Transcranial magnetic stimulation (TMS) is a method capable of transiently modulating neural excitability. Depending on the stimulation parameters information processing in the brain can be either enhanced or disrupted. This way the contribution of different brain areas involved in mental processes can be studied, allowing a functional decomposition of cognitive behavior both in the temporal and spatial domain, hence providing a functional resolution of brain/mind processes. The aim of the present paper is to argue that TMS (...) with its ability to draw causal inferences on function and its neural representations is a valuable neurophysiological tool for investigating the causal basis of neuronal functions and can provide substantive insight into the modern interdisciplinary and (anti)reductionist neurophilosophical debates concerning the relationships between brain functions and mental abilities. Thus, TMS can serve as a heuristic method for resolving causal issues in an arena where only correlative tools have traditionally been available. (shrink)

Transcranial magnetic stimulation (TMS) is a method capable of transiently modulating neural excitability. Depending on the stimulation parameters information processing in the brain can be either enhanced or disrupted. This way the contribution of different brain areas involved in mental processes can be studied, allowing a functional decomposition of cognitive behavior both in the temporal and spatial domain, hence providing a functional resolution of brain/mind processes. The aim of the present paper is to argue that TMS (...) with its ability to draw causal inferences on function and its neural representations is a valuable neurophysiological tool for investigating the causal basis of neuronal functions and can provide substantive insight into the modern interdisciplinary and (anti)reductionist neurophilosophical debates concerning the relationships between brain functions and mental abilities. Thus, TMS can serve as a heuristic method for resolving causal issues in an arena where only correlative tools have traditionally been available. (shrink)

Transcranial Magnetic Stimulation (TMS) is a non-invasive neurostimulatory and neuromodulatory technique increasingly used in clinical and research practices around the world. Historically, the ethical considerations guiding the therapeutic practice of TMS were largely concerned with aspects of subject safety in clinical trials. While safety remains of paramount importance, the recent US Food and Drug Administration approval of the Neuronetics NeuroStar TMS device for the treatment of specific medication-resistant depression has raised a number of additional ethical concerns, including (...) marketing, off-label use and technician certification. This article provides an overview of the history of TMS and highlights the ethical questions that are likely arise as the therapeutic use of TMS continues to expand. (shrink)

We can understand viewed scenes and extract task-relevant information within a few hundred milliseconds. This process is generally supported by three cortical regions that show selectivity for scene images: parahippocampal place area (PPA), medial place area (MPA) and occipital place area (OPA). Prior studies have focused on the visual information each region is responsive to, usually within the context of recognition or navigation. Here, we move beyond these tasks to investigate gaze allocation during scene viewing. Eye movements rely on a (...) scene’s visual representation to direct saccades, and thus foveal vision. In particular, we focus on the contribution of OPA, which is i) located in occipito-parietal cortex, likely feeding information into parts of the dorsal pathway critical for eye movements, and ii) contains strong retinotopic representations of the contralateral visual field. Participants viewed scene images for 1034 ms while their eye movements were recorded. On half of the trials, a 500 ms train of five transcranial magnetic stimulation (TMS) pulses was applied to the participant’s cortex, starting at scene onset. TMS was applied to the right hemisphere over either OPA or the occipital face area (OFA), which also exhibits a contralateral visual field bias but shows selectivity for face stimuli. Participants generally made an overall left-to-right, top-to-bottom pattern of eye movements across all conditions. When TMS was applied to OPA, there was an increased saccade latency for eye movements toward the contralateral relative to the ipsilateral visual field after the final TMS pulse (400ms). Additionally, TMS to the OPA biased fixation positions away from the contralateral side of the scene compared to the control condition, while the OFA group showed no such effect. There was no effect on horizontal saccade amplitudes. These combined results suggest that OPA might serve to represent local scene information that can then be utilized by visuomotor control networks to guide gaze allocation in natural scenes. (shrink)

In order to study whether there exist a period of activity in the human early visual cortex that contributes exclusively to visual awareness, we applied transcranial magnetic stimulation over the early visual cortex and measured subjective visual awareness during visual forced-choice symbol or orientation discrimination tasks. TMS produced one dip in awareness 60–120 ms after stimulus onset, while forced-choice orientation discrimination was suppressed between 60 and 90 ms and symbol discrimination between 60 and 120 ms. Thus, a (...) time window specific to visual awareness was found only in the orientation condition at 120 ms. The results imply that both conscious and unconscious perception depend on activity in early visual areas. On the basis of previous estimates of neural processing speed, we suggest that the late part of the activity period most likely involve local extrastriate–striate interactions which provide the contents for visual awareness but are not themselves sufficient for awareness to arise. (shrink)

Transcranial magnetic stimulation is a relatively non-invasive technique to interfere with the function of small cortical areas through currents induced by alternating magnetic fields emanating from a handheld coil placed directly above the targeted area. This technique has clear effects on a whole range of measures of brain function and has become an important research tool in neuropsychiatry. More recently, TMS has been studied in psychiatry mainly to assess its putative therapeutic effects in the treatment of (...) refractory major depression. Most studies indicate that both low-frequency TMS and higher frequency repetitive TMS may have some antidepressant properties. This is most interesting and opens a whole new avenue of low invasive techniques to stimulate the brain in major depression. However, definite therapeutic effects of clinical significance still remain to be demonstrated. (shrink)

BackgroundHigh frequency repetitive transcranial magnetic stimulation of the left dorsolateral prefrontal cortex has shown significant efficiency in the treatment of resistant depression. However in healthy subjects, the effects of rTMS remain unclear.ObjectiveOur aim was to determine the impact of 10 sessions of rTMS applied to the DLPFC on mood and emotion recognition in healthy subjects.DesignIn a randomised double-blind study, 20 subjects received 10 daily sessions of active or sham rTMS. The TMS coil was positioned on the left (...) DLPFC through neuronavigation. Several dimensions of mood and emotion processing were assessed at baseline and after rTMS with clinical scales, visual analogue scales, and the Ekman 60 faces test.ResultsThe 10 rTMS sessions targeting the DLPFC were well tolerated. No significant difference was found between the active group and the control group for clinical scales and the Ekman 60 faces test. Compared to the control group, the active rTM... (shrink)

