Balancing Interoception and Exteroception: Vestibular and Spatial Contributions to the Bodily Self

Experiencing the body as a coherent, stable, entity involves the dynamic integration of information from several internal (i.e. interoceptive) and external (i.e. exteroceptive) sensory sources, to produce a feeling that the body is mine (sense of body ownership), that I am in control (sense of agency) and I am aware of its movements (motor awareness). However, the exact contribution of these different sensory sources to self-consciousness, as well as the context in which we experience them, is still a matter of debate. This thesis aimed to investigate the neurocognitive mechanisms of body ownership, agency and motor awareness, including interoceptive (via affective touch), proprioceptive, exteroceptive (visuo-spatial) and vestibular contributions to body representation, in both healthy subjects and brain damaged patients. To examine the role of the vestibular and interoceptive systems in body ownership, a series of studies in healthy subjects was devised, using multisensory illusions (i.e. the rubber hand illusion; RHI), that involve the integration of interoceptive and exteroceptive sensory sources, and using electrical stimulation of the vestibular system (i.e. Galvanic Vestibular Stimulation; GVS). To investigate ownership, agency and motor awareness in neuropsychological patients with disorders of ownership and/or unawareness of motor deficits, behavioural manipulation of body ownership (via a rubber hand) and visual perspective (via a mirror) were tested. Finally, to explore underlying mechanisms of awareness of one’s own performance (i.e. meta-cognition), two studies were carried out in healthy subjects using behavioural manipulations of spatial reference frames (either centred on the subject, i.e. egocentric, or world-centred, i.e. allocentric). The results of these studies indicate that the vestibular system balances vision and proprioception according to contextual relevance: when there is no tactile stimulation, visual cues are stronger than proprioceptive ones (i.e. proprioceptive drifts are greater); when touch is delivered synchronously, this effect is enhanced (even more when touch is affective rather than neutral). However, when touch is only felt but not seen, the vestibular system downregulates vision in favour of proprioception (i.e. proprioceptive drifts are smaller), whilst the opposite happens when touch is only vicariously perceived via vision. Nevertheless, when the rubber hand is positioned in a non-biomechanically possible fashion, there appears to be no difference in proprioceptive drifts in comparison with anatomically plausible positions, suggesting that such rebalancing may be more related to basic multisensory integration processes underlying body representation. In patients with disorders of the self, visual cues seem to dominate over proprioceptive ones, leading to strong feelings of ownership of a rubber hand following mere exposure to it; however, the same is not true for agency, which seems to be more susceptible to changes in the environment (i.e. presence or absence of a visual feedback following attempted movement). Moreover, manipulating visual perspective using a mirror (from 1st to 3rd) seem to lead to a temporary remission of dis-ownership but not motor unawareness, suggesting that awareness may not be influenced by online changes in visual perspectives. Finally, when judging their own performance in a visuo-proprioceptive task from an egocentric rather than an allocentric perspective, healthy subjects appear less objective prospectively rather than during the task (i.e. their belief updating is biased when judging their ability to complete a task egocentrically). In sum, the work described above adds to the evidence that the sense of self derives from a complex integration of several sensory modalities, flexibly adjusting to the environment. Following brain damage, such flexibility may be impaired, even though it can be influenced by spatial perspective. Similarly, the point of reference from which we perceive stimuli affects the way we judge our own perceptual choices. Hence, the way we represent our bodily self is a dynamic process, constantly updated by exteroceptive and interoceptive incoming stimuli, regulated by the vestibular system. These findings could provide new avenues in rehabilitating disorders of the self (such as unawareness and dis-ownership)

Depersonalization disorder as a systematic downregulation of interoceptive signals

Depersonalisation disorder (DPD) is a psychopathological condition characterised by a feeling of detachment from one's own body and surrounding, and it is understood as emerging from the downregulation of interoceptive afferents. However, the precise mechanisms that drive this 'interoceptive silencing' are yet to be clarified. Here we present a computational and neurobiologically plausible model of DPD within the active inference framework. Specifically, we describe DPD as arising from disrupted interoceptive processing at higher levels of the cortical hierarchy where the interoceptive and exteroceptive streams are integrated. We simulated the behaviour of an agent subjected to a situation of high interoceptive activation despite the absence of a perceivable threat in the external environment. The simulation showed how a similar condition, if perceived as inescapable, would result in a downregulation of interoceptive signals, whilst leaving the exteroceptive ones unaffected. Such interoceptive silencing would force the agent to over-rely on exteroceptive information and would ultimately lead to the DPD phenomenology. Finally, our simulation shows that repeated exposure to similar situations over time will lead the agent to increasingly disengage from bodily responses even in the face of a less triggering situation, explaining how a single episode of depersonalization can lead to chronic DPD

