The neural mechanisms underlying genetic risk for schizophrenia, a highly heritable psychiatric condition, are still under investigation. New schizophrenia risk genes discovered through genome-wide association studies (GWAS), such as neurogranin (NRGN), can be used to identify these mechanisms. In this study we examined the association of two common NRGN risk single nucleotide polymorphisms (SNPs) with functional and structural brain-based intermediate phenotypes for schizophrenia. We obtained structural, functional MRI and genotype data of 92 schizophrenia patients and 114 healthy volunteers from the multisite Mind Clinical Imaging Consortium study. Two schizophrenia-associated NRGN SNPs (rs12807809 and rs12541) were tested for association with working memory-elicited dorsolateral prefrontal cortex (DLPFC) activity and surface-wide cortical thickness. NRGN rs12541 risk allele homozygotes (TT) displayed increased working memory-related activity in several brain regions, including the left DLPFC, left insula, left somatosensory cortex and the cingulate cortex, when compared to non-risk allele carriers. NRGN rs12807809 non-risk allele (C) carriers showed reduced cortical gray matter thickness compared to risk allele homozygotes (TT) in an area comprising the right pericalcarine gyrus, the right cuneus, and the right lingual gyrus. Our study highlights the effects of schizophrenia risk variants in the NRGN gene on functional and structural brain-based intermediate phenotypes for schizophrenia. These results support recent GWAS findings and further implicate NRGN in the pathophysiology of schizophrenia by suggesting that genetic NRGN risk variants contribute to subtle changes in neural functioning and anatomy that can be quantified with neuroimaging methods.

The side-effects of chemotherapy treatment are an increasingly important research focus as more cancer patients are reaching survivorship. While treatment allows for survival, it can also lead to problems which can significantly affect quality of life. Cognitive impairments after chemotherapy treatment are one such factor. First presented as anecdotal patient reports, over the last decade empirical evidence for this cognitive concern has been obtained. Much attention has been focused on post-chemotherapy research, yet little attention has been granted to these same patients’ cognition before treatment commences. Breast cancer (BC) patients face many obstacles before chemotherapy treatment such as: surgery and side-effects of anesthesia, increased cytokine activity, stress of a new disease diagnosis and upcoming challenges, and emotional burdens such as depression and anxiety. Many of these factors have independently been shown to affect cognitive abilities in both healthy populations as well as other patient groups. Therefore, the pre-treatment (or baseline) BC patient status warrants systematic study. This would then reduce mistakenly attributing carried-over cognitive deficits to side effects of chemotherapy. As well, it is possible that certain confounding variables may have neural manifestations at baseline that could be exacerbated by chemotherapy agents. The following thesis first presents a review paper which critically describes the current literature examining chemotherapy-related cognitive impairments (CRCIs), as well as possible confound variables affecting this population. Subsequently, three original research papers present pre-chemotherapy data showing significant neuroanatomical and neurofunctional differences in BC patients compared to controls. In particular, these neural differences are present in brain regions that have been reported in post-chemotherapy papers. This, as well as the effects of variables such as the number of days since surgery, depression and anxiety scores and more, support the initiative that research attention should increase focus on these patients at baseline in order to better understand their post-chemotherapy results.

Diss. (sammanfattning) Umeå : Umeå universitet, 2010.