The non-invasive stimulation techniques are already recognized as technology that allows neuroenhancement, specifically the Transcranial Magnetic Stimulation can be applied following potentiation protocols in order to enhance both cognitive and motor systems. Hand in hand with this capacity arises the ethical problem of its application. The objective of this contribution is to describe and discuss what ethical aspects have been established in relation to this current phenomenon. Thus, we will first describe the mechanisms and results of (...) non-invasive technology in relation to neuroenhancement, focusing on TMS enhancing protocols. Next, we will make a brief historical review of the ethical aspects established around the application of TMS and its ability to result in neuroenhancement. Finally, we will discuss the ethical aspects that have been described and new debates that arise from the previous ones, concluding in an expanded vision of addressing the discussion. (shrink)

Neuropsychological patients exhibiting category-selective visual agnosias provide unique insights into the cognitive functions of the human brain. Transcranial magnetic stimulation, in contrast, can be used to draw causal inferences, as one of the effects of the cortical disruption induced by magnetic stimulation is to act as a “virtual lesion” lasting from tens of milliseconds up to approximately one hour, depending on the type of stimulation. This specificity offers a unique advantage in psychological testing as (...) TMS can be used to test where and when cognitive computations are performed. This article briefly describes TMS, considers the small but growing number of studies that use TMS to disrupt face processing. It discusses how TMS can be used in the future to understand better how faces are cortically represented in the human brain. (shrink)

ObjectiveThe effects and possible mechanisms of cerebellar high-frequency repetitive transcranial magnetic stimulation on swallowing-related neural networks were studied using resting-state functional magnetic resonance imaging.MethodA total of 23 healthy volunteers were recruited, and 19 healthy volunteers were finally included for the statistical analysis. Before stimulation, the cerebellar hemisphere dominant for swallowing was determined by the single-pulse TMS. The cerebellar representation of the suprahyoid muscles of this hemisphere was selected as the target for stimulation with 10 (...) Hz rTMS, 100% resting motor threshold, and 250 pulses, with every 1 s of stimulation followed by an interval of 9 s. The motor evoked potential amplitude of the suprahyoid muscles in the bilateral cerebral cortex was measured before and after stimulation to evaluate the cortical excitability. Forty-eight hours after elution, rTMS was reapplied on the dominant cerebellar representation of the suprahyoid muscles with the same stimulation parameters. Rs-fMRI was performed before and after stimulation to observe the changes in amplitude of low-frequency fluctuation and regional homology at 0.01–0.08 Hz, 0.01–0.027 Hz, and 0.027–0.073 Hz.ResultsAfter cerebellar high-frequency rTMS, MEP recorded from swallowing-related bilateral cerebral cortex was increased. The results of rs-fMRI showed that at 0.01–0.08 Hz, ALFF was increased at the pons, right cerebellum, and medulla and decreased at the left temporal lobe, and ReHo was decreased at the left insular lobe, right temporal lobe, and corpus callosum. At 0.01–0.027 Hz, ALFF was decreased at the left temporal lobe, and ReHo was decreased at the right temporal lobe, left putamen, and left supplementary motor area.ConclusionRepetitive transcranial magnetic stimulation of the swallowing cortex in the dominant cerebellar hemisphere increased the bilateral cerebral swallowing cortex excitability and enhanced pontine, bulbar, and cerebellar spontaneous neural activity, suggesting that unilateral high-frequency stimulation of the cerebellum can excite both brainstem and cortical swallowing centers. These findings all provide favorable support for the application of cerebellar rTMS in the clinical practice. (shrink)

After spinal cord injury (SCI), motoneuron death occurs at and around the level of injury which induces changes in function and organization throughout the nervous system, including cortical changes. Muscle affected by SCI may consist of both innervated (accessible to voluntary drive) and denervated (inaccessible to voluntary drive) muscle fibers. Voluntary activation measured with transcranial magnetic stimulation (VATMS) can quantify voluntary cortical/subcortical drive to muscle but is limited by technical challenges including suboptimal stimulation of target muscle (...) relative to its antagonist. The motor evoked potential (MEP) in the biceps compared to the triceps (i.e., MEP ratio) may be a key parameter in the measurement of biceps VATMS after SCI. We used paired pulse TMS, which can inhibit or facilitate MEPs, to determine whether the MEP ratio affects VATMS in individuals with tetraplegia. Ten individuals with tetraplegia following cervical SCI and ten non-impaired individuals completed single pulse and paired pulse VATMS protocols. Paired pulse stimulation was delivered at 1.5, 10, and 30 ms inter-stimulus intervals (ISI). In both the SCI and non-impaired groups, the main effect of the stimulation pulse (paired pulse compared to single pulse) on VATMS was not significant in the linear mixed-effects models. In both groups for the stimulation parameters we tested, the MEP ratio was not modulated across all effort levels and did not affect VATMS. Linearity of the voluntary moment and superimposed twitch moment relation was lower in SCI participants compared to non-impaired. Poor linearity in the SCI group limits interpretation of VATMS. Future work is needed to address methodological issues that limit clinical application of VATMS. (shrink)

Transcranial magnetic stimulation is used to make inferences about relationships between brain areas and their functions because, in contrast to neuroimaging tools, it modulates neuronal activity. The central aim of this article is to critically evaluate to what extent it is possible to draw causal inferences from repetitive TMS data. To that end, we describe the logical limitations of inferences based on rTMS experiments. The presented analysis suggests that rTMS alone does not provide the sort of premises (...) that are sufficient to warrant strong inferences about the direct causal properties of targeted brain structures. Overcoming these limitations demands a close look at the designs of rTMS studies, especially the methodological and theoretical conditions which are necessary for the functional decomposition of the relations between brain areas and cognitive functions. The main points of this article are that TMS-based inferences are limited in that stimulation-related causal effects are not equivalent to structure-related causal effects due to TMS side effects, the electric field distribution, and the sensitivity of neuroimaging and behavioral methods in detecting structure-related effects and disentangling them from confounds. Moreover, the postulated causal effects can be based on indirect effects. A few suggestions on how to manage some of these limitations are presented. We discuss the benefits of combining rTMS with neuroimaging in experimental reasoning and we address the restrictions and requirements of rTMS control conditions. The use of neuroimaging and control conditions allows stronger inferences to be gained, but the strength of the inferences that can be drawn depends on the individual experiment’s designs. Moreover, in some cases, TMS might not be an appropriate method of answering causality-related questions or the hypotheses have to account for the limitations of this technique. We hope this summary and formalization of the reasoning behind rTMS research can be of use not only for scientists and clinicians who intend to interpret rTMS results causally but also for philosophers interested in causal inferences based on brain stimulation research. (shrink)

