Shifts in connectivity during procedural learning after motor cortex stimulation: A combined transcranial magnetic stimulation/functional magnetic resonance imaging study

Abstract

Inhibitory transcranial magnetic stimulation, of which continuous theta burst stimulation (cTBS) is a common form, has been used to inhibit cortical areas during investigations of their function. cTBS applied to the primary motor area (M1) depresses motor output excitability via a local effect and impairs procedural motor learning. This could be due to an effect on M1 itself and/or to changes in its connectivity with other nodes in the learning network. To investigate this issue, we used functional magnetic resonance imaging to measure changes in brain activation and connectivity during implicit procedural learning after real and sham cTBS of M1. Compared to sham, real cTBS impaired motor sequence learning, but caused no local or distant changes in brain activation. Rather, it reduced functional connectivity between motor (M1, dorsal premotor & supplementary motor areas) and visual (superior & inferior occipital gyri) areas. It also increased connectivity between frontal associative (superior & inferior frontal gyri), cingulate (dorsal & middle cingulate), and temporal areas. This potentially compensatory shift in coupling, from a motor-based learning network to an associative learning network accounts for the behavioral effects of cTBS of M1. The findings suggest that the inhibitory transcranial magnetic stimulation affects behavior via relatively subtle and distributed effects on connectivity within networks, rather than by taking the stimulated area “offline.”

Motor cortex inhibition by TMS reduces cognitive non-motor procedural learning when immediate incentives are present

“…There is also some evidence that the motor loop, including M1, has a role in WPT learning with feedback (Aron et al, 2004). As we and others have shown, inhibitory stimulation over M1 disrupts procedural motor learning; where learning relies on error signaling (Hadipour-Niktarash et al, 2007; Muellbacher et al, 2002; Robertson et al, 2005; Rosenthal et al, 2009; Steel et al, 2016; Wilkinson et al, 2015; Wilkinson et al, 2010). However, these experiments have all used tasks with an important motor learning component.…”

“…However, it is unlikely that M1, itself, is essential to procedural learning. An alternative explanation is provided by recent work from our laboratory (Steel et al, 2016) where cTBS of M1 caused no change in local activation during a motor procedural learning task, but disrupted connectivity in a distributed manner in a network associated with motor learning. Task-related connectivity simultaneously increased in another, previously described, learning network, which did not include M1.…”

“…The BG participate in functional loops with cortical regions implicated in learning (Alexander, Delong, & Strick, 1986; Rodriguez-Oroz et al, 2009) including the motor, limbic, and associative loops. Imaging and neurophysiological studies (Kantak, Sullivan, Fisher, Knowlton, & Winstein, 2010; Karni et al, 1995; Matsuzaka, Picard, & Strick, 2007) and evidence from inhibitory repetitive transcranial magnetic stimulation (rTMS) studies (Hadipour-Niktarash, Lee, Desmond, & Shadmehr, 2007; Muellbacher et al, 2002; Robertson, Press, & Pascual-Leone, 2005; Rosenthal, Roche-Kelly, Husain, & Kennard, 2009; Steel et al, 2016; Wilkinson et al, 2015; Wilkinson, Teo, Obeso, Rothwell, & Jahanshahi, 2010) show that the primary motor area (M1) is an important cortical node in the procedural motor learning network.…”

“…Inhibitory rTMS delivered to M1 during various phases of learning has implicated M1 in the acquisition, consolidation, and retention of visuo-motor knowledge (Hadipour-Niktarash et al, 2007; Muellbacher et al, 2002; Robertson et al, 2005; Rosenthal et al, 2009; Steel et al, 2016; Wilkinson et al, 2015; Wilkinson et al, 2010). In an fMRI study of visuo-motor skill learning before and after inhibitory rTMS delivered to M1, (Steel et al, 2016) we found that inhibition does not affect learning by taking M1 “offline” or creating the functional equivalent of a local, “virtual lesion.” Rather, it redistributes task-related connectivity between two learning networks less efficiently.…”

“…In an fMRI study of visuo-motor skill learning before and after inhibitory rTMS delivered to M1, (Steel et al, 2016) we found that inhibition does not affect learning by taking M1 “offline” or creating the functional equivalent of a local, “virtual lesion.” Rather, it redistributes task-related connectivity between two learning networks less efficiently.…”