The bodily self: Insights from clinical and experimental research

This review article summarizes neuropsychological descriptions of abnormal body representations in brain-damaged patients and recent neuroscientific investigations of their sensorimotor underpinnings in healthy participants. The first part of the article describes unilateral disorders of the bodily self, such as asomatognosia, feelings of amputation, supernumerary phantom limbs and somatoparaphrenia, as well as descriptions of non-lateralized disorders of the bodily self, including Alice in Wonderland syndrome and autoscopic hallucinations. Because the sensorimotor mechanisms of these disorders are unclear, we focus on clinical descriptions and insist on the importance of reporting clinical cases to better understand the full range of bodily disorders encountered in neurological diseases. The second part of the article presents the advantages of merging neuroscientific approaches of the bodily self with immersive virtual reality, robotics and neuroprosthetics to foster the understanding of the multisensory, motor and neural mechanisms of bodily representations

Establishing two principal dimensions of cognitive variation in Logopenic Progressive Aphasia

Logopenic Progressive Aphasia (LPA) is a neurodegenerative syndrome characterised by sentence repetition and naming difficulties arising from left-lateralised temporoparietal atrophy. Clinical descriptions of LPA largely concentrate on profiling language deficits, however, accumulating evidence points to the presence of cognitive deficits, even on tasks with minimal language demands. Although non-linguistic cognitive deficits in LPA are thought to scale with disease severity, patients at discrete stages of language dysfunction display overlapping cognitive profiles, suggesting individual-level variation in cognitive performance, independent of primary language dysfunction. To address this issue, we used principal component analysis to decompose individual-level variation in cognitive performance in 43 well-characterised LPA patients who underwent multi-domain neuropsychological assessments and structural neuroimaging. The principal component analysis solution revealed the presence of two, statistically independent factors, providing stable and clinically intuitive explanations for the majority of variance in cognitive performance in the syndrome. Factor 1 reflected ‘speech production and verbal memory’ deficits which typify LPA. Systematic variations were also confirmed on a second, orthogonal factor mainly comprising visuospatial and executive processes. Adopting a case-comparison approach, we further demonstrate that pairs of patients with comparable Factor 1 scores, regardless of their severity, diverge considerably on visuo-executive test performance, underscoring the inter-individual variability in cognitive profiles in comparably ‘logopenic’ patients. Whole-brain voxel-based morphometry analyses revealed that speech production and verbal memory factor scores correlated with left middle frontal gyrus, while visuospatial and executive factor scores were associated with grey matter intensity of right-lateralised temporoparietal, middle frontal regions and their underlying white matter connectivity. Importantly, LPA patients with poorer visuospatial and executive factor scores demonstrated greater right-lateralised temporoparietal and frontal atrophy. Our findings demonstrate the inherent variation in cognitive performance at an individual- and group-level in LPA, suggesting the presence of a genuine co-occurring cognitive impairment that is independent of language function and disease severity.This work was supported in part by funding to Forefront, a collaborative research group specialized to the study of frontotemporal dementia and motor neurone disease, from the National Health and Medical Research Council (NHMRC) of Australia program grant (APP1037746) and the Australian Research Council (ARC) Centre of Excellence in Cognition and its Disorders Memory Program (CE110001021). Siddharth Ramanan is supported by a Faculty of Science Ph.D. Research Scholarship from The University of Sydney. Olivier Piguet is supported by an NHMRC Senior Research Fellowship (APP1103258). Muireann Irish is supported by an ARC Future Fellowship (FT160100096) and an ARC Discovery Project (DP180101548). Matthew A. Lambon Ralph is supported by a UKRI-MRC Programme Grant (MR/R023883/1) and an ERC Advanced grant (GAP: 670428 - BRAIN2MIND_NEUROCOMP)

New techniques for neuro-rehabilitation: Transcranial Electric Stimulation and Virtual Reality

