Effective Intracerebral Connectivity in Acute Stroke: A TMS-EEG Study

Abstract

Stroke is a major cause of disability because of its motor and cognitive sequelae even when the acute phase of stabilization of vital parameters is overcome. The most important improvements occur in the first 8-12 weeks after stroke, indicating that it is crucial to improve our understanding of the dynamics of phenomena occurring in this time window to prospectively target rehabilitation procedures from the earliest stages after the event. Here, we studied the intracortical excitability properties of delivering transcranial magnetic stimulation (TMS) to the primary motor cortex (M1) of left and right hemispheres in 17 stroke patients who suffered a mono-lateral left hemispheric stroke, excluding pure cortical damage. All patients were studied within 10 days of symptom onset. TMS-evoked potentials (TEPs) were collected via a TMS-compatible electroencephalogram system (TMS-EEG) concurrently with motor-evoked responses (MEPs) induced in the contralateral first dorsal interosseous muscle. Comparison with age-matched healthy volunteers was made by collecting the same bilateral-stimulation data in nine healthy volunteers as controls. Excitability in the acute phase revealed relevant changes in the relationship between left lesioned and contralesionally right hemispheric homologous areas both for TEPs and MEPs. While the paretic hand displayed reduced MEPs compared to the non-paretic hand and to healthy volunteers, TEPs revealed an overexcitable lesioned hemisphere with respect to both healthy volunteers and the contra-lesion side. Our quantitative results advance the understanding of the impairment of intracortical inhibitory networks. The neuronal dysfunction most probably changes the excitatory/inhibitory on-center off-surround organization that supports already acquired learning and reorganization phenomena that support recovery from stroke sequelae.

Keywords: TMS–EEG; acute phase; center-on surround-off; central peripheral excitability; electromyography EMG; stroke.

Figure 1

Example of an EEG recording during TMS. (A). Original data averaged over the TMS stimulus (t = 0). (B). The data after replacing the [−3, 2] ms interval with the 5-ms interval of the baseline [−8, −3] ms.

Figure 2

TEP extraction. Example of cleaning the TMS–EEG data of a subject with stroke. In all boxes, t = 0 is the TMS stimulus delivery at the scalp. From top to bottom. First box: comparison between data referenced to Oz and data cleaned by the SOUND algorithm. Second box: data cleaned with SSP–SIR and ICA. Third box: Global field power envelope of the cleaned data. x-axis time in ms, y-axis in μV (first and second boxes), and μV² (third box). Fourth row: Topographies of the cleaned data at 5 time instants where an evoked field is clearly notable (latencies indicated in red in the second box).

Figure 3

TEP description. The same structure of boxes from second to fourth rows of Figure 2 showing the TMS-evoked EEG potentials in a stroke patient and a healthy volunteer in response to the TMS stimulation of left and right M1 (t = 0). The vertical scales are equal in the two hemispheres and both persons, μV for TEP and μV² for GFP.

Figure 4

Motor evoked potentials (MEP) for stimulation of the lesioned left and contra-lesion right hemispheres. Time scale refers to t = 0 as the TMS stimulus delivery at the scalp. In light blue: grand average of the patient group, in red: grand average of the control group. The MEP is significantly smaller in patients than in control subjects when TMS is performed in the left lesioned and larger than in controls in the right contra-lesion M1s.

Figure 5

After artifact removal analysis, Global Field Power of the responses induced by single-pulse M1 TMS (t = 0) describing the overall effective intracerebral connectivity of M1 projections. Stroke lesion was in the left hemisphere in all patients (black horizontal segments indicate a significant difference at p < 0.05).