhythm amplitude over the hand area of left sensorimotor cortex is evaluated (Fig. 1). This relationship was assessed by r2, the coefficient of determination, which is the proportion of the total variance of the two distributions (i.e. the distribution of EEG values for top targets and the distribution for bottom targets) that is accounted for by the difference in their means (Wonnacott and Wonnacott, 1977). Tek denek. TM Vaughan et al.: EEG-based communication: analysis of concurrent EMG activity. Electroenceph. clin. Neurophysiol. 107: 428–433 (1998).

40 Robot-kolların EEG ile kontrolü
MAL Nicolelis

41 EEG yardımıyla, bir robota kumanda edilmesi
Gerçek zamanlı neurophysiology: Çok sayıda beyin bölgesinden yapılan nöronal kayıtlar, tasarlanmakta olan motor davranışı saptayabilen bir bilgisayar modeline veriliyor. Bu modelin çıktısı da bir robotun kontrolünü sağlayabiliyor. MAL Nicolelis, S Riberio: Multielectrode recordings: the next steps. Current Opinion in Neurobiology 12: (2002)

42 Alzheimer hastalığı grubunda,
alfa bandındaki koherens değerlerinin normallere göre düşük olduğu bölgeler koherens: normal - hasta (AD) koherens farkı: Fig. 1. Differences of alpha band coherence (d-values) showing where coherence values are lower in the patient (Alzheimer’s Disease) group compared with normals. Coherence: A descriptive analysis of coherence modifications in the AD-patient (P) group, compared with normals (N), was performed by calculation of differences (d-values) between mean coherence values of the two groups, normalized to their standard deviation, for each pair of channels and for each frequency band: Values of coherence difference (d-values) are displayed by a series of topographic maps. A complete series is composed of 16 maps, each one showing the value of the parameter between the selected electrode and the remaining others. The position of a single map in the series represents the electrode taken into account: for example, the first map on the top left of Fig. 1 shows the decrease of alpha coherence between Fp1 and the remaining electrodes in the patient (AD) group, compared with normals (N). The color under each electrode position, in a selected electrode map, indicates the value of the mapped parameter between the pair of electrodes. Alpha coherence was significantly decreased in 6 patients, the decrease being more accentuated in the area near the electrode taken into account; a significant delta coherence increase was found in a few patients between frontal and posterior regions. The AD group showed a significant decrease of alpha band coherence, in particular in temporo parieto-occipital areas, more evident in patients with a more severe cognitive impairment. These abnormalities could reflect two different pathophysiological changes: the alpha coherence decrease could be related to alterations in cortico-cortical connections, whereas the delta coherence increase could be related to the lack of influence of subcortical cholinergic structures on cortical electrical activity. T. Locatellia, et al.: EEG coherence in Alzheimer’s disease. Electroenceph. clin. Neurophysiol. 106: 229–237 (1998)

43 Şizofreni ve P300 JM Ford et al.: Left temporal deficit of P300 in patients with schizophrenia: effects of task. Int. J. Psychophysiol. 38: (2000).

44 Deneğin motivasyonu P300 genliğini etkiliyor
20 denek: İkinci seansa başlarken, deneklerden, hedef uyarıya daha fazla dikkat etmeleri isteniyor. Bir yıl sonra, aynı denekler: İkinci seansa başlarken, deneklere ek bir talimat verilmiyor. MT Carrillo-de-la-Peña, F Cadaveira: The effect of motivational instructions on P300 amplitude. Neurophysiol. Clin. 30: (2000).

45 P300 genliği, şizofreni semptomlarının ağırlığı için bir ölçü olabilir
10 µV P300 genliği, pozitif semptomlar ile negatif korelasyon gösteriyor; fakat negatif semptomlarla bir ilişki göstermiyor . M Higashima: Auditory P300 amplitude as a state marker for positive symptoms in schizophrenia: cross-sectional and retrospective longitudinal studies. Schizophrenia Research 59: 147– 157 (2002).

46 Çeşitli hastalık ve rahatsızlıklarda P300
Pz Cz Fz P300, bilişsel işlevlerin bozulduğu bütün durumlarda etkileniyor. Ayırıcı tanı için şimdilik uygun değil. Fakat, diğer bulgularla birlikte kullanılırsa, tanıya çok yardımcı olabilir. J Polich, K Herbst: P300 as a clinical assay: rationale, evaluation, and findings. Int. J. Psychophysiol. 38: 3-19 (2000).