Abstract Schizophrenia and other psychotic disorders are severe and disabling mental disorders that break out during early adulthood, often when a person is in his/her early 20s. Furthermore, functional decline in many cognitive areas, including the ability to communicate in social interactions and impaired facial expression recognition, is typical to patients with schizophrenia. Understanding the risk factors of psychosis is essential as these disorders may be more amenable to treatment in their early stages. However, recognition of those at the highest risk of psychosis is challenging as no definitive biomarkers are available. Functional MRI is a promising tool that can potentially identify neural signals relating to the individual’s risk of psychosis onset. Psychotic disorders are etiologically heterogeneous disorders — both environmental and genetic factors have been linked to the onset of psychotic disorders. The most influential risk factor for a psychotic disorder is familial risk with genetic loading. The present study examines whether familial risk of psychosis (FR), the polygenic risk score for schizophrenia (PRS) and early adversity associate with brain response to faces. We used fMRI to measure blood oxygen level dependent (BOLD) response to faces. Our study showed that FR associated with deviant prefrontal cortex BOLD responses. In addition, we detected that interregional BOLD signal and grey matter volume varied as a function of PRS; the lowest functional and structural covariance was detected in individuals with high PRS. We also detected that early adversities associated with brain response to faces and that this association varied as a function of glucocorticoid receptor gene expression. Our findings indicate that the above risk factors of psychosis associate with brain response to faces. / Tiivistelmä Skitsofrenia ja muut psykoosisairaudet ovat vakavia mielenterveyden häiriöitä, jotka puhkeavat usein nuorella aikuisiällä. Eräs tyypillinen piirre psykoosisairauksille on vaikeus tunnistaa muiden ihmisten kasvonilmeitä. Psykoosisairauksien riskitekijöiden ymmärtäminen on tärkeää, sillä hoito tehoaa parhaiten sairastumisen alkuvaiheessa. Suurimmassa psykoosivaarassa olevien henkilöiden tunnistaminen on kuitenkin haastavaa, sillä luotettavia tautiin liittyviä biomarkkereita ei ole saatavilla. Toiminnallinen magneettikuvaus (fMRI) on lupaava työkalu, jolla saattaa olla tulevaisuudessa käyttöarvoa psykoosivaaraan liittyvien aivomuutosten tunnistamisessa. Etiologialtaan psyykoosisairaudet ovat heterogeenisiä: sekä ympäristö että perinnölliset tekijät vaikuttavat yksilön sairastumisriskiin. Voimakkain riskitekijä on suvullinen psykoosialttius. Tässä osajulkaisuväitöskirjassa tutkitaan suvullisen psykoosialttiuden, skitsofrenian polygeenisen riskipisteen (PRS) sekä varhaisten vastoinkäymisten yhteyttä aivojen kasvonilmeitä tulkitsevaan järjestelmään. Tutkimuksessa on hyödynnetty fMRI-kuvausta kasvonilmestimuluksen aikana. Tutkimuksessamme suvullinen psykoosialttius oli yhteydessä etuotsalohkon fMRI-signaalimuutoksiin. Tämän lisäksi havaitsimme, että kasvonilmejärjestelmän fMRI-signaalin ja harmaan aineen kovarianssi oli yhteydessä PRS:ään: matalin aivoalueiden välinen korrelaatio havaittiin henkilöillä, joiden PRS oli korkea. Havaitsimme myös, että varhaiset vastoinkäymiset ovat yhteydessä kasvonilmeiden aikaansaamiin aivovasteisiin. Tämä assosiaatio oli myös yhteydessä glukokortikoidireseptorin geenin ilmentymiseen. Väitöskirjan löydökset viittaavat siihen, että edellä mainitut psykoosin riskitekijät ovat yhteydessä kasvonilmeitä tulkitsevaan järjestelmään.

La mentalisation, ou la capacité d’élaborer des hypothèses sur les états mentaux d’autrui, a fait l’objet de nombreuses études durant les 20 dernières années dans le champ des neurosciences sociales. Toutefois, les bases neurales de cette fonction particulièrement complexe restent mal comprises, notamment en termes de connectivité structurale. Récemment, une organisation anatomo-fonctionnelle en double voie a été proposée. Selon ce modèle, les aspects réflexifs, inférentiels, de la mentalisation seraient sous-tendus par le faisceau cingulaire. Les aspects préréflexifs, identificatoires, seraient médiés, quant à eux, par le complexe faisceau arqué/partie latérale du faisceau longitudinal supérieur (FLS). L’objectif général de ce travail est d’apporter des données originales sur l’organisation anatomo-fonctionnelle du réseau neural impliqué dans la mentalisation basée sur les visages. Pour ce faire, nous avons utilisé comme modèle physiopathologique d’étude le gliome diffus de bas grade. Cette tumeur cérébrale primitive s’avère particulièrement intéressante pour l’étude du rôle de la substance blanche dans la cognition et ce pour deux raisons : (i) les cellules tumorales