Central auditory detection and pre-attentive discrimination in children

Central auditory processes to detection and pre-attentive discrimination in children were studied using auditory event related potentials (AERP). Discrimination potentials were elicited by infrequent deviant stimuli embedded pseudo-randomly in a sequence of frequent standard stimuli. The major obligatory components of the AERP, P85-120, N1 and N2 were recorded to stimuli that varied in complexity (pure tones to words). A later component evoked by deviant stimuli, termed the mismatch negativity (MMN), thought to reflect pre-attentive auditory discrimination processes that occur within the duration of echoic memory, was also noticed.Five groups of children were studied. 1. Experiments in normal adult and children controls were carried out to validate the methodology. MMN to duration and frequency deviance was dissociated temporally but not spatially. 2. Intracranial recordings revealed cortical activation in the peri-sylvian and frontal regions that was dependent on the complexity and context of the stimuli. 3. Scalp recordings in children who had undergone hemispherectomy provided a model of the scalp distribution of AERPs arising from one hemisphere and a comparison to the intracranial recordings. Significant differences in AERP components to pure tones and syllables suggested optimal processing by the intact left hemisphere. 4. Recordings in awake children with benign rolandic epilepsy show an alteration in the topography of the P85-120 component of the AERP contralateral to the hemisphere generating spikes during sleep. As there is no structural lesion these findings suggest long term effects of epileptic spikes. 5. In a previously poorly described group of children with normal peripheral hearing who have difficulties in challenging acoustic environments, the AERPs were sensitive to deficits in a behavioural test of central auditory processing. Other findings included the increase in latencies of AERP components with more complex stimuli and differing morphology/topography of the obligatory and mismatch components both to each other and between adults and children

The Role of Synaptic Tagging and Capture for Memory Dynamics in Spiking Neural Networks

Memory serves to process and store information about experiences such that this information can be used in future situations. The transfer from transient storage into long-term memory, which retains information for hours, days, and even years, is called consolidation. In brains, information is primarily stored via alteration of synapses, so-called synaptic plasticity. While these changes are at first in a transient early phase, they can be transferred to a late phase, meaning that they become stabilized over the course of several hours. This stabilization has been explained by so-called synaptic tagging and capture (STC) mechanisms. To store and recall memory representations, emergent dynamics arise from the synaptic structure of recurrent networks of neurons. This happens through so-called cell assemblies, which feature particularly strong synapses. It has been proposed that the stabilization of such cell assemblies by STC corresponds to so-called synaptic consolidation, which is observed in humans and other animals in the first hours after acquiring a new memory. The exact connection between the physiological mechanisms of STC and memory consolidation remains, however, unclear. It is equally unknown which influence STC mechanisms exert on further cognitive functions that guide behavior. On timescales of minutes to hours (that means, the timescales of STC) such functions include memory improvement, modification of memories, interference and enhancement of similar memories, and transient priming of certain memories. Thus, diverse memory dynamics may be linked to STC, which can be investigated by employing theoretical methods based on experimental data from the neuronal and the behavioral level. In this thesis, we present a theoretical model of STC-based memory consolidation in recurrent networks of spiking neurons, which are particularly suited to reproduce biologically realistic dynamics. Furthermore, we combine the STC mechanisms with calcium dynamics, which have been found to guide the major processes of early-phase synaptic plasticity in vivo. In three included research articles as well as additional sections, we develop this model and investigate how it can account for a variety of behavioral effects. We find that the model enables the robust implementation of the cognitive memory functions mentioned above. The main steps to this are: 1. demonstrating the formation, consolidation, and improvement of memories represented by cell assemblies, 2. showing that neuromodulator-dependent STC can retroactively control whether information is stored in a temporal or rate-based neural code, and 3. examining interaction of multiple cell assemblies with transient and attractor dynamics in different organizational paradigms. In summary, we demonstrate several ways by which STC controls the late-phase synaptic structure of cell assemblies. Linking these structures to functional dynamics, we show that our STC-based model implements functionality that can be related to long-term memory. Thereby, we provide a basis for the mechanistic explanation of various neuropsychological effects.2021-09-0