When we judge an action as morally right or wrong, we rely on our capacity to infer the actor's mental states. Here, we test the hypothesis that the right temporoparietal junction, an area involved in mental state reasoning, is necessary for making moral judgments. In two experiments, we used transcranial magnetic stimulation to disrupt neural activity in the RTPJ transiently before moral judgment and during moral judgment. In both experiments, TMS to the RTPJ led participants to rely (...) less on the actor's mental states. A particularly striking effect occurred for attempted harms : Relative to TMS to a control site, TMS to the RTPJ caused participants to judge attempted harms as less morally forbidden and more morally permissible. Thus, interfering with activity in the RTPJ disrupts the capacity to use mental states in moral judgment, especially in the case of attempted harms. (shrink)

Visual stimuli as well as transcranial magnetic stimulation can be used: to suppress the visibility of a target and to recover the visibility of a target that has been suppressed by another mask. Both types of stimulation thus provide useful methods for studying the microgenesis of object perception. We first review evidence of similarities between the processes by which a TMS mask and a visual mask can either suppress the visibility of targets or recover such suppressed (...) visibility. However, we then also point out a significant difference that has important implications for the study of the time course of unconscious and conscious visual information processing and for theoretical accounts of the processes involved. We present evidence and arguments showing: that visual masking techniques, by revealing more detailed aspects of target masking and target recovery, support a theoretical approach to visual masking and visual perception that must take into account activities in two separate neural channels or processing streams and, as a corollary, that at the current stage of methodological sophistication visual masks, by acting in more highly specifiable ways on these pathways, provide information about the microgenesis of form perception not available with TMS masks. (shrink)

GraphicalThirty healthy participants received 60 trials of intermittent SO tACS at an intensity of 2 mA. Motor cortical excitability was assessed using TMS-induced MEPs acquired across different oscillatory phases during and outlasting tACS, as well as at the start and end of the stimulation session. Mean MEP amplitude increased by ∼41% from pre- to post-tACS ; however, MEP amplitudes were not modulated with respect to the tACS phase.Converging evidence suggests that transcranial alternating current stimulation may entrain endogenous (...) neural oscillations to match the frequency and phase of the exogenously applied current and this entrainment may outlast the stimulation. However, observing entrainment in the electroencephalograph during stimulation is extremely difficult due to the presence of complex tACS artifacts. The present study assessed entrainment to slow oscillatory tACS by measuring motor cortical excitability across different oscillatory phases during and outlasting stimulation. 30 healthy participants received 60 trials of intermittent SO tACS at an intensity of 2 mA peak-to-peak. Motor cortical excitability was assessed using transcranial magnetic stimulation of the hand region of the primary motor cortex to induce motor evoked potentials in the contralateral thumb. MEPs were acquired at four time-points within each trial – early online, late online, early offline, and late offline – as well as at the start and end of the overall stimulation period. A significant increase in MEP amplitude was observed from pre- to post-tACS and from the first to the last tACS block. However, no phase-dependent modulation of excitability was observed. Therefore, although SO tACS had a facilitatory effect on motor cortical excitability that outlasted stimulation, there was no evidence supporting entrainment of endogenous oscillations as the underlying mechanism. (shrink)

Transcranial magnetic stimulation can cause measurable effects on neural activity and behavioral performance in healthy volunteers. In addition, TMS is increasingly used in clinical practice for treating various neuropsychiatric disorders. Unfortunately, TMS-induced effects show large intra- and inter-subject variability, hindering its reliability, and efficacy. One possible source of this variability may be the spontaneous fluctuations of neuronal oscillations. We present recent studies using multimodal TMS including TMS-EMG, TMS-tACS, and concurrent TMS-EEG-fMRI, to evaluate how individual oscillatory brain state (...) affects TMS signal propagation within targeted networks. We demonstrate how the spontaneous oscillatory state at the time of TMS influences both immediate and longer-lasting TMS effects. These findings indicate that at least part of the variability in TMS efficacy may be attributable to the current practice of ignoring oscillatory fluctuations during TMS. Ignoring this state-dependent spread of activity may cause great individual variability which so far is poorly understood and has proven impossible to control. We therefore also compare two technical solutions to directly account for oscillatory state during TMS, namely, to use tACS to externally control these oscillatory states and then apply TMS at the optimal brain state, or oscillatory state-triggered TMS. The described multimodal TMS approaches are paramount for establishing more robust TMS effects, and to allow enhanced control over the individual outcome of TMS interventions aimed at modulating information flow in the brain to achieve desirable changes in cognition, mood, and behavior. (shrink)

Depression is a widespread concern in the United States. Neuromodulation treatments are becoming more common but there is emerging concern for racial disparities in neuromodulation treatment utilization. This study focuses on Transcranial Magnetic Stimulation (TMS), a treatment for depression, and the structural and attitudinal barriers that racialized individuals face in accessing it. In January 2023 participants from the Twin Cities, Minnesota engaged in focus groups, coupled with an educational video intervention. Individuals self identified as non-white who had (...) no previous TMS exposure but had tried at least one treatment for their depression. Results revealed that the intervention did not notably change knowledge or stigma about TMS, but attitudes surrounding traveling for treatment changed. Notably, barriers like affordability, frequency of treatment, and lack of knowledge persist. Participants expressed a desire for more information, personal connection, and a tailored educational approach. The study suggests a need for multifaceted strategies to reduce disparities, focusing on education, community-based resources, and policy interventions. Immediate actions that can be taken include the creation of a TMS education program focused on patient engagement and awareness about TMS. (shrink)

