The neural correlates of topographical disorientation-a lesion analysis study.

Topographical disorientation refers to the selective inability to orient oneself in familiar surroundings. However, to date its neural correlates remain poorly understood. Here we use quantitative lesion analysis and a lesion network mapping approach in order to investigate seven patients with topographical disorientation. Our findings link not only the posterior parahippocampal gyrus (PHG) and retrosplenial cortex but also the lingual gyrus, the precuneus and the fusiform gyrus to topographical disorientation. We propose that topographical disorientation is due to the inability to integrate familiar landmarks within a framework of allocentric and egocentric orientation, supported by a neural network including the posterior PHG, the retrosplenial and the lingual cortex.

REM sleep and muscle atonia in brainstem stroke: A quantitative polysomnographic and lesion analysis study.

Important brainstem regions are involved in the regulation of rapid eye movement sleep. We hypothesized that brainstem stroke is associated with dysregulated rapid eye movement sleep and related muscle activity. We compared quantitative/qualitative polysomnography features of rapid eye movement sleep and muscle activity (any, phasic, tonic) between 15 patients with brainstem stroke (N = 46 rapid eye movement periods), 16 patients with lacunar/non-brainstem stroke (N = 40 rapid eye movement periods), 15 healthy controls (N = 62 rapid eye movement periods), and patients with Parkinson's disease and polysomnography-confirmed rapid eye movement sleep behaviour disorder. Further, in the brainstem group, we performed a magnetic resonance imaging-based lesion overlap analysis. The mean ratio of muscle activity to rapid eye movement sleep epoch in the brainstem group ("any" muscle activity 0.09 ± 0.15; phasic muscle activity 0.08 ± 0.14) was significantly lower than in the lacunar group ("any" muscle activity 0.17 ± 0.2, p < 0.05; phasic muscle activity 0.16 ± 0.19, p < 0.05), and also lower than in the control group ("any" muscle activity 0.15 ± 0.17, p < 0.05). Magnetic resonance imaging-based lesion analysis indicated an area of maximum overlap in the medioventral pontine region for patients with reduced phasic muscle activity index. For all groups, mean values of muscle activity were significantly lower than in the patients with Parkinson's disease and polysomnography-confirmed REM sleep behaviour disorder group ("any" activity 0.51 ± 0.26, p < 0.0001 for all groups; phasic muscle activity 0.42 ± 0.21, p < 0.0001 for all groups). For the tonic muscle activity in the mentalis muscle, no significant differences were found between the groups. In the brainstem group, contrary to the lacunar and the control groups, "any" muscle activity index during rapid eye movement sleep was significantly reduced after the third rapid eye movement sleep phase. This study reports on the impact of brainstem stroke on rapid eye movement atonia features in a human cohort. Our findings highlight the important role of the human brainstem, in particular the medioventral pontine regions, in the regulation of phasic muscle activity during rapid eye movement sleep and the ultradian distribution of rapid eye movement-related muscle activity.

Neuroscience robotics for controlled induction and real-time assessment of hallucinations.

Although hallucinations are important and frequent symptoms in major psychiatric and neurological diseases, little is known about their brain mechanisms. Hallucinations are unpredictable and private experiences, making their investigation, quantification and assessment highly challenging. A major shortcoming in hallucination research is the absence of methods able to induce specific and short-lasting hallucinations, which resemble clinical hallucinations, can be elicited repeatedly and vary across experimental conditions. By integrating clinical observations and recent advances in cognitive neuroscience with robotics, we have designed a novel device and sensorimotor method able to repeatedly induce a specific, clinically relevant hallucination: presence hallucination. Presence hallucinations are induced by applying specific conflicting (spatiotemporal) sensorimotor stimulation including an upper extremity and the torso of the participant. Another, MRI-compatible, robotic device using similar sensorimotor stimulation permitted the identification of the brain mechanisms of these hallucinations. Enabling the identification of behavioral and a frontotemporal neural biomarkers of hallucinations, under fully controlled experimental conditions and in real-time, this method can be applied in healthy participants as well as patients with schizophrenia, neurodegenerative disease or other hallucinations. The execution of these protocols requires intermediate-level skills in cognitive neuroscience and MRI processing, as well as minimal coding experience to control the robotic device. These protocols take ~3 h to be completed.

Robotically-induced hallucination triggers subtle changes in brain network transitions.

The perception that someone is nearby, although nobody can be seen or heard, is called presence hallucination (PH). Being a frequent hallucination in patients with Parkinson's disease, it has been argued to be indicative of a more severe and rapidly advancing form of the disease, associated with psychosis and cognitive decline. PH may also occur in healthy individuals and has recently been experimentally induced, in a controlled manner during fMRI, using MR-compatible robotics and sensorimotor stimulation. Previous neuroimaging correlates of such robot-induced PH, based on conventional time-averaged fMRI analysis, identified altered activity in the posterior superior temporal sulcus and inferior frontal gyrus in healthy individuals. However, no link with the strength of the robot-induced PH was observed, and such activations were also associated with other sensations induced by robotic stimulation. Here we leverage recent advances in dynamic functional connectivity, which have been applied to different psychiatric conditions, to decompose fMRI data during PH-induction into a set of co-activation patterns that are tracked over time, as to characterize their occupancies, durations, and transitions. Our results reveal that, when PH is induced, the identified brain patterns significantly and selectively increase their transition probabilities towards a specific brain pattern, centred on the posterior superior temporal sulcus, angular gyrus, dorso-lateral prefrontal cortex, and middle prefrontal cortex. This change is not observed in any other control conditions, nor is it observed in association with other sensations induced by robotic stimulation. The present findings describe the neural mechanisms of PH in healthy individuals and identify a specific disruption of the dynamics of network interactions, extending previously reported network dysfunctions in psychotic patients with hallucinations to an induced robot-controlled specific hallucination in healthy individuals.