Neuroplasticity, neural reuse, and the language module

What conception of mental architecture can survive the evidence of neuroplasticity and neural reuse in the human brain? In particular, what sorts of modules are compatible with this evidence? I aim to show how developmental and adult neuroplasticity, as well as evidence of pervasive neural reuse, forces us to revise the standard conception of modularity and spells the end of a hardwired and dedicated language module. I argue from principles of both neural reuse and neural redundancy that language is facilitated by a composite of modules (or module-like entities), few if any of which are likely to be linguistically special, and that neuroplasticity provides evidence that (in key respects and to an appreciable extent) few if any of them ought to be considered developmentally robust, though their development does seem to be constrained by features intrinsic to particular regions of cortex (manifesting as domain-specific predispositions or acquisition biases). In the course of doing so I articulate a schematically and neurobiologically precise framework for understanding modules and their supramodular interactions

Functional imaging studies of visual-auditory integration in man.

This thesis investigates the central nervous system's ability to integrate visual and auditory information from the sensory environment into unified conscious perception. It develops the possibility that the principle of functional specialisation may be applicable in the multisensory domain. The first aim was to establish the neuroanatomical location at which visual and auditory stimuli are integrated in sensory perception. The second was to investigate the neural correlates of visual-auditory synchronicity, which would be expected to play a vital role in establishing which visual and auditory stimuli should be perceptually integrated. Four functional Magnetic Resonance Imaging studies identified brain areas specialised for: the integration of dynamic visual and auditory cues derived from the same everyday environmental events (Experiment 1), discriminating relative synchronicity between dynamic, cyclic, abstract visual and auditory stimuli (Experiment 2 & 3) and the aesthetic evaluation of visually and acoustically perceived art (Experiment 4). Experiment 1 provided evidence to suggest that the posterior temporo-parietal junction may be an important site of crossmodal integration. Experiment 2 revealed for the first time significant activation of the right anterior frontal operculum (aFO) when visual and auditory stimuli cycled asynchronously. Experiment 3 confirmed and developed this observation as the right aFO was activated only during crossmodal (visual-auditory), but not intramodal (visual-visual, auditory-auditory) asynchrony. Experiment 3 also demonstrated activation of the amygdala bilaterally during crossmodal synchrony. Experiment 4 revealed the neural correlates of supramodal, contemplative, aesthetic evaluation within the medial fronto-polar cortex. Activity at this locus varied parametrically according to the degree of subjective aesthetic beauty, for both visual art and musical extracts. The most robust finding of this thesis is that activity in the right aFO increases when concurrently perceived visual and auditory sensory stimuli deviate from crossmodal synchrony, which may veto the crossmodal integration of unrelated stimuli into unified conscious perception

Defending the Multiple Realization Argument against the Identity Theory

A classic argument in the philosophy of mind is that the identity theory is false because mental state types are multiply realized in brain state types. In this dissertation I provide a detailed elaboration of the argument and a defense of it against a few of its prominent contemporary critics. Finally I offer empirical evidence from inter-species differences in humans and monkeys, and also from a case of extensive neural plasticity, which shows that mental state types are multiply realized in brain state types

The Biological Basis of Rapid Instructed Task Learning

The uniquely human ability to rapidly learn novel tasks from instructions is extremely important in everyday life, and yet its evolutionary origin and basis in the brain remain mysteries. In order to address these gaps in scientific knowledge, comparative human-monkey studies were consulted to predict the human brain areas involved in rapid instructed task learning (RITL). These predictions were tested using functional MRI (fMRI), magnetoencephalography (MEG), and a novel cognitive paradigm developed to systematically investigate the neural basis of RITL for the first time. In accordance with cross-species neuroanatomical differences, anterior prefrontal cortex (aPFC), anterior temporal lobe (aTL), dorsolateral prefrontal cortex (DLPFC), and posterior parietal cortex (PPC) were found to be involved in RITL. DLPFC and PPC formed a network involved in loading individual task semantics into working memory, while aPFC and aTL formed a network involved in integrating semantics in preparation for task performance. Both networks supported novel task set formation, which occurred in a bottom-up manner (semantic loading, then integration), and practiced task set retrieval, which occurred in a top-down manner (integration retrieval, then semantic loading). These findings suggest that RITL relies upon semantic loading by DLPFC and PPC, but that aPFC and aTL support semantic integration both dynamically during RITL and from long-term memory after extensive practice. More broadly, the findings suggest RITL is enabled in humans via a combination of enhanced symbolic processing (language), enhanced working memory manipulation (aPFC), and enhanced integrated semantic representation (aTL). The present document begins with a broad overview of RITL and related topics, such as its relation to animal cognition, other forms of learning, and cognitive control. These topics support several novel hypotheses regarding RITL and its likely basis in the brain. The fMRI study is then presented, verifying many of the hypotheses developed in the previous section. The MEG study is reported next, clarifying many of the questions about timing and causality suggested by the fMRI results. Finally, a general discussion integrates the results from both studies, expanding conclusions with an overview of brain connectivity findings, cross-species differences, and the role of neural hierarchies in RITL and cognition generally