Transcranial magnetic stimulation was used to test the functional role of parietal and prefrontal cortical regions activated during a playing card Guilty Knowledge Task. Single-pulse TMS was applied to 15 healthy volunteers at each of three target sites: left and right dorsolateral prefrontal cortex and midline parietal cortex. TMS pulses were applied at each of five latencies after the onset of a card stimulus. TMS applied to the parietal cortex exerted a latency-specific increase in inverse efficiency score (...) and in reaction time when subjects were instructed to lie relative to when asked to respond with the truth, and this effect was specific to when TMS was applied at 240 ms after stimulus onset. No effects of TMS were detected at left or right DLPFC sites. This manipulation with TMS of performance in a deception task appears to support a critical role for the parietal cortex in intentional false responding, particularly in stimulus selection processes needed to execute a deceptive response in the context of a GKT. However, this interpretation is only preliminary, as further experiments are needed to compare performance within and outside of a deceptive context to clarify the effects of deceptive intent. (shrink)

Synchronous oscillations are ubiquitous throughout the cortex, but the frequency of oscillations differs from area to area. To elucidate the mechanistic architectures underlying various rhythmic activities, we tested whether spontaneous neural oscillations in different local cortical areas and large-scale networks can be phase-entrained by direct perturbation with distinct frequencies of repetitive transcranial magnetic stimulation. While recording the electroencephalogram, we applied single-pulse TMS and rTMS at 5, 11, and 23 Hz over the motor or visual cortex. We assessed (...) local and global modulation of phase dynamics using the phase-locking factor. sp-TMS to the motor and the visual cortex triggered a transient increase in PLF in distinct frequencies that peaked at 21 and 8 Hz, respectively. rTMS at 23 Hz over the motor cortex and 11 Hz over the visual cortex induced a prominent and progressive increase in PLF that lasted for a few cycles after the termination of rTMS. Moreover, the local increase in PLF propagated to other cortical areas. These results suggest that distinct cortical areas have area-specific oscillatory frequencies, and the manipulation of oscillations in local areas impacts other areas through the large-scale oscillatory network with the corresponding frequency specificity. We speculate that rTMS that is close to area-specific frequencies enables direct manipulation of brain dynamics and is thus useful for investigating the causal roles of synchronous neural oscillations. Moreover, this technique could be used to treat clinical symptoms associated with impaired oscillations and synchrony. (shrink)

ObjectiveTwo subregions of the dorsolateral prefrontal cortex have been identified as effective repetitive transcranial magnetic stimulation targets for the “anxiosomatic” and “dysphoric” symptoms, respectively. We aimed to develop a convenient approach to locate these targets on the scalp.Materials and methodsIn a discovery experiment, the two personalized targets were precisely identified on 24 subjects using a neuronavigation system. Then, a localized approach was developed based on individual scalp landmarks. This “landmark-based approach” was replicated and validated in an independent (...) cohort. Reliability of the approach was tested by calculating the correlation of both the inter-rater and intra-rater results. Validity was tested by comparing the mean distance between the personalized and landmark-based targets to the TMS spatial resolution. We further conducted a total of 24 sham rTMS sessions to estimate the misplacement between the coil center and target during a 10-min stimulation without neuronavigation.ResultsThe parameters of the “landmark-based approach” in the discovery experiment were replicated well in an independent cohort. Using discovery parameters, we successfully identified the symptom-specific targets in the independent cohort. Specifically, the mean distance between the personalized and landmark-based targets on the cortex was not significantly larger than 5 mm. However, the personalized and landmark-based targets distance exceeded 5 mm in more than 50% of subjects. During the 10-min sham rTMS session, the average coil misplacement was significantly larger than 5 mm.ConclusionThe “landmark-based approach” can conveniently and reliably locate the two symptom-specific targets at group level. However, the accuracy was highly varied at individual level and further improvement is needed. (shrink)

While the various therapeutic neurotechnologies currently in development—TMS, tDCS, and related treatment modalities—have the potential to greatly augment the treatment of a spectrum of diseases an...

IntroductionTranscranial magnetic stimulation is a consolidated procedure for the treatment of depression, with several meta-analyses demonstrating its efficacy. Theta-burst stimulation is a modification of TMS with similar efficacy and shorter session duration. The geriatric population has many comorbidities and a high prevalence of depression, but few clinical trials are conducted specifically for this age group. TBS could be an option in this population, offering the advantages of few side effects and no pharmacological interactions. Therefore, our aim is (...) to investigate the efficacy of TBS in geriatric depression.Clinical trial registration[https://clinicaltrials.gov/ct2/], identifier [NCT04842929]. (shrink)

Transcranial magnetic stimulation can be used to mask visual stimuli, disrupting visual task performance or preventing visual awareness. While TMS masking studies generally fix stimulation intensity, we hypothesized that varying the intensity of TMS pulses in a masking paradigm might inform several ongoing debates concerning TMS disruption of vision as measured subjectively versus objectively, and pre-stimulus versus post-stimulus TMS masking. We here show that both pre-stimulus TMS pulses and post-stimulus TMS pulses could strongly mask visual stimuli. (...) We found no dissociations between TMS effects on the subjective and objective measures of vision for any masking window or intensity, ruling out the option that TMS intensity levels determine whether dissociations between subjective and objective vision are obtained. For the post-stimulus time window particularly, we suggest that these data provide new constraints for models of vision and visual awareness. Finally, our data are in line with the idea that pre-stimulus masking operates differently from conventional post-stimulus masking. (shrink)

