Cortical spreading depression of vascular low-frequency fluctuations in patients with Subarachnoid Haemorrhage

It has been suggested that vascular low-frequency fluctuations reflect a brain default mode and they are used to study topography of dysfunction in neurological and psychiatric diseases with functional MRI. Progressive ischaemic damage in the human brain is associated with cortical spreading depolarisations (CSD) leading to depression of the default mode. In a proof of concept approach, we here investigated whether cortical spreading depression of vascular low-fequency fluctuations accompanies CSD independently of whether hyperperfusion (normal coupling), no change of regional cerebral blood flow (rCBF) (uncoupling) or a hypoperfusion (inverse coupling) is coupled to CSD. For this purpose, electrocorticogram and rCBF were recorded in seven patients with aneurysmal subarachnoid haemorrhage and one patient with traumatic brain injury using subdural opto-/electrode strips. Spreading depression of vascular low-frequency fluctuations occurred in correlation with spreading depression of neuronal activity independently of the perfusion changes. Severe forms of inverse neurovascular coupling (cortical spreading ischaemia) were associated with structural damage and are suggested as a novel disease mechanism in the human brain.