A Neurocognitive Approach to the Study of Private Speech

The paper presents the current state of the art of research identifying the neurophysiological and neuroanatomical substrates of private speech, both in typical and clinical (or atypical) populations. First, it briefly describes the evolution of private speech research, which goes from classic traditions as the naturalistic and referential paradigms to the neurocognitive approach. An overview of the neurophysiological (e.g., event-related potentials or ERPs) and neuroimaging techniques (e.g., functional magnetic resonance imaging or fMRI) is also presented. The next three sections review empirical works about the neurocognitive basis of private speech, across three groups of techniques: ERPs; fMRI/MRI; and other neuroimaging techniques (positron emission tomography [PET], magnetoencephalogram [MEG], and repetitive transcranial magnetic stimulation [rTMS]). Such neurocognitive research analyzes the neural activity of individuals during a variety of task settings, including spontaneous and instructed overt and inner private speech use, subvocal verbalizations, and silent and overt reading. The fifth section focuses on electrophysiological and neuroimaging studies of private speech in atypical populations, for example: schizophrenia, pure alexia, hearing impairment, blindness, social phobia, alexithymia, Parkinson, and multiple sclerosis. The neurocognitive study of the various forms of private speech appears to be very promising in the understanding of these pathologies. Lastly, the advances and new challenges in the field are discussed.Este trabajo presenta el estado actual de la investigación que identifica los sustratos neurofisiológicos y neuroanatómicos del lenguaje privado, tanto en poblaciones típicas como en clínicas (o atípicas). Primero describe brevemente la evolución de la investigación del lenguaje privado, que van desde las tradiciones clásicas como los paradigmas naturalistas y referenciales al abordaje neurocognitivo. También se presenta una revisión de las técnicas neurofisiológicas (por ejemplo, potenciales relacionados con eventos o ERPs) y de neuroimagen (por ejemplo, imagen de resonancia magnética funcional o fMRI). Las siguientes tres secciones revisan los trabajos empíricos sobre la base neurocognitiva del lenguaje privado a través de tres grupos de técnicas: ERPs; fMRI/MRI; y otras técnicas de neuroimagen (tomografía de emisión de positrones [PET], magnetoencefalograma [MEG] y la estimulación magnética repetitiva transcraneal [rTMS]). Esta investigación neurocognitiva analiza la actividad neuronal de los individuos durante diversas tareas, incluyendo el uso del lenguaje privado espontáneo y observable bajo instrucciones y el lenguaje privado interno, las verbalizaciones subvocales y la lectura silenciosa y observable. La quinta sección se centra en los estudios electrofisiológicos y de neuroimágenes del lenguaje privado en poblaciones atípicas, por ejemplo, esquizofrenia, alexia pura, hipoacusia, ceguera, fobia social, alexithymia, Parkinson, y esclerosis múltiple. El estudio neurocognitivo de varias formas del lenguaje privado parece muy prometedor para la comprensión de estas patologías. Por último, se comentan los avances y los nuevos retos en el campo