Transcranial magnetic stimulation (TMS) of the visual cortex can induce phosphenes as can non-diagnostic ultrasound, the latter while participants have closed their eyes during Stimulation. Here we sought to study potential alteration of a visual target (a white crosshair) due to application of diagnostic ultrasound to the visual cortex. We applied a randomized series of actual or sham diagnostic ultrasound to the visual cortex of healthy participants while they stared at a visual target, with the ultrasound (...) device placed where TMS elicited phosphenes. These participants observed percepts 7 out of 10 times, consisting of extra or extensions of lines relative to the original crosshair, and additional colors. Observation of a percept occurred an average of 53.7 +/- 2.6% of the time over the course of the experiment for these participants. In contrast, 7 out of 10 participants exposed to sham-only diagnostic ultrasound observed comparable percepts an average of 36.3 +/ 1.9% of the time, a statistically significant difference (p < 0.00001). Moreover, on average, participants exposed to a combination of sham and actual ultrasound reported a net increase of 47.9 percentage points in the likelihood that they would report a visual effect by the end of the experiment. Our experiment demonstrated that a random combination of sham-only and actual diagnostic ultrasound applied to the visual cortex of participants increased the likelihood that they would observe visual effects, but not the type of effects, with that likelihood increasing over the course of the experiment. From this we conclude that repeated exposures by diagnostic ultrasound made the visual cortex more responsive to stimulation of their visual cortex by the visual target. These observations, consistent with other’s observation of effects of diagnostic ultrasound stimulation of human motor cortex and amygdala, as well as the FDA approved nature of diagnostic ultrasound, may lead to increased study of diagnostic ultrasound applied to human brain. (shrink)

Transcranial direct current stimulation over the contralateral primary motor cortex of the target muscle has been described to enhance corticospinal excitability, as measured with transcranial magnetic stimulation. Recently, tDCS targeting the brain regions functionally connected to the contralateral primary motor cortex was reported to enhance corticospinal excitability more than conventional tDCS. We compared the effects of motor network tDCS, 2 mA conventional tDCS, and sham tDCS on corticospinal excitability in 21 healthy participants in a randomized, (...) single-blind within-subject study design. We applied tDCS for 12 min and measured corticospinal excitability with TMS before tDCS and at 0, 15, 30, 45, and 60 min after tDCS. Statistical analysis showed that neither motor network tDCS nor conventional tDCS significantly increased corticospinal excitability relative to sham stimulation. Furthermore, the results did not provide evidence for superiority of motor network tDCS over conventional tDCS. Motor network tDCS seems equally susceptible to the sources of intersubject and intrasubject variability previously observed in response to conventional tDCS. (shrink)

Electroencephalography (EEG) is a non-invasive method to identify markers of treatment response in major depressive disorder (MDD). In this review, existing literature was assessed to determine how EEG markers change with different modalities of MDD treatments, and to synthesize the breadth of EEG markers used in conjunction with MDD treatments. PubMed and EMBASE were searched from 2000 to 2021 for studies reporting resting EEG (rEEG) and transcranial magnetic stimulation combined with EEG (TMS-EEG) measures in patients undergoing MDD (...) treatments. The search yielded 966 articles, 204 underwent full-text screening, and 51 studies were included for a narrative synthesis of findings along with confidence in the evidence. In rEEG studies, non-linear quantitative algorithms such as theta cordance and theta current density show higher predictive value than traditional linear metrics. Although less abundant, TMS-EEG measures show promise for predictive markers of brain stimulation treatment response. Future focus on TMS-EEG measures may prove fruitful, given its ability to target cortical regions of interest related to MDD. (shrink)

As cognitive neuroscience has advanced, the list of prospective internal, biological enhancements has steadily expanded. Education and training, as well as the use of external information‐processing devices, may be labeled as “conventional” means of cognition enhancement (CE). They are often well established and culturally accepted. By contrast, methods of enhancing cognition through “unconventional” means, such as ones involving deliberately created nootropic drugs, gene therapy, or neural implants, are nearly all to be regarded as experimental at the present time. Transcranial (...) magnetic stimulation (TMS), genetic interventions, brain‐computer interfaces and new senses are highly experimental and unlikely to be important over the next 15 years. Many of the concerns about enhancement are nonspecific to the tools used to achieve it, which means that enhancement–ethic scrutiny should also apply to nonbiological external enhancements. (shrink)

IntroductionThe prefrontal cortex plays a crucial role in cognition, particularly in executive functions. Cortical reactivity measured with Transcranial Magnetic Stimulation combined with Electroencephalography is altered in pathological conditions, and it may also be a marker of cognitive status in middle-aged adults. In this study, we investigated the associations between cognitive measures and TMS evoked EEG reactivity and explored whether the effects of this relationship were related to neurofilament light chain levels, a marker of neuroaxonal damage.MethodsFifty two healthy (...) middle-aged adults from the Barcelona Brain Health Initiative cohort underwent TMS-EEG, a comprehensive neuropsychological assessment, and a blood test for NfL levels. Global and Local Mean-Field Power, two measures of cortical reactivity, were quantified after left prefrontal cortex stimulation, and cognition was set as the outcome of the regression analysis. The left inferior parietal lobe was used as a control stimulation condition.ResultsLocal reactivity was significantly associated with working memory and reasoning only after L-PFC stimulation. No associations were found between NfL and cognition. These specific associations were independent of the status of neuroaxonal damage indexed by the NfL biomarker and remained after adjusting for age, biological sex, and education.ConclusionOur results demonstrate that TMS evoked EEG reactivity at the L-PFC, but not the L-IPL, is related to the cognitive status of middle-aged individuals and independent of NfL levels, and may become a valuable biomarker of frontal lobe-associated cognitive function. (shrink)

ObjectiveThe time interval between transcranial magnetic stimulation pulses affects evoked muscle responses when the targeted muscle is resting. This necessitates using sufficiently long inter-pulse intervals. However, there is some evidence that the IPI has no effect on the responses evoked in active muscles. Thus, we tested whether voluntary contraction could remove the effect of the IPI on TMS motor evoked potentials.MethodsIn our study, we delivered sets of 30 TMS pulses with three different IPIs to the left primary (...) motor cortex. These measurements were performed with the resting and active right hand first dorsal interosseous muscle in healthy participants. MEP amplitudes were recorded through electromyography.ResultsWe found that the IPI had no significant effect on the MEP amplitudes in the active muscle, whereas in the resting muscle, the IPI significantly affected the MEP amplitudes, decreasing the MEP amplitude of the 2 s IPI.ConclusionsThese results show that active muscle contraction removes the effect of the IPI on the MEP amplitude. Therefore, using active muscles in TMS motor mapping enables faster delivery of TMS pulses, reducing measurement time in novel TMS motor mapping studies. (shrink)

