Activity of anatomically defined regions of the human cerebral cortex, through connectivity produces functional heterogeneity represented by behavioral aspect. Basic physiological substrate of the ...interconnection between anatomical subregions is a subject of continuous research. Focal epilepsy, exclusive cortical disease, is an excellent model for the exploration of the neurobiological basis of functional anatomy. Specifically, cortical irritative phenomenon in a region (the final pathophysiological product of epileptogenesis in epileptogenic lesion), in addition to the initial symptoms, leads to a large number of different, time-conditioned, combination of the clinical symptoms and signs - behavior patterns during epileptic seizure. Sequential arrangement of signs and symptoms is determined by the propagation of abnormal electrical activity in the cortex and anatomical pathways from the generator to the close and distant brain regions. Preferential path of the propagation is part of the epileptic network’s neurodiversity that is dominantly uniform at the individual level. Although minor inter-individual variations has been given, it is believed that the number of combinations in the pattern of behavior in focal seizures in the human species is final. The primary goal of the doctoral dissertation was to determine the clinical correlation between defined epileptic symptoms and signs (semiology) and localization of epileptogenic lesions. We performed a clinical-anatomic correlation of a representative sample of patients with focal epilepsy, treated at the Department of Neurology, Clinical Center of Serbia, according to modern trends in epileptology. The results of the material analyzed demonstrate the complexity of the epileptic network upgraded to a physiological level of connectivity, as well as certain regularities, which support existing neurobiological concept of functional anatomy and determine the clinical belief in modern epileptology. Coherent oscillations and epileptic activity generates behavioral phenomena, such as the complete cessation of motor activity or oroalimentary automatisms, most common signs in the analyzed population. Behavioral arrest, an early sign, suggests the limited activity of the cerebral cortex, with the probable disruption in cortico-subcortico-spinal pathways. Oroalimentary automatisms, the phenomenon of the second half of seizures, are possible product of the activation and inhibitory stimuli in wider cortical regions with the final resultant in the archaic behavior. Epigastric and psychic aura are among the most frequent subjective experiences in analyzed patients; central autonomic network, viscerotopic presentation in narrowly localized cortex and interplay of paleo-and neo-cortex are likely pathophysiological mechanisms of these symptoms. In defined subpopulations interferance of the heterogeneity of semiological signs with demographic characteristics is shown, but the analysis indicated a pronounced homogenization of some of the analyzed variables, depending on the anatomical localization epileptogenic zone, which is methodologically and conceptually in the study, equal to the epileptogenic lesion. A substantial majority in the analyzed cohort demonstrated epileptogenic lesion, which is usually localized in the mesial temporal region. Hippocampal sclerosis and focal cortical dysplasia are pathological substrates of focal epilepsy in two-thirds of the analyzed patients. Subgroups with lesions in the mesial temporal cortex and lateral lobes, insula and occipital lobe, have homogeneous and defined patterns of behavior. Phenomenology of the mesial temporal lobe epilepsy consists of a combination of activation and inhibition in the limbic system, vegetative cortex (predominantly right), a memory circuit (predominantly left), and propagation in the basal ganglia and the intermittent interruption of cortico-subcortico-spinal system. Activation that arises in medial temporal region contains four subclusters of the semiological signs. In the lateral temporal epilepsy dominated nosology that stands in the background, along with some of the signs of mesial temporal epilepsy, is activation of the auditory eloquent cortex and areas of the perisilvian and posterior regions. Insular clinical presentation incorporates mainly vegetative signs and symptoms which are generated in the frontal operculum region. Occipital cortex initially generates visual symptoms, followed by a consistent dual propagation (to the frontal and temporal lobe), whose symptoms are contained in subclusters of a local activation in medial frontal and temporal cortex or secondary generalization. The data analyzed in the epileptogenic lesion subgroups in the dorsolateral frontal and parietal cortex are insufficient for uniform conclusion. Subpopulation without epileptogenic lesion has associated clinical features, which include a tendency to seizures with secondary generalization and nocturnal chronobiological presentation. Nonlesional subpopulation has indirect determinants of the epileptogenic process in frontal region. A comprehensive analysis of extensively studied patterns of behaviour in focal seizures suggests the existence of epileptic network, composed of strict and defined anatomo-functional units, which have a generating capacity of preferential connectivity, most likely achieved by permanent communication between pacemaker and neighboring regions by abnormal electrical activity.
