Functional Assessment of Magno, Parvo and Konio-Cellular Pathways; Current State and Future Clinical Applications

The information generated by cone photoreceptors in the retina is compressed and transferred to higher processing centers through three distinct types of ganglion cells known as magno, parvo and konio cells. These ganglion cells, which travel from the retina to the lateral geniculate nucleus (LGN) and then to the primary visual cortex, have different structural and functional characteristics, and are organized in distinct layers in the LGN and the primary visual cortex. Magno cells are large, have thick axons and usually collect input from many retinal cells. Parvo cells are smaller, with fine axons and less myelin than mango cells. Konio cells are diverse small cells with wide fields of input consisting of different cells types. The three cellular pathways also differ in function. Magno cells respond rapidly to changing stimuli, while parvo cells need time to respond. The distinct patterns of structure and function in these cells have provided an opportunity for clinical assessment of their function. Functional assessment of these cells is currently used in the field of ophthalmology where frequency-doubling technology perimetry selectively assesses the function of magno cells. Evidence has accrued that the three pathways show characteristic patterns of malfunctions in multiple sclerosis, schizophrenia, Parkinson’s and Alzheimer’s diseases, and several other disorders. The combination of behavioral assessment with other techniques, such as event related potentials and functional magnetic resonance imaging, seems to bear promising future clinical applications

The photopic negative response in autism spectrum disorder

Background: Visual function can be atypical in autism spectrum disorder and structural imaging of the ganglion cell layers has been reported to differ in these individuals. Therefore, we sought to investigate if the photopic negative response of the full field electroretinograms, a measure of ganglion cell function, could help explain the visual perceptual differences in autism spectrum disorder and support the structural changes observed. / Methods: Participants (n = 55 autism spectrum disorder, aged 5.4–26.7 years) and control (n = 87, aged 5.4–27.3 years) were recruited for the study. Full-field light-adapted electroretinograms using a Troland protocol with 10 flash strengths from −0.367 to 1.204 log photopic cd.s.m−2 were recorded in each eye. The photopic negative response amplitudes at Tmin and at t = 72 ms were compared between groups along with the a- and b-wave values. / Results: There were no significant interactions between groups for the Photopic Negative Response measures of amplitude or time (p > 0.30). There was a group interaction between groups and flash strengths for the b-wave amplitude as previously reported (p < 0.001). / Conclusion: The photopic negative response results suggest that there are no significant differences in the summed retinal ganglion cell responses produced by a full-field stimulus

Neural synchrony in cortical networks : history, concept and current status

Following the discovery of context-dependent synchronization of oscillatory neuronal responses in the visual system, the role of neural synchrony in cortical networks has been expanded to provide a general mechanism for the coordination of distributed neural activity patterns. In the current paper, we present an update of the status of this hypothesis through summarizing recent results from our laboratory that suggest important new insights regarding the mechanisms, function and relevance of this phenomenon. In the first part, we present recent results derived from animal experiments and mathematical simulations that provide novel explanations and mechanisms for zero and nero-zero phase lag synchronization. In the second part, we shall discuss the role of neural synchrony for expectancy during perceptual organization and its role in conscious experience. This will be followed by evidence that indicates that in addition to supporting conscious cognition, neural synchrony is abnormal in major brain disorders, such as schizophrenia and autism spectrum disorders. We conclude this paper with suggestions for further research as well as with critical issues that need to be addressed in future studies

Neural synchrony in cortical networks : history, concept and current status

Following the discovery of context-dependent synchronization of oscillatory neuronal responses in the visual system, the role of neural synchrony in cortical networks has been expanded to provide a general mechanism for the coordination of distributed neural activity patterns. In the current paper, we present an update of the status of this hypothesis through summarizing recent results from our laboratory that suggest important new insights regarding the mechanisms, function and relevance of this phenomenon. In the first part, we present recent results derived from animal experiments and mathematical simulations that provide novel explanations and mechanisms for zero and nero-zero phase lag synchronization. In the second part, we shall discuss the role of neural synchrony for expectancy during perceptual organization and its role in conscious experience. This will be followed by evidence that indicates that in addition to supporting conscious cognition, neural synchrony is abnormal in major brain disorders, such as schizophrenia and autism spectrum disorders. We conclude this paper with suggestions for further research as well as with critical issues that need to be addressed in future studies

