The Reorganization of Primary Auditory Cortex by Invasion of Ectopic Visual Inputs

Brain injury is a serious clinical problem. The success of recovery from brain injury involves functional compensation in the affected brain area. We are interested in general mechanisms that underlie compensatory plasticity after brain damage, particularly when multiple brain areas or multiple modalities are included. In this thesis, I studied the function of auditory cortex after recovery from neonatal midbrain damage as a model system that resembles patients with brain damage or sensory dysfunction. I addressed maladaptive changes of auditory cortex after invasion by ectopic visual inputs. I found that auditory cortex contained auditory, visual, and multisensory neurons after it recovered from neonatal midbrain damage (Mao et al. 2011). The distribution of these different neuronal responses did not show any clustering or segregation. As might be predicted from the fact that auditory neurons and visual neurons were intermingled throughout the entire auditory cortex, I found that residual auditory tuning and tonotopy in the rewired auditory cortex were compromised. Auditory tuning curves were broader and tonotopic maps were disrupted in the experimental animals. Because lateral inhibition is proposed to contribute to refinement of sensory maps and tuning of receptive fields, I tested whether loss of inhibition is responsible for the compromised auditory function in my experimental animals. I found an increase rather than a decrease of inhibition in the rewired auditory cortex, suggesting that broader tuning curves in the experimental animals are not caused by loss of lateral inhibition. These results suggest that compensatory plasticity can be maladaptive and thus impair the recovery of the original sensory cortical function. The reorganization of brain areas after recovery from brain damage may require stronger inhibition in order to process multiple sensory modalities simultaneously. These findings provide insight into compensatory plasticity after sensory dysfunction and brain damage and new information about the role of inhibition in cross-modal plasticity. This study can guide further research on design of therapeutic strategies to encourage adaptive changes and discourage maladaptive changes after brain damage, sensory/motor dysfunction, and deafferentation

Sensor Fusion in the Perception of Self-Motion

This dissertation has been written at the Max Planck Institute for Biological Cybernetics (Max-Planck-Institut für Biologische Kybernetik) in Tübingen in the department of Prof. Dr. Heinrich H. Bülthoff. The work has universitary support by Prof. Dr. Günther Palm (University of Ulm, Abteilung Neuroinformatik). Main evaluators are Prof. Dr. Günther Palm, Prof. Dr. Wolfgang Becker (University of Ulm, Sektion Neurophysiologie) and Prof. Dr. Heinrich Bülthoff.amp;lt;bramp;gt;amp;lt;bramp;gt; The goal of this thesis was to investigate the integration of different sensory modalities in the perception of self-motion, by using psychophysical methods. Experiments with healthy human participants were to be designed for and performed in the Motion Lab, which is equipped with a simulator platform and projection screen. Results from psychophysical experiments should be used to refine models of the multisensory integration process, with an mphasis on Bayesian (maximum likelihood) integration mechanisms.amp;lt;bramp;gt;amp;lt;bramp;gt; To put the psychophysical experiments into the larger framework of research on multisensory integration in the brain, results of neuroanatomical and neurophysiological experiments on multisensory integration are also reviewed

