Time-dependent activation of parieto-frontal networks for directing attention to tactile space. A study with paired transcranial magnetic stimulation pulses in right-brain-damaged patients with extinction

Tactile extinction has been interpreted as an attentional disorder, closely related to hemineglect, due to hyperactivation of the unaffected hemisphere, resulting in an ipsilesional attentional bias. Paired transcranial magnetic stimulation (TMS) techniques, with a subthreshold conditioning stimulus (CS) followed at various interstimulus intervals (ISIs) by a suprathreshold test stimulus (TS), are useful for investigating intracortical inhibition and facilitation in the human motor cortex. In the present work, we investigated the effects of paired TMS over the posterior parietal and frontal cortex of the unaffected hemisphere in a group of eight right-brain-damaged patients with tactile extinction who were carrying out a bimanual tactile discrimination task. The aim of the study was to verify if paired TMS could induce selective inhibition or facilitation of the unaffected hemisphere depending on the ISI, resulting, respectively, in an improvement and a worsening of contralesional extinction. In addition, we wanted to investigate if the effects of parietal and frontal TMS on contralesional extinction appeared at different intervals, suggesting time-dependent activation in the cortical network for the processing of tactile spatial information. Paired TMS stimuli with a CS and a TS, separated by two ISIs of 1 and 10 ms, were applied over the left parietal and frontal cortex after various intervals from the presentation of bimanual cutaneous stimuli. Single-test parietal TMS stimuli improved the patients' performance, whereas paired TMS had distinct effects depending on the ISI: at ISI = 1 ms the improvement in extinction was greater than that induced by single-pulse TMS; at ISI = 10 ms we observed worsening of extinction, with complete reversal of the effects of single-pulse TMS. Compared with TMS delivered over the frontal cortex, parietal TMS improved the extinction rate in a time window that began earlier. These findings shed further light on the mechanism of tactile extinction, suggesting relative hyperexcitability of the parieto-frontal network in the unaffected hemisphere, which is amenable to study and modulation by paired TMS pulses. In addition, the results show time-dependent processing of tactile spatial information in the parietal and frontal cortices, with a bimodal distribution of activity, at least in the attentional network of the unaffected hemisphere.