Circadian Rhythms and Measures of CNS/Autonomic Interaction

The physiological role and relevance of the mechanisms sustaining circadian rhythms have been acknowledged. Abnormalities of the circadian and/or sleep-wakefulness cycles can result in major metabolic disorders or behavioral/professional inadequacies and stand as independent risk factors for metabolic, psychiatric, and cerebrovascular disorders and early markers of disease. Neuroimaging and clinical evidence have documented functional interactions between autonomic (ANS) and CNS structures that are described by a concept model (Central Autonomic Network) based on the brain-heart two-way interplay. The circadian rhythms of autonomic function, ANS-mediated processes, and ANS/CNS interaction appear to be sources of variability adding to a variety of environmental factors, and may become crucial when considering the ANS major role in internal environment constancy and adaptation that are fundamental to homeostasis. The CNS/ANS interaction has not yet obtained full attention and systematic investigation remains overdue. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.Peer reviewe

Modulation of brain and behavioural responses to cognitive visual stimuli with varying signal-to-noise ratios

Abstract Objective: To study behavioral and brain responses to variations in signal-to-noise ratio (SNR) of cognitive visual stimuli. Methods: We presented meaningful words visually, embedded in varying amounts of dynamic noise, and utilized magnetoencephalography (MEG) to measure responses to the words. A multidipole model of the evoked fields was constructed to quantify the strengths and latencies of the neuronal sources at each noise level. The recognition rates of the words were measured in separate behavioral sessions. Results: MEG revealed sequential activation of occipital and occipito-temporal areas (latencies 130-250 and 170-350 ms, respectively) followed by activity in superior temporal cortex (230-640 ms). The strengths and latencies of all identified sources followed functions similar to the SNR of the stimulus. The peak amplitudes and shortest latencies of all sources coincided with the maximum SNR of the stimulus. The occipito-temporal and temporal sources as well as the word recognition rate accurately followed the SNR of the stimulus whereas the early occipital source exhibited a more peaked dependence on the SNR. Conclusions: Evoked responses expectedly peaked at the maximum SNR of the stimulus. Interestingly, early visual responses showed sharper peaks than longer-latency sources as a function of the noise level. This can be understood as the higher-level processes analyzing the stimuli more holistically and thus being less sensitive to the salience of simple visual features. The similar noise-dependence of the longerlatency sources and the recognition rate provides new evidence for the relevance of these activations in the recognition of written words. Significance: This study contributes to the understanding of brain activity evoked by degraded stimuli with cognitive content

Biocompatibility of a Conjugated Polymer Retinal Prosthesis in the Domestic Pig

The progressive degeneration of retinal photoreceptors is one of the most significant causes of blindness in humans. Conjugated polymers represent an attractive solution to the field of retinal prostheses, and a multi-layer fully organic prosthesis implanted subretinally in dystrophic Royal College of Surgeons (RCS) rats was able to rescue visual functions. As a step toward human translation, we report here the fabrication and in vivo testing of a similar device engineered to adapt to the human-like size of the eye of the domestic pig, an excellent animal paradigm to test therapeutic strategies for photoreceptors degeneration. The active conjugated polymers were layered onto two distinct passive substrates, namely electro-spun silk fibroin (ESF) and polyethylene terephthalate (PET). Naive pigs were implanted subretinally with the active device in one eye, while the contralateral eye was sham implanted with substrate only. Retinal morphology and functionality were assessed before and after surgery by means of in vivo optical coherence tomography and full-field electroretinogram (ff-ERG) analysis. After the sacrifice, the retina morphology and inflammatory markers were analyzed by immunohistochemistry of the excised retinas. Surprisingly, ESF-based prostheses caused a proliferative vitreoretinopathy with disappearance of the ff-ERG b-wave in the implanted eyes. In contrast, PET-based active devices did not evoke significant inflammatory responses. As expected, the subretinal implantation of both PET only and the PET-based prosthesis locally decreased the thickness of the outer nuclear layer due to local photoreceptor loss. However, while the implantation of the PET only substrate decreased the ff-ERG b-wave amplitude with respect to the pre-implant ERG, the eyes implanted with the active device fully preserved the ERG responses, indicating an active compensation of the surgery-induced photoreceptor loss. Our findings highlight the possibility of developing a new generation of conjugated polymer/PET-based prosthetic devices that are highly biocompatible and potentially suitable for subretinal implantation in patients suffering from degenerative blindnes

