Does cerebrovascular disease affect the coupling between neuronal activity and local haemodynamics?

Abstract

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.

Early Prediction of Functional Recovery after Experimental Stroke: Functional Magnetic Resonance Imaging, Electrophysiology, and Behavioral Testing in Rats

“…Kim et al (2005) discussed stroke-related alterations in hemodynamic coupling, which were controversially reported in human BOLD fMRI studies of sensorimotor stroke recovery (Pineiro et al, 2002;Rossini et al, 2004;Krainik et al, 2005). Two of these human studies reported a decreased BOLD signal in both affected and unaffected sensorimotor cortices of stroke patients compared with age-matched controls (Pineiro et al, 2002;Rossini et al, 2004). In contrast to these observations, we did not observe uncoupling of neuronal activity and BOLD response in both hemispheres but a coupled alteration of both neuronal activity and hemodynamic response.…”

“…Here, we show that, during the first 7 weeks after 1 h of MCA occlusion, the neurovascular coupling remains preserved at all times. Kim et al (2005) discussed stroke-related alterations in hemodynamic coupling, which were controversially reported in human BOLD fMRI studies of sensorimotor stroke recovery (Pineiro et al, 2002;Rossini et al, 2004;Krainik et al, 2005). Two of these human studies reported a decreased BOLD signal in both affected and unaffected sensorimotor cortices of stroke patients compared with age-matched controls (Pineiro et al, 2002;Rossini et al, 2004).…”

“…The studies performed so far used contrast-enhanced changes of cerebral blood volume (CBV) instead of blood oxygenation leveldependent (BOLD) MR imaging, to visualize brain activation and its recovery. Furthermore, in those reports, measurements of hemodynamic changes had not been combined with direct assessment of electrical activity to investigate mechanisms of neurovascular coupling, thus omitting the chance to systematically assess controversial reports about alterations of neurovascular coupling after focal brain ischemia in humans (Pineiro et al, 2002;Rossini et al, 2004;Krainik et al, 2005).…”

Visualization of Altered Neurovascular Coupling in Chronic Stroke Patients using Multimodal Functional MRI

“…As a consequence of these changes in hemodynamics, neuronal activity is not necessarily coupled to regional CBF and CBV changes to the same degree as in healthy subjects. Rossini et al (2004) performed a combined Figure 2 Representative block-averaged time courses for (A) a control subject and (B-D) three patients. Gray areas depict the stimulus period.…”

Restorative and Compensatory Changes in the Brain During Early Motor Recovery from Hemiparetic Stroke: a Functional MRI Study

“…BOLD-dependent capillary density and draining veins and the perfusion of brain tissue may differ between damaged and undamaged tissues, especially at acute stages of stroke. fMRI activation can even be lost in stroke patients because of altered vasomotor reactivity, demonstrating uncoupling of neuronal activity and fMRI activation (Rossini et al, 2004;Binkofski & Seitz 2004;Murata et al, 2006). In our study, paretic hand movement at the acute stage resulted in reduced motor cortex activation in the damaged hemisphere, especially in patients with cortical infarction.…”