Nägemistaju automaatsete protsesside eksperimentaalne uurimine

Väitekirja elektrooniline versioon ei sisalda publikatsiooneVäitekiri keskendub nägemistaju protsesside eksperimentaalsele uurimisele, mis on suuremal või vähemal määral automaatsed. Uurimistöös on kasutatud erinevaid eksperimentaalseid katseparadigmasid ja katsestiimuleid ning nii käitumuslikke- kui ka ajukuvamismeetodeid. Esimesed kolm empiirilist uurimust käsitlevad liikumisinformatsiooni töötlust, mis on evolutsiooni käigus kujunenud üheks olulisemaks baasprotsessiks nägemistajus. Esmalt huvitas meid, kuidas avastatakse liikuva objekti suunamuutusi, kui samal ajal toimub ka taustal liikumine (Uurimus I). Nägemistaju uurijad on pikka aega arvanud, et liikumist arvutatakse alati mõne välise objekti või tausta suhtes. Meie uurimistulemused ei kinnitanud taolise suhtelise liikumise printsiibi paikapidavust ning toetavad pigem seisukohta, et eesmärkobjekti liikumisinformatsiooni töötlus on automaatne protsess, mis tuvastab silma põhjas toimuvaid nihkeid, ja taustal toimuv seda eriti ei mõjuta. Teise uurimuse tulemused (Uurimus II) näitasid, et nägemissüsteem töötleb väga edukalt ka seda liikumisinformatsiooni, millele vaatleja teadlikult tähelepanu ei pööra. See tähendab, et samal ajal, kui inimene on mõne tähelepanu hõlmava tegevusega ametis, suudab tema aju taustal toimuvaid sündmusi automaatselt registreerida. Igapäevaselt on inimese nägemisväljas alati palju erinevaid objekte, millel on erinevad omadused, mistõttu järgmiseks huvitas meid (Uurimus III), kuidas ühe tunnuse (antud juhul värvimuutuse) töötlemist mõjutab mõne teise tunnusega toimuv (antud juhul liikumiskiiruse) muutus. Näitasime, et objekti liikumine parandas sama objekti värvimuutuse avastamist, mis viitab, et nende kahe omaduse töötlemine ajus ei ole päris eraldiseisev protsess. Samuti tähendab taoline tulemus, et hoolimata ühele tunnusele keskendumisest ei suuda inimene ignoreerida teist tähelepanu tõmbavat tunnust (liikumine), mis viitab taas kord automaatsetele töötlusprotsessidele. Neljas uurimus keskendus emotsionaalsete näoväljenduste töötlusele, kuna need kannavad keskkonnas hakkamasaamiseks vajalikke sotsiaalseid signaale, mistõttu on alust arvata, et nende töötlus on kujunenud suuresti automaatseks protsessiks. Näitasime, et emotsiooni väljendavaid nägusid avastati kiiremini ja kergemini kui neutraalse ilmega nägusid ning et vihane nägu tõmbas rohkem tähelepanu kui rõõmus (Uurimus IV). Väitekirja viimane osa puudutab visuaalset lahknevusnegatiivsust (ingl Visual Mismatch Negativity ehk vMMN), mis näitab aju võimet avastada automaatselt erinevusi enda loodud mudelist ümbritseva keskkonna kohta. Selle automaatse erinevuse avastamise mehhanismi uurimisse andsid oma panuse nii Uurimus II kui Uurimus IV, mis mõlemad pakuvad välja tõendusi vMMN tekkimise kohta eri tingimustel ja katseparadigmades ning ka vajalikke metodoloogilisi täiendusi. Uurimus V on esimene kogu siiani ilmunud temaatilist teadustööd hõlmav ülevaateartikkel ja metaanalüüs visuaalsest lahknevusnegatiivsusest psühhiaatriliste ja neuroloogiliste haiguste korral, mis panustab oluliselt visuaalse lahknevusnegatiivsuse valdkonna arengusse.The research presented and discussed in the thesis is an experimental exploration of processes in visual perception, which all display a considerable amount of automaticity. These processes are targeted from different angles using different experimental paradigms and stimuli, and by measuring both behavioural and brain responses. In the first three empirical studies, the focus is on motion detection that is regarded one of the most basic processes shaped by evolution. Study I investigated how motion information of an object is processed in the presence of background motion. Although it is widely believed that no motion can be perceived without establishing a frame of reference with other objects or motion on the background, our results found no support for relative motion principle. This finding speaks in favour of a simple and automatic process of detecting motion, which is largely insensitive to the surrounding context. Study II shows that the visual system is built to automatically process motion information that is outside of our attentional focus. This means that even if we are concentrating on some task, our brain constantly monitors the surrounding environment. Study III addressed the question of what happens when multiple stimulus qualities (motion and colour) are present and varied, which is the everyday reality of our visual input. We showed that velocity facilitated the detection of colour changes, which suggests that processing motion and colour is not entirely isolated. These results also indicate that it is hard to ignore motion information, and processing it is rather automatically initiated. The fourth empirical study focusses on another example of visual input that is processed in a rather automatic way and carries high survival value – emotional expressions. In Study IV, participants detected emotional facial expressions faster and more easily compared with neutral facial expressions, with a tendency towards more automatic attention to angry faces. In addition, we investigated the emergence of visual mismatch negativity (vMMN) that is one of the most objective and efficient methods for analysing automatic processes in the brain. Study II and Study IV proposed several methodological gains for registering this automatic change-detection mechanism. Study V is an important contribution to the vMMN research field as it is the first comprehensive review and meta-analysis of the vMMN studies in psychiatric and neurological disorders