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

Sensor fusion in distributed cortical circuits

The substantial motion of the nature is to balance, to survive, and to reach perfection. The evolution in biological systems is a key signature of this quintessence. Survival cannot be achieved without understanding the surrounding world. How can a fruit fly live without searching for food, and thereby with no form of perception that guides the behavior? The nervous system of fruit fly with hundred thousand of neurons can perform very complicated tasks that are beyond the power of an advanced supercomputer. Recently developed computing machines are made by billions of transistors and they are remarkably fast in precise calculations. But these machines are unable to perform a single task that an insect is able to do by means of thousands of neurons. The complexity of information processing and data compression in a single biological neuron and neural circuits are not comparable with that of developed today in transistors and integrated circuits. On the other hand, the style of information processing in neural systems is also very different from that of employed by microprocessors which is mostly centralized. Almost all cognitive functions are generated by a combined effort of multiple brain areas. In mammals, Cortical regions are organized hierarchically, and they are reciprocally interconnected, exchanging the information from multiple senses. This hierarchy in circuit level, also preserves the sensory world within different levels of complexity and within the scope of multiple modalities. The main behavioral advantage of that is to understand the real-world through multiple sensory systems, and thereby to provide a robust and coherent form of perception. When the quality of a sensory signal drops, the brain can alternatively employ other information pathways to handle cognitive tasks, or even to calibrate the error-prone sensory node. Mammalian brain also takes a good advantage of multimodal processing in learning and development; where one sensory system helps another sensory modality to develop. Multisensory integration is considered as one of the main factors that generates consciousness in human. Although, we still do not know where exactly the information is consolidated into a single percept, and what is the underpinning neural mechanism of this process? One straightforward hypothesis suggests that the uni-sensory signals are pooled in a ploy-sensory convergence zone, which creates a unified form of perception. But it is hard to believe that there is just one single dedicated region that realizes this functionality. Using a set of realistic neuro-computational principles, I have explored theoretically how multisensory integration can be performed within a distributed hierarchical circuit. I argued that the interaction of cortical populations can be interpreted as a specific form of relation satisfaction in which the information preserved in one neural ensemble must agree with incoming signals from connected populations according to a relation function. This relation function can be seen as a coherency function which is implicitly learnt through synaptic strength. Apart from the fact that the real world is composed of multisensory attributes, the sensory signals are subject to uncertainty. This requires a cortical mechanism to incorporate the statistical parameters of the sensory world in neural circuits and to deal with the issue of inaccuracy in perception. I argued in this thesis how the intrinsic stochasticity of neural activity enables a systematic mechanism to encode probabilistic quantities within neural circuits, e.g. reliability, prior probability. The systematic benefit of neural stochasticity is well paraphrased by the problem of Duns Scotus paradox: imagine a donkey with a deterministic brain that is exposed to two identical food rewards. This may make the animal suffer and die starving because of indecision. In this thesis, I have introduced an optimal encoding framework that can describe the probability function of a Gaussian-like random variable in a pool of Poisson neurons. Thereafter a distributed neural model is proposed that can optimally combine conditional probabilities over sensory signals, in order to compute Bayesian Multisensory Causal Inference. This process is known as a complex multisensory function in the cortex. Recently it is found that this process is performed within a distributed hierarchy in sensory cortex. Our work is amongst the first successful attempts that put a mechanistic spotlight on understanding the underlying neural mechanism of Multisensory Causal Perception in the brain, and in general the theory of decentralized multisensory integration in sensory cortex. Engineering information processing concepts in the brain and developing new computing technologies have been recently growing. Neuromorphic Engineering is a new branch that undertakes this mission. In a dedicated part of this thesis, I have proposed a Neuromorphic algorithm for event-based stereoscopic fusion. This algorithm is anchored in the idea of cooperative computing that dictates the defined epipolar and temporal constraints of the stereoscopic setup, to the neural dynamics. The performance of this algorithm is tested using a pair of silicon retinas

