Sham transcranial magnetic stimulation (TMS) approaches are widely used in basic and clinical research to ensure that observed effects are due to the intended neural manipulation instead of being caused by various possible side effects. We here critically discuss several methodological aspects of sham TMS. Importantly, we propose to carefully distinguish between the placebo versus sensory side effects of TMS. In line with this conceptual distinction, we describe current limitations of sham TMS approaches in the context of placebo effects and blinding success, followed by a short review of our own work demonstrating that the sensory side effects of sham TMS are not unspecific as often falsely assumed. Lastly, we argue that sham TMS approaches are inherently insufficient as full-fledged control conditions as they fail to demonstrate the specificity of TMS effects to a particular brain area or time point of stimulation. Sham TMS should therefore only complement alternative control strategies in TMS research.

BackgroundVoluntary shifts of visuospatial attention are associated with a lateralization of parieto-occipital alpha power (7-13Hz), i.e. higher power in the hemisphere ipsilateral and lower power contralateral to the locus of attention. Recent noninvasive neuromodulation studies demonstrated that alpha power can be experimentally increased using transcranial alternating current stimulation (tACS).Objective/HypothesisWe hypothesized that tACS at alpha frequency over the left parietal cortex induces shifts of attention to the left hemifield. However, spatial attention shifts not only occur voluntarily (endogenous/ top-down), but also stimulus-driven (exogenous/ bottom-up). To study the task-specificity of the potential effects of tACS on attentional processes, we administered three conceptually different spatial attention tasks.Methods36 healthy volunteers were recruited from an academic environment. In two separate sessions, we applied either high-density tACS at 10Hz, or sham tACS, for 35–40 minutes to their left parietal cortex. We systematically compared performance on endogenous attention, exogenous attention, and stimulus detection tasks.ResultsIn the endogenous attention task, a greater leftward bias in reaction times was induced during left parietal 10Hz tACS as compared to sham. There were no stimulation effects in either the exogenous attention or the stimulus detection task.ConclusionThe study demonstrates that high-density tACS at 10Hz can be used to modulate visuospatial attention performance. The tACS effect is task-specific, indicating that not all forms of attention are equally susceptible to the stimulation.

Voluntary allocation of visual attention is controlled by top-down signals generated within the Frontal Eye Fields (FEFs) that can change the excitability of lower-level visual areas. However, the mechanism through which this control is achieved remains elusive. Here, we emulated the generation of an attentional signal using single-pulse transcranial magnetic stimulation to activate the FEFs and tracked its consequences over the visual cortex. First, we documented changes to brain oscillations using electroencephalography and found evidence for a phase reset over occipital sites at beta frequency. We then probed for perceptual consequences of this top-down triggered phase reset and assessed its anatomical specificity. We show that FEF activation leads to cyclic modulation of visual perception and extrastriate but not primary visual cortex excitability, again at beta frequency. We conclude that top-down signals originating in FEF causally shape visual cortex activity and perception through mechanisms of oscillatory realignment.

Several competing theories on the mechanisms underlying attentional control have emerged over the years that, despite their substantial differences, all emphasize the importance of hemispheric asymmetries. Transcranial magnetic stimulation (TMS) has proven particularly successful in teasing them apart by selective perturbation of the dorsal and ventral fronto-parietal network. We here critically review the TMS literature and show that hemispheric asymmetries within the dorsal attention network differ between parietal and frontal cortex. Specifically, posterior parietal cortex seems to be characterized by a contralateral bias of each hemisphere and competition between them. In contrast, the right frontal eye field seems to be involved in shifting attention toward both hemifields, whereas left frontal eye field is only involved on shifting attention toward the contralateral hemifield. In the light of presented evidence, we propose to revise the functional-anatomical model originally proposed by Corbetta and Shulman (2011, 2002) and introduce a hybrid model of hemispheric asymmetries in attentional control.

Transcranial magnetic stimulation (TMS) allows non-invasive manipulation of brain activity during active task performance. Because every TMS pulse is accompanied by non-neural effects such as a clicking sound and somato-sensation on the head, control conditions are required to ensure that changes in task behavior are indeed due to the induced neural effects. However, the non-neural effects of TMS in the context of a given task performance are largely unknown and, consequently, it is unclear what constitutes a valid control condition. We explored the non-neural effects of TMS on visual target detection. Participants received single pulse sham TMS to each hemisphere at different time points prior to target appearance during a visual target detection task. It was hypothesized that the clicking sound of a sham TMS pulse differentially affects performance depending on the location of the coil and the timing of the pulse.Our results show that, first, sham TMS caused a facilitation of reaction times when preceding the target stimulus by 150, 200, and 250 ms, whereas earlier and later time windows were not effective. Second, positioning the TMS coil ipsilateral instead of contralateral relative to the target stimulus improved reaction times. Third, infrequent noTMS trials that were interleaved with sham TMS trials had oddball-like properties resulting in increased reaction times during noTMS. The clicking sound produced by sham TMS influences task performance in multiple ways. These non-neural effects of TMS need to be controlled for in TMS research and the present findings provide an empirical basis for deciding what constitutes a valid control condition.