Neural mechanisms underlying conscious and unconscious vision. Evidence from event-related potentials and transcranial magnetic stimulation

Vision affords us with the ability to consciously see, and use this information in our behavior. While research has produced a detailed account of the function of the visual system, the neural processes that underlie conscious vision are still debated. One of the aims of the present thesis was to examine the time-course of the neuroelectrical processes that correlate with conscious vision. The second aim was to study the neural basis of unconscious vision, that is, situations where a stimulus that is not consciously perceived nevertheless influences behavior. According to current prevalent models of conscious vision, the activation of visual cortical areas is not, as such, sufficient for consciousness to emerge, although it might be sufficient for unconscious vision. Conscious vision is assumed to require reciprocal communication between cortical areas, but views differ substantially on the extent of this recurrent communication. Visual consciousness has been proposed to emerge from recurrent neural interactions within the visual system, while other models claim that more widespread cortical activation is needed for consciousness. Studies I-III compared models of conscious vision by studying event-related potentials (ERP). ERPs represent the brain’s average electrical response to stimulation. The results support the model that associates conscious vision with activity localized in the ventral visual cortex. The timing of this activity corresponds to an intermediate stage in visual processing. Earlier stages of visual processing may influence what becomes conscious, although these processes do not directly enable visual consciousness. Late processing stages, when more widespread cortical areas are activated, reflect the access to and manipulation of contents of consciousness. Studies IV and V concentrated on unconscious vision. By using transcranial magnetic stimulation (TMS) we show that when early visual cortical processing is disturbed so that subjects fail to consciously perceive visual stimuli, they may nevertheless guess (above chance-level) the location where the visual stimuli were presented. However, the results also suggest that in a similar situation, early visual cortex is necessary for both conscious and unconscious perception of chromatic information (i.e. color). Chromatic information that remains unconscious may influence behavioral responses when activity in visual cortex is not disturbed by TMS. Our results support the view that early stimulus-driven (feedforward) activation may be sufficient for unconscious processing. In conclusion, the results of this thesis support the view that conscious vision is enabled by a series of processing stages. The processes that most closely correlate with conscious vision take place in the ventral visual cortex ~200 ms after stimulus presentation, although preceding time-periods and contributions from other cortical areas such as the parietal cortex are also indispensable. Unconscious vision relies on intact early visual activation, although the location of visual stimulus may be unconsciously resolved even when activity in the early visual cortex is interfered with.

The effects of maternal hyperglycemia on human umbilical vascular gene expression and neonatal rat lung development

Background: Maternal diabetes affects many fetal organ systems, including the vasculature and the lungs. The offspring of diabetic mothers have respiratory adaptation problems after birth. The mechanisms are multifactorial and the effects are prolonged during the postnatal period. An increasing incidence of diabetic pregnancies accentuates the importance of identifying the pathological mechanisms, which cause the metabolic and genetic changes that occur in offspring, born to diabetic mothers. Aims and methods: The aim of this thesis was to determine changes both in human umbilical cord exposed to maternal type 1 diabetes and in neonatal rat lungs after streptozotocin-induced maternal hyperglycemia, during pregnancy. Rat lungs were used as a model for the potential disease mechanisms. Gene expression alterations were determined in human umbilical cords at birth and in rat pup lungs at two week of age. During the first two postnatal weeks, rat lung development was studied morphologically and histologically. Further, the effect of postnatal hyperoxia on hyperglycemia-primed rat lungs was investigated at one week of age to mimic the clinical situation of supplemental oxygen treatment. Results: In the umbilical cord, maternal diabetes had a major negative effect on the expression of genes involved in blood vessel development. The genes regulating vascular tone were also affected. In neonatal rat lungs, intrauterine hyperglycemia had a prolonged effect on gene expression during late alveolarization. The most affected pathway was the upregulation of extracellular matrix proteins. Newborn rat lungs exposed to intrauterine hyperglycemia had thinner saccular walls without changes in airspace size, a smaller relative lung weight and lung total tissue area, and increased cellular apoptosis and proliferation compared to control lungs, possibly reflecting an aberrant maturational adaptation. At one and two weeks of age, cell proliferation and secondary crest formation were accelerated in hyperglycemia-exposed lungs. Postnatal hyperoxic exposure, alone caused arrested alveolarization with thin-walled and enlarged alveoli. In contrast, the dual exposure of intrauterine hyperglycemia and postnatal hyperoxia resulted in the phenotype of thick septa together with arrested alveolarization and decreased number of small pulmonary arteries. Conclusions: Maternal diabetic environment seems to alter the umbilical cord gene expression profile of the regulation of vascular development and function. Fetal hyperglycemia may additionally affect the genetic regulation of the postnatal lung development and may actually induce prolonged structural alterations in neonatal lungs together with a modifying effect on the deleterious pulmonary exposure of postnatal hyperoxia. This, combined with the novel human umbilical cord gene data could serve as stepping stones for future therapies to curb developmental aberrations.