Unresponsive wakefulness syndrome: a new name for the vegetative state or apallic syndrome

BACKGROUND: Some patients awaken from coma (that is, open the eyes) but remain unresponsive (that is, only showing reflex movements without response to command). This syndrome has been coined vegetative state. We here present a new name for this challenging neurological condition: unresponsive wakefulness syndrome (abbreviated UWS). DISCUSSION: Many clinicians feel uncomfortable when referring to patients as vegetative. Indeed, to most of the lay public and media vegetative state has a pejorative connotation and seems inappropriately to refer to these patients as being vegetable-like. Some political and religious groups have hence felt the need to emphasize these vulnerable patients' rights as human beings. Moreover, since its first description over 35 years ago, an increasing number of functional neuroimaging and cognitive evoked potential studies have shown that physicians should be cautious to make strong claims about awareness in some patients without behavioral responses to command. Given these concerns regarding the negative associations intrinsic to the term vegetative state as well as the diagnostic errors and their potential effect on the treatment and care for these patients (who sometimes never recover behavioral signs of consciousness but often recover to what was recently coined a minimally conscious state) we here propose to replace the name. CONCLUSION: Since after 35 years the medical community has been unsuccessful in changing the pejorative image associated with the words vegetative state, we think it would be better to change the term itself. We here offer physicians the possibility to refer to this condition as unresponsive wakefulness syndrome or UWS. As this neutral descriptive term indicates, it refers to patients showing a number of clinical signs (hence syndrome) of unresponsiveness (that is, without response to commands) in the presence of wakefulness (that is, eye opening)

Measures of CNS-Autonomic Interaction and Responsiveness in Disorder of Consciousness

Neuroimaging studies have demonstrated functional interactions between autonomic (ANS) and brain (CNS) structures involved in higher brain functions, including attention and conscious processes. These interactions have been described by the Central Autonomic Network (CAN), a concept model based on the brain-heart two-way integrated interaction. Heart rate variability (HRV) measures proved reliable as non-invasive descriptors of the ANS-CNS function setup and are thought to reflect higher brain functions. Autonomic function, ANS-mediated responsiveness and the ANS-CNS interaction qualify as possible independent indicators for clinical functional assessment and prognosis in Disorders of Consciousness (DoC). HRV has proved helpful to investigate residual responsiveness in DoC and predict clinical recovery. Variability due to internal (e.g. homeostatic and circadian processes) and environmental factors remains a key independent variable and systematic research with this regard is warranted. The interest in bidirectional ANS-CNS interactions in a variety of physiopathological conditions is growing, however these interactions have not been extensively investigated in DoC. In this brief review we illustrate the potentiality of brain-heart investigation by means of HRV analysis in assessing patients with DoC. The authors’ opinion is that this easy, inexpensive and non-invasive approach may provide useful information in the clinical assessment of this challenging patient population

Stochastic resonance improves vision in the severely impaired

Abstract We verified whether a stochastic resonance paradigm (SR), with random interference (“noise”) added in optimal amounts, improves the detection of sub-threshold visual information by subjects with retinal disorder and impaired vision as it does in the normally sighted. Six levels of dynamic, zero-mean Gaussian noise were added to each pixel of images (13 contrast levels) in which alphabet characters were displayed against a uniform gray background. Images were presented with contrast below the subjective threshold to 14 visually impaired subjects (age: 22–53 yrs.). The fraction of recognized letters varied between 0 and 0.3 at baseline and increased in all subjects when noise was added in optimal amounts; peak recognition ranged between 0.2 and 0.8 at noise sigmas between 6 and 30 grey scale values (GSV) and decreased in all subjects at noise levels with sigma above 30 GSV. The results replicate in the visually impaired the facilitation of visual information processing with images presented in SR paradigms that has been documented in sighted subjects. The effect was obtained with low-level image manipulation and application appears readily possible: it would enhance the efficiency of today vision-improving aids and help in the development of the visual prostheses hopefully available in the future