Adaptation to Leftward Shifting Prisms Alters Motor Interhemispheric Inhibition

Abstract

Adaptation to rightward shifting prisms (rightward prism adaptation, RPA) ameliorates neglect symptoms in patients while adaptation to leftward shifting prisms (leftward prism adaptation, LPA) induces neglect-like behaviors in healthy subjects. It has been hypothesized that prism adaptation (PA) modulates interhemispheric balance between the parietal cortices by inhibiting the posterior parietal cortex (PPC) contralateral to the prismatic deviation, but PA's effects on interhemispheric inhibition (IHI) have not been directly investigated. Since there are hyper-excitable connections between the PPC and primary motor cortex (M1) in the left hemisphere of neglect patients, we reasoned that LPA might mimic right hemisphere lesions by reducing parietal IHI, hyper-exciting the left PPC and PPC-M1 connections, and in turn altering IHI at the motor level. Namely, we hypothesized that LPA would increase IHI from the left to the right M1. We examined changes in left-to-right and right-to-left IHI between the 2 M1s using the ipsilateral silent period (iSP) (Meyer et al. 1995) before and after either LPA or RPA. The iSP was significantly longer after LPA but only from left-to-right and it did not change at all after RPA. This is the first physiological demonstration that LPA alters IHI in the healthy brain.

Keywords: TMS; ipsilateral silent period; prism adaptation; visuospatial neglect.

Figure 1.

Figure displays hypothesized pathways of action of PA. “Red arrows” represent interhemispheric inhibitory connections both at baseline (left panel) and after PA (middle and right panels). “Black arrows” represent the action of PA as proposed by Pisella et al. (2006): PA (both LPA and RPA) critically depends on the cerebellum and exerts its subsequent after-effects by initially inhibiting the PPC contralateral to the prism deviation. The mechanism of action of LPA (middle panel) would be as follows: LPA would mimic the effect of RH lesions by reducing right-to-left parietal IHI (Koch et al. 2011) and increasing left PPC excitability (Kinsbourne 1977). Given the functional connections between PPC-M1 (Karabanov et al. 2012; Chao et al. 2013), their hyperexcitability in the LH of neglect patients (Koch et al. 2008), and the critical fact that anodal tDCS over PPC modifies intrahemispheric circuits within M1 (Rivera-Urbina et al. 2015), LPA would increase excitatory intrahemispheric connections in the LH (“white arrow”) and subsequently increase IHI from left-to-right at the motor level (M1). We predict no change from right-to-left M1 because changes in IHI in one direction can occur without modifying the reverse (Murase et al. 2004; Stinear et al. 2015). In contrast, because RPA (right panel) inhibits the left PPC (black arrow), based on the recent finding by Koch et al. (2011) that left PPC does not seem to inhibit its homolog, we predicted no subsequent change in right PPC excitability and thus no change of IHI between the 2 M1s after RPA. Note that we did not predict a direct action of PA on the PPC-M1 contralateral to the prism deviation via a reduction of intrahemispheric PPC-M1 connectivity because cathodal tDCS over PPC has been shown not to alter intracortical motor circuits within the same hemisphere as measured by short-interval intracortical inhibition or facilitation (SICI or ICF) (Rivera-Urbina et al. 2015).

Figure 2.

Examples of iSP measurements from one representative subject in the LPA group separated by Session (pre-PA and post-PA) and Hemisphere (LH (left FDI)—upper row, and RH (right FDI)—bottom row). All data are averages of 20 single-trial rectified sweeps with TMS applied at time 0. Horizontal lines indicate the upper and lower variation limits of the prestimulus EMG level. Vertical dashed lines indicate iSP onset and offset.