The neural processes generating visual phenomenal consciousness: ERP and neuronavigated brain stimulation studies

One of the greatest conundrums to the contemporary science is the relation between consciousness and brain activity, and one of the specifi c questions is how neural activity can generate vivid subjective experiences. Studies focusing on visual consciousness have become essential in solving the empirical questions of consciousness. Th e main aim of this thesis is to clarify the relation between visual consciousness and the neural and electrophysiological processes of the brain. By applying electroencephalography and functional magnetic resonance image-guided transcranial magnetic stimulation (TMS), we investigated the links between conscious perception and attention, the temporal evolution of visual consciousness during stimulus processing, the causal roles of primary visual cortex (V1), visual area 2 (V2) and lateral occipital cortex (LO) in the generation of visual consciousness and also the methodological issues concerning the accuracy of targeting TMS to V1. Th e results showed that the fi rst eff ects of visual consciousness on electrophysiological responses (about 140 ms aft er the stimulus-onset) appeared earlier than the eff ects of selective attention, and also in the unattended condition, suggesting that visual consciousness and selective attention are two independent phenomena which have distinct underlying neural mechanisms. In addition, while it is well known that V1 is necessary for visual awareness, the results of the present thesis suggest that also the abutting visual area V2 is a prerequisite for conscious perception. In our studies, the activation in V2 was necessary for the conscious perception of change in contrast for a shorter period of time than in the case of more detailed conscious perception. We also found that TMS in LO suppressed the conscious perception of object shape when TMS was delivered in two distinct time windows, the latter corresponding with the timing of the ERPs related to the conscious perception of coherent object shape. Th e result supports the view that LO is crucial in conscious perception of object coherency and is likely to be directly involved in the generation of visual consciousness. Furthermore, we found that visual sensations, or phosphenes, elicited by the TMS of V1 were brighter than identically induced phosphenes arising from V2. Th ese fi ndings demonstrate that V1 contributes more to the generation of the sensation of brightness than does V2. Th e results also suggest that top-down activation from V2 to V1 is probably associated with phosphene generation. The results of the methodological study imply that when a commonly used landmark (2 cm above the inion) is used in targeting TMS to V1, the TMS-induced electric fi eld is likely to be highest in dorsal V2. When V1 was targeted according to the individual retinotopic data, the electric fi eld was highest in V1 only in half of the participants. Th is result suggests that if the objective is to study the role of V1 with TMS methodology, at least functional maps of V1 and V2 should be applied with computational model of the TMS-induced electric fi eld in V1 and V2. Finally, the results of this thesis imply that diff erent features of attention contribute diff erently to visual consciousness, and thus, the theoretical model which is built up of the relationship between visual consciousness and attention should acknowledge these diff erences. Future studies should also explore the possibility that visual consciousness consists of several processing stages, each of which have their distinct underlying neural mechanisms.

The Impact of Neonatal Antibiotic Exposure on Atopic Sensitisation by the Age of 12 Months

Varhaislapsuuden antibioottialtistuksen vaikutus atooppiseen herkistymiseen 12 kuukauden ikään mennessä Bakteerien vaikutus terveyteen on merkittävä: ne ovat toisaalta hengenvaarallisten infektioiden aiheuttajia, mutta samanaikaisesti niiden läsnäolo on välttämätöntä terveen immuunipuolustuksen kehittymiseksi. Ensimmäisen elinvuoden aikana suoliston bakteerikanta on altis ulkoisten tekijöiden vaikutuksille. Varhaislapsuuden antibioottihoidolla voi olla tuhoisat seuraukset eri bakteerilajien suhteille, ja sen tiedetään altistavan erilaisille immuunivälitteisille sairauksille, kuten atopialle. Ei ole kuitenkaan selvitetty, onko tämä vaikutus johtunut käynnissä olevan infektion aiheuttamista muutoksista kehittyvään immuunijärjestelmään vai onko siihen ollut syynä infektioon aloitettu antibioottihoito. Tässä tutkimuksessa selvitettiin eroja kahden, varhaista antibioottihoitoa saaneen ryhmän välillä ja päätetapahtumaksi katsottiin myöhemmin lapsuudessa ilmenevä atopiataipumus. Toinen ryhmä sai antibioottihoitoa kliinisesti todistettuun bakteeri-infektioon (varhaiseen sepsikseen). Toinen ryhmä taas sai antibioottihoidon pelkästään infektioepäilyyn eli ns. empiirisen hoidon, joka lopetettiin alle viiden vuorokauden kuluessa kun katsottiin, ettei oireiden taustalla ollutkaan bakteeri-infektiota. Mukana vertailussa oli lisäksi ryhmä, joka ei saanut lainkaan varhaista antibioottihoitoa. Antibioottihoidon pitkäaikaisvaikutusta arvioitiin ihon prick-testillä, joka kertoo atopiaan liittyvästä IgE-välitteisestä herkistymisestä. Varhaisella antibioottihoidolla tarkoitetaan tässä alle 72 tunnin sisällä syntymästä alkanutta hoitoa G-penisilliinin ja gentamysiinin yhdistelmällä. Tutkimuksen aineisto koostui 755 vastasyntyneen lapsen seurantadatasta, joka saatiin neljän käynnissä olevan allergian ehkäisytutkimuksen aineistosta. Tutkimuksen mukaanottokriteereinä pidettiin sitä, että saatavilla oli tiedot sekä mahdollisen antibioottialtistuksen kestosta että ihon prick-testituloksesta joko 6 tai 12 kuukauden iässä. Tulokset analysoitiin logistisella regressioanalyysillä huomioiden mahdolliset sekoittavat tekijät: äidin allergia, ennenaikaisuus, tutkimusprobiootti, imetyksen kesto, äidin raskauden aikainen tupakointi ja synnytystapa. Potilasryhmässä, joka sai antibioottihoitoa ilman samanaikaista infektiota, nähtiin tilastollisesti merkittävästi vähemmän positiivisia prick-testituloksia verrattuna lapsiin, jotka eivät altistuneet antibiooteille. Tulos on merkittävä, sillä se osoittaa, että varhaisella antibioottihoidolla on kauaskantoisia vaikutuksia kehittyvään immuunijärjestelmään.