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Noninvasive brain stimulation (NIBS) techniques are widely used tools for the study and rehabilitation of cognitive functions. Different NIBS approaches aim to enhance or impair different cognitive processes. The methodological focus for achieving this has been on stimulation protocols that are considered either inhibitory or facilitatory. However, despite more than three decades of use, their application is based on incomplete and overly simplistic conceptualizations of mechanisms of action. Such misconception limits the usefulness of these approaches in the basic science and clinical domains. In this review, we challenge this view by arguing that stimulation protocols themselves are neither inhibitory nor facilitatory. Instead, we suggest that all induced effects reflect complex interactions of internal and external factors. Given these considerations, we present a novel model in which we conceptualize NIBS effects as an interaction between brain activity and the characteristics of the external stimulus. This interactive model can explain various phenomena in the brain stimulation literature that have been considered unexpected or paradoxical. We argue that these effects no longer seem paradoxical when considered from the viewpoint of state dependency. [ABSTRACT FROM AUTHOR]

The focal lesion alters the excitation–inhibition (E–I) balance and healthy functional connectivity patterns, which may recover over time. One possible mechanism for the brain to counter the insult is global reshaping functional connectivity alterations. However, the operational principles by which this can be achieved remain unknown. We propose a novel equivalence principle based on structural and dynamic similarity analysis to predict whether specific compensatory areas initiate lost E–I regulation after lesion. We hypothesize that similar structural areas (SSAs) and dynamically similar areas (DSAs) corresponding to a lesioned site are the crucial dynamical units to restore lost homeostatic balance within the surviving cortical brain regions. SSAs and DSAs are independent measures, one based on structural similarity properties measured by Jaccard Index and the other based on post-lesion recovery time. We unravel the relationship between SSA and DSA by simulating a whole brain mean field model deployed on top of a virtually lesioned structural connectome from human neuroimaging data to characterize global brain dynamics and functional connectivity at the level of individual subjects. Our results suggest that wiring proximity and similarity are the 2 major guiding principles of compensation-related utilization of hemisphere in the post-lesion functional connectivity re-organization process. [ABSTRACT FROM AUTHOR]

White matter hyperintensity (WMH) lesions on T2 fluid‐attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) and changes in adjacent normal‐appearing white matter can disrupt computerized tract reconstruction and result in inaccurate measures of structural brain connectivity. The virtual lesion approach provides an alternative strategy for estimating structural connectivity changes due to WMH. To assess the impact of using young versus older subject diffusion MRI data for virtual lesion tractography, we leveraged recently available diffusion MRI data from the Human Connectome Project (HCP) Lifespan database. Neuroimaging data from 50 healthy young (39.2 ± 1.6 years) and 46 healthy older (74.2 ± 2.5 years) subjects were obtained from the publicly available HCP‐Aging database. Three WMH masks with low, moderate, and high lesion burdens were extracted from the WMH lesion frequency map of locally acquired FLAIR MRI data. Deterministic tractography was conducted to extract streamlines in 21 WM bundles with and without the WMH masks as regions of avoidance in both young and older cohorts. For intact tractography without virtual lesion masks, 7 out of 21 WM pathways showed a significantly lower number of streamlines in older subjects compared to young subjects. A decrease in streamline count with higher native lesion burden was found in corpus callosum, corticostriatal tract, and fornix pathways. Comparable percentages of affected streamlines were obtained in young and older groups with virtual lesion tractography using the three WMH lesion masks of increasing severity. We conclude that using normative diffusion MRI data from young subjects for virtual lesion tractography of WMH is, in most cases, preferable to using age‐matched normative data. [ABSTRACT FROM AUTHOR]