47 Bir parametrenin NORMAL / HASTA
ayırımı amacıyla kullanılabilirliği için, o parametrenin değişme katsayısı (CV) önemli bir ölçüttür. S.D. SAĞLIK HASTALIK Değişme katsayısı: CV = S.S./ortalama KESİNLİKLE NORMAL KESİNLİKLE HASTA P300 latansı, labratuvar testlerinin çoğundan daha küçük ‘CV’ ye sahip Laboratuvar testleri CV (%) Kolesterol : HDL : Trigliseridler : Plasma Kortizol : Glukoz : Serum hızı : 19.5 Hemoglobin & Potasyum : 3.2-8 TSH : 9-45 J Polich, K Herbst: P300 as a clinical assay: rationale, evaluation, and findings. Int. J. Psychophysiol. 38: 3-19 (2000).

48 P50 baskılanması (sensory gating) schizophrenia migraine
A Ambrosini et al.: Reduced gating of middle-latency auditory evoked potentials (P50) in migraine patients: another indication of abnormal sensory processing? Neurosci. Let. 306: (2001). RJ Erwin et al.: P50 abnormalities in schizophrenia: relationship to clinical and neuropsychological indices of attention. Schizophr. Res. 33: 157–167 (1998).

49 EEG ve ERP parametreleri,
kişilik özelliklerinin ve psikiyatrik bozuklukların elektrofizyolojik endofenotipleridir. Twin and family studies of the human electroencephalogram: a review and a meta-analysis C.E.M. van Beijsterveldt, G.C.M. van Baal / Biological Psychology 61 (2002) Alfa (8-12 Hz) frekans bandındaki EEG gücü (h2: 79%) Vogel, 2000; Boomsma et al., 1997; van Beijsterveldt and Boomsma, 1994) EEG alfa tepe frekansı (çok yüksek MZ ikiz korelasyonu, fakat düşük DZ korelasyonu (h2: 81%) Christian et al., 1996; Lykken et al., 1982; Posthuma et al., 2001b; Stassen et al., 1999 P300 amplitüdü ve latansı (yüksek genetik etkiler; sırasıyla, h2: 65% ve 51%) P50 baskılanması (duyusal kapılama; şizofreni için bir biyolojik işaret, Freedman et al., 1991; 2000) Myles-Worsley et al., 1996; Young et al., 1996 (h2: 44%) EEG koherensi -elektrot kombinasyonları üzerinden ortalanmış- (h2: 60, 65 ve 60%; θ, α ve β için) van Baal et al., 2001a; van Beijsterveldt et al. (1998a) N400 anlam uyumsuzluğu yanıtı (normallerde, ipucu olmadan; alkol-bağımlılarında, ipucu olsa da; Porjesz and Begleiter, 1996) Almasy et al., 2001 (h2: 9-41%; elektroda bağlı olarak, oksipitalde maksimum) Gecikmeli yanıtlama görevinde Yavaş Dalga (çalışma belleği yükü; Ruchkin et al., 1995) Hansell et al., 2001 (h2: 35-37% ve 51-52%; sırasıyla, prefrontal and parietal bölgelerde) [ h2 : Kalıtsallık (heritability): Genetik faktörlerden gelen varyansın toplam varyans içindeki yüzdesi.] Individual differences in psychiatric disorders can for a large part be explained by genetic influences, usually expressed in heritabilities (_/h2: the percentage genetic variance of total, observed variance). For example, the heritability of schizophreniais estimated to be approximately 80% (Cardno and Gottesman, 2000), and theheritability estimates of alcoholism liability ranges from 50 to 60% (Prescott and Kendler, 1999). Despite the large genetic contribution, it has proven difficult to find specific ‘genes of psychopathology’. One promising strategy to identify such genes is to study the neurophysiological processes associated with psychopathology (Carlson et al., 1999; Kuperberg and Stephan, 2000; Polich and Bloom, 1999). It is believed that these neurophysiological processes, the so-called ‘endophenotypes’ of psychiatric disorders, have a more simple genetic architecture, and, therefore, provide more power in gene finding approaches (Boomsma et al., 1997; Kosslyn and Plomin, 2000; de Geus et al., 2001). Good endophenotypes of psychiatric disorders should be (1) meaningfully associated with the disorder; (2) stable over time, and; (3) under significant genetic control (Almasy et al., 2001; Cornblatt and Malhotra, 2001; de Geus et al., 2001). Electroencephalographic (EEG) and event related potential (ERP) parameters are obvious endophenotypes in psychiatry. Much research supports the first criterion for these endophenotypes, i.e. a significant association between various EEG and ERP parameters and psychopathological behavior. One consistent finding, for example, is that reduced P300 amplitude is associated with an increased risk for alcoholism (Porjesz et al., 1998; Porjesz et al., this issue). A similar reduction is seen in unaffected family members of alcoholics, so it is assumed that the P300 reduction indexes the liability for this disorder instead of reflecting its effects. The second criterion of temporal stability of EEG power and ERPs has also held up in virtually all studies done so far. For example, test_/retest correlation coefficients for EEG power are around 0.8 for both absolute and relative power (Pollock et al., 1991; Salinsky et al., 1991) and test_/retest correlations for P300 latency in auditory tasks range from 0.32 to 0.84, and for amplitude from 0.67 to 0.93 (Segalowitz and Barnes, 1993). The third criterion will be the main topic of this paper: to what extent are individual differences in electrophysiological measures determined by genetic and environmental factors? The relative influences of genetic factors in human behavior can be studied noninvasively with twin, adoption or family studies, in which the resemblance for a trait among family members at a given level of genetic relationship is compared. For instance, in the twin design, the resemblance between identical, monozygotic twin pairs (MZ) is compared with the resemblance between fraternal, dizygotic twin pairs (DZ). MZ twin pairs are genetically identical to each other, whereas, fraternal twins share, on average, 50% of their segregating genes. In contrast, sharing of environmental factors is assumed to be highly comparable for MZ and DZ twins. On this biometrical basis, a set of expectations can be generated for the MZ and DZ correlations under various models that differ in the presence and the size of the expected genetic and environmental contribution. With the help of structural equation modeling, the observed resemblance in twins is compared with the expected values from all conceivable models. The best model is the model where the discrepancies between the observed and expected statistics are minimal. This best fitting model can be used to derive the estimates of variance attributable to additive effects of alleles at multiple loci (a2), non-additive genetic effects due to interaction of alleles at a locus (d2), common environmental effects (c2) that are shared by all siblings in a family, and nonshared environmental effects (e2), that are unique to each sibling (Neale and Cardon, 1992). Broad heritability is the proportion of observed, phenotypic variance that can be explained by all sources of genetic factors, and equals to (a2_/d2)/(a2_/c2_/e2_/d2). Narrow heritability, or just heritability, is the proportion of observed variation accounted for by the additive genetic component. This paper will begin by briefly reviewing the twin and family studies on the heritability of EEG and ERPs (listed in Tables 1 and 2). These were tracked in the standard way by using web-based resources (keywords: twin, genetics, heritability, ERP, EEG) supported by inspection of the reference section of the papers found. The main aim of our review was to identify papers with a comparable methodology that could be used in a structural equation modeling meta-analysis. This metaanalysis constitutes the second part of this paper. Why do a meta-analysis? Twin and family research on the causes of individual differences require large samples (hundreds of subjects) in order to obtain meaningful statistical power. This needs to be reconciled with the time-consuming nature and the relatively large expenses involved in electrophysiological measurements. Many of the existing studies had sufficient power to robustly detect familial contribution, but may have lacked the power to discriminate additive from non-additive genetic transmission or to separate genetic from common environmental influences. As a consequence, large discrepancies are visible in the results of the papers summarized in Tables 1 and 2. With a meta-analysis of all comparable studies reporting twin correlations on ERP and EEG measures, we hoped to resolve some of these discrepancies. Specifically, we hoped to obtain more accurate estimates of the genetic and environmental contribution to individual differences in the human EEG. C.E.M. van Beijsterveldt, G.C.M. van Baal / Biological Psychology 61 (2002) 111_/

