Pulses of transcranial magnetic stimulation (TMS) over occipital cortex can induce transient visual percepts called phosphenes. Phosphenes are an interesting stimulus for the study of the human visual system, constituting conscious percepts without visual inputs, elicited by neural activation beyond retinal and subcortical processing stages in the visual hierarchy. The same TMS pulses, applied at threshold intensity phosphene threshold (PT), will prompt phosphene reports on half of all trials (“P-yes”) but not on the other half (“P-no”). Contrasting brain activity (P-yes > P-no) can provide unique information on neural mechanisms underlying conscious percepts, as has been demonstrated by published EEG studies. Yet to our knowledge no articles reporting analogous contrasts with functional magnetic resonance imaging (fMRI) have been published. Since it seems unlikely that such studies have never been performed, this straightforward and technically feasible idea may have been explored in multiple failed, and unpublished, attempts. Here, we argue why such unsuccessful attempts, even small-scale, best be shared. We also report our own failed attempt to find phosphene-related activity in fMRI. Threshold phosphenes are weak percepts, and their detection subjective and difficult. If fMRI correlates of phosphenes are obtainable with this contrast, small-scale (‘pilot’) measurements may not be sufficiently powerful to detect them. At the same time, due to the challenges and costs invol The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Pulses of transcranial magnetic stimulation (TMS) over occipital cortex can induce transient visual percepts called phosphenes. Yet to our knowledge no articles reporting analogous contrasts with functional magnetic resonance imaging (fMRI) have been published. Since it seems unlikely that such studies have never been performed, this straightforward and technically feasible idea may have been explored in multiple failed, and unpublished, attempts. Here, we argue why such unsuccessful attempts, even small-scale, best be shared. We also report our own failed attempt to find phosphene-related activity in fMRI. Threshold phosphenes are weak percepts, and their detection subjective and difficult. phosphenes TMS fMRI null result simultaneous pmc-status-qastatus 0 pmc-status-live yes pmc-status-embargo no pmc-status-released yes pmc-prop-open-access yes pmc-prop-olf no pmc-prop-manuscript no pmc-prop-legally-suppressed no pmc-prop-has-pdf yes pmc-prop-has-supplement yes pmc-prop-pdf-only no pmc-prop-suppress-copyright no pmc-prop-is-real-version no pmc-prop-is-scanned-article no pmc-prop-preprint no pmc-prop-in-epmc yes pmc-license-ref CC BY Introduction Transcranial magnetic stimulation (TMS) pulses applied to occipital cortex can elicit transient conscious visual percepts, known as phosphenes, without any visual stimulation. Participants can keep their eyes closed, be blindfolded ( de Graaf et al., 2017a ), or fixate with eyes open. The experience is fleeting, but spatially specific, retinotopically organized relative to the stimulated cortical area, and relatively reliable as observers gain experience reporting on their perception ( Marg and Rudiak, 1994 ; Kammer, 1999 ; Kammer et al., 2005 ). The TMS intensity required to elicit phosphenes on half the trials is called the phosphene threshold (PT). Stimulating repeatedly at threshold opens up a range of interesting research questions, if brain activity can be measured concurrently. One problem in this search is that brain mechanisms related to conscious experience usually coincide with brain mechanisms related to unconscious processing ( de Graaf et al., 2012 ; de Graaf and Sack, 2014 ; Gallotto et al., 2017 ). Ideally, one would bypass early stages of visual processing (retina, subcortical nuclei), or even induce conscious visual experiences without presenting visual inputs at all. These goals are approximated by the use of TMS-induced phosphenes as stimuli. Simultaneous neuroimaging might thus allow a ‘cleaner’ mapping of specifically awareness-related neural mechanisms as compared to alternative paradigms. We tested three further experienced phosphene perceivers in single measurements of four functional runs, analyzed on the group-level. Transcranial magnetic stimulation was applied in the scanner to occipital cortex, with participants lying on top of the coil in supine position. TMS intensity was informally calibrated individually and adapted across and within sessions to achieve and maintain the following conditions: TMS at PT, which should lead to approximately 50% P-yes trials and 50% P-no trials, TMS sub-threshold, and TMS supra-threshold. TMS intensity conditions were pseudo-randomized within runs, with computer control of intensity on a trial-by-trial basis. Yet, at least within occipital cortex, but really across the whole brain, we found no convincing activations that might underlie phosphene perception. Final Remarks Why might it be difficult to find neural mechanisms differentiating P-yes from P-no trials? Caparelli et al. (2010) But in many trials, the decision is not so easy; stimulation at threshold may elicit very weak and fleeting phosphene experiences, not always straightforward to judge as P-yes or P-no. Perhaps it ultimately is a case of a weak effect requiring larger numbers of trials and participants to detect. A problem may then be that there are technical and financial challenges involved in TMS-fMRI, and many attempts may not proceed beyond a limited set of measurements (pilot) if results are not encouraging. That is even more reason to share experiences and attempts to perform experiments such as these.

Transcranial magnetic stimulation applied over the occipital pole is able to induce the perception of light flashes called phosphenes. For phosphene detection and threshold measurement subjects are usually blindfolded or investigated in the dark. The question that we posed here is whether phosphene thresholds change with variations in ambient light. In six subjects we measured thresholds under four different conditions: closed eyes (5 min adaptation) and 0.5, 100, and 3,200 cd/m(2) background illumination. No systematic change in phosphene thresholds was observed with different lighting conditions. In three subjects we repeated the measurements after one week and again found similar values with no systematic modulation. Our data show that cortical excitability does not change with different light adaptation levels. This confirms that the main adaptation to light takes place at subcortical levels, namely at the retina. The practical conclusion is that it is unnecessary to blindfold subjects when determining phosphene thresholds.