Recovery of motor and cognitive performances after a neurological illness remains a significant challenge for rehabilitation specialists. The traditional rehabilitative interventions are usually delivered using a multidisciplinary approach, whose results are not always satisfactory. These limitations in functional recovery have led researchers to consider alternative approaches. The hypothesis of providing new therapeutic possibilities in the different patients treated is, as a rehabilitator, very rewarding and represents a challenge for the future. The application of simple and low-cost techniques, defined by the literature as "unconventional" or “novel”, can provide new ideas not only in the field of research but above all of application in clinical reality.A suitable approach to improve the rehabilitation outcome is to utilize these novel rehabilitation techniques that act as a substitute or an addition to the traditional ones. In this context, some recent approaches have been proposed that might increase the effectiveness of a traditional treatment. Among them, two techniques have been demonstrated to be very promising, namely non-invasive brain stimulation (NIBS) and Virtual Reality (VR).In light of the foregoing, my thesis has been divided into two main lines of research, namely: a) the study of the effects of transcranial direct current stimulation (tDCS) in different neurological conditions; b) the application of VR (used alone or combined with tDCS) in the treatment of some neurocognitive disorders. A semi-immersive VR tool (ReMOVES system) has been used as a user-friendly platform providing activities based on exergames

Investigating the interplay of the human attentional and vestibular systems using transcranial magnetic stimulation

The aim of this doctoral thesis was to investigate the relationship between the processing of vestibular information, on the one hand, and higher cognitive functions such as visual (spatial) attention and perceptual decision making, on the other. In order to draw causal inference about the role of specific cortical regions in this interplay, two experimental studies were conducted which combined psychophysical task designs using verticality judgment tasks with transcranial magnetic stimulation (TMS). The first study employed a simultaneous TMS-EEG approach to examine the role of the right intraparietal sulcus (IPS) within the dorsal parietal cortex in verticality judgments – a cortical area that has repeatedly been associated with both the visual attention and vestibular systems. Facilitatory effects of right IPS TMS on the bias of verticality perception were reported and mirrored by EEG results, which pointed to a normalization of individual perceptual biases reflected in a fronto-central ERP component following the stimulation. In contrast, no effects of left IPS TMS on either behavioural or electrophysiological measures were observed and right IPS TMS did not modulate performance in a control task that used the same set of stimuli (vertical Landmark task). These findings point to a causal role of the right IPS in the neuronal implementation of upright perception and strengthen the notion of vestibular-attentional coupling. In the second study verticality judgments had to be made under different levels of perceptual demand to address the question of how perceptual decision making interacts with vestibular processing. Stimuli adapted from those used in the first study were presented in a visual search setting, which required perceptual and response switches, in a way that varied attentional demands. This task was combined with offline theta-burst TMS applied to the dorsal medial frontal cortex (dMFC). The dMFC has been found to crucially contribute to perceptual decision making and is connected to core parts of the vestibular cortical network. Analysis of distinct features of behavioural performance before as compared to following dMFC TMS revealed a specific involvement of the dMFC in establishing the precision and accuracy of verticality judgments, particularly under conditions of high perceptual load. In summary, the results of the two studies support the idea of a functional link between the processing of vestibular information, (spatial) attention, and perceptual decision making, giving rise to higher vestibular cognition. Moreover, they suggest that on a cortical level this interplay is achieved within a network of multimodal processing regions such as the parietal and frontal cortices

The AI Neuropsychologist: Automatic scoring of memory deficits with deep learning

Memory deficits are a hallmark of many different neurological and psychiatric conditions. The Rey-Osterrieth complex figure (ROCF) is the state–of-the-art assessment tool for neuropsychologists across the globe to assess the degree of non-verbal visual memory deterioration. To obtain a score, a trained clinician inspects a patient’s ROCF drawing and quantifies deviations from the original figure. This manual procedure is time-consuming, slow and scores vary depending on the clinician’s experience, motivation and tiredness. Here, we leverage novel deep learning architectures to automatize the rating of memory deficits. For this, a multi-head convolutional neural network was trained on 20225 ROCF drawings. Unbiased ground truth ROCF scores were obtained from crowdsourced human intelligence. The neural network outperforms both online raters and clinicians. Our AI-powered scoring system provides healthcare institutions worldwide with a digital tool to assess objectively, reliably and time-efficiently the performance in the ROCF test from hand-drawn images