Explore how anatomical measurements and field modeling can be leveraged to improve investigations of transcranial magnetic stimulation (TMS) effects on both motor and non-motor TMS targets. TMS motor effects (targeting the primary motor cortex [M1]) were evaluated using the resting motor threshold (rMT), while TMS non-motor effects (targeting the superior temporal gyrus [STG]) were assessed using a pain memory task. Anatomical measurements included scalp-cortex distance (SCD) and cortical thickness (CT), whereas field modeling encompassed the magnitude of the electric field (E) induced by TMS. Anatomical measurements and field modeling values differed significantly between M1 and STG. For TMS motor effects, rMT was correlated with SCD, CT, and E values at M1 (p < 0.05). No correlations were found between these metrics for the STG and TMS non-motor effects (pain memory; all p-values > 0.05). Although anatomical measurements and field modeling are closely related to TMS motor effects, their relationship to non-motor effects – such as pain memory – appear to be much more tenuous and complex, highlighting the need for further advancement in our use of TMS and virtual lesion paradigms. [ABSTRACT FROM AUTHOR]

Introduction: Continuous theta-burst stimulation (cTBS) has been used as an effective tool in inducing inhibitory aftereffect within a short time periods in the motor cortex; this has been demonstrated in the language network to a limited degree with controversial effect. In this study, we aimed to delineate the oine effect of cTBS-induced changes to the left posterior inferior frontal gyrus (pIFG) in healthy subjects using functional magnetic resonance imaging (fMRI). Methods: Twenty healthy, normal subjects (mean age: 30.84 years) were recruited. They all were right-handed and had no contra-indications for fMRI or cTBS. They were randomly assigned into the treatment group or the sham control group. Results: ANOVA showed that cTBS had a significant main effect only when the sham treatment was subtracted from the real stimulation in left superior temporal, left inferior frontal gyrus, thalamus, and right insular cortex (uncorrected p < 0.002). The subjects' post-cTBS condition differed significantly from their pre-cTBS condition in the left pIFG (uncorrected p < 0.002). There were interactions in the pIFG, bilateral superior parietal lobules, left superior temporal, left supramarginal, and left cuneus areas. The application of cTBS induced increased BOLD signals in language-related networks by stimulating the left pIFG (BA 44). This implies that inhibiting the pIFG led to increased use of language network resources. Conclusion: This study demonstrated cTBS-induced changes in the language network caused by stimulation of the left pIFG. Based on these findings, future studies on the therapeutic effects of cTBS on the right Broca's homolog area are warranted. [ABSTRACT FROM AUTHOR]

Background: Previous reports suggested the potential benefit of chemesthesis in the form of carbonated water (CW) integrated within dysphagia rehabilitation protocols. Here, we examined the effects of CW within a repeated swallowing protocol following focal suppression to pharyngeal cortical representation as a prelude to its application in dysphagic patients. Methods: Fourteen healthy volunteers participated in a 3‐arm study. Each participant underwent baseline corticobulbar pharyngeal and thenar motor‐evoked potential (MEP) measurements with Transcranial Magnetic Stimulation (TMS). Subjects were then conditioned with 1Hz repetitive (r)TMS to induce focal unilateral suppression of the corticopharyngeal hotspot before randomization to each of three arms with 40 swallows of CW, non‐CW and saliva swallowing on separate days. Corticobulbar and thenar MEPs were collected for up to 1 h and analyzed using repeated measures (rm)ANOVA. Results: A 2‐way rmANOVA for Intervention x Time showed a significant effect of Intervention (F(1,13) = 7.519, p = 0.017) in both ipsi‐ and contra‐lesional corticopharyngeal projections. Carbonation showed superiority in facilitating change by increasing pharyngeal cortical MEPs compared to non‐CW (z = −3.05, p = 0.002) and saliva swallowing (z = −2.6, p = 0.008). No change in thenar representation (control) was observed nor in MEP latencies from both pharyngeal and thenar musculature. Conclusions: We conclude that interventional paradigms with CW have the capacity to reverse the effects of a focal suppression with 1Hz rTMS more strongly than non‐CW or saliva swallowing alone, producing site specific bi‐hemispheric changes in corticopharyngeal excitability. Our data suggest that carbonation produces the effects through a mainly cortical mechanism. [ABSTRACT FROM AUTHOR]

