[Brain stimulation: the most direct form of neurostimulation]. / Hersenstimulatie: de meest directe vorm van neuromodulatie.

BACKGROUND: Brain stimulation is the most direct form of neuromodulation. Direct brain stimulation is an older procedure that has taken various forms, but 'non-invasive brain stimulation' is a more recent development. AIM: To provide an overview of the current arsenal of non-invasive brain stimulation techniques. METHOD: We discuss the underlying principles, the pros and cons, and the applicability of non-invasive brain stimulation in experimental research and treatment of neuropsychiatric disorders. RESULTS: Non-invasive brain stimulation is a direct form of neuromodulation, which is not invasive, harmful or painful. Its effects are in principle temporary, which makes the technique suitable for experimental research. At the same time, temporary effects can have lasting clinical consequences, if they target neuroplasticity to aid rehabilitation or alleviate symptoms. CONCLUSION: Whereas the value of non-invasive brain stimulation for research purposes is undisputed, its efficacy and value as a treatment for neuropsychiatric disorders are still being debated. Nevertheless, the accumulated evidence about the clinical efficacy of the treatment for certain disorders is sufficiently compelling to start thinking about European regulations and standard medical insurance coverage.

Frequency-specific transcranial neuromodulation of alpha power alters visuospatial attention performance.

Transcranial alternating current stimulation (tACS) at 10 Hz has been shown to modulate spatial attention. However, the frequency-specificity and the oscillatory changes underlying this tACS effect are still largely unclear. Here, we applied high-definition tACS at individual alpha frequency (IAF), two control frequencies (IAF+/-2Hz) and sham to the left posterior parietal cortex and measured its effects on visuospatial attention performance and offline alpha power (using electroencephalography, EEG). We revealed a behavioural and electrophysiological stimulation effect relative to sham for IAF but not control frequency stimulation conditions: there was a leftward lateralization of alpha power for IAF tACS, which differed from sham for the first out of three minutes following tACS. At a high value of this EEG effect (moderation effect), we observed a leftward attention bias relative to sham. This effect was task-specific, i.e., it could be found in an endogenous attention but not in a detection task. Only in the IAF tACS condition, we also found a correlation between the magnitude of the alpha lateralization and the attentional bias effect. Our results support a functional role of alpha oscillations in visuospatial attention and the potential of tACS to modulate it. The frequency-specificity of the effects suggests that an individualization of the stimulation frequency is necessary in heterogeneous target groups with a large variation in IAF.

Seeing in the dark: Phosphene thresholds with eyes open versus closed in the absence of visual inputs.

BACKGROUND: Voluntarily opening or closing our eyes results in fundamentally different input patterns and expectancies. Yet it remains unclear how our brains and visual systems adapt to these ocular states. OBJECTIVE/HYPOTHESIS: We here used transcranial magnetic stimulation (TMS) to probe the excitability of the human visual system with eyes open or closed, in the complete absence of visual inputs. METHODS: Combining Bayesian staircase procedures with computer control of TMS pulse intensity allowed interleaved determination of phosphene thresholds (PT) in both conditions. We measured parieto-occipital EEG baseline activity in several stages to track oscillatory power in the alpha (8-12 Hz) frequency-band, which has previously been shown to be inversely related to phosphene perception. RESULTS: Since closing the eyes generally increases alpha power, one might have expected a decrease in excitability (higher PT). While we confirmed a rise in alpha power with eyes closed, visual excitability was actually increased (PT was lower) with eyes closed. CONCLUSIONS: This suggests that, aside from oscillatory alpha power, additional neuronal mechanisms influence the excitability of early visual cortex. One of these may involve a more internally oriented mode of brain operation, engaged by closing the eyes. In this state, visual cortex may be more susceptible to top-down inputs, to facilitate for example multisensory integration or imagery/working memory, although alternative explanations remain possible.

Null results in TMS: from absence of evidence to evidence of absence.

It is always difficult to interpret null results. But as a research method, transcranial magnetic stimulation (TMS) has so many degrees of freedom that null results are often dismissed as meaningless. We feel that this may be unnecessary, if not counterproductive. Null results seem to inherently fulfill an important role in brain mapping. In fact, without null results, neuroimaging as an enterprise would not make sense. We argue that null results are similarly important in TMS research. By itself, neuroimaging research leaves room for doubt concerning whether or not an activated region is actually necessary for intact task performance. Interference methods such as TMS can therefore complement brain research by testing the functional relevance of that region. However, if then only positive TMS results are taken seriously, the brain interference paradigm seems less informative than promised. But how can null results inform us if they only constitute absence of evidence? We suggest that three main arguments contravene interpretation of null results in TMS. These we call the localization argument, the neural efficacy argument, and the power argument. We proceed to discuss in turn how, and under which conditions, each of these arguments may be nuanced. These considerations lead us to value null results along a gradient of meaningfulness, rather than a dichotomy. This perspective may open up a new range of TMS applications, where research questions about the lack of functional relevance of a particular brain region become valid. In this context we make specific recommendations on experimentation and interpretation. We propose that it is often not only meaningful to interpret null results, but also useful to make such findings available to the community, especially now that improved methods and an expanded knowledge base make null results more interpretable than they have been in the past.