Sensor fusion in distributed cortical circuits

The substantial motion of the nature is to balance, to survive, and to reach perfection. The evolution in biological systems is a key signature of this quintessence. Survival cannot be achieved without understanding the surrounding world. How can a fruit fly live without searching for food, and thereby with no form of perception that guides the behavior? The nervous system of fruit fly with hundred thousand of neurons can perform very complicated tasks that are beyond the power of an advanced supercomputer. Recently developed computing machines are made by billions of transistors and they are remarkably fast in precise calculations. But these machines are unable to perform a single task that an insect is able to do by means of thousands of neurons. The complexity of information processing and data compression in a single biological neuron and neural circuits are not comparable with that of developed today in transistors and integrated circuits. On the other hand, the style of information processing in neural systems is also very different from that of employed by microprocessors which is mostly centralized. Almost all cognitive functions are generated by a combined effort of multiple brain areas. In mammals, Cortical regions are organized hierarchically, and they are reciprocally interconnected, exchanging the information from multiple senses. This hierarchy in circuit level, also preserves the sensory world within different levels of complexity and within the scope of multiple modalities. The main behavioral advantage of that is to understand the real-world through multiple sensory systems, and thereby to provide a robust and coherent form of perception. When the quality of a sensory signal drops, the brain can alternatively employ other information pathways to handle cognitive tasks, or even to calibrate the error-prone sensory node. Mammalian brain also takes a good advantage of multimodal processing in learning and development; where one sensory system helps another sensory modality to develop. Multisensory integration is considered as one of the main factors that generates consciousness in human. Although, we still do not know where exactly the information is consolidated into a single percept, and what is the underpinning neural mechanism of this process? One straightforward hypothesis suggests that the uni-sensory signals are pooled in a ploy-sensory convergence zone, which creates a unified form of perception. But it is hard to believe that there is just one single dedicated region that realizes this functionality. Using a set of realistic neuro-computational principles, I have explored theoretically how multisensory integration can be performed within a distributed hierarchical circuit. I argued that the interaction of cortical populations can be interpreted as a specific form of relation satisfaction in which the information preserved in one neural ensemble must agree with incoming signals from connected populations according to a relation function. This relation function can be seen as a coherency function which is implicitly learnt through synaptic strength. Apart from the fact that the real world is composed of multisensory attributes, the sensory signals are subject to uncertainty. This requires a cortical mechanism to incorporate the statistical parameters of the sensory world in neural circuits and to deal with the issue of inaccuracy in perception. I argued in this thesis how the intrinsic stochasticity of neural activity enables a systematic mechanism to encode probabilistic quantities within neural circuits, e.g. reliability, prior probability. The systematic benefit of neural stochasticity is well paraphrased by the problem of Duns Scotus paradox: imagine a donkey with a deterministic brain that is exposed to two identical food rewards. This may make the animal suffer and die starving because of indecision. In this thesis, I have introduced an optimal encoding framework that can describe the probability function of a Gaussian-like random variable in a pool of Poisson neurons. Thereafter a distributed neural model is proposed that can optimally combine conditional probabilities over sensory signals, in order to compute Bayesian Multisensory Causal Inference. This process is known as a complex multisensory function in the cortex. Recently it is found that this process is performed within a distributed hierarchy in sensory cortex. Our work is amongst the first successful attempts that put a mechanistic spotlight on understanding the underlying neural mechanism of Multisensory Causal Perception in the brain, and in general the theory of decentralized multisensory integration in sensory cortex. Engineering information processing concepts in the brain and developing new computing technologies have been recently growing. Neuromorphic Engineering is a new branch that undertakes this mission. In a dedicated part of this thesis, I have proposed a Neuromorphic algorithm for event-based stereoscopic fusion. This algorithm is anchored in the idea of cooperative computing that dictates the defined epipolar and temporal constraints of the stereoscopic setup, to the neural dynamics. The performance of this algorithm is tested using a pair of silicon retinas

Neural basis of the neurological diagnostic power of vibrotactile sensory testing

As with most other injuries and disorders, the prognosis of neurological impairment is dependent upon early and accurate detection. Likewise, after an appropriate diagnosis has been made, it is important to start the patient on an effective treatment plan. Often a clinician prescribes a medication and asks the patient to come back for a follow-up appointment. It would be extremely beneficial if the clinician could instead conduct a quantitative assessment to immediately determine the effectiveness of a prescribed treatment. Our research utilizes non-invasive, non-painful tactile sensory assessments which could assist in the timely, accurate detection for neurological impairments and their corresponding treatments by quantifying minute changes in cortical functionality. Unfortunately, despite the potential to use these diagnostic assessments for a broad scope of neurological impairments (e.g. alcoholism, chronic pain, concussion, and autism), the neurological basis behind many of these diagnostic assessments are unclear. In other words, while the assessments found variations between these focus groups and healthy controls, there is not enough neurological context to fully explain the findings. To address the issue, the primary goal of this research was to establish a neurological basis for the results of these sensory assessments. Once understood, these quantitative assessments could become valuable tools in future clinical applications for the diagnosis of neurological disorders. The central goal of this study was to provide experimental evidence of a cortical mechanism that was hypothesized to be of fundamental importance in tactile perception. Based upon microelectrode recording analysis of the cortical response to various vibrotactile stimulations (cats and non-human primates), we describe two forms of cortical contrast: spatial and temporal. Those results suggest that improved cortical contrast may be important for enhancing tactile sensory perception. To test this hypothesis, we conducted a variety of tactile sensory assessments on healthy controls including frequency discrimination, amplitude discrimination, and temporal order judgment. The results of the human sensory studies are in full agreement with our basic, animal neurological studies. In conclusion, human performance on those quantitative sensory tests can be used as an indicator of the functionality of the cortical mechanisms responsible for spatial and temporal contrast enhancement.Doctor of Philosoph

Disentangling neuronal pre- and post-response activation in the acquisition of goal-directed behavior through the means of co-registered EEG-fMRI