Brain electric fields, belief in the paranormal, and reading of emotion words

The present work reports two experiments on brain electric correlates of cognitive and emotional functions. (1) Studying paranormal belief, 35-channel resting EEG (10 believers and 13 skeptics) was analyzed with "Low Resolution Electromagnetic Tomography" (LORETA) in seven frequency bands. LORETA gravity centers of all bands shifted to the left in believers vs. sceptics, and showed that believers had stronger left fronto-temporo-parietal activity than skeptics. Self-rating of affective attitude showed believers to be less negative than skeptics. The observed EEG lateralization agreed with the ‘valence hypothesis’ that posits predominant left hemispheric processing for positive emotions. (2) Studying emotions, positive and negative emotion words were presented to 21 subjects while "Event-Related Potentials" (ERPs) were recorded. During word presentation (450 ms), 13 microstates (steps of information processing) were identified. Three microstates showed different potential maps for positive vs. negative words; LORETA functional imaging showed stronger activity in microstate #4 (106-122 ms) for positive words right anterior, for negative words left central; in #6 (138-166 ms) for positive words left anterior, for negative words left posterior; in #7 (166-198 ms), for positive words right anterior, for negative words right central. In conclusion: during word processing, the extraction of emotion content starts as early as 106 ms after stimulus onset; the brain identifies emotion content repeatedly in three separate, brief microstate epochs; and, this processing of emotion content in the three microstates involves different brain mechanisms to represent the distinction positive vs. negative valence.Die Arbeit umfasst zwei Experimente zu hirnelektrischen Korrelaten kognitiver und emotionaler Funktionen. (1) Glauben an paranormale Phänomene: 35-Kanal Ruhe-EEG (10 Gläubige, 13 Skeptiker) wurde mit "Low Resolution Electromagnetic Tomography" (LORETA) analysiert (7 EEG-Frequenzbänder). LORETA zeigte Links-Verschiebung der Schwerpunkte aller Bänder bei Gläubigen durch erhöhte Aktivität links fronto-temporo-parietal. Die Affektive Haltung war im Selbst-Rating bei Gläubigen weniger negativ als bei Skeptikern. Die EEG-Lateralisierung passt zur Valenz-Hypothese emotionaler Verarbeitung, die vorwiegend linkshemisphärische Aktivität bei positiver Emotion postuliert. (2) Zur Emotions-Verarbeitung wurden 21 Versuchspersonen emotional positive und negative Wörter gezeigt und dabei "Event-Related Potentials" (ERPs) registriert. 13 Mikrozustände (Informations-Verarbeitungsschritte) wurden während der Darbietungszeit (450 ms) identifiziert. In 3 Mikrozuständen unterschieden sich die topographischen ERP-Karten für positive und negative Wörter. LORETA zeigte erhöhte Aktivität im Mikrozustand #4 (106-122 ms) für positive Wörter rechts anterior, für negative links zentral; im Mikrozustand #6 (138-166 ms) für positive Wörter links anterior, für negative links posterior; im Mikrozustand #7 (166-198 ms) für positive Wörter rechts anterior, für negative rechts zentral. Zusammenfassend: die Extraktion emotionalen Gehalts beginnt bereits 106 ms nach Stimulusbeginn, umfasst repetitiv drei separate, kurze Verarbeitungsschritte, und erfolgt in diesen Schritten auf unterschiedliche Art, d.h. benutzt unterschiedliche Hirnmechanismen zur Inkorporation der Unterscheidung positiv-negativ

