Rethinking the role of sham TMS

Sham 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

Hemispheric Differences within the Fronto-Parietal Network Dynamics Underlying Spatial Imagery

Spatial imagery refers to the inspection and evaluation of spatial features (e.g., distance, relative position, configuration) and/or the spatial manipulation (e.g., rotation, shifting, reorienting) of mentally generated visual images. In the past few decades, psychophysical as well as functional brain imaging studies have indicated that any such processing of spatially coded information and/or manipulation based on mental images (i) is subject to similar behavioral demands and limitations as in the case of spatial processing based on real visual images, and (ii) consistently activates several nodes of widely distributed cortical networks in the brain. These nodes include areas within both, the dorsal fronto-parietal as well as ventral occipito-temporal visual processing pathway, representing the “what” versus “where” aspects of spatial imagery. We here describe evidence from functional brain imaging and brain interference studies indicating systematic hemispheric differences within the dorsal fronto-parietal networks during the execution of spatial imagery. Importantly, such hemispheric differences and functional lateralization principles are also found in the effective brain network connectivity within and across these networks, with a direction of information flow from anterior frontal/premotor regions to posterior parietal cortices. In an attempt to integrate these findings of hemispheric lateralization and fronto-to-parietal interactions, we argue that spatial imagery constitutes a multifaceted cognitive construct that can be segregated in several distinct mental sub processes, each associated with activity within specific lateralized fronto-parietal (sub) networks, forming the basis of the here proposed dynamic network model of spatial imagery

Interindividual variability and intraindividual reliability of intermittent theta burst stimulation-induced neuroplasticity mechanisms in the healthy brain

We combined patterned TMS with EMG in several sessions of a within-subject design to assess and characterize intraindividual reliability and interindividual variability of TMS-induced neuroplasticity mechanisms in the healthy brain. Intermittent theta burst stimulation (iTBS) was applied over M1 to induce long-term potentiation-like mechanisms as assessed by changes in corticospinal excitability. Furthermore, we investigated the association between the observed iTBS effects and individual differences in prolonged measures of corticospinal excitability. Our results show that iTBS-induced measures of neuroplasticity suffer from high variability between individuals within a single assessment visit and from low reliability within individuals across two assessment visits. This indicates that both group and individual effects of iTBS on corticospinal excitability cannot be assumed to be reliable and therefore need to be interpreted with caution, at least when measured by changes in the amplitudes of motor-evoked potentials.</p

Automatic and Intentional Number Processing Both Rely on Intact Right Parietal Cortex: A Combined fMRI and Neuronavigated TMS Study

Practice and training usually lead to performance increase in a given task. In addition, a shift from intentional toward more automatic processing mechanisms is often observed. It is currently debated whether automatic and intentional processing is subserved by the same or by different mechanism(s), and whether the same or different regions in the brain are recruited. Previous correlational evidence provided by behavioral, neuroimaging, modeling, and neuropsychological studies addressing this question yielded conflicting results. Here we used transcranial magnetic stimulation (TMS) to compare the causal influence of disrupting either left or right parietal cortex during automatic and intentional numerical processing, as reflected by the size congruity effect and the numerical distance effect, respectively. We found a functional hemispheric asymmetry within parietal cortex with only the TMS-induced right parietal disruption impairing both automatic and intentional numerical processing. In contrast, disrupting the left parietal lobe with TMS, or applying sham stimulation, did not affect performance during automatic or intentional numerical processing. The current results provide causal evidence for the functional relevance of right, but not left, parietal cortex for intentional, and automatic numerical processing, implying that at least within the parietal cortices, automatic, and intentional numerical processing rely on the same underlying hemispheric lateralization

When and How to Interpret Null Results in NIBS: A Taxonomy Based on Prior Expectations and Experimental Design

Experiments often challenge the null hypothesis that an intervention, for instance application of non-invasive brain stimulation (NIBS), has no effect on an outcome measure. In conventional statistics, a positive result rejects that hypothesis, but a null result is meaningless. Informally, however, researchers often do find null results meaningful to a greater or lesser extent. We present a model to guide interpretation of null results in NIBS research. Along a “gradient of surprise,” from Replication nulls through Exploration nulls to Hypothesized nulls, null results can be less or more surprising in the context of prior expectations, research, and theory. This influences to what extent we should credit a null result in this greater context. Orthogonal to this, experimental design choices create a “gradient of interpretability,” along which null results of an experiment, considered in isolation, become more informative. This is determined by target localization procedure, neural efficacy checks, and power and effect size evaluations. Along the latter gradient, we concretely propose three “levels of null evidence.” With caveats, these proposed levels C, B, and A, classify how informative an empirical null result is along concrete criteria. Lastly, to further inform, and help formalize, the inferences drawn from null results, Bayesian statistics can be employed. We discuss how this increasingly common alternative to traditional frequentist inference does allow quantification of the support for the null hypothesis, relative to support for the alternative hypothesis. It is our hope that these considerations can contribute to the ongoing effort to disseminate null findings alongside positive results to promote transparency and reduce publication bias