50 UYARIM GÖREV YA DA BEYİN
Özel olarak tasarlanmış uyaranlar, uyarım paradigmaları ya da görevler yardımıyla, duyusal ve kognitif sistemler selektif olarak uyarılabilirler. konuşma, müzik bellek ve öğrenme ilişkilendirme dikkat algı kognitif süreçler kognitif sürece özel stimulus ve/veya görev paradigması (örneğin, ’oddball’ ve düğmeye basma) UYARIM YA DA GÖREV ‘top-down / bottom-up’ etkileşimler duyusal süreçler somatosensoryel BEYİN görsel şiddet işitsel incelik non-spesifik uyaranlar (algılanabilen herhangi bir stimulus) Yer harekete ilişkin alt-modaliteye özel stimululus (örneğin, lateral doğrultuda kayma) modaliteye özel stimulus (örneğin, bir sesin başlaması)

51 EEG ve UYARILMIŞ POTANSİYEL LABORATUVARI
(H.Ü. Tıp Fakültesi, Biyofizik AD) ARAŞTIRMA ALANLARI Duyusal mekanizmalar (EP) İşitsel sistem Görsel sistem Kognitif süreçler (ERP) Kısa süreli bellek (MMN) Dikkat (N2, P300) Modaliteler-arası etkileşim Hareket ERD/ERS Nicel EEG Beyin haritalama Dipol kaynak analizi Hayvan çalışmaları (kedi, sıçan, guinea pig; stereotaksik teknikler) Prof.Dr. Pekcan Ungan Yrd.Doç.Dr. Süha Yağcıoğlu Araş.Gör.Dr. A. Ruhi Soylu Araş.Gör. Nurhan Erbil