A neurocognitive approach to the study of private speech

The paper presents the current state of the art of research identifying the neurophysiological and neuroanatomical substrates of private speech, both in typical and clinical (or atypical) populations. First, it briefly describes the evolution of private speech research, which goes from classic traditions as the naturalistic and referential paradigms to the neurocognitive approach. An overview of the neurophysiological (e.g., event-related potentials or ERPs) and neuroimaging techniques (e.g., functional magnetic resonance imaging or fMRI) is also presented. The next three sections review empirical works about the neurocognitive basis of private speech, across three groups of techniques: ERPs; fMRI/MRI; and other neuroimaging techniques (positron emission tomography [PET], magnetoencephalogram [MEG], and repetitive transcranial magnetic stimulation [rTMS]). Such neurocognitive research analyzes the neural activity of individuals during a variety of task settings, including spontaneous and instructed overt and inner private speech use, subvocal verbalizations, and silent and overt reading. The fifth section focuses on electrophysiological and neuroimaging studies of private speech in atypical populations, for example: schizophrenia, pure alexia, hearing impairment, blindness, social phobia, alexithymia, Parkinson, and multiple sclerosis. The neurocognitive study of the various forms of private speech appears to be very promising in the understanding of these pathologies. Lastly, the advances and new challenges in the field are discussed. Keywords: private speech, neurocognition, neurolinguistics, psychopathologies, language disorders Este trabajo presenta el estado actual de la investigación que identifica los sustratos neurofisiológicos y neuroanatómicos del lenguaje privado, tanto en poblaciones típicas como en clínicas (o atípicas). Primero describe brevemente la evolución de la investigación del lenguaje privado, que van desde las tradiciones clásicas como los paradigmas naturalistas y referenciales al abordaje neurocognitivo. También se presenta una revisión de las técnicas neurofisiológicas (por ejemplo, potenciales relacionados con eventos o ERPs) y de neuroimagen (por ejemplo, imagen de resonancia magnética funcional o fMRI). Las siguientes tres secciones revisan los trabajos empíricos sobre la base neurocognitiva del lenguaje privado a través de tres grupos de técnicas: ERPs; fMRI/MRI; y otras técnicas de neuroimagen (tomografía de emisión de positrones [PET], magnetoencefalograma [MEG] y la estimulación magnética repetitiva transcraneal [rTMS]). Esta investigación neurocognitiva analiza la actividad neuronal de los individuos durante diversas tareas, incluyendo el uso del lenguaje privado espontáneo y observable bajo instrucciones y el lenguaje privado interno, las verbalizaciones subvocales y la lectura silenciosa y observable. La quinta sección se centra en los estudios electrofisiológicos y de neuroimágenes del lenguaje privado en poblaciones atípicas, por ejemplo, esquizofrenia, alexia pura, hipoacusia, ceguera, fobia social, alexithymia, Parkinson, y esclerosis múltiple. El estudio neurocognitivo de varias formas del lenguaje privado parece muy prometedor para la comprensión de estas patologías. Por último, se comentan los avances y los nuevos retos en el campo. Palabras clave: lenguaje privado, neurocognición, neurolingüística, psicopatologías, trastornos del lenguaj

Construction of embedded fMRI resting-state functional connectivity networks using manifold learning

We construct embedded functional connectivity networks (FCN) from benchmark resting-state functional magnetic resonance imaging (rsfMRI) data acquired from patients with schizophrenia and healthy controls based on linear and nonlinear manifold learning algorithms, namely, Multidimensional Scaling, Isometric Feature Mapping, Diffusion Maps, Locally Linear Embedding and kernel PCA. Furthermore, based on key global graph-theoretic properties of the embedded FCN, we compare their classification potential using machine learning. We also assess the performance of two metrics that are widely used for the construction of FCN from fMRI, namely the Euclidean distance and the cross correlation metric. We show that diffusion maps with the cross correlation metric outperform the other combinations

Regional and Hemispheric Determinants of Language Laterality: Implications for Preoperative fMRI

Language is typically a function of the left hemisphere but the right hemisphere is also essential in some healthy individuals and patients. This inter-subject variability necessitates the localization of language function, at the individual level, prior to neurosurgical intervention. Such assessments are typically made by comparing left and right hemisphere language function to determine “language lateralization” using clinical tests or fMRI. Here, we show that language function needs to be assessed at the region and hemisphere specific level, because laterality measures can be misleading. Using fMRI data from 82 healthy participants, we investigated the degree to which activation for a semantic word matching task was lateralized in 50 different brain regions and across the entire cortex. This revealed two novel findings. First, the degree to which language is lateralized across brain regions and between subjects was primarily driven by differences in right hemisphere activation rather than differences in left hemisphere activation. Second, we found that healthy subjects who have relatively high left lateralization in the angular gyrus also have relatively low left lateralization in the ventral precentral gyrus. These findings illustrate spatial heterogeneity in language lateralization that is lost when global laterality measures are considered. It is likely that the complex spatial variability we observed in healthy controls is more exaggerated in patients with brain damage. We therefore highlight the importance of investigating within hemisphere regional variations in fMRI activation, prior to neuro-surgical intervention, to determine how each hemisphere and each region contributes to language processing. Hum Brain Mapp, 2010. © 2010 Wiley-Liss, Inc