Behavior is considered goal-directed when the actor integrates information about the subsequent outcome of an action (Balleine & O'Doherty, 2010; Dickinson & Balleine, 1994; Kiesel & Koch, 2012), potentially enabling the anticipation of consequences of an action. Thus, it requires prior acquisition of knowledge about the current contingencies between behavioral responses and their outcomes under certain stimulus conditions (J. Hoffmann & Engelkamp, 2013). This association chain enables events lying in the future to be mentally represented and assessed in terms of value and achievability. However, while neural correlates of instructed goal-directed action integration processes have already been examined in a functional magnetic resonance imaging (fMRI) study using this paradigm (Ruge & Wolfensteller, 2015), there has been no information if those processes are also reflected in Electroencephalography (EEG) and if so which specific EEG parameters are modulated by them. This dissertation set out to investigate neurocognitive mechanisms of instructed outcome response learning utilizing two different imaging methods, namely EEG and fMRI. Study 1 was an exploratory study to answer the question what kinds of learning-related EEG correlates were to expect. The O-R outcome integration specific EEG correlates identified in Study 1 served as regressors in a unified general linear model (EEG-informed fMRI analysis) in the co-registered EEG-fMRI study (Study 2). One of the key questions in this study was if the EEG signal could help to differentiate between BOLD pre-response activation associated with processes related to response preparation or initiation and activation associated with post-response outcome integration processes. The foundation to both studies of this work was an experimental paradigm of instructed S-R-O learning, which included a learning and a test phase. Stimuli were four abstract visual patterns that differed in each block. Each visual stimulus required a distinct manual response and was predictably followed by a distinct auditory outcome. Instructions were delivered via a “guided implementation” procedure in which the instruction was embedded within the first three successful behavioral implementation trials. In these first three trials, the visual stimulus was followed by an imperative stimulus highlighting the correct response. The guided implementation phase was followed by an unguided implementation phase where the correct response now had to be retrieved from memory. Behaviorally, the strength of acquired O-R associations can be analyzed via O-R compatibility effects measured in a subsequent outcome-priming test phase (Greenwald, 1970). In this test phase a previously learned outcome becomes an imperative stimulus that requires either the response, which produced that outcome in the preceding learning phase (O-R compatible), or a response, which produced a different outcome (O-R incompatible). The experimental design was embedded into an EEG recording setup in study 1 while study 2 comprised a simultaneous EEG-fMRI recording setup in which EEG scalp potentials were continuously recorded during the experimental session inside the MR scanner bore. Study 1 revealed various ERP markers correlated with outcome response learning. An ERP post-response anterior negativity following auditory outcomes was increasingly attenuated as a function of the acquired association strength. This suggests that previously reported action-induced sensory attenuation effects under extensively trained free choice conditions can be established within few repetitions of specific R-O pairings under forced choice conditions. Furthermore, an even more rapid development of a post-response but pre-outcome fronto-central positivity, which was reduced for high R-O learners, might indicate the rapid deployment of preparatory attention towards predictable outcomes. Finally, the study identified a learning-related stimulus-locked activity modulation within the visual P1-N1 latency range, which was thought to reflect the multi-sensory integration of the perceived antecedent visual stimulus with the anticipated auditory outcome. In general, study 2 was only partially able to replicate the EEG activity dynamics related to the formation of bidirectional R-O associations that were observed in study 1. Primarily, it was able to confirm the modulation in EEG negativity in the visual P1-N1 latency range over the learning course. The EEG-informed analysis revealed that learning-related modulations of the P1-N1 complex are functionally coupled to activation in the orbitofrontal cortex (OFC). More specifically, growing attenuation of the EEG negativity increase from early to late SRO repetition levels in high R-O learners was associated with an increase in activation in the OFC. An additional exploratory EEG analysis identified a recurring post outcome effect at central electrode sites expressed in a stronger negativity in late compared to early learning stages. This effect was present in both studies and showed no correlation with any of the behavioral markers of learning. The EEG-informed fMRI analysis resulted in a pattern of distinct functional couplings of this