Transcranial magnetic stimulation (TMS) is a tool for inducing transient disruptions of neural activity noninvasively in conscious human volunteers. In recent years, the investigative domain of TMS has expanded and now encompasses causal structure-function relationships across the whole gamut of cognitive functions and associated cortical brain regions. Consequently, the importance of how to determine the target stimulation site has increased and a number of alternative methods have emerged. Comparison across studies is precluded because different studies necessarily use different tasks, sites, TMS conditions, and have different goals. Here, therefore, we systematically compare four commonly used TMS coil positioning approaches by using them to induce behavioral change in a single cognitive study. Specifically, we investigated the behavioral impact of right parietal TMS during a number comparison task, while basing TMS localization either on (i) individual fMRI-guided TMS neuronavigation, (ii) individual MRI-guided TMS neuronavigation, (iii) group functional Talairach coordinates, or (iv) 10-20 EEG position P4. We quantified the exact behavioral effects induced by TMS using each approach, calculated the standardized experimental effect sizes, and conducted a statistical power analysis in order to calculate the optimal sample size required to reveal statistical significance. Our findings revealed a systematic difference between the four approaches, with the individual fMRI-guided TMS neuronavigation yielding the strongest and the P4 stimulation approach yielding the smallest behavioral effect size. Accordingly, power analyses revealed that although in the fMRI-guided neuronavigation approach five participants were sufficient to reveal a significant behavioral effect, the number of necessary participants increased to n = 9 when employing MRI-guided neuronavigation, to n = 13 in case of TMS based on group Talairach coordinates, and to n = 47 when applying TMS over P4. We discuss these graded effect size differences in light of the revealed interindividual variances in the actual target stimulation site within and between approaches.

People suffering from developmental dyscalculia encounter difficulties in automatically accessing numerical magnitudes [1-3]. For example, when instructed to attend to the physical size of a number while ignoring its numerical value, dyscalculic subjects, unlike healthy participants, fail to process the irrelevant dimension automatically and subsequently show a smaller size-congruity effect (difference in reaction time between incongruent [e.g., a physically large 2 and a physically small 4] and congruent [e.g., a physically small 2 and a physically large 4] conditions), and no facilitation (neutral [e.g., a physically small 2 and a physically large 2] versus congruent) [3]. Previous imaging studies determined the intraparietal sulcus (IPS) as a central area for numerical processing [4-11]. A few studies tried to identify the brain dysfunction underlying developmental dyscalculia but yielded mixed results regarding the involvement of the left [12] or the right [13] IPS. Here we applied fMRI-guided TMS neuronavigation to disrupt left- or right-IPS activation clusters in order to induce dyscalculic-like behavioral deficits in healthy volunteers. Automatic magnitude processing was impaired only during disruption of right-IPS activity. When using the identical paradigm with dyscalculic participants, we reproduced a result pattern similar to that obtained with nondyscalculic volunteers during right-IPS disruption. These findings provide direct evidence for the functional role of right IPS in automatic magnitude processing.

Aggressive behavior poses a threat to human collaboration and social safety. It is of utmost importance to identify the functional mechanisms underlying aggression and to develop potential interventions capable of reducing dysfunctional aggressive behavior already at a brain level. We here experimentally shifted fronto-cortical asymmetry to manipulate the underlying motivational emotional states in both male and female participants while assessing the behavioral effects on proactive and reactive aggression. Thirty-two healthy volunteers received either anodal transcranial direct current stimulation to increase neural activity within right dorsolateral prefrontal cortex, or sham stimulation. Aggressive behavior was measured with the Taylor Aggression Paradigm. We revealed a general gender effect, showing that men displayed more behavioral aggression than women. After the induction of right fronto-hemispheric dominance, proactive aggression was reduced in men. This study demonstrates that non-invasive brain stimulation can reduce aggression in men. This is a relevant and promising step to better understand how cortical brain states connect to impulsive actions and to examine the causal role of the prefrontal cortex in aggression. Ultimately, such findings could help to examine whether the brain can be a direct target for potential supportive interventions in clinical settings dealing with overly aggressive patients and/or violent offenders.

The noninvasive methods of cognitive neuroscience offer new possibilities to study language. We used neuronavigated multisite transcranial magnetic stimulation (TMS) to determine the functional relevance of 1) the posterior part of left superior temporal gyrus (Wernicke's area), 2) a midportion of Broca's area (slightly posterior/superior to apex of vertical ascending ramus), and 3) the midsection of the left middle temporal gyrus (MTG), during overt picture naming. Our chronometric TMS design enabled us to chart the time points at which neural activity in each of these regions functionally contributes to overt speech production. Our findings demonstrate that the midsection of left MTG becomes functionally relevant at 225 ms after picture onset, followed by Broca's area at 300 ms and Wernicke's area at 400 ms. Interestingly, during this late time window, the left MTG shows a second peak of functional relevance. Each area thus contributed during the speech production process at different stages, suggesting distinct underlying functional roles within this complex multicomponential skill. These findings are discussed and framed in the context of psycholinguistic models of speech production according to which successful speaking relies on intact, spatiotemporally specific feed forward and recurrent feedback loops within a left-hemispheric fronto-temporal brain connectivity network.