Employees’ support strategies for mental wellbeing during and beyond the COVID-19 pandemic: Recommendations for employers in the UK workforce

Throughout the COVID-19 pandemic, and beyond for many businesses, employees have had to adapt to new ways of working due to disruptions in traditional practices. It is therefore crucial to understand the new challenges that employees are facing when it comes to taking care of their mental wellbeing at work. To that end, we distributed a survey to full-time UK employees (N = 451) to explore how supported they felt throughout the pandemic, and to identify whether there are any additional types of support they would like to receive. We also compared employees’ intentions to seek help before versus during the COVID-19 pandemic, and assessed their current attitudes toward mental health. Based on direct employee feedback, our results show remote workers felt more supported throughout the pandemic compared to hybrid workers. We also found that employees who had previously experienced an episode of anxiety or depression were significantly more likely to want extra support at work compared to those who had not. Furthermore, employees were significantly more likely to seek help for their mental health during the pandemic compared to before. Interestingly, the largest increase in intentions to seek help during the pandemic compared to before was with digital health solutions. Finally, we found that the strategies managers have adopted to better support their employees, an employee’s mental health history, and their attitude to mental health all contributed to significantly increasing the likelihood that an employee would disclose a mental health concern to their line manager. We provide recommendations that encourage organisations to make changes to better support their employees, and we highlight the importance of mental health awareness training for both managers and employees. This work is of particular interest to organisations who are looking to tailor their current employee wellbeing offer to a post-pandemic world

Paradoxical facilitation after depotentiation protocol can precede dyskinesia onset in early Parkinson’s disease

Loss of dopamine, a key modulator of synaptic signalling, and subsequent pulsatile non-physiological levodopa replacement is believed to underlie altered neuroplasticity in Parkinson's disease (PD). Animal models suggest that maladaptive plasticity (e.g. deficient depotentiation at corticostriatal synapses) is key in the development of levodopa-induced dyskinesia (LID), a common complication following levodopa replacement in PD. Human studies using transcranial magnetic stimulation protocols have shown similar depotentiation deficit in patients with LID. We hypothesized that subtle depotentiation deficits should precede LID if these deficits are mechanistically linked to LID onset. Moreover, patients on pulsatile levodopa-based therapy may show these changes earlier than those treated with levodopa-sparing strategies. We recruited 22 early non-dyskinetic PD patients (<5 years since diagnosis) and 12 age-matched healthy controls. We grouped patients into those on Levodopa-Based (n = 11) and Levodopa-Sparing therapies (n = 11). Patients were selected to obtain groups matched for age and disease severity. We used a theta-burst stimulation protocol to investigate potentiation and depotentiation in a single session. We report significant depotentiation deficits in the Levodopa-Based group, compared to both Levodopa-Sparing and Healthy Control groups. Potentiation and Depotentiation responses were similar between Levodopa-Sparing and Healthy Control groups. Although differences persist after accounting for potential confounds (e.g. levodopa-equivalent dose), these results may yet be caused by differences in disease severity and cumulative levodopa-equivalent dose as discussed in the text. In conclusion, we show for the first time that paradoxical facilitation in response to depotentiation protocols can occur in PD even prior to LID onset

Transcranial magnetic stimulation of the precuneus enhances memory and neural activity in prodromal Alzheimer's disease

Memory loss is one of the first symptoms of typical Alzheimer's disease (AD), for which there are no effective therapies available. The precuneus (PC) has been recently emphasized as a key area for the memory impairment observed in early AD, likely due to disconnection mechanisms within large-scale networks such as the default mode network (DMN). Using a multimodal approach we investigated in a two-week, randomized, sham-controlled, double-blinded trial the effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) of the PC on cognition, as measured by the Alzheimer Disease Cooperative Study Preclinical Alzheimer Cognitive Composite in 14 patients with early AD (7 females). TMS combined with electroencephalography (TMS-EEG) was used to detect changes in brain connectivity. We found that rTMS of the PC induced a selective improvement in episodic memory, but not in other cognitive domains. Analysis of TMS-EEG signal revealed an increase of neural activity in patients' PC, an enhancement of brain oscillations in the beta band and a modification of functional connections between the PC and medial frontal areas within the DMN. Our findings show that high-frequency rTMS of the PC is a promising, non-invasive treatment for memory dysfunction in patients at early stages of AD. This clinical improvement is accompanied by modulation of brain connectivity, consistently with the pathophysiological model of brain disconnection in AD