Background: The dorsal premotor cortex (PMd) is a key region in bimanual coordination. However, causal evidence linking PMd functionality during motor planning and execution to movement quality is lacking. Objective: We investigated how left (PMdL) and right PMd (PMdR) are causally involved in planning and executing bimanual movements, using short-train repetitive transcranial magnetic stimulation (rTMS). Additionally, we explored to what extent the observed rTMS-induced modulation of performance could be explained by rTMS-induced modulation of PMd-M1 interhemispheric interactions (IHI). Methods: Twenty healthy adults (mean age ± SD = 22.85 ± 3.73 years) participated in two sessions, in which either PMdL or PMdR was targeted with rTMS (10 Hz) in a pseudo-randomized design. PMd functionality was transiently modulated during the planning or execution of a complex bimanual task, whereby the participant was asked to track a moving dot by controlling two dials. The effect of rTMS on several performance measures was investigated. Concurrently, rTMS-induced modulation of PMd-M1 IHI was measured using a dual-coil paradigm, and associated with the rTMS-induced performance modulation. Results: rTMS over PMdL during planning increased bilateral hand movement speed (p = 0.03), thereby improving movement accuracy (p = 0.02). In contrast, rTMS over PMdR during both planning and execution induced deterioration of movement stability (p = 0.04). rTMS-induced modulation of PMd-M1 IHI during planning did not predict rTMS-induced performance modulation. Conclusion: The current findings support the growing evidence on PMdL dominance during motor planning, as PMdL was crucially involved in planning the speed of each hand, subserving bimanual coordination accuracy. Moreover, the current results suggest that PMdR fulfills a role in continuous adjustment processes of movement.

Repetitive TMS (rTMS) with a frequency of 5–10 Hz is widely used for language mapping. However, it may be accompanied by discomfort and is limited in the number and reliability of evoked language errors. We, here, systematically tested the influence of different stimulation frequencies (i.e., 10, 30, and 50 Hz) on tolerability, number, reliability, and cortical distribution of language errors aiming at improved language mapping. 15 right‐handed, healthy subjects (m = 8, median age: 29 yrs) were investigated in two sessions, separated by 2–5 days. In each session, 10, 30, and 50 Hz rTMS were applied over the left hemisphere in a randomized order during a picture naming task. Overall, 30 Hz rTMS evoked significantly more errors (20 ± 12%) compared to 50 Hz (12 ± 8%; p <.01), whereas error rates were comparable between 30/50 and 10 Hz (18 ± 11%). Across all conditions, a significantly higher error rate was found in Session 1 (19 ± 13%) compared to Session 2 (13 ± 7%, p <.05). The error rate was poorly reliable between sessions for 10 (intraclass correlation coefficient, ICC =.315) and 30 Hz (ICC =.427), whereas 50 Hz showed a moderate reliability (ICC =.597). Spatial reliability of language errors was low to moderate with a tendency toward increased reliability for higher frequencies, for example, within frontal regions. Compared to 10 Hz, both, 30 and 50 Hz were rated as less painful. Taken together, our data favor the use of rTMS‐protocols employing higher frequencies for evoking language errors reliably and with reduced discomfort, depending on the region of interest. [ABSTRACT FROM AUTHOR]

The dorsal premotor cortex (PMd) is a key region in bimanual coordination. However, causal evidence linking PMd functionality during motor planning and execution to movement quality is lacking. We investigated how left (PMd L) and right PMd (PMd R) are causally involved in planning and executing bimanual movements, using short-train repetitive transcranial magnetic stimulation (rTMS). Additionally, we explored to what extent the observed rTMS-induced modulation of performance could be explained by rTMS-induced modulation of PMd-M1 interhemispheric interactions (IHI). Twenty healthy adults (mean age ± SD = 22.85 ± 3.73 years) participated in two sessions, in which either PMd L or PMd R was targeted with rTMS (10 Hz) in a pseudo-randomized design. PMd functionality was transiently modulated during the planning or execution of a complex bimanual task, whereby the participant was asked to track a moving dot by controlling two dials. The effect of rTMS on several performance measures was investigated. Concurrently, rTMS-induced modulation of PMd-M1 IHI was measured using a dual-coil paradigm, and associated with the rTMS-induced performance modulation. rTMS over PMd L during planning increased bilateral hand movement speed (p = 0.03), thereby improving movement accuracy (p = 0.02). In contrast, rTMS over PMd R during both planning and execution induced deterioration of movement stability (p = 0.04). rTMS-induced modulation of PMd-M1 IHI during planning did not predict rTMS-induced performance modulation. The current findings support the growing evidence on PMd L dominance during motor planning, as PMd L was crucially involved in planning the speed of each hand, subserving bimanual coordination accuracy. Moreover, the current results suggest that PMd R fulfills a role in continuous adjustment processes of movement. • rTMS was used to determine causal associations between PMd and bimanual coordination. • PMd L encodes the required speed for each hand during motor planning. • PMd R fulfills a role in continuous adjustment of planned and ongoing movement. [ABSTRACT FROM AUTHOR]

