A global neuronal workspace model of functional neurological disorders.

We introduce here a general model of Functional Neurological Disorders based on the following hypothesis: a Functional Neurological Disorder could correspond to a consciously initiated voluntary top-down process causing involuntary lasting consequences that are consciously experienced and subjectively interpreted by the patient as involuntary. We develop this central hypothesis according to Global Neuronal Workspace theory of consciousness, that is particularly suited to describe interactions between conscious and non-conscious cognitive processes. We then present a list of predictions defining a research program aimed at empirically testing their validity. Finally, this general model leads us to reinterpret the long-debated links between hypnotic suggestion and functional neurological disorders. Driven by both scientific and therapeutic goals, this theoretical paper aims at bringing closer the psychiatric and neurological worlds of functional neurological disorders with the latest developments of cognitive neuroscience of consciousness.

Are we aware of neural activity in primary visual cortex? A neuropsychological case study.

OBJECTIVE: According to a seminal hypothesis stated by Crick and Koch in 1995, one is not aware of neural activity in primary visual cortex (V1) because this region lacks reciprocal connections with prefrontal cortex (PFC). METHODS: We provide here a neuropsychological illustration of this hypothesis in a patient with a very rare form of cortical blindness: ventral and dorsal cortical pathways were lesioned bilaterally while V1 areas were partially preserved. RESULTS: Visual stimuli escaped conscious perception but still activated V1 regions that were functionally disconnected from PFC. INTERPRETATION: These results are consistent with the hypothesis of a causal role of PFC in visual awareness.

Pupil dilation response elicited by violations of auditory regularities is a promising but challenging approach to probe consciousness at the bedside.

Pupil dilation response (PDR) has been proposed as a physiological marker of conscious access to a stimulus or its attributes, such as novelty. In a previous study on healthy volunteers, we adapted the auditory "local global" paradigm and showed that violations of global regularity elicited a PDR. Notably without instructions, this global effect was present only in participants who could consciously report violations of global regularities. In the present study, we used a similar approach in 24 non-communicating patients affected with a Disorder of Consciousness (DoC) and compared PDR to ERPs regarding diagnostic and prognostic performance. At the group level, global effect could not be detected in DoC patients. At the individual level, the only patient with a PDR global effect was in a MCS and recovered consciousness at 6 months. Contrasting the most regular trials to the most irregular ones improved PDR's diagnostic and prognostic power in DoC patients. Pupillometry is a promising tool but requires several methodological improvements to enhance the signal-to-noise ratio and make it more robust for probing consciousness and cognition in DoC patients.

Hypnotic Induction of Deafness to Elementary Sounds: An Electroencephalography Case-Study and a Proposed Cognitive and Neural Scenario.

Hypnosis can be conceived as a unique opportunity to explore how top-down effects can influence various conscious and non-conscious processes. In the field of perception, such modulatory effects have been described in distinct sensory modalities. In the present study we focused on the auditory channel and aimed at creating a radical deafness to elementary sounds by a specific hypnotic suggestion. We report here a single case-study in a highly suggestible healthy volunteer who reported a total hypnotically suggested deafness. We recorded high-density scalp EEG during an auditory odd-ball paradigm before and after hypnotic deafness suggestion. While both early auditory event-related potentials to sounds (P1) and mismatch negativity component were not affected by hypnotic deafness, we observed a total disappearance of the late P3 complex component when the subject reported being deaf. Moreover, a centro-mesial positivity was present exclusively during the hypnotic condition prior to the P3 complex. Interestingly, source localization suggested an anterior cingulate cortex (ACC) origin of this neural event. Multivariate decoding analyses confirmed and specified these findings. Resting state analyses confirmed a similar level of conscious state in both conditions, and suggested a functional disconnection between auditory areas and other cortical areas. Taken together these results suggest the following plausible scenario: (i) preserved early processing of auditory information unaffected by hypnotic suggestion, (ii) conscious setting of an inhibitory process (ACC) preventing conscious access to sounds, (iii) functional disconnection between the modular and unconscious representations of sounds and global neuronal workspace. This single subject study presents several limits that are discussed and remains open to alternative interpretations. This original proof-of-concept paves the way to a larger study that will test the predictions stemming from our theoretical model and from this first report.

