Search bioRxiv⌕ Search

Biology subjects

Bernasconi, F.

Publications and source records attributed to Bernasconi, F..

11 recordsLinked to original sources

Presence Hallucination Induction through Robotically Mediated Somatomotor Conflicts: a pooled analysis of 26 experiments

Hallucinations are significant symptoms in psychiatric and neurodegenerative diseases, that may indicate advanced disease progression or worse disease forms. They are also frequent in healthy individuals, especially elderly or bereaved. Despite their relevance, studying hallucinations in controlled laboratory conditions remains challenging given the limited procedures inducing clinically relevant hallucinations. We have previously developed a robotics-based protocol capable of inducing a specific clinically relevant hallucination, presence hallucination (PH), in both healthy individuals and patients. Using this approach, we have systematically investigated the sensitivity and intensity of PH-induction, as well as its effects on various sensory, behavioral and cognitive aspects. In the present study, we pooled individual-participant data from 26 in-house experiments (totaling 580 individuals) and conducted a Bayesian analysis to estimate effects and moderators of PH-induction. PH-induction was reliably induced with a medium effect-size, and individuals with schizotypal traits were more sensitive. Furthermore, we identified that PH-induction may not strongly depend on altered agency, but found a synergistic relationship between passivity and induced PH. Collectively these results elucidate the role of somatomotor processes in aberrant own body perceptions, advance understanding of psychosis, and provide powerful statistical priors for future studies.

neuroscience↗

Connectome-based brain fingerprints predict early cognitive decline in Parkinson's patients with minor hallucinations

Individual variability in connectome organization offers a unique framework for capturing patient-specific alterations and advancing personalized models in medicine. Minor hallucinations (MH) affect up to 40% of Parkinsons disease (PD) patients and are early indicators of cognitive decline and dementia, hence crucial for early intervention. While previous studies focused on group-level differences, connectome-based brain fingerprinting enables deeper, individualized analysis of neural change. Applying this approach to PD patients with and without MH using resting-state fMRI, we show that each patient exhibited unique brain fingerprint, revealing rich quantifiable personalized features with medical relevance. MH-patients showed a loss of subject-specific features in brain networks linked to cognitive health, while somatosensory regions - typically less distinctive - became more prominent, emphasizing their role in MH pathogenesis. These differences enabled to identify - in an entirely data driven manner - patient-specific networks linked to early subclinical cognitive alterations, as well differential spatial fingerprinting organization linked to cortical densities of neurotransmitters. These findings reveal a distinct, patient-specific connectomic signature that differentiates PD patients with MH, uncovering early neural markers for precision medicine in PD.

neuroscience↗

Inverse Finite Element Framework Combining Ultrasound Imaging and Inflation Testing of PVA Artery Phantoms

The clinical decision to establish if a patient with carotid disease should undergo surgical intervention is primarily based on the percent stenosis. Whilst this applies for high-grade stenosed vessels (>70%), it falls short for other cases. Due to the heterogeneity of plaque tissue, probing the mechanics of the tissue would likely provide further insights into why some plaques are more prone to rupture. Mechanical characterisation of such tissue is nontrivial, however, due to the difficulties in collecting fresh, intact plaque tissue and using physiologically relevant mechanical testing of such material. The use of polyvinyl alcohol (PVA) is thus highly convenient because of its acoustic properties and tuneable mechanical properties. MethodsThe aim of this study is to demonstrate the potential of polyvinyl alcohol phantoms to simulate atherosclerotic features. In addition, a testing and simulation framework is developed for full PVA vessel material characterization using ring tensile testing and inflation testing combined with non-invasive ultrasound imaging and computational modelling. ResultsStrain stiffening behaviour was observed in PVA through ring tensile tests, particularly at high freeze-thaw cycles. Inflation testing of bi-layered phantoms featuring lipid pool inclusions demonstrated high strains at shoulder regions. The application of an inverse finite element framework successfully recovered boundaries and determined the shear moduli for the PVA wall to lie within the range 27 kPa to 53 kPa. ConclusionThe imaging-modelling framework presented facilitates the use and characterisation of arterial mimicking phantoms to further explore plaque rupture. It also shows translational potential for non-invasive mechanical characterisation of atherosclerotic plaques to improve the identification of clinically relevant metrics of plaque vulnerability.