Language is sustained by large-scale networks in the human brain. Stroke often severely affects function and network dynamics. However, the adaptive potential of the brain to compensate for lesions is poorly understood. A key question is whether upregulation of the right hemisphere is adaptive for language recovery. Targeting the potential for short-term reorganization in the lesioned brain, we applied 'virtual lesions' over left anterior or posterior inferior frontal gyrus (IFG) in post-stroke patients with left temporo-parietal lesions prior to functional neuroimaging. Perturbation of the posterior IFG selectively delayed phonological decisions and decreased phonological activity. The individual response delay was correlated with the upregulation of the lesion homologue, likely reflecting compensation. Moreover, stronger individual tract integrity of the right superior longitudinal fascicle was associated with lesser disruption. Our results provide evidence for functional and structural underpinnings of plasticity in the lesioned language network, and a compensatory role of the right hemisphere.

Grapevine rust Phakopsora euvitis is an important disease in tropical and subtropical grapevine-producing areas, and both American (Vitis labrusca) and European (Vitis vinifera) grapevine species are sensitive to rust. Grapevine rust can cause early plant defoliation, reducing photosynthesis and photoassimilate supply and storage. This study evaluated the photosynthetic damage induced by varying grapevine rust intensities in leaves of V. vinifera cv. Moscato Giallo and V. labrusca cv. Niagara Rosada. The disease effect in tissues adjacent to the lesion, called virtual lesion (β), was estimated for photosynthetic variables, considering measurements taken in both healthy and diseased tissues. The average lesion size was higher in V. vinifera (0.66 mm2) than in V. labrusca (0.24 mm2). A water-soaked halo around the lesion was observed only in V. vinifera. The β-values estimated for the photosynthetic rate were 4.99 for V. labrusca and 5.93 for V. vinifera, taking into account the water-soaked and sporulating areas. When considering only the sporulating area, the β-value increased to 11.49 in V. vinifera. Grapevine rust had similar negative effects on photosynthesis in both species with increasing disease severity. While stomatal conductance was slightly affected, the pathogen caused significant reductions in the effective quantum efficiency of photosystem II and the instantaneous carboxylation efficiency of V. vinifera and V. labrusca with increasing disease severity. The β-value of instantaneous carboxylation efficiency was higher in V. vinifera (9.26) than in V. labrusca (4.76). In conclusion, Phakopsora euvitis dramatically affects photosynthesis in both V. vinifera cv. Moscato Giallo and V. labrusca cv. Niagara Rosada, causing large virtual lesions and substantial damage to the photochemical and biochemical reactions associated with CO2 assimilation. [ABSTRACT FROM AUTHOR]