Although theories that examine direct links between behavior and brain remain incomplete, it is known that brain expansion significantly correlates with caloric and oxygen demands. Therefore, one of the principles governing evolutionary cognitive neuroscience is that cognitive abilities that require significant brain function (and/or structural support) must be accompanied by significant fitness benefit to offset the increased metabolic demands. One such capacity is self-awareness (SA), which (1) is found only in the greater apes and (2) remains unclear in terms of (...) both cortical underpinning and possible fitness benefit. In the current experiment, transcranial magnetic stimulation (TMS) was applied to the prefrontal cortex during a spatial perspective-taking task involving self and other viewpoints. It was found that delivery of TMS to the right prefrontal region disrupted self-, but not other-, perspective. These data suggest that self-awareness may have evolved in concert with other right hemisphere cognitive abilities. (shrink)

There is mounting evidence that non-invasive brain stimulation devices - transcranial direct current stimulation and transcranial magnetic stimulation could be used for cognitive enhancement. However, the regulatory environment surrounding such uses of stimulation devices is less clear than for stimulant drugs—a fact that has already been commercially exploited by several companies. In this paper, the mechanism of action, uses and adverse effects of non-invasive neurostimulation devices are reviewed, along with social and ethical challenges (...) pertaining to their use as cognitive enhancements. Two regulatory approaches that could be used to facilitate responsible use of these devices as products and services are outlined. Apart from establishing the urgently needed comprehensive regulatory framework, they might provide a starting point for establishing long term physiological and social effects of enhancement uses of tDCS and TMS. (shrink)

Categorical predictions have been proposed as the key mechanism supporting the fast pace of syntactic composition in language. Accordingly, grammar-based expectations are formed—e.g., the determiner “a” triggers the prediction for a noun—and facilitate the analysis of incoming syntactic information, which is then checked against a single or few other word categories. Previous functional neuroimaging studies point towards Broca’s area in the left inferior frontal gyrus as one fundamental cortical region involved in categorical prediction during incremental language processing. Causal evidence for (...) this hypothesis is however still missing. In this study, we combined Electroencephalography and Transcranial Magnetic Stimulation to test whether Broca’s area is functionally relevant in predictive mechanisms for language. We transiently perturbed Broca’s area during the first word in a two-word construction, while simultaneously measuring the Event-Related Potential correlates of syntactic composition. We reasoned that if Broca’s area is involved in predictive mechanisms for syntax, disruptive TMS during the first word would mitigate the difference in the ERP responses for predicted and unpredicted categories in basic two-word constructions. Contrary to this hypothesis, perturbation of Broca’s area at the predictive stage did not affect the ERP correlates of basic composition. The correlation strength between the electrical field induced by TMS and the ERP responses further confirmed this pattern. We discuss the present results considering an alternative account of the role of Broca’s area in syntactic composition, namely the bottom-up integration of words into constituents, and of compensatory mechanisms within the language predictive network. (shrink)

In a recently published study combining transcranial magnetic stimulation and electroencephalography (TMS-EEG), an early component of TMS-evoked potentials (TEPs), i.e., M1-P15, was proposed as a measure of transcallosal inhibition between motor cortices. Given that early TEPs are known to be highly variable, further evidence is needed before M1-P15 can be considered a reliable index of effective connectivity. Here, we conceived a new preregistered TMS-EEG study with two aims. The first aim was validating the M1-P15 as a cortical (...) index of transcallosal inhibition by replicating previous findings on its relationship with the ipsilateral silent period (iSP) and with performance in bimanual coordination. The second aim was inducing a task-dependent modulation of transcallosal inhibition. A new sample of 32 healthy right-handed participants underwent behavioral motor tasks and TMS-EEG recording, in which left and right M1 were stimulated both during bimanual tasks and during an iSP paradigm. Hypotheses and methods were preregistered before data collection. Results show a replication of our previous findings on the positive relationship between M1-P15 amplitude and the iSP normalized area. Differently, the relationship between M1-P15 latency and bimanual coordination was not confirmed. Finally, M1-P15 amplitude was modulated by the characteristics of the bimanual task the participants were performing, and not by the contralateral hand activity during the iSP paradigm. In sum, the present results corroborate our previous findings in validating the M1-P15 as a cortical marker of transcallosal inhibition and provide novel evidence of its task-dependent modulation. Importantly, we demonstrate the feasibility of preregistration in the TMS-EEG field to increase methodological rigor and transparency. (shrink)

The article addresses the production of reproducibility as a topic that has become acutely relevant in the recent discussions on the replication crisis in science. It brings the ethnomethodological stance on reproducibility into the discussions, claiming that reproducibility is necessarily produced locally, on the shop floor, with methodological guidelines serving as references to already established practices rather than their origins. The article refers to this argument empirically, analyzing how a group of novice neuroscientists performs a series of measurements in a (...) transcranial magnetic stimulation experiment. Based on ethnography and video analysis, the article traces a history of the local measurement procedure invented by the researchers in order to overcome the experimental uncertainty. The article aims to demonstrate how reproducibility of the local procedure is achieved in the shop floor work of the practitioners and how the procedure becomes normalized and questioned as incorrect in the course of experimental practice. It concludes that the difference between guidelines and practical actions is not problematic per se; what may be problematic is that researchers can be engaged in different working projects described by the same instruction. (shrink)

The neural basis of phonological working memory was investigated through an examination of the effects of irrelevant speech distractors and disruptive neural stimulation from transcranial magnetic stimulation. Embedded processes models argue that the same regions involved in speech perception are used to support phonological WM whereas buffer models assume that a region separate from speech perception regions is used to support WM. Thus, according to the embedded processes approach but not the buffer approach, irrelevant speech and (...) TMS to the speech perception region should disrupt the decoding of phonological WM representations. According to the buffer account, decoding of WM items should be possible in the buffer region despite distraction and should be disrupted with TMS to this region. Experiment 1 used fMRI and representational similarity analyses with a delayed recognition memory paradigm using nonword stimuli. Results showed that decoding of memory items in the speech perception regions was possible in the absence of distractors. However, the decoding evidence in the left STG was susceptible to interference from distractors presented during the delay period whereas decoding in the proposed buffer region persisted. Experiment 2 examined the causal roles of the speech processing region and the buffer region in phonological WM performance using TMS. TMS to the SMG during the early delay period caused a disruption in recognition performance for the memory nonwords, whereas stimulations at the STG and an occipital control region did not affect WM performance. Taken together, results from the two experiments are consistent with predictions of a buffer model of phonological WM, pointing to a critical role of the left SMG in maintaining phonological representations. (shrink)