Simple systems for the study of learning mechanisms - A report of an NRP work session, volume 4, number 2, 2-3 June 1965

Actual and potential biological preparations for studying learning mechanisms, with interest centered on insects and mollusk

Blind to Their Blindness: A History of the Denial of Illness

For many historians, sociologists, and anthropologists of medicine, "disease" and "illness" are not equivalent. Whereas "disease" denotes the physician's ostensibly objective criteria, "illness" emphasizes the patient's subjective experience. This dissertation examines that distinction precisely at a point where it breaks down, in the history of a diagnosis called "anosognosia," also known as the denial of illness.History of Scienc

Functional neuroimaging in subjects at high genetic risk of schizophrenia

Schizophrenia is an incapacitating psychiatric disorder characterized by hallucinations and delusions with a lifetime risk of around 1% worldwide. It is a highly heritable disorder which generally becomes manifest in early adult life. The established condition has been associated with structural and functional brain abnormalities, principally in prefrontal and temporal lobes, but it is unclear whether such abnormalities are related to inherited vulnerability, medication effects, or the presence of symptoms. Furthermore, the mechanisms by which the pre-morbid state switches into florid psychosis are unknown. The Edinburgh High Risk Study is designed to address these issues. The first phase (1994-1999) employed repeated clinical, neuropsychological assessments and structural imaging. In the current phase (1999-2004) functional magnetic resonance imaging (fMRI) has been added to the tests used previously.As part of the Edinburgh High Risk Study, this study used a covert verbal initiation fMRI task (the Hayling Sentence Completion Test) known to elicit frontal and temporal activation, to examine a large number of young participants at high risk of developing schizophrenia for genetic reasons, in comparison with a matched group of healthy controls. Subjects were scanned at baseline, and after approximately one year. At the time of the baseline scan none of the participants met criteria for any psychiatric disorder, however, a number of subjects reported isolated psychotic symptoms on direct questioning. Over the course of the entire study (1994-2004), 21 individuals developed schizophrenia according to standard diagnostic criteria. Four of these subjects made the transition over the course of the current study (1999-2004), i.e. subsequent to the baseline functional scanThere were three main aims of the current study (i) to use fMRI to identify the neural correlates of state and trait effects in high risk individuals, (ii) to determine ifit is possible to distinguish those who subsequently become ill from those who remain well using functional imaging, and (iii) to determine if patterns of brain activity change with the transition to illness, or vary with changes in symptomatic status of these individuals.Regarding the first aim, group differences of apparent genetic origin were found in prefrontal, thalamic, cerebellar regions, and differences in activation in those with symptoms were found in the parietal lobe. Functional connectivity analysis examining interactions between these regions also indicated similar abnormalities. These results may therefore reflect inherited deficits, and the earliest changes associated with the psychotic state, respectively. Although only a small number of subjects became ill over the course of the current study («=4), initial findings suggested abnormalities in medial prefrontal and medial temporal regions (with an indication of parietal lobe dysfunction) were able to distinguish those who later became ill versus those that remained well. Finally, there were also indications of changes in activation patterns over time in a subgroup of subjects with varying symptomatic status.To conclude, these results are consistent with previous findings in the Edinburgh High Risk Study - what is inherited by the high risk individuals is a state of heightened vulnerability manifesting, in the case of functional imaging, as abnormalities in activation and/or connectivity in preffontal-thalamiccerebellar and prefrontal-parietal regions. These finding also suggest that there are additional differences seen in those with psychotic symptoms, and to some extent in those who subsequently go on to develop the disorder. These results are not confounded by anti-psychotic medication since all subjects were anti-psychotic naive at the time of assessment. The lack of findings traditionally associated with the established illness (dorsolateral prefrontal cortex and lateral temporal lobe) indicate these may be specifically associated with the established state, or when performance differences become manifest. Overall therefore these findings reveal information regarding the pathophysiology of the state of vulnerability to the disorder and about the mechanisms involved in the development of schizophrenia or schizophrenic symptomatology