bioengineering↗

Digital-robotic markers for hallucinations in Parkinson's disease

Hallucinations are frequent non-motor symptoms in Parkinsons disease (PD) associated with dementia and higher mortality. Despite their high clinical relevance, current assessments of hallucinations are based on verbal self-reports and interviews that are limited by important biases. Here, we used virtual reality (VR), robotics, and digital online technology to quantify presence hallucination (PH) in laboratory and home-based settings. We establish that elevated numerosity estimation of digital humans in VR is a digital marker for experimentally induced PH in healthy participants, as confirmed across several control conditions and analyses. We translated the digital marker (numerosity estimation) to an online procedure that 170 PD patients carried out remotely at their homes, revealing that PD patients with disease-related PH (but not control PD patients) showed higher numerosity estimation. Numerosity estimation enables quantitative monitoring of hallucinations, is an easy-to-use unobtrusive online method, reaching people far away from medical centers, translating neuroscientific findings using robotics and VR, to patients homes without specific equipment or trained staff.

neuroscience↗

Subcortical correlates of consciousness with human single neuron recordings

Subcortical brain structures such as the subthalamic nucleus or the thalamus are involved in regulating motor and cognitive behavior. However, their contribution to perceptual consciousness is still unclear, due to the inherent difficulties of recording subcortical neuronal activity in humans. Here, we asked neurological patients undergoing surgery for deep brain stimulation to detect weak vibrotactile stimuli applied on their hand while recording single neuron activity from the tip of a microelectrode. We isolated putative single neurons in the subthalamic nucleus and thalamus. A significant proportion of neurons modulated their activity while participants were expecting a stimulus. We found that the firing rate of 23% of these neurons differed between detected and undetected stimuli. Our results provide direct neurophysiological evidence of the involvement of the subthalamic nucleus and the thalamus for the detection of vibrotactile stimuli, thereby calling for a less cortico-centric view of the neural correlates of consciousness.

neuroscience↗

Robotically-induced auditory-verbal hallucinations: combining self-monitoring and strong perceptual priors

Inducing hallucinations under controlled experimental conditions in non-hallucinating individuals represents a novel research avenue oriented towards understanding complex hallucinatory phenomena, avoiding confounds observed in patients. Auditory-verbal hallucinations (AVH) are one of the most common and distressing psychotic symptoms, whose etiology remains largely unknown. Two prominent accounts portray AVH either as a deficit in auditory-verbal self-monitoring, or as a result of overly strong perceptual priors. In order to test both theoretical models and evaluate their potential integration, we developed a robotic procedure able to induce self-monitoring perturbations (consisting of sensorimotor conflicts between poking movements and corresponding tactile feedback) and a perceptual prior associated with otherness sensations (i.e., feeling the presence of a non-existing another person). Here, in two independent studies, we show that this robotic procedure led to AVH-like phenomena in healthy individuals, which was further associated with delusional ideation. Specifically, a condition with stronger sensorimotor conflicts induced more AVH-like sensations (self-monitoring), while, in the otherness-related experimental condition, there were more AVH-like sensations when participants were detecting other-voice stimuli, compared to detecting self-voice stimuli (strong-priors). By demonstrating an experimental procedure able to induce AVH-like sensations in non-hallucinating individuals, we shed new light on AVH phenomenology, thereby integrating self-monitoring and strong-priors accounts.

neuroscience↗

Theta oscillations and minor hallucinations in Parkinson's disease reveal decrease in frontal lobe functions and later cognitive decline

Cognitive decline and hallucinations are common and debilitating non-motor symptoms, occurring during later phases of Parkinsons disease (PD). Minor hallucinations (MH), appear at early phases and have been suggested to predict cognitive impairment in PD, however, this has not been well-established by clinical research. Here, we investigated whether non-demented PD patients with MH show altered brain oscillations and whether such MH-related electrophysiological changes are associated with cognitive impairments that increase over time. Combining model-driven EEG analysis with neuropsychiatric and neuropsychological examinations in 75 PD patients, we reveal enhanced frontal theta oscillations in PD patients suffering from MH and link these oscillatory changes with lower cognitive frontal-subcortical functions. Neuropsychological follow-up examinations five years later confirmed MH-specific theta oscillations and revealed a stronger decline in frontal-subcortical functions in MH-patients with stronger frontal theta alterations, defining an MH and theta oscillation-based early marker of a cognitive decline in PD.

neuroscience↗

Single neurons in thalamus and subthalamic nucleus process cardiac and respiratory signals in humans