IntroductionPrevious transcranial magnetic stimulation studies have revealed that the activity of the primary motor cortex ipsilateral to an active hand plays an important role in motor control. The aim of this study was to investigate whether the ipsi-M1 excitability would be influenced by goal-directed movement and laterality during unilateral finger movements.MethodTen healthy right-handed subjects performed four finger tapping tasks with the index finger: simple tapping task, Real-word task, Pseudoword task, and Visually guided tapping task. In the Tap (...) task, the subject performed self-paced simple tapping on a touch screen. In the real-word task, the subject tapped letters displayed on the screen one by one to create a Real-word. Because the action had a specific purpose, this task was considered to be goal-directed as compared to the Tap task. In the Pseudoword task, the subject tapped the letters to create a pseudoword in the same manner as in the Real-word task; however, the word was less meaningful. In the VT task, the subject was required to touch a series of illuminated buttons. This task was considered to be less goal-directed than the Pseudoword task. The tasks were performed with the right and left hand, and a rest condition was added as control. Single- and paired-pulse TMS were applied to the ipsi-M1 to measure corticospinal excitability and short- and long-interval intracortical inhibition in the resting first dorsal interosseous muscle.ResultsWe found the smaller SICI in the ipsi-M1 during the VT task compared with the resting condition. Further, both SICI and LICI were smaller in the right than in the left M1, regardless of the task conditions.DiscussionWe found that SICI in the ipsi-M1 is smaller during visual illumination-guided finger movement than during the resting condition. Our finding provides basic data for designing a rehabilitation program that modulates the M1 ipsilateral to the moving limb, for example, for post-stroke patients with severe hemiparesis. (shrink)

Transcranial Magnetic Stimulation is a technique that may aid researchers in their attempts to elucidate the underlying brain functions involved in consciousness. By employing TMS along with other neuroimaging methods and case studies, researchers may be aided in addressing their various hypotheses. Employing the ‘brain as mobile’ analogy, it may be possible to determine the individual contributions of single elements of the brain without upsetting the overall balance.

Although theories that examine direct links between behavior and brain remain incomplete, it is known that brain expansion significantly correlates with caloric and oxygen demands. Therefore, one of the principles governing evolutionary cognitive neuroscience is that cognitive abilities that require significant brain function (and/or structural support) must be accompanied by significant fitness benefit to offset the increased metabolic demands. One such capacity is self-awareness (SA), which (1) is found only in the greater apes and (2) remains unclear in terms of (...) both cortical underpinning and possible fitness benefit. In the current experiment, transcranial magnetic stimulation (TMS) was applied to the prefrontal cortex during a spatial perspective-taking task involving self and other viewpoints. It was found that delivery of TMS to the right prefrontal region disrupted self-, but not other-, perspective. These data suggest that self-awareness may have evolved in concert with other right hemisphere cognitive abilities. (shrink)

This chapter contains sections titled: Is Simulation a Natural Category? Simulation and Respects of Similarity Simulation and Motor Cognition Simulation and Face‐based Emotion Attribution Simulation is a Robust and Theoretically Interesting Category References.

Research on electroencephalogram (EEG) characteristics associated with major depressive disorder (MDD) has accumulated diverse neurophysiologic findings related to the content, topography, neurochemistry, and functions of EEG oscillations. Significant progress has been made since the first landmark EEG study on affective disorders by Davidson 35 years ago. A systematic account of these data is important and necessary for building a consistent neuropsychophysiologic model of MDD and other affective disorders. Given the extensive data on frequency-dependent functional significance of EEG oscillations, a frequency (...) domain approach may reveal the types of brain functions involved and disturbed in MDD. In this review, we systematize and integrate diverse and often unconnected observations on the content, topography, neurochemistry, and functions of EEG oscillations involved in MDD within the general concept of an EEG oscillatory pattern. (shrink)

The output from motor neuron pools is influenced by the integration of synaptic inputs originating from descending corticomotor and spinal reflex pathways. In this study, using paired non-invasive brain and peripheral nerve stimulation, we investigated how descending corticomotor pathways influence the physiologic recruitment order of the soleus Hoffmann reflex. Eleven neurologically unimpaired adults completed an assessment of transcranial magnetic stimulation -conditioning of the soleus H-reflex over a range of peripheral nerve stimulation intensities. Unconditioned H-reflex recruitment (...) curves were obtained by delivering PNS pulses to the posterior tibial nerve. Subsequently, TMS-conditioned H-reflex recruitment curves were obtained by pairing PNS with subthreshold TMS at short and long intervals. We evaluated unconditioned and TMS-conditioned H-reflex amplitudes along the ascending limb, peak, and descending limb of the H-reflex recruitment curve. Our results revealed that, for long-interval facilitation, TMS-conditioned H-reflex amplitudes were significantly larger than unconditioned H-reflex amplitudes along the ascending limb and peak of the H-reflex recruitment curve. Additionally, significantly lower PNS intensities were needed to elicit peak H-reflex amplitude for long-interval facilitation compared to unconditioned. These findings suggest that the influence of descending corticomotor pathways, particularly those mediating long-interval facilitation, contribute to changing the recruitment gain of the motor neuron pool, and can inform future methodological protocols for TMS-conditioning of H-reflexes. By characterizing and inducing short-term plasticity in circuitry mediating short- and long-interval TMS-conditioning of H-reflex amplitudes, future studies can investigate supraspinal and spinal circuit contributions to abnormal motor control, as well as develop novel therapeutic targets for neuromodulation. (shrink)