Cerebellar theta burst stimulation in stroke patients with ataxia

Evidence for effective improvement of the symptoms of cerebellar stroke is still limited. Here, we investigated the effects of repetitive transcranial magnetic stimulation (rTMS) applied over the injured cerebellar hemisphere in six patients with posterior circulation stroke. We applied a two-week course of cerebellar intermittent theta burst stimulation (iTBS). Before and after the iTBS treatment, paired-pulse TMS methods were used to explore: i) the functional connectivity between the cerebellar hemisphere and the contralateral primary motor cortex (M1), by means of the cerebellar brain inhibition (CBI) protocol; and ii) the intracortical circuits in the contralateral M1, by means of the short intra-cortical inhibition (SICI) and intra-cortical facilitation (ICF) protocols. Patients were also evaluated using the Modified International Cooperative Ataxia Rating Scale (MICARS). Cerebellar iTBS induced a decrease in CBI and an increase in ICF at an interstimulus interval of 15 msec. These neurophysiological changes were paralleled by a clinical improvement, shown by the MICARS posture and gait subscale scores. Cerebellar iTBS could be a promising tool to promote recovery of cerebellar stroke patients

Cerebellar theta burst stimulation in stroke patients with ataxia

Evidence for effective improvement of the symptoms of cerebellar stroke is still limited. Here, we investigated the effects of repetitive transcranial magnetic stimulation (rTMS) applied over the injured cerebellar hemisphere in six patients with posterior circulation stroke. We applied a two-week course of cerebellar intermittent theta burst stimulation (iTBS). Before and after the iTBS treatment, paired-pulse TMS methods were used to explore: i) the functional connectivity between the cerebellar hemisphere and the contralateral primary motor cortex (M1), by means of the cerebellar brain inhibition (CBI) protocol; and ii) the intracortical circuits in the contralateral M1, by means of the short intra-cortical inhibition (SICI) and intra-cortical facilitation (ICF) protocols. Patients were also evaluated using the Modified International Cooperative Ataxia Rating Scale (MICARS). Cerebellar iTBS induced a decrease in CBI and an increase in ICF at an interstimulus interval of 15 msec. These neurophysiological changes were paralleled by a clinical improvement, shown by the MICARS posture and gait subscale scores. Cerebellar iTBS could be a promising tool to promote recovery of cerebellar stroke patients

Cerebellar theta burst stimulation in stroke patients with ataxia

Evidence for effective improvement of the symptoms of cerebellar stroke is still limited. Here, we investigated the effects of repetitive transcranial magnetic stimulation (rTMS) applied over the injured cerebellar hemisphere in six patients with posterior circulation stroke. We applied a two-week course of cerebellar intermittent theta burst stimulation (iTBS). Before and after the iTBS treatment, paired-pulse TMS methods were used to explore: i) the functional connectivity between the cerebellar hemisphere and the contralateral primary motor cortex (M1), by means of the cerebellar brain inhibition (CBI) protocol; and ii) the intracortical circuits in the contralateral M1, by means of the short intra-cortical inhibition (SICI) and intra-cortical facilitation (ICF) protocols. Patients were also evaluated using the Modified International Cooperative Ataxia Rating Scale (MICARS). Cerebellar iTBS induced a decrease in CBI and an increase in ICF at an interstimulus interval of 15 msec. These neurophysiological changes were paralleled by a clinical improvement, shown by the MICARS posture and gait subscale scores. Cerebellar iTBS could be a promising tool to promote recovery of cerebellar stroke patients

Vestibular modulation of multisensory integration during actual and vicarious tactile stimulation

© 2019 Society for Psychophysiological Research.The vestibular system has been shown to contribute to multisensory integration by balancing conflictual sensory information. It remains unclear whether such modulation of exteroceptive (e.g., vision), proprioceptive, and interoceptive (e.g., affective touch) sensory sources is influenced by epistemically different aspects of tactile stimulation (i.e., felt from within vs. seen, vicarious touch). In the current study, we aimed to (a) replicate previous findings regarding the effects of galvanic stimulation of the right vestibular network in multisensory integration, and (b) examine vestibular contributions to multisensory integration when touch is felt but not seen (and vice versa). During artificial vestibular stimulation (LGVS, i.e., right vestibular stimulation), RGVS (i.e., bilateral stimulation), and sham (i.e., placebo stimulation), healthy participants (N = 36, Experiment 1; N = 37, Experiment 2) looked at a rubber hand while either their own unseen hand or the rubber hand were touched by affective or neutral touch. We found that (a) LGVS led to enhancement of vision over proprioception during visual only conditions (replicating our previous findings), and (b) LGVS (versus sham) favored proprioception over vision when touch was felt (Experiment 1), with the opposite results when touch was vicariously perceived via vision (Experiment 2) and with no difference between affective and neutral touch. We showed how vestibular signals modulate the weight of each sensory modality according to the context in which they are perceived and that such modulation extends to different aspects of tactile stimulation: felt and seen touch are differentially balanced in multisensory integration according to their epistemic relevance.Peer reviewedFinal Accepted Versio