Hyperexcitability of parietal-motor functional connections in the intact left-hemisphere of patients with neglect

Abstract

Hemispatial neglect is common after unilateral brain damage, particularly to perisylvian structures in the right-hemisphere (RH). In this disabling syndrome, behaviour and awareness are biased away from the contralesional side of space towards the ipsilesional side. Theoretical accounts of this in terms of hemispheric rivalry have speculated that the intact left-hemisphere (LH) may become hyper-excitable after a RH lesion, due to release of inhibition from the damaged hemisphere. We tested this directly using a novel twin-coil transcranial magnetic stimulation (TMS) approach to measure excitability within the intact LH of neglect patients. This involved applying a conditioning TMS pulse over left posterior parietal cortex (PPC), in order to test its effect on the amplitude of motor evoked potentials (MEPs) produced by a subsequent test pulse over left motor cortex (M1). Twelve RH stroke patients with neglect, an age-matched group of eight RH stroke patients without neglect, and 10 healthy controls were examined. We found that excitability of left PPC-M1 circuits was higher in neglect patients than the other groups, and related to the degree of neglect on clinical cancellation tests. A follow-up found that 1 Hz repetitive TMS over left PPC normalized this over-excitability, and also ameliorated visual neglect on an experimental measure with chimeric objects. Our results provide 'direct' evidence for pathological over-excitability of the LH in the neglect syndrome, as quantified by left PPC influences on left M1, with implications for possible treatment.

Figures

Figure 1

Summary of lesions and overlap in our sample of right-hemisphere stroke patients with neglect (NS+, top row) and those without neglect (NS-) participating in the study. The color-scale at bottom-right of each row indicates the proportion of patients (higher for colors further to the right in the scale).

Figure 2

Resting Motor Thresholds (RMT) in the left motor cortex did not differ between the two groups of patients (NS+ and NS-) and the healthy control group (HS). Means and standard errors shown. MSO=maximal stimulator output.

Figure 3

A conditioning TMS stimulus (CS) was applied at (A) 90% or (B) 110% of resting motor threshold (RMT) over left posterior parietal cortex (PPC) at a site corresponding to the inferior parietal lobe and angular gyrus near the caudal intraparietal sulcus, as different inter-stimulus-intervals (ISIs, shown across the x-axis of each graph) relative to a test stimulus (TS) pulse to left M1. The panels shows the left PPC-M1 effects (relative to an M1 pulse alone) obtained after PPC conditioning in the three different groups for Experiment 1. The intensity of the test stimulus (TS) was fixed to evoke an MEP of approximately 1 mV peak to peak in the relaxed left first dorsal interosseus (FDI). Pathologically increased left PPC-M1 effects were observed selectively in the neglect group at CS intensity of 90% RMT (see left graph, A). Errors bars indicate S.E.M.. * indicate significant differences in pairwise tests between NS+ and NS- groups; ° indicate significant differences at between NS+ and HS (i.e. healthy control subject) groups, all at p

Figure 4

In patients with neglect the individual amount of facilitation induced by PPC conditioning at 90% RMT at ISI=4 ms correlated with number of left side omissions in the line barrage (r=0.69; p

Figure 5

The panel shows the changes induced by the left PPC 1 Hz rTMS treatment (600 stimuli at 90% RMT) on the left PPC-M1 connectivity effects. (A) The pathologically increased left PPC-M1 effects observed in the neglect group at intensity of 90% RMT (see also Experiment 1 and Figure 3) pre-rTMS were significantly reduced and indeed eliminated (relative to the NS- control group of patients) post rTMS in the NS+ group. (B) No significant changes were detected in the NS+ group at CS intensity of 110% RMT. (C and D) rTMS did not change the normal pattern for the NS-group at either intensity of CS. Errors bars indicate S.E.M.; * indicate p value

Figure 6

In neglect patients positive effects of treatment were detected in 7 out of 10 patients as showed by the graph in which for each patient the individual peak of facilitation of PPC-M1 connectivity with CS at 90% RMT and ISI=4 ms was plotted before and after rTMS procedure.