This study aimed to investigate whether the effect of mental practice can be enhanced by providing neurofeedback based on transcranial magnetic stimulation -induced motor evoked potentials. Twenty-four healthy, right-handed subjects were enrolled in this study. The subjects were randomly allocated into two groups: a group that was given correct TMS feedback and a group that was given randomized false TMS feedback. The subjects imagined pushing the switch with just timing, when the target circle overlapped a cross at (...) the center of the computer monitor. In the Real-FB group, feedback was provided to the subjects based on the MEP amplitude measured in the trial immediately preceding motor imagery. In contrast, the subjects of the Sham-FB group were provided with a feedback value that was independent of the MEP amplitude. TMS was applied when the target, moving from right to left, overlapped the cross at the center of the screen, and the MEP amplitude was measured. The MEP was recorded in the right first dorsal interosseous muscle. We evaluated the pre-mental practice and post-mental practice motor performance in both groups. As a result, a significant difference was observed in the percentage change of error values between the Real-FB group and the Sham-FB group. Furthermore, the MEP was significantly different between the groups in the 4th and 5th sets. Therefore, it was suggested that TMS-induced MEP-based neurofeedback might enhance the effect of mental practice. (shrink)

Short-term motor practice leads to plasticity in the primary motor cortex. The purpose of this study is to investigate the factors that determine the increase in corticospinal tract excitability after motor practice, with special focus on two factors; “the level of muscle activity” and “the presence/absence of a goal of keeping the activity level constant.” Fifteen healthy subjects performed four types of rapid thumb adduction in separate sessions. In the “comfortable task” and “forceful task”, the subjects adducted their thumb using (...) comfortable and strong forces. In the “comfortable with a goal task” and “forceful with a goal task”, subjects controlled the muscle activity at the same level as in the C and F, respectively, by adjusting the peak electromyographic amplitude within the target ranges. Paired associative stimulation, which combines peripheral nerve stimulation and transcranial magnetic stimulation, with an inter-stimulus interval of 25 ms was also done. Before and after the motor tasks and PAS25, TMS was applied to the M1. None of the four tasks showed any temporary changes in behavior, meaning no learning occurred. Motor-evoked potential amplitude increased only after the FG and it exhibited a positive correlation with the MEP increase after PAS25, suggesting that FG and PAS25 share at least similar plasticity mechanisms in the M1. Resting motor threshold decreased only after FG, suggesting that FG would also be associated with the membrane depolarization of M1 neurons. These results suggest task-dependent plasticity from the synergistic effect of forceful muscle activity and of setting a goal of keeping the activity level constant. (shrink)

Self-enhancement is the biasing of one’s view of oneself in a positive direction. The brain correlates of self-enhancement remain unclear though it has been reported that the medial prefrontal cortex may be important for producing self-enhancing responses. Previous studies have not examined whether the neural correlates of self-enhancement depend on the particular domain in which individuals are enhancing themselves. Both moralistic and egoistic words were presented to participants while transcranial magnetic stimulation was applied to the MPFC, precuneus (...) or in a sham orientation. Participants were asked to make decisions as to the words describing themselves, some of which were positive and some of which were negative. It was found the MPFC TMS significantly disrupted egoistic self-enhancement when TMS was delivered to the MPFC. Judgments involving moralistic words were not influenced by TMS. These data provide further evidence that MPFC is involved in self-enhancement, and that the role of MPFC may be selective in this regard. (shrink)

BackgroundTranscranial direct current stimulation targeting the primary motor hand area may induce lasting shifts in corticospinal excitability, but after-effects show substantial inter-individual variability. Functional magnetic resonance imaging can probe after-effects of TDCS on regional neural activity on a whole-brain level.ObjectiveUsing a double-blinded cross-over design, we investigated whether the individual change in corticospinal excitability after TDCS of M1-HAND is associated with changes in task-related regional activity in cortical motor areas.MethodsSeventeen healthy volunteers received 20 min of real or sham TDCS (...) on separate days in randomized order. Real and sham TDCS used the classic bipolar set-up with the anode placed over right M1-HAND. Before and after each TDCS session, we recorded motor evoked potentials from the relaxed left first dorsal interosseus muscle after single-pulse transcranial magnetic stimulation of left M1-HAND and performed whole-brain fMRI at 3 Tesla while participants completed a visuomotor tracking task with their left hand. We also assessed the difference in MEP latency when applying anterior-posterior and latero-medial TMS pulses to the precentral hand knob.ResultsReal TDCS had no consistent aftereffects on mean MEP amplitude, task-related activity or motor performance. Individual changes in MEP amplitude, measured directly after real TDCS showed a positive linear relationship with individual changes in task-related activity in the supplementary motor area and AP-LM MEP latency.ConclusionFunctional aftereffects of classical bipolar anodal TDCS of M1-HAND on the motor system vary substantially across individuals. Physiological features upstream from the primary motor cortex may determine how anodal TDCS changes corticospinal excitability. (shrink)

Previous studies on body ownership illusions have shown that under certain multimodal conditions, healthy people can experience artificial body-parts as if they were part of their own body, with direct physiological consequences for the real limb that gets ‘substituted’. In this study we wanted to assess (a) whether healthy people can experience ‘missing’ a body-part through illusory ownership of an amputated virtual body, and (b) whether this would cause corticospinal excitability changes in muscles associated with the ‘missing’ body-part. Forty right-handed (...) participants saw a virtual body from a first person perspective but for half of them the virtual body was missing a part of its right arm. Single pulse transcranial magnetic stimulation was applied before and after the experiment to left and right motor cortices. Motor evoked potentials (MEPs) were recorded from the first dorsal interosseous (FDI) and the extensor digitorum communis (EDC) of each hand. We found that the stronger the illusion of amputation and arm ownership, the more the reduction of MEP amplitudes of the EDC muscle for the contralateral sensorimotor cortex. In contrast, no association was found for the EDC amplitudes in the ipsilateral cortex and for the FDI amplitudes in both contralateral and ipsilateral cortices. Our study provides evidence that a short-term illusory perception of missing a body-part can trigger inhibitory effects on corticospinal pathways and importantly in the absence of any limb deafferentation or disuse. (shrink)