Association of Clinical, Biological, and Brain Magnetic Resonance Imaging Findings With Electroencephalographic Findings for Patients With COVID-19.

Importance: There is evidence of central nervous system impairments associated with coronavirus disease 2019 (COVID-19) infection, including encephalopathy. Multimodal monitoring of patients with COVID-19 may delineate the specific features of COVID-19-related encephalopathy and guide clinical management. Objectives: To investigate clinical, biological, and brain magnetic resonance imaging (MRI) findings in association with electroencephalographic (EEG) features for patients with COVID-19, and to better refine the features of COVID-19-related encephalopathy. Design, Setting, and Participants: This retrospective cohort study conducted in Pitié-Salpêtrière Hospital, Paris, France, enrolled 78 hospitalized adults who received a diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-Cov2) and underwent EEG between March 30 and June 11, 2020. Exposures: Detection of SARS-CoV-2 from a nasopharyngeal specimen using a reverse transcription-polymerase chain reaction assay or, in the case of associated pneumonia, on a computed tomography scan of the chest. Main Outcomes and Measures: Data on the clinical and paraclinical features of the 78 patients with COVID-19 were retrieved from electronic patient records. Results: Of 644 patients who were hospitalized for COVID-19, 78 (57 men [73%]; mean [SD] age, 61 [12] years) underwent EEG. The main indications for EEG were delirium, seizure-like events, and delayed awakening in the intensive care unit after stopping treatment with sedatives. Sixty-nine patients showed pathologic EEG findings, including metabolic-toxic encephalopathy features, frontal abnormalities, periodic discharges, and epileptic activities. Of 57 patients who underwent brain MRI, 41 showed abnormalities, including perfusion abnormalities, acute ischemic lesions, multiple microhemorrhages, and white matter-enhancing lesions. Fifty-five patients showed biological abnormalities, including dysnatremia, kidney failure, and liver dysfunction, the same day as the EEG. The results of cerebrospinal fluid analysis were negative for SARS-Cov-2 for all tested patients. Nine patients who had no identifiable cause of brain injury outside COVID-19 were further isolated; their brain injury was defined as COVID-19-related encephalopathy. They represented 1% (9 of 644) of patients with COVID-19 requiring hospitalization. Six of these 9 patients had movement disorders, 7 had frontal syndrome, 4 had brainstem impairment, 4 had periodic EEG discharges, and 3 had MRI white matter-enhancing lesions. Conclusions and Relevance: The results from this cohort of patients hospitalized with COVID-19 suggest there are clinical, EEG, and MRI patterns that could delineate specific COVID-19-related encephalopathy and guide treatment strategy.

Importance, limits and caveats of the use of "disorders of consciousness" to theorize consciousness.

The clinical and fundamental exploration of patients suffering from disorders of consciousness (DoC) is commonly used by researchers both to test some of their key theoretical predictions and to serve as a unique source of empirical knowledge about possible dissociations between consciousness and cognitive and/or neural processes. For instance, the existence of states of vigilance free of any self-reportable subjective experience [e.g. "vegetative state (VS)" and "complex partial epileptic seizure"] originated from DoC and acted as a cornerstone for all theories by dissociating two concepts that were commonly equated and confused: vigilance and conscious state. In the present article, we first expose briefly the major achievements in the exploration and understanding of DoC. We then propose a synthetic taxonomy of DoC, and we finally highlight some current limits, caveats and questions that have to be addressed when using DoC to theorize consciousness. In particular, we show (i) that a purely behavioral approach of DoC is insufficient to characterize the conscious state of patients; (ii) that the comparison between patients in a minimally conscious state (MCS) and patients in a VS [also coined as unresponsive wakefulness syndrome (UWS)] does not correspond to a pure and minimal contrast between unconscious and conscious states and (iii) we emphasize, in the light of original resting-state positron emission tomography data, that behavioral MCS captures an important but misnamed clinical condition that rather corresponds to a cortically mediated state and that MCS does not necessarily imply the preservation of a conscious state.