Change blindness: eradication of gestalt strategies

Arrays of eight, texture-defined rectangles were used as stimuli in a one-shot change blindness (CB) task where there was a 50% chance that one rectangle would change orientation between two successive presentations separated by an interval. CB was eliminated by cueing the target rectangle in the first stimulus, reduced by cueing in the interval and unaffected by cueing in the second presentation. This supports the idea that a representation was formed that persisted through the interval before being 'overwritten' by the second presentation (Landman et al, 2003 Vision Research 43149–164]. Another possibility is that participants used some kind of grouping or Gestalt strategy. To test this we changed the spatial position of the rectangles in the second presentation by shifting them along imaginary spokes (by ±1 degree) emanating from the central fixation point. There was no significant difference seen in performance between this and the standard task [F(1,4)=2.565, p=0.185]. This may suggest two things: (i) Gestalt grouping is not used as a strategy in these tasks, and (ii) it gives further weight to the argument that objects may be stored and retrieved from a pre-attentional store during this task

Development of an Experimental EEG Paradigm to Investigate Dysfunctions in Schizophrenia: Predicting the Sensory Consequences of One’s Own Actions

Background: Prediction mechanisms are crucial for efficient perception of the environment and ourselves as well as for discrimination between self-generated and external changed situations. Known as the internal forward model, an efference copy of the motor plan prepares the sensory areas for the reafferent feedback of one’s own planned actions. In case of a match between predicted and actual sensory feedback, further processing of the sensory consequences can be damped. This can be seen in suppressed N1-ERP amplitudes in EEG as well as attenuated intensity perception in behavioural data. Moreover, agency for self-generated actions can be attributed correctly by means of this mechanism, whereas external actions cannot prepare the sensory cortex with efference copy and therefore are identified as externally-generated. Dysfunctions in the prediction mechanism for self-generated actions result in a mismatch in the internal forward model, which in turn results in external attribution of agency as well as abnormal neurophysiological and behavioural correlates. Disturbed prediction mechanisms and failure in efference copy are suggested to be a reason for several positive symptoms of schizophrenia like sensory hallucinations and passivity experiences. Hypotheses/Objective: In the first part of our study, we investigated efference copy based predictions in healthy subjects in an extensive button press experiment. We hypothesised that the analyses of a selected number of visual trials with the same intensity will be sufficient to show N1-ERP suppression in active conditions. We expected that the second stimulus is perceived as more intense significantly more often in active conditions. With the main aim to develop an optimised and suitable experiment for patients, we hypothesised clearer N1-ERP and behavioural effects after changing the experimental setup in the second part of our study by altering the time intervals, shortening the overall duration, changing the presentation format and focussing on the visual condition only. Finally, we suggested that participants are able to perform the optimised task well. We expected this to be evidenced by the Post-Experiment Questionnaire. Material and Methods: Participants pressed actively or passively a button followed by visual stimuli displayed on a computer monitor. Consequently, they judged whether the first or second stimulus was brighter by pressing one of the defined keys. For the total duration of the experiments, we recorded EEG. Additionally, participants were asked to complete a questionnaire about the optimised experiment to assess