New trends in the empirical study of consciousness: Measures and mechanisms

Understanding what makes us conscious is one of the major frontiers of science. There are two main approaches to the mystery of consciousness. The first regards conscious states (i.e., being conscious) and how certain global states (e.g., of arousal) can support the formation of any conscious experience. Insights into the neural processes underlying the capacity for consciousness stem from studying brain dynamics in conditions where consciousness is altered or diminished, such as physiological sleep, pharmacological manipulations or pathological conditions following severe brain lesions. A second approach to consciousness regards the formation of specific conscious contents (i.e., being conscious of something specific). By devising experimental paradigms in which stimuli can be either perceived consciously or not, it is possible to investigate the mechanisms supporting the formation of a specific conscious experience. Yet, for both these ‘state’ and ‘content’ approaches of consciousness, the development of reliable and objective markers of consciousness remains an open challenge.

Driven by this and the need to better understand the underlying mechanisms of consciousness, a significant body of empirical research has emerged over the past decades. This includes both computational and experimental studies, which have shed light on the mechanisms and neural correlates supporting conscious experience(s). These studies have also sought to develop empirical measures of consciousness. However, many questions remain, particularly regarding the experimental paradigms and metrics used for accurately assessing consciousness.

This special issue gathers 12 novel articles investigating mechanisms and measures for the empirical study of consciousness. A first line of work focuses on cases where conscious processing is reduced pharmacologically via anaesthetic agents. Hönigsperger and colleagues (2024) use a mouse model to show that during transitions from wakefulness to sevoflurane anaesthesia, neural complexity in the somatosensory cortex diminishes and at the same time firing rates and long-range connections decrease in deep cortical layers. Advances in our understanding of thalamo-cortical mechanisms supporting consciousness, as well as the role of different proteins, receptors, and the action of anaesthetic agents therein, are then reviewed by Zhuo (2024). Last, Osaka and colleagues (2024) investigate at a macroscopic level, the behavioural consequences of anaesthesia, and show that as the depth of anaesthesia progresses, word categorical judgments can be largely preserved, while working memory is progressively impaired.

A second series of articles explores how variations in conscious processing manifest in our everyday lives, in terms of mind blanking, metacognition and ‘bizarre’ experiences or sleep. Kaufmann and colleagues (2024) review two prevailing models of mind blanking, which view this state as a stream of consciousness interruption, versus a mental void in awareness, and propose how those can be experimentally tested. Another manifestation of awareness with strong behavioural relevance for our daily lives is that of reality and error monitoring. Regarding error monitoring, the neural substrates and meta-cognitive models allowing us to monitor our errors are reviewed by Öztel and Balcı (2024). Focusing on reality monitoring, Denzer and colleagues (2024) used immersive virtual reality to simulate realistic or dream-like, bizarre scenarios and show that an electroencephalography (EEG) signature in the form of a microstate was related to the suppression of bizarre mismatch in the virtual environment. Moving from dream-like scenarios to actual sleep, Alnes and colleagues (2024) characterized the information content of auditory EEG responses in wakefulness and sleep, showing that the complexity and spectral slope of auditory responses are modulated by sleep stages, a finding that can be applicable also for patient studies, which often rely on auditory stimulation to probe capacity for consciousness.

The third and last line of research represented in this special issue investigates how empirical measures of consciousness can benefit patients suffering from loss of consciousness. Auditory stimulation paradigms are often used to probe the capacity for consciousness at the patients' bedside, albeit without a clear consensus on the type of stimulation. Rutiku and colleagues (2024) explore in healthy controls the sensitivity of traditional auditory paradigms, relying on the mismatch negativity (MMN) or P3b response as well as of the local–global paradigm, and show a high similarity between the P3b response and global effects, but clear differences between a classical MMN and local effects, prompting future studies to make more informed choices about their auditory stimulation protocols. Another study, by Șerban and colleagues (2024), presented patients with impaired consciousness after an ischaemic stroke with auditory stimuli, comprising of the subject's own name or name in reverse, and showed that their default oscillatory EEG macrostates contained less posterior theta activity compared to healthy controls.

In addition to auditory stimulations, this special issue also explores the potential of cortical perturbations for disentangling consciousness levels at the patients' bedside. Casarotto and colleagues (2024) show that cortical perturbations, quantified via the perturbational complexity index, can more consistently and reliably dissociate minimally conscious patients than spontaneous EEG rhythms without stimulation, which are often inconclusive. The use of multi-modal techniques for clinical assessments of patients with disorders of consciousness is also supported by a systematic review which supports their feasibility, but also raises the need for future studies to employ multi-modal diagnostic approaches as an a priori design, rather than an afterthought (Gallucci et al., 2024). Last, the advantage of multi-modal investigations of consciousness is showcased in a case study of a patient with akinetic mutism, a rare neurological syndrome whose clinical manifestation overlaps with disorders of consciousness (Comanducci et al., 2024). In this case study, Comanducci and colleagues (2024) combine spontaneous and evoked EEG with imaging to illustrate that this patient has preserved markers for consciousness, despite behavioural unresponsiveness, while at the same time, they shed light on the underlying pathophysiology.

In summary, the articles in this special issue draw on a broad spectrum of experimental and theoretical approaches, encompassing physiological states, pharmacological interventions, and clinical conditions that influence both the states and contents of consciousness. Collectively, this issue advances the empirical study of consciousness and opens up new avenues for exploring the intriguing question of what allows us to be conscious of the world around us.

Athina Tzovara: Conceptualization; writing—original draft. Thomas Andrillon: Conceptualization; writing—original draft. Katrin H. Preller: Conceptualization; writing—original draft. Simone Sarasso: Conceptualization; writing—original draft.

KHP is currently an employee of Boehringer Ingelheim GmbH & Co KG. SS is an advisor of Intrinsic Powers, a spin-off of the University of Milan. AT is mentioned as co-inventor in a patent application No. EP22386068.5 owned by the University of Bern. The patent is currently not licensed. All other authors declare no conflict of interest.