TMS affects moral judgment, showing the role of DLPFC and TPJ in cognitive and emotional processing

Decision-making involves a complex interplay of emotional responses and reasoning processes. In this study, we use TMS to explore the neurobiological substrates of moral decisions in humans. To examining the effects of TMS on the outcome of a moral-decision, we compare the decision outcome of moral-personal and moral-impersonal dilemmas to each other and examine the differential effects of applying TMS over the right DLPFC or right TPJ. In this comparison, we find that the TMS-induced disruption of the DLPFC during the decision process, affects the outcome of the moral-personal judgment, while TMS-induced disruption of TPJ affects only moral-impersonal conditions. In other words, we find a double-dissociation between DLPFC and TPJ in the outcome of a moral decision. Furthermore, we find that TMS-induced disruption of the DLPFC during non-moral, moral-impersonal, and moral-personal decisions lead to lower ratings of regret about the decision. Our results are in line with the dual-process theory and suggest a role for both the emotional response and cognitive reasoning process in moral judgment. Both the emotional and cognitive processes were shown to be involved in the decision outcome

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

Oscillatory delta and theta frequencies differentially support multiple items encoding to optimize memory performance during the digit span task

The human brain has limited storage capacity often challenging the encoding and recall of a long series of multiple items. Different encoding strategies are therefore employed to optimize performance in memory processes such as chunking where particular items are ‘grouped’ to reduce the number of items to store artificially. Additionally, related to the position of an item within a series, there is a tendency to remember the first and last items on the list better than the middle ones, which calls the “serial position effect”. Although relatively well-established in behavioral research, the neuronal mechanisms underlying such encoding strategies and memory effects remain poorly understood. Here, we used event-related EEG oscillation analyses to unravel the neuronal substrates of serial encoding strategies and effects during the behaviorally controlled execution of the digit span task. We recorded EEG in forty-four healthy young-adult participants during a backward digit span (ds) task with two difficulty levels (i.e., 3-ds and 5-ds). Participants were asked to recall the digits in reverse order after the presentation of each set. We analyzed the pattern of event-related delta and theta oscillatory power in the time-frequency domain over fronto-central and parieto-occipital areas during the item (digit) list encoding, focusing on how these oscillatory responses changed with each subsequent digit being encoded in the series. Results showed that the development of event-related delta power evoked by digits in each series matched the ‘serial position curve’, with higher delta power being present during the first, and especially last, digits as compared to digits presented in the middle of a set, for both difficulty levels. Event-related theta power, in contrast, rather resembled a neural correlate of a chunking pattern where, during the 5-ds encoding, a clear change in event-related theta occurred around the third/fourth positions, with decreasing power values for later digits. This suggests that different oscillatory mechanisms linked to different frequency bands may code for the different encoding strategies and effects in serial item presentation. Furthermore, recall-EEG correlations suggested that participants with higher fronto-central delta responses during digit encoding showed also higher recall scores. The here presented findings contribute to our understanding of the neural oscillatory mechanisms underlying multiple item encoding, directly informing recent efforts towards memory enhancement through targeted oscillation-based neuromodulation.Türkiye Bilimsel ve Teknolojik Araştırma Kurum

The Involvement of Endogenous Neural Oscillations in the Processing of Rhythmic Input: More Than a Regular Repetition of Evoked Neural Responses

It is undisputed that presenting a rhythmic stimulus leads to a measurable brain response that follows the rhythmic structure of this stimulus. What is still debated, however, is the question whether this brain response exclusively reflects a regular repetition of evoked responses, or whether it also includes entrained oscillatory activity. Here we systematically present evidence in favour of an involvement of entrained neural oscillations in the processing of rhythmic input while critically pointing out which questions still need to be addressed before this evidence could be considered conclusive. In this context, we also explicitly discuss the potential functional role of such entrained oscillations, suggesting that these stimulus-aligned oscillations reflect, and serve as, predictive processes, an idea often only implicitly assumed in the literature