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

Structural Connectivity in Down Syndrome and Alzheimer’s Disease

Down syndrome (DS) arises from the triplication of chromosome 21, which leads to an atypical neurodevelopment and the overproduction of the amyloid precursor protein, predisposing to early Alzheimer’s disease (AD). Not surprisingly, trisomy 21 is widely considered a model to study predementia stages of AD. After decades, in which neural loss was the main focus, research in AD is now moving toward understanding the neurodegenerative aspects affecting white matter. Motivated by the development of magnetic resonance imaging (MRI)-based diffusion techniques, this shift in focus has led to several exploratory studies on both young and older individuals with DS. In this review, we synthesise the initial efforts made by researchers in characterising in-vivo structural connectivity in DS, together with the AD footprint on top of such pre-existing connectivity related to atypical brain development. The white matter structures found to be affected in DS are the corpus callosum and all the main long-association fibres, namely the inferior fronto-occipital fasciculus, the inferior and superior longitudinal fasciculus, the uncinate fasciculus and the cingulum bundle. Furthermore, the cingulum bundle and the corpus callosum appear to be particularly sensitive to early AD changes in this population. Findings are discussed in terms of their functional significance, alongside methodological considerations and implications for future research

Structural Connectivity in Down Syndrome and Alzheimer’s Disease

Down syndrome (DS) arises from the triplication of chromosome 21, which leads to an atypical neurodevelopment and the overproduction of the amyloid precursor protein, predisposing to early Alzheimer’s disease (AD). Not surprisingly, trisomy 21 is widely considered a model to study predementia stages of AD. After decades, in which neural loss was the main focus, research in AD is now moving toward understanding the neurodegenerative aspects affecting white matter. Motivated by the development of magnetic resonance imaging (MRI)-based diffusion techniques, this shift in focus has led to several exploratory studies on both young and older individuals with DS. In this review, we synthesise the initial efforts made by researchers in characterising in-vivo structural connectivity in DS, together with the AD footprint on top of such pre-existing connectivity related to atypical brain development. The white matter structures found to be affected in DS are the corpus callosum and all the main long-association fibres, namely the inferior fronto-occipital fasciculus, the inferior and superior longitudinal fasciculus, the uncinate fasciculus and the cingulum bundle. Furthermore, the cingulum bundle and the corpus callosum appear to be particularly sensitive to early AD changes in this population. Findings are discussed in terms of their functional significance, alongside methodological considerations and implications for future research