Behavioural manipulations of parietal lobe function

The aim of this thesis was to develop a novel behavioural technique to disrupt parietal function in order to induce top-down cortical modulation of low-level brain structures, namely the brainstem mediated vestibulo- ocular reflex and the early visual cortex. The premise of the technique was based upon using stimuli that engaged overlapping neuronal networks. To this end, we employed a technique that involved concurrent vestibular activation and viewing of bistable perceptual visual stimuli or performing visualised spatial attention tasks. The thesis presents data that shows the ability of this technique to induce a handedness related cortical modulation of the vestibulo-ocular reflex and modulation of the early visual cortex. Subsequently we applied trans-cranial direct stimulation to directly disrupt parietal inter-hemispheric balance in order to induce an asymmetrical modulation of the VOR and propose a revised computational model for vestibular processing. The results from these experiments present the first behavioural demonstration that vestibular cortical processing is strongly lateralised to the non-dominant hemisphere. We propose that this technique developed and validated in this thesis can be used to further probe and investigate cognitive parietal function such as numerical cognition and human decision making.Open Acces

Event-related electroencephalographic lateralizations mark individual differences in spatial and nonspatial visual selection

Selective attention controls the distribution of our visual sys- tem's limited processing resources to stimuli in the visual field. Two independent parameters of visual selection can be quantified by modeling an individual's performance in a partial-report task based on the computational theory of visual attention (TVA): (i) top-down control α, the relative attentional weight- ing of relevant over irrelevant stimuli, and (ii) spatial bias wλ, the relative attentional weighting of stimuli in the left versus right hemifield. In this study, we found that visual event-related electroencephalographic lateralizations marked interindividual differences in these two functions. First, individuals with better top-down control showed higher amplitudes of the posterior contralateral negativity than individuals with poorer top-down control. Second, differences in spatial bias were reflected in asymmetries in earlier visual event-related lateralizations de- pending on the hemifield position of targets; specifically, individuals showed a positivity contralateral to targets presented in their prioritized hemifield and a negativity contralateral to targets presented in their nonprioritized hemifield. Thus, our findings demonstrate that two functionally different aspects of attentional weighting quantified in the respective TVA parameters are reflected in two different neurophysiological measures: The observer-dependent spatial bias influences selection by a bottom-up processing advantage of stimuli appearing in the prioritized hemifield. By contrast, task-related target selection governed by top-down control involves active enhancement of target, and/or suppression of distractor, processing. These results confirm basic assumptions of the TVA framework, complement the functional interpretation of event-related lateralization components in selective attention studies, and are of relevance for the development of neurocognitive attentional assessment procedures

Using neuro-cognitive modelling to link attention deficits to structural and functional brain changes

‘Visual attention’ is an emerging property of interconnected neural networks, in which the interconnections are biased to promote targets over distracting stimuli. It has been shown that efficiency of the attention system is lost after many kinds of brain damage, with each presumably effecting different aspects of basic visual attention functions. Yet, our understanding of these processes is limited by the methodological shortcomings of classical neuropsychological assessment. The overarching goal of the current thesis was to overcome these constrains and thereby extend the link between attention deficits and underlying brain changes. The here used approach incorporates parametric measurement of visual attention derived from the computational Theory of Visual Attention (TVA, Bundesen, 1990) and modern magnetic resonance imaging techniques. Project 1 of the current thesis applied a combined TVA–neuroimaging analysis in a neurodevelopmental model (preterm birth) to relate attention deficits with changes in functional connectivity networks. We found that pre- versus full-term born adults show a selective reduction of visual short-term memory capacity. The remarkable changes we observed in attention-related large-scale brain networks of the occipital and posterior parietal cortices were most pronounced in those preterm born individuals with the most preserved attention functions. This finding was interpreted as evidence for a compensatory reorganization of functional connectivity in order to ameliorate the advert consequences of preterm birth on visual short-term memory. Project 2 of this thesis applied a combined TVA-neuroimaging analysis in a neurodegenerative model (posterior cortical atrophy) to relate attention deficits with structural changes in grey and white matter morphometry. Compared to healthy control participants, patients with posterior cortical atrophy suffered from a selective disturbance of visual processing speed. The individual rate of processing speed slowing was a valid predictor for the severity of simultanagnosia, the core symptom in this clinical condition. We further found wide-spread atrophy in occipital as well as parietal and to a smaller degree in temporal brain areas. White matter degeneration in the superior parietal lobe, rather than atrophy of any grey matter cluster, was significantly associated with patients’ impaired processing speed. Based on these results we propose that disruption of white matter pathways especially within the superior parietal lobe leads to reduced processing speed which then results in the overt clinical symptoms of simultanagnosia. Altogether, projects of the current thesis expanded the link between specific attention deficits and underlying brain damage by using neuro-cognitive modelling. We demonstrated that parametric measurements of attention facilitate, in the role of intermediate cognitive constructs, the mapping between etiological factors and behavioral outcomes. Identifying predictable behavior-brain relationships in attention disorders may offer new perspectives for diagnosis and treatment. The clinical application of an integrated TVA-neuroimaging analysis could additionally compliment insights from healthy participants toward understanding the principles of normal visual attention as well as identifying their neuronal basis