parameter with different brain regions, each correlated with different behavioral markers of S-R-O learning. First of all, increased coupling between the late EEG negativity and activation in the supplementary motor area (SMA) was positively correlated with the O-R compatibility effect. Thus, high R-O learners exhibited a stronger coupling than low R-O learners. Secondly, increased couplings between the late EEG negativity and activation in the somatosensory cortex as well as the dorsal caudate, on the other hand, were positively correlated with individual reaction time differences between early and late stages of learning. Regarding activation patterns prior to the behavioral response the results indicate that the OFC could serve as a (multimodal) hub for integrating stimulus information and information about its associated outcome in an early pre-stage of action selection and initiation. Learnt S-O contingencies would facilitate initiating the motor program of the action of choice. Hence, the earlier an outcome is anticipated (based on stimulus outcome associations), the better it will be associated with its response, eventually leading to stronger O-R compatibility effects later on. Thus, one could speculate that increased activation in response to S-R-O mappings possibly embodies a marker for the ongoing transition from mere stimulus-based behavior to a goal-directed behavior throughout the learning course. Post-response brain activation revealed a seemingly two-fold feedback integration stream of O-R contingencies. On one hand the SMA seems to be engaged in bidirectional encoding processes of O-R associations. The results promote the general idea that the SMA is involved in the acquisition of goal-directed behavior (Elsner et al., 2002; Melcher, Weidema, Eenshuistra, Hommel, & Gruber, 2008; Melcher et al., 2013). Together with prior research (Frimmel, Wolfensteller, Mohr, & Ruge, 2016) this notion can be generalized not only to extensive learning phases but also to learning tasks in which goal-directed behavior is acquired in only few practice trials. However, there is an ongoing debate on whether SMA activation can be clearly linked to sub-processes prior or subsequent to an agent’s action (Nachev, Kennard, & Husain, 2008). The results of this work provide additional evidence favoring an involvement of the SMA only following a performed action in response to an imperative stimulus and even more, subsequent to the perception of its ensuing effect. This may give rise to the interpretation that the SMA is associated with linking the motor program of the performed action to the sensory program of the perceived effect, hence establishing and strengthening O-R contingencies. Furthermore, the analysis identified an increased coupling of a late negativity in the EEG signal and activation in the dorsal parts of the caudate as well as the somatosensory cortex. The dorsal caudate has not particularly been brought into connection with O-R learning so far. I speculate that the coupling effect in this part of the caudate reflects an ongoing process of an early automatization of the acquired behavior. It has already be shown in a similar paradigm that behavior can be automatized within only few repetitions of novel instructed S-R mappings (Mohr et al., 2016).:Table of contents Table of contents II List of Figures IV List of Tables VI List of Abbreviations VII 1 Summary 1 1.1 Introduction 1 1.2 Study Objectives 2 1.3 Methods 3 1.4 Results 4 1.5 Discussion 4 2 Theoretical Background 7 2.1 Introduction 7 2.2 Theories of acquiring goal-directed behavior 9 2.2.1 Instrumental learning 9 2.2.1.1 Behavioral aspects 9 2.2.1.2 Neurophysiological correlates 14 2.2.2 Acquisition of goal-directed behavior according to ideomotor theory 16 2.2.2.1 Behavioral aspects 16 2.2.2.2 Neurophysiological correlates 22 2.3 Summary 25 2.4 Methodological background 26 2.4.1 Electroencephalography (EEG) 26 2.4.2 Functional magnetic resonance imaging (fMRI) 28 2.4.3 Co-registered EEG-fMRI 29 3 General objectives and research questions 34 4 Study 1 – Learning-related brain-electrical activity dynamics associated with the subsequent impact of learnt action-outcome associations 36 4.1 Introduction 36 4.2 Methods 39 4.3 Results 47 4.4 Discussion 60 5 Study 2 - Within trial distinction of O-R learning-related BOLD activity with the means of co-registered EEG information 64 5.1 Introduction 64 5.2 Methods 66 5.3 Results 86 5.4 Discussion 101 6 Concluding general discussion 109 6.1 Brief assessment of study objectives 109 6.2 Novel insights into rapid instruction based S-R-O learning? 109 6.2.1 Early stimulus outcome information retrieval indicates the transition from stimulus based behavior to goal-directed action 110 6.2.2 Post-response encoding and consolidation of O-R contingencies enables goal-directedness of behavior 112 6.3 Critical reflection of the methodology and outlook 116 6.3.1 Strengths and limitations of this work 116 6.3.2 Data quality assessment 117 6.3.3 A common neural foundation for EEG and fMRI? 119 6.3.4 How can co-registered EEG-fMRI contribute to a better understanding of the human brain? 121 6.4 General Conclusion 123 7 References 124 Danksagung Erklärun