Fronto-Temporal Disconnection Within the Presence Hallucination Network in Psychotic Patients With Passivity Experiences.

Psychosis, characterized by hallucinations and delusions, is a common feature of psychiatric disease, especially schizophrenia. One prominent theory posits that psychosis is driven by abnormal sensorimotor predictions leading to the misattribution of self-related events. This misattribution has been linked to passivity experiences (PE), such as loss of agency and, more recently, to presence hallucinations (PH), defined as the conscious experience of the presence of an alien agent while no person is actually present. PH has been observed in schizophrenia, Parkinson's disease, and neurological patients with brain lesions and, recently, the brain mechanisms of PH (PH-network) have been determined comprising bilateral posterior middle temporal gyrus (pMTG), inferior frontal gyrus (IFG), and ventral premotor cortex (vPMC). Given that the experience of an alien agent is a common feature of PE, we here analyzed the functional connectivity within the PH-network in psychotic patients with (N = 39) vs without PE (N = 26). We observed reduced fronto-temporal functional connectivity in patients with PE compared to patients without PE between the right pMTG and the right and left IFG of the PH-network. Moreover, when seeding from these altered regions, we observed specific alterations with brain regions commonly linked to auditory-verbal hallucinations (such as Heschl's gyrus). The present connectivity findings within the PH-network extend the disconnection hypothesis for hallucinations to the specific case of PH and associates the PH-network with key brain regions for frequent psychotic symptoms such as auditory-verbal hallucinations, showing that PH are relevant to the study of the brain mechanisms of psychosis and PE.

Robot-induced hallucinations in Parkinson's disease depend on altered sensorimotor processing in fronto-temporal network.

Hallucinations in Parkinson's disease (PD) are disturbing and frequent non-motor symptoms and constitute a major risk factor for psychosis and dementia. We report a robotics-based approach applying conflicting sensorimotor stimulation, enabling the induction of presence hallucinations (PHs) and the characterization of a subgroup of patients with PD with enhanced sensitivity for conflicting sensorimotor stimulation and robot-induced PH. We next identify the fronto-temporal network of PH by combining MR-compatible robotics (and sensorimotor stimulation in healthy participants) and lesion network mapping (neurological patients without PD). This PH-network was selectively disrupted in an additional and independent cohort of patients with PD, predicted the presence of symptomatic PH, and associated with cognitive decline. These robotics-neuroimaging findings extend existing sensorimotor hallucination models to PD and reveal the pathological cortical sensorimotor processes of PH in PD, potentially indicating a more severe form of PD that has been associated with psychosis and cognitive decline.

Common and distinct brain networks of autoscopic phenomena.

OBJECTIVE: Autoscopic phenomena (AP) are illusory own body reduplications characterized by the visual perception of a second own body in extrapersonal space, and include three main forms: autoscopic hallucination (AH), heautoscopy (HAS) and out-of-body-experience (OBE). Past research showed that lesions were heterogeneously distributed and affected many different brain regions within and across patients, while small case series suggested that AP lesions converge in temporo-parietal and parieto-occipital cortex. As only few studies investigated each form of AP separately, it remains unknown whether the three AP are characterized by common and distinct brain mechanisms. METHODS: Here, we applied lesion network analysis in 26 neurological AP patients and determined their common and distinct functional connectivity patterns. RESULTS: We report that all localize to a single common brain network at the bilateral temporo-parietal junction, further associated with specific patterns of functional connectivity, defining each type of AP. OBE resulted from a brain network connected to bilateral angular gyrus, right precuneus, and right inferior frontal gyrus, differing from AH with a brain network connected to bilateral precuneus, inferior temporal gyrus, and cerebellum. HAS resulted from a brain network connected to left inferior frontal gyrus, left insula and left parahippocampus. CONCLUSION: The present data identify the temporo-parietal junction as the common core region for AP and show that each form of AP recruits additional specific networks, associated with different sensorimotor and self-related sub-networks.

TbCAPs: A toolbox for co-activation pattern analysis.

Functional magnetic resonance imaging provides rich spatio-temporal data of human brain activity during task and rest. Many recent efforts have focussed on characterising dynamics of brain activity. One notable instance is co-activation pattern (CAP) analysis, a frame-wise analytical approach that disentangles the different functional brain networks interacting with a user-defined seed region. While promising applications in various clinical settings have been demonstrated, there is not yet any centralised, publicly accessible resource to facilitate the deployment of the technique. Here, we release a working version of TbCAPs, a new toolbox for CAP analysis, which includes all steps of the analytical pipeline, introduces new methodological developments that build on already existing concepts, and enables a facilitated inspection of CAPs and resulting metrics of brain dynamics. The toolbox is available on a public academic repository at https://c4science.ch/source/CAP_Toolbox.git. In addition, to illustrate the feasibility and usefulness of our pipeline, we describe an application to the study of human cognition. CAPs are constructed from resting-state fMRI using as seed the right dorsolateral prefrontal cortex, and, in a separate sample, we successfully predict a behavioural measure of continuous attentional performance from the metrics of CAP dynamics (R â€‹= â€‹0.59).