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

A study of Clinico-Neuroradiologic Correlation in Patients with Dementia

INTRODUCTION: Dementia is characterized by decline in the cognitive functioning of an individual that significantly affects the quality of life and intrudes into the activity of daily living. The prevalence of dementia is increasing and is on the rise. This is due to the increased longevity that has resulted in increasing proportions of elderly population in whom the prevalence of dementia is higher. Dementia is defined by the DSM 5 criteria as decline from previously established baseline in the at least one of the cognitive domains: Memory and learning, executive function, language, complex attention, social cognition and perceptual motor function and it affects the activities of daily living. The symptoms in these patients do not occur exclusively during delirium and are not explainable by psychiatric disorder. AIM OF THE STUDY: To study the association between clinical deficits in cognitive domains of attention, memory and language in subjects with dementia and the neuroimaging correlates of the corresponding networks. OBJECTIVES: 1. To evaluate clinical deficits in cognitive domains of attention, memory and language in subjects with dementia. 2. To study the neuroimaging findings in subjects of Dementia on MR voxel based morphometry, MR diffusion tensor imaging and 18-Fluorodeoxyglucose Positron Emission Tomography in corresponding networks of attention, language and memory respectively. 3. To determine neuroimaging correlates of deficits in attention, language and memory in subjects with dementia in corresponding networks of attention, language and memory respectively. MATERIALS AND METHODS: Subjects attending dementia and cognitive neurosciences clinic at Rajiv Gandhi Government General Hospital, Chennai (RGGGH) were enrolled in the study. A total of 60 patients and 30 controls were recruited for the study. All the subjects were well informed about the study and the consent forms were obtained prior to the assessments. All the patients in the study underwent clinical examination for establishing the diagnosis of dementia. After the clinical assessment the subjects under investigation underwent four different types of assessments. The assessments include neuropsychological assessments, Voxel based Morphometry, Diffusion Tensor Imaging (for both controls and cases), and FDG-PET (for cases alone). METHODOLOGY: A random sample of 60 patients and 30 age-gender matched controls were selected from dementia and cognitive neurosciences clinic at Rajiv Gandhi Government General Hospital(RGGGH), Chennai during Dec. 2014 – Feb. 2018. The study was approved by Institutional Ethical Committee of Rajiv Gandhi Government General Hospital, Chennai. Neuropsychological tests were performed after obtaining consents from the subjects or caretakers. Patients were selected on the basis of MoCA scores where a case with a MoCA score of below 27 and satisfying the inclusion/exclusion criteria has been treated as a patient and included in the present study. The following clinical assessments were made on each patient: Addenbrooke‘s Cognitive Examination III (ACE III), Wechsler‘s Memory Scale (WMS), Trail Making Test A & B (TMT), Auditory Verbal Learning Test (AVLT) and scores were assessed accordingly. Neuropsychological aspects of both patients and controls were assessed by a single trained clinical psychologist. RESULTS: Before carrying out the major study, a pilot study was conducted taking a random sample of 10 patients and 10 controls. Reliability and validity of the protocols used for carrying out the major study were computed using appropriate statistical tools such as Cronbach‘s alpha for reliability and expert opinion on the validity of the protocols. Reliability analysis was carried out using split half method and the Cronbach alpha for part 1 of the protocol was obtained as 0.913 and for part 2 it was 0.993. The overall reliability of the protocol was 0.937 indicating high reliability of the test schedule used in the present study. CONCLUSIONS: Patients and controls were well differentiated in all the neuro-psychological parameters, MoCA, Addenbrook‘s Cognitive Score, WMS, AVLT, Digit Span, Story Recall, and Complex figure. Patients are found to have low scores in all these aspects compared to controls. Stepwise regression analysis indicates scores in only five parameters, namely attention, memory, AVLT, Digit span, and complex figure are enough to classify a person as having dementia or a normal person with a prediction accuracy of nearly 99 per cent. All these neuro psychological parameters are interrelated to one another. Inter correlations of neuro psychological parameters are very high among patients compared to controls in the present study. Analysis of Diffusion Tensor Imaging indicates that the white matter tract, Superior Longitudinal Fasciculus does not play any major role in attention and language domain. In contrast, Fornix has a major role to play in the memory domain. All the metrics of DTI show significant difference between patients and controls in the white matter tract Fornix on either side of the brain. As far as the DTI metrics are concerned, all the metrics have the same levels on both sides of brain of patients and controls. In most of the white matter tracts, the metrics, RD, MD, and AD are found to be high among patients compared to controls. FA is found to be low among patients in white matter tracts like IFO and Fornix. The analysis of diffusion metrics suggests the varying involvement of the white matter fasciculi of the respective domains. Analysis of FDG PET data indicates that about 70 per cent to 93 per cent of patients have hypometabolism in all the five cortical areas of attention domain- frontal association, posterior cingulate, parietal association, anterior cingulate, and caudate regions on either side of brain. Similarly 77 to 91 per cent of patients have hypometabolism in cortical areas of language domain, frontal association, temporal association and parietal association regions on either side of brain. About 85 to 89 per cent of patients have hypometabolism on either side of anterior cingulate regions. Voxel based Morphometry analysis clearly indicated that the patients and controls are significantly different in the following gray matter hubs of Attention Network : Dorsolateral Prefrontal Cortex, Frontal Eye Field, Occipital Eye Field, Cingulate Cortex and Superior Parietal Lobule. Similar scenario is seen in gray matter hubs of language Network: Broca's Area, Wernicke's Area, and Geschwind‘s Area (Inferior Parietal Lobule). In gray matter hubs of Memory Network: Uncus, Hippocampus, and Nucleus Accumbens areas, patients are found to be significantly different from the controls