Aktivnost anatomski definisanih regiona humanog cerebralnog korteksa, kroz konektivnost, proizvodi funkcionalnu heterogenost reprezentovanu kroz bihejvioralni aspekt. Bazični fiziološki supstrat interkonekcije anatomskih podregiona predmet je stalnih istraživanja. Fokalna epilepsija, kao eksluzivna kortikalna bolest, odličan je model za eksploraciju neurobiološke osnove funkcionalne anatomije. Tačnije, iritativni kortikalni fenomen u jednom regionu (finalni patofiziološki produkt epileptogeneze u epileptogenoj leziji), pored inicijalnog simptoma, dovedu do većeg broja različitih, vremenski uslovljenih, kombinacija kliničkih simptoma i znakova – obrazaca ponašanja tokom epileptičnog napada. Sekvencijalni raspored simptoma i znakova determinisan je propagacijom abnormalne električne aktivnosti kroz korteks i anatomske puteve, od generatora do bliskih i udaljenih moždanih regiona. Preferencijalni put propagacije deo je neurodiveziteta epileptične mreže i dominantno je uniforman na individualnom nivou. Iako su poznate i manje inter-individualne varijacije, veruje se da je broj kombinacija u obrascu ponašanja tokom fokalnog epileptičnog napada, u ljudskoj vrsti, konačan. Primarni cilj doktorske disertacije bio je utvrđivanje korelacije klinički definisanih epileptičnih simptoma i znakova (semiologije) i lokalizacije epileptogene lezije. Učinjena je kliničko-anatomska korelacija na reprezentativnom uzorku bolesnika sa fokalnom epilepsijom, obrađenih na Klinici za neurologiju Kliničkog Centra Srbije, shodno, trendovima moderne epileptologije. Rezultati na analiziranom materijalu demonstriraju kompleksnost epileptične mreže nadgrađene na fiziološkom nivou konektivnosti, ali i izvesne zakonomernosti, koje podupiru postojeći neurobiološki koncept funkcionalne anatomije i utvrđuju klinička uverenja u modernoj epileptologiji. Koherentna i oscilatorna epileptična aktivnost generiše bihejvioralne fenomene, poput potpunog prestanka motorne aktivnosti ili oroalimentarnih automatizmama, znakova koji su najčešći u analiziranoj populaciji. Bihejvioralni arest, rani znak, sugeriše na limitiranu aktivnost u cerebralnom korteksu, uz verovatnu disrupciju kortiko-subkortiko-spinalnih veza. Oroalimentarni automatizmi, fenomen druge polovine epileptičnog napada, mogući su proizvod aktivacionih i inhibitornih stimulusa više kortikalnih regiona sa finalnom rezultantom u arhaičnom ponašanju. Epigastrična i psihička aura najfrekventniji su među subjektivnim doživljajima analiziranih bolesnika; centralna autonomna mreža, viscerotopna prezentacija usko lokalizovanog korteksa i međuigra paleo- i neo-korteksa verovatni su patofiziološki mehanizmi ovih simptoma. U definisanim subpopulacijama pokazano je da izvesna heterogenost semioloških znakova interferira sa demografskim karakteristikama, ali je analiza ukazala na naglašenu homogenizaciju pojedinih analiziranih varijabli, zavisno od anatomske lokalizacije epileptogene zone, koja je, metodološki i konceptualno za potrebe studije, izjednačena sa epileptogenom lezijom. Kod značajne većine u analiziranoj kohorti demonstrirana je epileptogena lezija, koja je najčešće lokalizovana u mezijalnom temporalnom regionu. Hipokampusna skleroza i fokalna kortikalna displazija patološki su supstrati fokalnih epilepsija kod dve trećine analiziranih. Podgrupe sa lezijama u mezijalnom i lateralnom korteksu temporalnog lobusa, insuli i okcipitalnom lobusu, imaju homogene i definisane obrasce ponašanja. Fenomenologija mezijalne temporalne epilepsije sastoji se od kombinacije rezultata aktivacije i inhibicije limbičkog sistema, vegetativnog korteksa (dominantno desno), memorijskog kruga (dominantno levo), propagacije u bazalne ganglije i intermitentnog prekida kortiko-subkortiko-spinalnog sistema. Aktivacija koja proističe iz mezijalnog temporalnog regiona sadrži četiri subklastera semioloških znakova. U lateralnoj temporalnoj epilepsiji dominira nozologija u čijoj pozadini stoji, uz neke od znakova mezijalne temporalne epilepsije, aktivacija elokventnih zona auditivnog korteksa i posteriornog perisilvijevog regiona. Insularna klinička prezentacija inkorporira uglavnom vegetativne znake i znakove koji se generišu u frontalnom operkulumu. Okcipitalni korteks inicijalno generiše vizuelne simptome, iza kojih sledi dosledna dvojna propagacija (prema frontalnom i temporalnom lobusu), čiji simptomi su sadržani u subklasterima lokalne aktivacije mezijalnog frontalnog ili temporalnog korteksa i sekundarne generalizacije. Analizirani podaci u
