Establish Which Brain Regions Constitute the Physical Substrate of Consciousness in the Brain: Within-State Paradigms During Seizures
INSTITUTE: University of Wisconsin-Madison / Department of Psychiatry / Center for Sleep and Consciousness
PROJECT LEADER: Melanie Boly
PROJECT DURATION: 3 years
LAB WEBSITE: Boly Lab
Identifying which brain regions and activity patterns support subjective experience in humans is at the core of the neuroscience of consciousness. In this context, the characterization of neural signatures of loss of consciousness during epileptic seizures is critical. This is because, unlike in other altered states of consciousness, the hallmark of epileptic activity is the presence of increases in neuronal firing which can be more or less widespread depending on the severity of seizures. Previous studies suggested that loss of consciousness during focal seizures is linked to increased slow-wave activity in areas distant from the epileptic focus. However, these studies conflated loss of responsiveness with loss of consciousness. In the present project we will use high density EEG (hd-EEG) and intracranial recordings combined with a within-state approach to differentiate the neural signatures of loss of responsiveness from those of loss of consciousness. We will do so by combining behavioral evaluation with the sampling of reports of experiences just after the seizures have ended. We will also investigate differences in neural signatures of loss of consciousness between seizures that remain focal and seizures that secondarily generalize.
Results so far indicate that during seizures that remain focal, increased slow-wave activity in the frontal cortex tracks loss of responsiveness, while slow-wave activity in parietal cortex best tracks loss of consciousness (Fig. 1). Interestingly, loss of consciousness during seizures that become secondarily generalized seems to differ: instead of increased slow-wave activity, there is an increase in high gamma activity, again localized in posterior regions of the cortex (Fig. 2). These promising results suggest that 1) the neural correlates of loss of consciousness during seizures best localize to posterior cortex; 2) depending of the severity of the seizure, both the presence of bistable cortical dynamics (reflected by slow waves) or increases in brain activity (reflected by high gamma activity) can cause loss of consciousness. If confirmed in larger patient samples, the two findings would have important implications to constrain neuroscientific theories of consciousness.
Figure 1. Frontal lobe slow-wave activity tracks loss of responsiveness during focal seizures, while parietal lobe slow-wave activity tracks loss of consciousness.
Figure 2. Left panel: Loss of consciousness during the pre-generalization phase of generalized tonic-clonic seizures is accompanied by a paradoxical widespread decrease slow-wave activity, while after generalization, slow-wave activity emerges within the whole cortex. Right panel: high gamma activity in temporo-parietal cortex more consistently tracks loss of consciousness during generalized tonic-clonic seizures: it is increased in pre-generalization phase only when patients lose consciousness (unC), but not when patients show preserved consciousness (C); and it remains increased post-generalization when all patients lose consciousness.
Broader Impact:
After more than three decades of research, the neural substrate of consciousness in the human brain remains a matter of debate. Unlike other altered states of consciousness, epileptic seizures are characterized by increases in neuronal firing – which are more intense and widespread when seizures are more severe. Thus, the identification of neuronal activity patterns predictive of loss of consciousness during seizures can provide crucial constraints for neuroscientific theories of consciousness. Only by identifying mechanisms linking consciousness and the brain that are consistent across both physiological and pathological conditions can we hope to build a coherent scientific explanation for the neural basis of subjective experience. From there, we can proceed to develop new interventions to modulate experience in positive ways and improve quality of life in a large number of both patients and healthy subjects.
Publication:
Juan E, Gorska UJ, Kozma C, Papantonatos C, Bugnon T, Denis C, Kremen V, Worrell G, Struck AF, Bateman LM, Merricks EM, Blumenfeld H, Tononi G, Schevon C, Boly M. Distinct signatures of loss of consciousness during Focal Impaired Awareness versus Focal to Bilateral Tonic-Clonic seizures. BioRXiv. 2021. doi: https://doi.org/10.1101/2021.10.01.462586