se propagent préférentiellement le long des fibres blanches ; (ii) l’exérèse chirurgicale est souvent réalisée en condition éveillée avec cartographie fonctionnelle peropératoire pour permettre d’identifier, et ainsi de préserver, les structures fonctionnelles, notamment de substance blanche.Dans une première étude, grâce aux stimulations électriques peropératoires, nous avons pu identifier un vaste réseau cortico-sous-cortical impliqué dans la mentalisation. L’analyse des déconnexions induites par les stimulations de la substance blanche nous a permis de mettre clairement en évidence, et ce pour la première fois, le rôle du faisceau occipito-frontal inférieur (FOFI) tout en confirmant celui du FLS. Dans une deuxième étude, en utilisant des techniques de cartographie lésionnelle chez des patients ayant été opérés, nous avons démontré que les troubles permanents, non compensables, de la mentalisation étaient expliqués par l’atteinte du faisceau arqué. Enfin, dans une dernière étude, en combinant l’imagerie par résonance magnétique fonctionnelle de repos (IRMfr) et les sites corticaux démasqués pendant la chirurgie, nous avons pu générer de véritables cartographies fonctionnelles du réseau cortical de la mentalisation, très similaires à celles observées en imagerie fonctionnelle classique.De façon générale, nos découvertes suggèrent que la mentalisation basée sur les visages reposerait sur l’intégrité d’au moins deux faisceaux associatifs de substance blanche. Elles permettent également de valider l’utilisation combinée de l’IRMfr et des stimulations corticales en tant qu’approche originale pour cartographier les réseaux neurocognitifs.En plus de ces considérations fondamentales, nos résultats ont des implications cliniques, notamment pour la cartographie fonctionnelle peropératoire. Ils permettent en outre de mieux comprendre les pathologies cérébrales caractérisées par un trouble de la mentalisation et une atteinte des voies de substance blanche. / Mentalizing, or the ability of human beings to make assumptions about other people’s mental states, has been the subject of many studies over the last 20 years. The neural bases and especially the white matter connectivity of this complex cognitive function is still poorly understood. Recently, an anatomo-functional organization into two neural pathways has been proposed. According to this model, it is assumed that the reflective, inferential aspects of mentalizing is underpinned by the cingulum. The reflexive, identificatory aspects of mentalizing are thought to be mediated, for their part, by the arcuate fascicle and the lateral part of the superior longitudinal fascicle. The main purpose of this scientific work is to provide original data on the anatomo-functional organization of the neural network involved in the face-based mentalizing. We used as a pathophysiological study model diffuse low-grade gliomas. These primary brain tumors are particularly interesting for the study of the functional role of the white matter for two reasons: (i) the tumor cells propagate preferentially along the white matter fibers; (ii) the surgical resection is often performed in awake condition with intraoperative functional mapping to identify, and thus to preserve functional structures, including the white matter.In our first study, using intraoperative electrical stimulation, we were able to identify a large cortico-subcortical mentalizing network. The analysis of the disconnections induced by the stimulation of the white matter allowed us to clearly highlight, for the first time, the role of the inferior fronto-occipital fascicle. We also confirmed the already established role of the superior longitudinal fascicle in mentalizing. In a second study, using lesion mapping analyses in patients operated on for a diffuse low-grade glioma, we demonstrated that the long-term, non-compensatory mentalizing deficit was explained by the involvement of the arcuate fascicle. Finally, in a third study combining resting-state functional MRI and the cortical sites unmasked during surgery, we were able to identify a large cortical mentalizing networks, which were very similar to those identified by classical task-based functional imaging.In general, our findings suggest that the face-based mentalizing would require the integrity of at least two associative white matter fascicles. They also validate the combined use of resting-state functional MRI and direct cortical stimulations as an original approach to map neurocognitive networks.In addition to these fundamental considerations, our results have also clinical implications, especially regarding the intraoperative functional mapping. They also provide a better understanding of brain pathologies characterized by both mentalizing deficit and white matter impairment.

