Local sleep-like cortical reactivity in the awake brain after focal injury

Abstract

The functional consequences of focal brain injury are thought to be contingent on neuronal alterations extending beyond the area of structural damage. This phenomenon, also known as diaschisis, has clinical and metabolic correlates but lacks a clear electrophysiological counterpart, except for the long-standing evidence of a relative EEG slowing over the injured hemisphere. Here, we aim at testing whether this EEG slowing is linked to the pathological intrusion of sleep-like cortical dynamics within an awake brain. We used a combination of transcranial magnetic stimulation and electroencephalography (TMS/EEG) to study cortical reactivity in a cohort of 30 conscious awake patients with chronic focal and multifocal brain injuries of ischaemic, haemorrhagic and traumatic aetiology. We found that different patterns of cortical reactivity typically associated with different brain states (coma, sleep, wakefulness) can coexist within the same brain. Specifically, we detected the occurrence of prominent sleep-like TMS-evoked slow waves and off-periods—reflecting transient suppressions of neuronal activity—in the area surrounding focal cortical injuries. These perilesional sleep-like responses were associated with a local disruption of signal complexity whereas complex responses typical of the awake brain were present when stimulating the contralesional hemisphere. These results shed light on the electrophysiological properties of the tissue surrounding focal brain injuries in humans. Perilesional sleep-like off-periods can disrupt network activity but are potentially reversible, thus representing a principled read-out for the neurophysiological assessment of stroke patients, as well as an interesting target for rehabilitation.

Peripheral sensory stimulation elicits global slow waves by recruiting somatosensory cortex bilaterally

“…However, this model does not recapitulate the graded ischemic injury observed in the penumbra of natural strokes. In the setting of a true ischemic penumbra, EEG studies in humans have demonstrated that SW sleep activity is increased around infarcts (57) in tandem with the emergence of pathological peri-infarct SWs during wakefulness (58). Thus, stroke may disrupt SWs by divergent mechanisms, both due to death of circuits generating SWs, as well as dysfunction in surviving neurons in the periinfarct zone.…”

Connectivity Measures Differentiate Cortical and Subcortical Sub-Acute Ischemic Stroke Patients

“…Recent findings based on TMS, fMRI and EEG studies pointed out that cortico-subcortical and subcortical stroke patients have different cortical activity and excitability levels of the motor cortex ( Luft et al, 2004 ; Thickbroom et al, 2015 ; Lamola et al, 2016 ; Fanciullacci et al, 2017 ; Sarasso et al, 2020 ). However, the impact of these differences on functional outcome has not been fully elucidated yet.…”

Mechanisms Underlying Disorders of Consciousness: Bridging Gaps to Move Toward an Integrated Translational Science

“…Future approaches should seek relationships and convergence between metrics derived from information theory, graph theory, and dynamical systems theory and strive to connect them with structural measures. Contemporary examples include the recent link found between PCI and subcortical atrophy [ 76 ] and the recent association between focal cortical lesions and the generation of pathological slow waves, disconnection, and lost complexity [ 77 , 78 ].…”

“…This could be further enhanced through comparison with results from sleep and anesthesia research, in which microscopic mechanisms have been more comprehensively probed in preclinical work [ 87 ], producing mechanistic frameworks that span from whole-brain phenomena, such as individual susceptibility, to anesthetic-state transitions (neural inertia), all the way to genetic susceptibility factors for anesthesia [ 38 , 88 , 89 ]. Indeed, work in rodents and cortical slices alike has recently demonstrated that neuronal “off” periods determine a dramatic collapse of large-scale interactions and complexity during non-REM sleep and anesthesia [ 90 – 92 ], which can also be assessed by using EEG coupled with TMS in humans with brain damage [ 77 , 78 ].…”