Verbal and nonverbal communication in schizophrenia - New insights from uni- and multimodal brain imaging

Socio-cognitive symptoms represent prominent and often strongly impairing deficits in patients with schizophrenia and they are tightly intertwined with dysfunctional communicative representations or systems. In particular, deficient verbal and nonverbal social information processing is associated with decreased functional outcome and prominent difficulties in everyday social interactions. Some specific aspects of verbal and nonverbal communication in schizophrenia have been thoroughly assessed by previous studies, particularly semantic priming at word level (verbal-cognitive domain) as well as face and facial emotion recognition (nonverbal-affective domain) and rather broad sociocognitive functions including Theory of Mind (ToM). However, only very little is known about disease-related alterations in more complex language functions, such as pragmatic (e.g. non-literal) language comprehension, or emotion processing from social cues other than the face, such as human body language. To this end, the present dissertation intended to investigate neurophysiological correlates of verbal and nonverbal socio-communicative (dys)functions in schizophrenia that have so far been rarely investigated using functional imaging, namely pragmatic language (verbalcognitive domain, 2 studies) and emotional body language (nonverbal-affective domain, 2 studies) processing. Neurophysiological activity was assessed by means of functional nearinfrared spectroscopy (fNIRS) measurements, either applied alone (unimodal imaging) or combined with electroencephalography (EEG; multimodal imaging). These specific neuroimaging methods have been chosen because they are characterised by high ecological validity and a relatively high flexibility regarding their applicability in varying contexts, implying a great potential of these techniques to assess social communicative functions in schizophrenia that are highly relevant for everyday social interactions. Taken together, the results obtained in the four studies revealed 1) that fNIRS measurements – either unimodally applied or combined with EEG – are useful to detect cortical activation associated with verbal-cognitive and nonverbal-affective information processing. 2) Patients with schizophrenia show significant alterations in these neurophysiological processes along with impaired recognition of pragmatic language (verbal-cognitive domain) and emotional body language (nonverbal-affective domain). The findings complement previous studies on more commonly assessed sociocommunicative dysfunctions in schizophrenia (altered semantic priming and facial expression perception). The present work provides a holistic overview over different social communication dysfunctions that may be apparent in patients suffering from schizophrenia and their accessibility via fNIRS and EEG-fNIRS measurements, respectively. Hereby, all project parts focused on an innovative implementation of neuroimaging methods that may be particularly promising for future directions in neuropsychiatric research. The findings are discussed in the light of contemporary models of pragmatic language comprehension as well as nonverbal social information processing. Moreover, they are integrated into current concepts of schizophrenia, particularly with respect to etiological models and neurocognitive frameworks as well as the endophenotype concept.Sozial-kognitive Symptome stellen ein markantes und häufig stark beeinträchtigendes Defizit von Patienten mit schizophrener Erkrankung dar, welches eng mit Dysfunktionen in Kommunikation und Interaktion verknüpft ist. Hierbei sind insbesondere Einschränkungen in der Verarbeitung verbal und nonverbal dargebotener sozialer Information mit einem verminderten generellen Funktionsniveau sowie deutlichen Schwierigkeiten bei alltäglichen sozialen Interaktionen assoziiert. Einige spezifische Teilbereiche verbaler und nonverbaler Kommunikation bei Schizophrenie wurden bereits in früheren Studien zum Teil ausführlich untersucht, wie beispielsweise semantische Bahnung (Priming) auf Wortebene (verbalkognitive Ebene), (emotionale) Gesichtsverarbeitung (nonverbal-affektive Ebene) sowie weniger scharf umgrenzte sozial-kognitive Funktionen einschließlich Theory of Mind (ToM). Bislang ist jedoch wenig bekannt über störungsbezogene Veränderungen komplexer Sprachverarbeitung, wie pragmatisches (z. B. nicht-wörtlich gemeintes) Sprachverstehen, oder der Verarbeitung von Emotionen auf Basis sozialer Reize, die nicht auf Gesichter beschränkt sind, wie beispielsweise menschliche Körpersprache. Die vorliegende Dissertation befasst sich daher mit der Untersuchung neurophysiologischer Korrelate solcher verbaler und nonverbaler kommunikativer (Dys-)Funktionen bei Schizophrenie, die bislang nur wenig mittels funktioneller Bildgebung untersucht worden sind. Hierbei werden zum einen pragmatische Sprache (verbal-kognitive Ebene) und zum anderen emotionale Körpersprache (nonverbal-affektive Ebene) fokussiert. Die Erfassung neurophysiologischer Aktivität erfolgt mithilfe der Methode der funktionellen Nahinfrarot-Spektroskopie (fNIRS), welche hierbei entweder allein (unimodale Messungen) oder in Kombination mit Elektroenzephalographie (EEG, multimodale Messungen) zum Einsatz kommt. Diese bildgebenden Verfahren wurden insbesondere aufgrund ihrer hohen ökologischen Validität und flexiblen Anwendbarkeit in verschiedensten Untersuchungs-Situationen ausgewählt, welche ein hohes Potential beider Methoden zur validen und ökonomischen Untersuchung alltagsrelevanter kommunikativer Funktionen bei Schizophrenie nahe legen. Zusammengefasst ergaben die in den vier Studien erbrachten Ergebnisse folgendes Bild: (1) fNIRS Messungen, sowohl uni- als auch multimodal (hier: in Kombination mit EEG) angewendet, bilden eine nützliche Methode zur realitätsnahen Erfassung kortikaler Aktivierung, die mit verbal-kognitiver und nonverbal-affektiver Informationsverarbeitung in Zusammenhang stehen. (2) Patienten mit Schizophrenie zeigen signifikante Veränderungen dieser neurophysiologischen Prozesse, welche behavioral mit einem verminderten pragmatischem Sprachverstehen (verbal-kognitive Ebene) sowie Einschränkungen im Erkennen emotionaler Körpersprache (nonverbal-affektive Ebene) einhergehen. Diese Befunde ergänzen frühere Studien zu weniger komplexen, aber bislang häufiger untersuchten sozio-kommunikativen Dysfunktionen bei Schizophrenie (z. B. verändertes semantisches Priming sowie beeinträchtigte Verarbeitung von Gesichtsausdrücken). Die Befunde werden vor dem Hintergrund theoretischer Modelle zum pragmatischen Sprachverstehen sowie der Verarbeitung nonverbaler sozialer Information diskutiert. Darüber hinaus werden die Ergebnisse in aktuelle Konzepte der Schizophrenie integriert, insbesondere im Hinblick auf äthiologische Modelle und neurokognitive Erklärungsansätze der Erkrankung. Zudem wird eine Einordnung der hier untersuchten kommunikativen Funktionen in das Endophänotypenkonzept versucht

Applying the Free-Energy Principle to Complex Adaptive Systems

The free energy principle is a mathematical theory of the behaviour of self-organising systems that originally gained prominence as a unified model of the brain. Since then, the theory has been applied to a plethora of biological phenomena, extending from single-celled and multicellular organisms through to niche construction and human culture, and even the emergence of life itself. The free energy principle tells us that perception and action operate synergistically to minimize an organism’s exposure to surprising biological states, which are more likely to lead to decay. A key corollary of this hypothesis is active inference—the idea that all behavior involves the selective sampling of sensory data so that we experience what we expect to (in order to avoid surprises). Simply put, we act upon the world to fulfill our expectations. It is now widely recognized that the implications of the free energy principle for our understanding of the human mind and behavior are far-reaching and profound. To date, however, its capacity to extend beyond our brain—to more generally explain living and other complex adaptive systems—has only just begun to be explored. The aim of this collection is to showcase the breadth of the free energy principle as a unified theory of complex adaptive systems—conscious, social, living, or not