This PhD thesis investigated the role of the basal ganglia in memory and motor inhibition. Recent neuroimaging evidence suggests a supramodal network of inhibition involving the lateral prefrontal cortex. Here we examined whether this supramodal network also includes subcortical structures, such as the basal ganglia. Despite their well-established role in motor control, the basal ganglia are repeatedly activated but never interpreted during memory inhibition. We first used a series of meta-analyses to confirm the consistent involvement of the basal ganglia across studies using memory and motor inhibition tasks (including the Go/No-Go, Think/No-Think, and Stop-signal tasks), and discovered that there may be different subprocesses of inhibition. For instance, while the Go/No-Go task may require preventing a response from taking place, the Think/No-Think and Stop-signal tasks may require cancelling an emerging or ongoing response. We then conducted an fMRI study to examine how the basal ganglia interact with other putative supramodal regions (e.g., DLPFC) to achieve memory and motor inhibition during prevention and cancellation. Through dynamic causal modelling (DCM), we found that both DLPFC and basal ganglia play effective roles to achieve inhibition in the task-specific regions (hippocampus for memory inhibition; primary motor cortex (M1) for motor inhibition). Specifically, memory inhibition requires a DLPFC-basal ganglia-hippocampus pathway, whereas motor inhibition requires a basal ganglia-DLPFC-M1 pathway. We correlated DCM coupling parameters with behavioural indices to examine the relationship between network dynamics during prevention and cancellation and the successfulness of inhibition. However, due to constraints with DCM parameter estimates, caution is necessary when interpreting these results. Finally, we used diffusion weighted imaging to explore the anatomical connections supporting functions and behaviour. Unfortunately, we were unable to detect any white matter variability in relation to effective connectivity or behaviour during the prevention or cancellation processes of memory and motor inhibition at this stage. This PhD thesis provides essential INITIAL evidence that not only are the basal ganglia consistently involved in memory and motor inhibition, but these structures are effectively engaged in these tasks, achieving inhibition through task-specific pathways. We will discuss our findings, interpretations, and future directions in the relevant chapters.

Dystonia is a neurological syndrome characterized by the involuntary contraction of opposing muscles, causing twisting movements or abnormal postures (modified by Fahn, 1987). Writer's cramp is the most common form of task-specific focal dystonia. In the first study, patients with writer's cramp were evaluated for differences in cortical activation during movements likely to induce cramps (complex movements) and movements which rarely lead to dystonia (simple movements). Although complex patient movements during fMRI were never associated with dystonic cramps, they exhibited abnormally decreased cortical activity. This was not observed in simple movements and was unrelated to the character of handwriting or the presence/absence of visual feedback. Our results support the theory of dualistic sensorimotor system behavior in writer's cramp. As the somatosensory system is believed to be affected in focal dystonia, we focused on modulation of the primary somatosensory cortex (SI) induced by repetitive transcranial magnetic stimulation (rTMS) in the second study, in order to improve writer's cramp. In conclusion, 1 Hz rTMS of the SI cortex can improve manifestations of writer's cramp while increasing cortical activity in both hemispheres. Handwriting as well as subjective assessment improved in most...

Muitas operações cognitivas requerem velocidade de processamento de informação (VPI) suficiente para serem executadas dentro do prazo permitido, sendo que VPI retardada geralmente está subjacente a déficits atencionais. A desaceleração no tempo de resposta é particularmente evidente em pacientes com traumatismo crânio-encefálico, doença de Parkinson, depressão, demência e esclerose múltipla (EM). A importância de compreender os déficits de VPI e o desenvolvimento de programas efetivos de reabilitação é, portanto, crítico. Devido à sua alta validade preditiva e à sua fácil administração, o Symbol Digit Modalities Test (SDMT) é um dos testes clínicos mais amplamente utilizados para a avaliação cognitiva de pacientes com menor VPI. No entanto, além de avaliar a presença e gravidade de seus déficits, é interessante determinar as regiões cerebrais responsáveis por essa função e sua integração. Devido à sua não invasividade e ao seu bom nível de confiabilidade, a técnica de Imagem de Ressonância Magnética Funcional Dependente do Nível de Oxigenação no Sangue (BOLD-fMRI) é a ferramenta mais apropriada para esse fim. Logo, o objetivo do presente estudo foi o mapeamento funcional cerebral de VPI durante o desempenho de uma tarefa (SDMT) adaptada para o ambiente da ressonância em um grupo de voluntários saudáveis jovens. 