Teresa Schuhmann

Optimizing functional accuracy of tms in cognitive studies: A comparison of methods

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.

Virtual dyscalculia induced by parietal-lobe TMS impairs automatic magnitude processing

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.

Speaking of Which: Dissecting the Neurocognitive Network of Language Production in Picture Naming

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 (Wernickes area), 2) a midportion of Brocas 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 Brocas area at 300 ms and Wernickes 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.

The temporal characteristics of functional activation in Broca's area during overt picture naming

The opercular and triangular sections of the inferior frontal gyrus, also known as Brocas area, have been shown to be involved in various language tasks. In the current study we investigated both the functional role, as well as the precise temporal involvement of Brocas area during picture naming. We applied online event-related transcranial magnetic stimulation (TMS) to Brocas area at five different time points after picture presentation, aiming to cover the complete language production process. Applying real TMS at 300 msec after picture presentation led to an increase in picture naming latency, whereas sham stimulation and real stimulation at earlier and later time windows did not result in any changes in reaction time (RT). Our methodological approach enabled us to get insight into the temporal characteristics of the involvement of this brain area during picture naming. Making use of this information and directly relating it to psycholinguistic models, we conclude that Brocas area may be involved in the process of syllabification during overt speech production.

Out of control: Evidence for anterior insula involvement in motor impulsivity and reactive aggression

Inhibiting impulsive reactions while still defending ones vital resources is paramount to functional self-control and successful development in a social environment. However, this ability of successfully inhibiting, and thus controlling ones impulsivity, often fails, leading to consequences ranging from motor impulsivity to aggressive reactions following provocation. Although inhibitory failure represents the underlying mechanism, the neurocognition of social aggression and motor response inhibition have traditionally been investigated in separation. Here, we aimed to directly investigate and compare the neural mechanisms underlying the failure of inhibition across those different modalities of self-control. We used functional imaging to reveal the overlap in neural correlates between failed motor response inhibition (measured by a go/no-go task) and reactive aggression (measured by the Taylor aggression paradigm) in healthy males. The core overlap of neural correlates was located in the anterior insula, suggesting common anterior insula involvement in motor impulsivity as well as reactive aggression. This evidence regarding an overarching role of the anterior insula across different modalities of self-control enables an integrative perspective on insula function and a better integration of cognitive, social and emotional factors into a comprehensive model of impulsivity. Furthermore, it can eventually lead to a better understanding of clinical syndromes involving inhibitory deficits.

The role of right prefrontal and medial cortex in response inhibition: Interfering with action restraint and action cancellation using transcranial magnetic brain stimulation

The ability of inhibiting impulsive urges is paramount for human behavior. Such successful response inhibition has consistently been associated with activity in pFC. The current study aims to unravel the differential involvement of different areas within right pFC for successful action restraint versus action cancellation. These two conceptually different aspects of action inhibition were measured with a go/no-go task (action restraint) and a stop signal task (action cancellation). Localization of relevant prefrontal activation was based on fMRI data. Significant task-related activation during successful action restraint was localized for each participant individually in right anterior insula (rAI), right superior frontal gyrus, and pre-SMA. Activation during successful action cancellation was localized in rAI, right middle frontal gyrus, and pre-SMA. Subsequently, fMRI-guided continuous thetaburst stimulation was applied to these regions. Results showed that the disruption of neural activity in rAI reduced both the ability to restrain (go/no-go) and cancel (stop signal) responses. In contrast, continuous thetaburst stimulation-induced disruption of the right superior frontal gyrus specifically impaired the ability to restrain from responding (go/no-go), while leaving the ability for action cancellation largely intact. Stimulation applied to right middle frontal gyrus and pre-SMA did not affect inhibitory processing in neither of the two tasks. These findings provide a more comprehensive perspective on the role of pFC in inhibition and cognitive control. The results emphasize the role of inferior frontal regions for global inhibition, whereas superior frontal regions seem to be specifically relevant for successful action restraint.

Symbolic action priming relies on intact neural transmission along the retino-geniculo-striate pathway

Recent psychophysics studies suggest that the behavioral impact of a visual stimulus and its conscious visual recognition underlie two functionally dissociated neuronal processes. Previous TMS studies have demonstrated that certain features of a visual stimulus can still be processed despite TMS-induced disruption of perception. Here, we tested whether symbolic action priming also remains intact despite TMS-induced masking of the prime. We applied single-pulse TMS over primary visual cortex at various temporal intervals from 20 ms to 120 ms during a supraliminal action priming paradigm. This TMS protocol enabled us to identify at what exact time point a TMS-induced activity disruption of primary visual cortex interferes with conscious visual perception of the prime versus (un)conscious behavioral priming of the visual target stimulus. We also introduced spatial uncertainty by presenting visual stimuli either above or below the fixation cross, while the TMS pulse was always targeting the prime presented below fixation. We revealed that TMS over primary visual cortex interferes with both conscious visual perception and symbolic behavioral priming in a temporarily and spatially specific manner, i.e., only when disrupting primary visual cortex at approximately the same temporal stage between 60 and 100 ms after prime onset, and only for those prime stimuli presented below fixation. These findings are in disagreement with the idea of subliminal action priming being mediated by neural pathways bypassing striate cortex, and rather suggest that symbolic action priming relies on an intact neural transmission along the retino-geniculo-striate pathway. The implications of our findings for previous reports of residual visual processing during striate TMS are discussed.

Reducing proactive aggression through non-invasive brain stimulation

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.

Be nice if you have to — the neurobiological roots of strategic fairness

Social norms, such as treating others fairly regardless of kin relations, are essential for the functioning of human societies. Their existence may explain why humans, among all species, show unique patterns of prosocial behaviour. The maintenance of social norms often depends on external enforcement, as in the absence of credible sanctioning mechanisms prosocial behaviour deteriorates quickly. This sanction-dependent prosocial behaviour suggests that humans strategically adapt their behaviour and act selfishly if possible but control selfish impulses if necessary. Recent studies point at the role of the dorsolateral prefrontal cortex (DLPFC) in controlling selfish impulses. We test whether the DLPFC is indeed involved in the control of selfish impulses as well as the strategic acquisition of this control mechanism. Using repetitive transcranial magnetic stimulation, we provide evidence for the causal role of the right DLPFC in strategic fairness. Because the DLPFC is phylogenetically one of the latest developed neocortical regions, this could explain why complex norm systems exist in humans but not in other social animals.

Charting the functional relevance of Broca's area for visual word recognition and picture naming in Dutch using fMRI-guided TMS

Magnetoencephalography (MEG) has shown pseudohomophone priming effects at Brocas area (specifically pars opercularis of left inferior frontal gyrus and precentral gyrus; LIFGpo/PCG) within ∼100ms of viewing a word. This is consistent with Brocas area involvement in fast phonological access during visual word recognition. Here we used online transcranial magnetic stimulation (TMS) to investigate whether LIFGpo/PCG is necessary for (not just correlated with) visual word recognition by ∼100ms. Pulses were delivered to individually fMRI-defined LIFGpo/PCG in Dutch speakers 75-500ms after stimulus onset during reading and picture naming. Reading and picture naming reactions times were significantly slower following pulses at 225-300ms. Contrary to predictions, there was no disruption to reading for pulses before 225ms. This does not provide evidence in favour of a functional role for LIFGpo/PCG in reading before 225ms in this case, but does extend previous findings in picture stimuli to written Dutch words.