Visceral signals are constantly processed by our central nervous system, enable homeostatic regulation, and influence perception, emotion, and cognition. While visceral processes at cortical level have been extensively studied using non-invasive imaging techniques, very few studies have investigated how this information is processed at the single neuron level, both in humans and animals. Subcortical regions, relaying signals from peripheral interoceptors to cortical structures, are particularly understudied and how visceral information is processed in thalamic and subthalamic structures remains largely unknown. Here, we took advantage of intraoperative microelectrode recordings in patients undergoing surgery for deep brain stimulation (DBS) to investigate the activity of single neurons related to cardiac and respiratory functions in three subcortical regions: Ventral Intermedius nucleus (Vim) and Ventral caudalis nucleus (Vc) of the thalamus, and subthalamic nucleus (STN). We report that the activity of a large portion of the recorded neurons (about 70%) was modulated by either the heartbeat, the cardiac inter-beat interval, or the respiration. These cardiac and respiratory response patterns varied largely across neurons both in terms of timing and their kind of modulation. We observed neurons with increases or decreases in firing rate in response to either the heartbeat or the inter-beat interval. Peaks of neural activity were found at different phases of the cardiac and respiratory cycles. Whereas most neurons only responded to one of the tested signals, a substantial proportion of these visceral neurons (30%) was responsive to more than one of the tested signals, underlining specialization and integration of cardiac and respiratory signals in STN and thalamic neurons. By extensively describing for the first time single unit activity related to cardiorespiratory function in thalamic and subthalamic neurons, our results highlight the major role of these subcortical regions in the processing of visceral signals.

neuroscience↗

Sensorimotor hallucinationsin Parkinson's disease

Hallucinations in Parkinsons disease (PD) are one of the most disturbing non-motor symptoms, affect half of the patients, and constitute a major risk factor for adverse clinical outcomes such as psychosis and dementia. Here we report a robotics-based approach, enabling the induction of a specific clinically-relevant hallucination (presence hallucination, PH) under controlled experimental conditions and the characterization of a PD subgroup with enhanced sensorimotor sensitivity for such robot-induced PH. Using MR-compatible robotics in healthy participants and lesion network mapping analysis in neurological non-PD patients, we identify a fronto-temporal network that was associated with PH. This common PH-network was selectively disrupted in a new and independent sample of PD patients and predicted the presence of symptomatic PH. These robotics-neuroimaging findings determine the behavioral and neural mechanisms of PH and reveal pathological cortical sensorimotor processes of PH in PD, identifying a more severe form of PD associated with psychosis and cognitive decline.

neuroscience↗

Sensorimotor conflicts alter perceptual and action monitoring

Bodily self-consciousness is defined as a set of prereflective representations of integrated bodily signals giving rise to self-identification, self-location and first-person perspective. While bodily self-consciousness is known to modulate perception, little is known about its influence on higher-level cognitive processes. Here, we manipulated bodily self-consciousness by applying sensorimotor conflicts while participants performed a perceptual task followed by confidence judgments. Results showed that sensorimotor conflicts altered perceptual monitoring by decreasing metacognitive performance. In a second experiment, we replicated this finding and extended our results by showing that sensorimotor conflicts also altered action monitoring, as measured implicitly through intentional binding. In a third experiment, we showed that effects on perceptual monitoring were induced specifically by sensorimotor conflicts related to the trunk and not to the hand. Taken together, our results suggest that bodily self-consciousness may serve as a scaffold for perceptual and action monitoring.

neuroscience↗

Audio-tactile and peripersonal space processing around the trunk in human parietal and temporal cortex: an intracranial EEG study

Interactions with the environment happen by the medium of the body within ones peripersonal space (PPS) - the space surrounding the body. Studies in monkey and humans have highlighted a multisensory distributed cortical network representing the PPS. However, electrophysiological evidence for a multisensory encoding of PPS in humans is lacking. Here, we recorded for the first time intracranial electroencephalography (iEEG) in humans while administering tactile stimulation (T) on the trunk, approaching auditory stimuli (A), and the combination of the two (AT). To map PPS, in AT trials, tactile stimulation was delivered when the sound was far, at an intermediate location, or close to the body. We first identified electrodes showing AT multisensory integration (i.e., AT vs. A+T): 19% of the recording electrodes. Among those electrodes, we identified those showing a PPS effect (30% of the AT electrodes), i.e., a modulation of the evoked response to AT stimulation as a function of the distance between the sound and body. For most sites, AT multisensory integration and PPS effects had similar spatiotemporal characteristics, with an early response (~50ms) in the insular cortex, and later responses (~200ms) in pre- and post-central gyri. Superior temporal cortex showed a different response pattern with AT multisensory integration at ~100ms without PPS effect. These results, representing the first iEEG delineation of PPS processing in humans, show that PPS processing happens at neural sites where also multisensory integration occurs and at similar time periods, suggesting that PPS representation (around the trunk) is based on a spatial modulation of multisensory integration.

neuroscience↗