16 controles saudáveis destros foram recrutados e submetidos à avaliação cognitiva com a versão oral do SDMT antes da aquisição de imagens. IRM foi adquirida em um sistema de 3T (Philips Achieva). Imagens funcionais (BOLD) foram adquiridas com uma sequência EPI. O experimento consistiu de seis blocos de 30 s de controle intercalados com cinco blocos de 30 segundos de tarefa (SDMT). Durante os blocos de tarefa, um símbolo foi apresentado a cada 2 segundos e ao participante foi requerido que associasse o número correspondente ao símbolo apresentado baseando-se em uma chave de resposta. Durante os blocos de controle, um número foi apresentado a cada 2 segundos e ao participante foi requerido que lesse silenciosamente o número em questão. Mapas paramétricos estatísticos foram obtidos para estudo de localização funcional utilizando o Modelo Linear Geral com um regressor boxcar convoluído com uma função de resposta hemodinâmica canônica (p-FDR < 0,01). Foi realizada a correlação bivariada entre as séries temporais médias das regiões associadas à tarefa para estudo de integração funcional (p-FDR < 0.0001). As informações de localização e integração funcionais foram inseridas em analise de conectividade efetiva. Ativações foram observadas na rede frontoparietal e no córtex occipital para análises individual e em grupo. Análise de conectividade efetiva para a arquitetura do sistema revelou o declive em posição serial com o giro lingual, o cúneo e duas regiões paralelas (pré-cúneo e lóbulo parietal superior), a partir do qual a informação converge para o giro frontal inferior e se bifurca para os giros frontais médios esquerdo e direito. Um modelo de rede envolvendo áreas relacionadas à VPI foi obtido e pode servir como referência para investigações futuras deste processo cognitivo em grupos clínicos, combinadas com estudos de neuroplasticidade cerebral. / Many cognitive operations require sufficient information processing speed (IPS) to be executed within the allowed time frame, with delayed IPS often underlining attentional deficits. The deceleration in response time is particularly evident in patients with traumatic brain injury, Parkinson\'s disease, depression, dementia and multiple sclerosis (MS). The importance of understanding IPS deficits and developing effective rehabilitation programs is therefore critical. Because of its high predictive validity and easy administration, the Symbol Digit Modalities Test (SDMT) is one of the most widely used clinical tests for the cognitive assessment of patients with lower IPS. However, in addition to evaluating the presence and severity of its deficits, it is interesting to determine the brain regions responsible for this function and its integration. Because of its non-invasiveness and its good level of reliability, the BOLD-fMRI technique is the most appropriate tool for this purpose. Therefore, the aim of the present study was the functional brain function mapping of IPS during the performance of a task (SDMT) adapted to the resonance environment in a group of healthy young volunteers. 16 healthy right controls were recruited and submitted to cognitive assessment with the oral version of SDMT prior to image acquisition. MRI was acquired in a 3T system (Philips Achieva). Functional images (BOLD) were acquired with an EPI sequence. The experiment consisted of six blocks of 30 s of control intercalated with five blocks of 30 seconds of task (SDMT). During the task blocks, a symbol was displayed every 2 seconds and the participant was required to associate the number corresponding to the displayed symbol based on a response key. During the control blocks, a number was displayed every 2 seconds and the participant was required to silently read the number in question. Statistical parametric maps were obtained for functional localization study using the General Linear Model with a boxcar regressor convolved with a canonical hemodynamic response function (p-FDR <0.01). The bivariate correlation between the mean time series of the regions associated with the task for functional integration study (p-FDR <0.0001) was performed. The functional location and integration information was inserted into effective connectivity analysis. Activations were observed in the frontoparietal network and in the occipital cortex for individual and group analyzes. Effective connectivity analysis for the system architecture revealed the declive in serial position with the lingual gyrus, the cuneus and two parallel regions (precuneus and superior parietal lobule), from which the information converges to the inferior frontal gyrus and bifurcates to the left and right middle turns. A network model involving areas related to IPS has been obtained and may serve as a reference for future investigations of this cognitive process in clinical groups, combined with studies of cerebral neuroplasticity.

