Interneuronal assemblies reflect early neural reorganization after operative revascularization

The human brain is capable of remarkable spontaneous recovery after a cerebral infarct. It is now clear that brain stimulation can quantify as well as facilitate these recovery mechanisms (Khedr et al. 2005) mostly in patients with cerebral ischemic infarcts (Hummel et al. 2006). Patients with a high grade internal cerebral artery (ICA) stenosis who receive operative revascularization, allow us to monitor a well defined baseline, postoperative reperfusion and functional recovery. E.g. it is unclear how revascularization is related to compensatory mechanisms, or more specifically the role of intracortical (IC) interneuronal and cortico-spinal (CS) neuronal assemblies in this process.

The object of this study was to see whether hypoperfusioned brain areas restore function during the first week after revascularization. We measured CS and IC excitability with navigated-TMS in 13 patients suffering from ICA-occlusion who underwent extracranial-intracranial bypass surgery.

Interneuronal assemblies were investigated with paired pulse TMS protocols with a subthreshold conditioning stimulus at 80% of the resting motor threshold (RMT) and a suprathreshold test stimulus at 120% of the RMT (Kujirail et al. 1993, Ziemann et al. 1996) before and 6 days after surgery. This quantifies both intracortical facilitation (ICF) related to glutamatergic (Liepert et al 1997) and intracortical inhibition (ICI) related to GABAergic interneuronal (Ziemann et al 1996) assemblies. CS excitability was defined by single-pulse TMS in terms of recruitment curves (RC).

Before surgery IC excitability was significantly reduced in the affected hemisphere and vice versa in the unaffected one (p<0,05). Postoperative IC excitability was not significantly different between hemispheres. This functional lateralization of IC measures was not reflected in CS excitability as there was no significant hemispheric but rather a unspecific pre- versus postoperative difference in the RCs (p<0,05).

We conclude, that early compensatory mechanisms are reflected in interneuronal but not in CS activity. These findings suggest a very early presentation of transcallosal disinhibition after a cerebral lesion in line with findings at later stages of recovery (Liepert et al 2000). The indication for bypass-surgery being mainly prevention of further damage our data suggests that the intervention goes beyond purely sustaining the status quo and that it can unmask neural mechanisms related to recovery processes.