The relationship between neurophysiological and cerebrovascular-metabolic findings in patients affected by severe cerebrovascular deficits was investigated by comparing magnetoencephalographic (MEG-evoked fields) and blood oxygen level-dependent functional MRI (BOLD fMRI) responses to median nerve electric stimulation. Despite the use of identical stimuli, the two techniques elicited always-detectable responses in the control group (10 subjects), but demonstrated uncorrelated activation properties in our patient sample (10 subjects). All patients showed clear MEG signals in both the affected and unaffected hemispheres, indicating well synchronized, stimulus-locked firing of neurons in the primary sensorimotor cortex, but some patients showed no fMRI activation in either the affected or the unaffected hemisphere. In order to clarify the origin of this uncoupling, we investigated the possible role of lesion site, white matter hyperintensities, current medication, risk factors, anatomy of the neck vessels, and cerebral vasomotor reactivity (VMR) as measured by transcranial Doppler (TCD) during CO2 inhalation. Neither neuronal activation properties nor any of the considered factors were related to the lack of fMRI activation, with the exception of altered vasomotor reactivity, which was, on the contrary, strongly related. Preserved VMR was paired with absent BOLD bilaterally in the only patient affected by microangiopathy. This finding suggests that BOLD contrast could be more sensitive than TCD to chronic microvascular impairments, measuring small- rather than large- vessel reactivity.