Na área de processamento de sinais biomédicos a extração de informação, baseada em um conjunto de medidas adquiridas no tempo, é considerada de suma importância. A qualidade desta informação extraída permite avaliar o funcionamento dos diversos órgãos. Objetivos: (1) propor o método de análise de componentes dependentes para auxiliar a extração de componentes de interesse, a partir de medidas multivariadas; (2) caraterizar as componentes extraídas através de representações em termos de tempo e freqüência, e espectro de potência; e, (3) aplicar o método e avaliar as componentes de interesse extraídas no contexto real MCGf, MGG e fMRI. A proposta para a extração fundamenta-se no método chamado de Análise de Componentes Dependentes ACD. As medidas a serem processadas são multivariadas a partir de sensores distribuídos, espacialmente, no corpo humano dando origem a um conjunto de dados correlacionados no tempo e/ou no espaço. Observa-se que os sinais de interesse raramente são registrados de forma isolada, e sim misturados com outros sinais superpostos, ruído e artefatos fisiológicos ou ambientais, onde a relação sinal-ruído é geralmente baixa. Nesse contexto, a estratégia a ser utilizada baseia-se na ACD, que permitirá extrair um pequeno número de fontes, de potencial interesse, com informações úteis. A estratégia ACD para extração de informação é aplicada em três importantes problemas, na área de processamento de sinais biomédicos: (1) detecção do sinal do feto em magnetocardiografia fetal (MCGf); (2) detecção da atividade de resposta elétrica do estômago em magnetogastrografia (MGG); e, (3) detecção de regiões ativas do cérebro em experimentos de imagens por ressonância magnética funcional (Functional Magnetic Resonance Imaging, fMRI). Os resultados, nos três casos estudados, mostraram que o método utilizado, como estratégia, é efetivo e computacionalmente eficiente para extração de sinais de interesse. Concluímos, baseados nas aplicações, que o método proposto é eficaz, mostrando seu potencial para futuras pesquisas clínicas._________________________________________________________________________________________ ABSTRACT: An important goal in biomedical signal processing is the extraction of information based on a set of physiological measurements made along time. Generally, biomedical signals are electromagnetic measurements. Those measurements (usually made with multichannel equipment) are registered using spatially distributed sensors around some areas of the human body, originating a set of time and/or space correlated data. The signals of interest are rarely registered alone, being usually observed as a mixture of other spurious, noisy signals (sometimes superimposed) and environmental or physiological artifacts. More over, the signal-to-noise ratio is generally low. In many applications, a big number of sensors are available, but just a few sources are of interest and the remainder can be considered noise. For such kind of applications, it is necessary to develop trustful, robust and effective learning algorithms that allow the extraction of only a few sources potentially of interest and that hold useful information. The strategy used here for extraction of sources is applied in three important problems in biomedical signal processing: (1) detection of the fetal magnetocardiogram signal (fMCG); (2) detection of the electrical activity of the stomach in magnetogastrograms (MGG); and (3) detection of active regions of the brain in experiments in functional Magnetic Resonance Imaging (fMRI). The results, within the three cases of study, showed that the DCA method used as strategy is effective and computationally efficient on extraction of desired signals.