Posterior cerebral artery (PCA) infarcts and dreaming : a neuropsychological study

Recent case reports have shown that global loss of dreaming can result from medial occipitotemporal lesions. These findings have cast doubt on Solms's reformulation of Charcot-Wilbrand Syndrome (CWS) into two distinct disorders of dreaming, and caused substantial confusion in dream research as far as the neurological correlates of dreaming are concerned. This study attempted to confirm these case reports and determine whether there were any characteristics unique to the lesions among patients who had lost the ability to dream following damage to medial occipito-temporal cortex. Nine participants (three non-dreamers and six dreamers) who had suffered non-hemorrhagic infarction in the territory of the posterior cerebral artery were recruited in this study. Case histories and neuroradiological data were used to compare the lesion sites of non-dreamers with dreamers. It was confirmed that complete loss of dreaming could result from lesions in medial occipito-temporal cortex. It was found that non-dreamers always suffered bilateral cortical damage as opposed to dreamers who all suffered unilateral damage. The lesions in the non-dreamers tended to be more posterior than the dreamers. It was further speculated that concomitant damage to the thalamus or parietal areas played a role in the causation of heteromodal loss of dreaming. The implications of these findings were discussed in relation to CWS, Solms's dream system, and dream-function research. Finally, future directions were considered

Using neuro-cognitive modelling to link attention deficits to structural and functional brain changes

‘Visual attention’ is an emerging property of interconnected neural networks, in which the interconnections are biased to promote targets over distracting stimuli. It has been shown that efficiency of the attention system is lost after many kinds of brain damage, with each presumably effecting different aspects of basic visual attention functions. Yet, our understanding of these processes is limited by the methodological shortcomings of classical neuropsychological assessment. The overarching goal of the current thesis was to overcome these constrains and thereby extend the link between attention deficits and underlying brain changes. The here used approach incorporates parametric measurement of visual attention derived from the computational Theory of Visual Attention (TVA, Bundesen, 1990) and modern magnetic resonance imaging techniques. Project 1 of the current thesis applied a combined TVA–neuroimaging analysis in a neurodevelopmental model (preterm birth) to relate attention deficits with changes in functional connectivity networks. We found that pre- versus full-term born adults show a selective reduction of visual short-term memory capacity. The remarkable changes we observed in attention-related large-scale brain networks of the occipital and posterior parietal cortices were most pronounced in those preterm born individuals with the most preserved attention functions. This finding was interpreted as evidence for a compensatory reorganization of functional connectivity in order to ameliorate the advert consequences of preterm birth on visual short-term memory. Project 2 of this thesis applied a combined TVA-neuroimaging analysis in a neurodegenerative model (posterior cortical atrophy) to relate attention deficits with structural changes in grey and white matter morphometry. Compared to healthy control participants, patients with posterior cortical atrophy suffered from a selective disturbance of visual processing speed. The individual rate of processing speed slowing was a valid predictor for the severity of simultanagnosia, the core symptom in this clinical condition. We further found wide-spread atrophy in occipital as well as parietal and to a smaller degree in temporal brain areas. White matter degeneration in the superior parietal lobe, rather than atrophy of any grey matter cluster, was significantly associated with patients’ impaired processing speed. Based on these results we propose that disruption of white matter pathways especially within the superior parietal lobe leads to reduced processing speed which then results in the overt clinical symptoms of simultanagnosia. Altogether, projects of the current thesis expanded the link between specific attention deficits and underlying brain damage by using neuro-cognitive modelling. We demonstrated that parametric measurements of attention facilitate, in the role of intermediate cognitive constructs, the mapping between etiological factors and behavioral outcomes. Identifying predictable behavior-brain relationships in attention disorders may offer new perspectives for diagnosis and treatment. The clinical application of an integrated TVA-neuroimaging analysis could additionally compliment insights from healthy participants toward understanding the principles of normal visual attention as well as identifying their neuronal basis