the performance and suitability. Results: For both experiments, we found significantly smaller N1 peak values in active trials than in passive conditions in healthy subjects. The difference between the two experiments themselves was not significant. Behavioural data for intensity perception showed no significant difference, neither in the individual experiments nor in comparing the two. In patients with schizophrenia, we found no significant results for the optimised experiment. However, patients as well as healthy subjects were able to perform well in the optimised experiment assessed by the Post-Experiment Questionnaire. Discussion: Our electrophysiological results go in line with prior research in healthy subjects in both experiments. We showed that the analyses of a selected number of visual trials with the same intensity was sufficient to show N1-ERP suppression in active conditions in the extensive experiment. In contrast to our expectations for the behavioural task, we did not find a significant difference between the two conditions for both experiments. This stands in contrast to the under¬standing of sensory attenuation that self-initiated actions perceived as less intense than external ones. Therefore, further changes and studies are needed to show more robust effects for the visual system whereas most of the former studies focus on the other sensory modalities. However, the development of an EEG study which is suitable for patients with schizophrenia was successful regarding the Post-Experiment Questionnaire data. Conclusion: In conclusion, we demonstrated evidence of the neural (but not behavioural) mechanism in the visual modality. With the main aim to develop an experimental paradigm for patients to investigate dysfunctions in schizophrenia, we showed the suitability of the task assessed by the Post-Experiment Questionnaire. Further studies with a larger sample of patients are required to give more insight into the psychopathology and impaired predictive mechanisms in the visual domain in schizophrenia

Neural markers of suppression in impaired binocular vision

Even after conventional patching treatment, individuals with a history of amblyopia typically lack good stereo vision. This is often attributed to atypical suppression between the eyes, yet the specific mechanism is still unclear. Guided by computational models of binocular vision, we tested explicit predictions about how neural responses to contrast might differ in individuals with impaired binocular vision. Participants with a history of amblyopia (N = 25), and control participants with typical visual development (N = 19) took part in the study. Neural responses to different combinations of contrast in the left and right eyes, were measured using both electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). Stimuli were sinusoidal gratings with a spatial frequency of 3c/deg, flickering at 4 Hz. In the fMRI experiment, we also ran population receptive field and retinotopic mapping sequences, and a phase-encoded localiser stimulus, to identify voxels in primary visual cortex (V1) sensitive to the main stimulus. Neural responses in both modalities increased monotonically with stimulus contrast. When measured with EEG, responses were attenuated in the weaker eye, consistent with a fixed tonic suppression of that eye. When measured with fMRI, a low contrast stimulus in the weaker eye substantially reduced the response to a high contrast stimulus in the stronger eye. This effect was stronger than when the stimulus-eye pairings were reversed, consistent with unbalanced dynamic suppression between the eyes. Measuring neural responses using different methods leads to different conclusions about visual differences in individuals with impaired binocular vision. Both of the atypical suppression effects may relate to binocular perceptual deficits, e.g. in stereopsis, and we anticipate that these measures could be informative for monitoring the progress of treatments aimed at recovering binocular vision