Abstract Several anaesthetics are able to induce a burst-suppression (B-S) pattern in the electroencephalogram (EEG) during deep levels of anaesthesia. A burst-suppression pattern consists of alternating high amplitude bursts and periods of suppressed background activity. All monitors measuring the adequacy of anaesthesia recognize the EEG B-S as one criterion. A better understanding of EEG burst-suppression is important in understanding the mechanisms of anaesthesia. The aim of the study was to acquire a more comprehensive understanding of the function of neural pathways during deep anaesthesia. The thesis is comprised of four prospective clinical studies with EEG recordings from 64 patients, and of one experimental study of a porcine model of epilepsy with EEG registrations together with BOLD fMRI during isoflurane anaesthesia (II). In study I, somatosensory cortical evoked responses to median nerve stimulation were studied under sevoflurane anaesthesia at EEG B-S levels. In study III, The EEGs of three Parkinson`s patients were observed to describe the characteristics of B-S during propofol anaesthesia using scalp electrodes and depth electrodes in the subthalamic nucleus. In study IV, EEG topography was observed in 20 healthy children under anaesthesia mask induction with sevoflurane. Twenty male patients were randomized to either controlled hyperventilation or spontaneous breathing groups for anaesthesia mask induction with sevoflurane in study V. EEG alterations in relation to haemodynamic responses were examined in studies IV and V. Somatosensory information reached the cortex even during deep anaesthesia at EEG burst-suppression level. Further processing of these impulses in the cortex was suppressed. The EEG slow wave oscillations were synchronous over the entire cerebral cortex, while spindles and sharp waves were produced by the sensorimotor cortex. The development of focal epileptic activity could be detected as a BOLD signal increase, which preceded the EEG spike activity. The epileptogenic property of sevoflurane used at high concentrations especially during hyperventilation but also during spontaneous breathing together with heart rate increase, was confirmed in healthy children and male. Spike- and polyspike waveforms concentrated in a multifocal manner frontocentrally. / Tiivistelmä Useat anestesia-aineet pystyvät aiheuttamaan aivosähkökäyrän (EEG) purskevaimentuman syvän anestesian aikana. Purskevaimentuma koostuu EEG:n suuriamplitudisten purskeiden sekä vaimentuneen taustatoiminnan vaihtelusta. Kaikkien anestesian syvyyttä mittaavien valvontalaitteiden toiminta perustuu osaltaan EEG:n purskevaimentuman tunnistamiseen. Tämän ilmiön parempi tunteminen on tärkeää anestesiamekanismien ymmärtämiseksi. Tutkimuksen päämääränä oli saada kattavampi käsitys hermoratojen toiminnasta syvässä anestesiassa. Väitöskirjatyö koostuu neljästä prospektiivisesta yhteensä 64 potilaan EEG-rekisteröinnit sisältävästä tutkimuksesta sekä yhdestä kokeellisen epilepsiatutkimuksen koe-eläintyöstä, jossa porsailla käytettiin isofluraanianestesiassa sekä EEG-rekisteröintejä sekä että magneettikuvantamista (fMRI) samanaikaisesti (II). Ensimmäisessä osatyössä tutkittiin keskihermon stimulaation aiheuttamia somatosensorisia herätepotentiaaleja aivokuorella EEG:n purskevaimentumatasolla sevofluraanianestesian aikana. Kolmannessa osatyössä selvitettiin propofolianestesian aiheuttamaa EEG:n purskevaimentumaa kolmelta Parkinsonin tautia sairastavalta potilaalta käyttäen sekä pintaelektrodien että subtalamisen aivotumakkeen syväelektrodien rekisteröintejä. Neljännessä osatyössä tutkittiin EEG:n topografiaa 20:llä terveeellä lapsella indusoimalla anestesia sevofluraanilla. Kaksikymmentä miespotilasta nukutettiin sevofluraanilla ja heidät satunnaistettiin joko kontrolloidun hyperventilaation tai spontaanin hengityksen ryhmiin osatyössä V. EEG-muutoksia sekä niiden yhteyttä verenkiertovasteisiin selviteltiin molemmissa osatöissä IV ja V. Omasta kehosta tuleviin tuntoärsykkeisiin liittyvä somatosensorinen informaatio saavutti aivokuoren myös syvässä EEG:n purskevaimentumatasoisessa anestesiassa. Impulssien jatkokäsittely aivokuorella oli kuitenkin estynyt. EEG:n hidasaaltotoiminta oli synkronista koko aivokuoren alueella, sen sijaan unisukkulat ja terävät aallot paikantuivat sensorimotoriselle aivokuorelle. Paikallisen epileptisen toiminnan kehittyminen oli mahdollista havaita jo ennen piikikkäiden EEG:n aaltomuotojen ilmaantumista edeltävänä BOLD-ilmiöön liittyvänä aivoverenkierron lisääntymisenä. Sevofluraanin epileptogeenisyys varmistui erityisesti hyperventilaation, mutta myös spontaanin hengityksen yhteydessä ja näihin liittyi sykkeen nousu sekä terveillä lapsilla että miehillä. Piikkejä ja monipiikkejä käsittävien aaltomuotojen keskittymistä esiintyi otsalohkon keskialueilla.