While the involvement of the left inferior frontal gyrus (IFG) in language production is undisputed, the role of specific subregions at different representational levels remains unclear. Some studies suggest a division of anterior and posterior regions for semantic and phonological processing, respectively. Crucially, evidence thus far only comes from correlative neuroimaging studies, but the functional relevance of the involvement of these subregions during a given task remains elusive. We applied repetitive transcranial magnetic stimulation (rTMS) over anterior and posterior IFG (aIFG/pIFG), and vertex as a control site, while participants performed a category member and a rhyme generation task. We found a functional‐anatomical double dissociation between tasks and subregions. Naming latencies were significantly delayed in the semantic task when rTMS was applied to aIFG (relative to pIFG and vertex). In contrast, we observed a facilitation of naming latencies in the phonological task when rTMS was applied to pIFG (relative to aIFG and vertex). The results provide first causal evidence for the notion that anterior portions of the IFG are selectively recruited for semantic processing while posterior regions are functionally specific for phonological processing during word production. These findings shed light on the functional parcellation of the left IFG in language production. [ABSTRACT FROM AUTHOR]

Computational modeling of the spontaneous dynamics over the whole brain provides critical insight into the spatiotemporal organization of brain dynamics at multiple resolutions and their alteration to changes in brain structure (e.g. in diseased states, aging, across individuals). Recent experimental evidence further suggests that the adverse effect of lesions is visible on spontaneous dynamics characterized by changes in resting state functional connectivity and its graph theoretical properties (e.g. modularity). These changes originate from altered neural dynamics in individual brain areas that are otherwise poised towards a homeostatic equilibrium to maintain a stable excitatory and inhibitory activity. In this work, we employ a homeostatic inhibitory mechanism, balancing excitation and inhibition in the local brain areas of the entire cortex under neurological impairments like lesions to understand global functional recovery (across brain networks and individuals). Previous computational and empirical studies have demonstrated that the resting state functional connectivity varies primarily due to the location and specific topological characteristics of the lesion. We show that local homeostatic balance provides a functional recovery by re-establishing excitation–inhibition balance in all areas that are affected by lesion. We systematically compare the extent of recovery in the primary hub areas (e.g. default mode network (DMN), medial temporal lobe, medial prefrontal cortex) as well as other sensory areas like primary motor area, supplementary motor area, fronto-parietal and temporo-parietal networks. Our findings suggest that stability and richness similar to the normal brain dynamics at rest are achievable by re-establishment of balance. [ABSTRACT FROM AUTHOR]

With the advent of non-invasive brain stimulation (NIBS), a new decade in the study of language has started. NIBS allows for testing the functional relevance of language-related brain activation and enables the researcher to investigate how neural activation changes in response to focal perturbations. This review focuses on the application of NIBS in the healthy brain. First, some basic mechanisms will be introduced and the prerequisites for carrying out NIBS studies of language are addressed. The next section outlines how NIBS can be used to characterize the contribution of the stimulated area to a task. In this context, novel approaches such as multifocal transcranial magnetic stimulation and the condition-and-perturb approach are discussed. The third part addresses the combination of NIBS and neuroimaging in the study of plasticity. These approaches are particularly suited to investigate short-term reorganization in the healthy brain and may inform models of language recovery in post-stroke aphasia. [ABSTRACT FROM AUTHOR]

Background The rapid adaptation of actions to changes in the environment is crucial for survival. We previously demonstrated a joint contribution of left dorsal premotor cortex (PMd) and left supramarginal gyrus (SMG) to action reprogramming. However, we did not probe the contribution of PMd to the speed and accuracy of action reprogramming and how the functional relevance of PMd changes in the presence of a dysfunctional SMG. Objective This study further dissociated the unique contribution of left PMd and SMG to action reprogramming. Specifically, we tested whether the critical contribution of PMd during action reprogramming depends on the functional integrity of SMG. Methods Adopting a condition-and-perturb repetitive transcranial magnetic stimulation (rTMS) approach, we first transiently conditioned left SMG with 1 Hz offline rTMS and then perturbed PMd activity with online rTMS whilst human subjects performed a spatially-precued reaction time task. Results Relative to sham rTMS, effective online perturbation of left PMd significantly impaired both the response speed and accuracy in trials that were invalidly pre-cued and required the subject to reprogram the prepared action. Moreover, the disruptive effect of rTMS over left PMd on response speed became stronger after SMG had been conditioned with offline rTMS. Conclusions These results corroborate the notion that left PMd and SMG jointly contribute to rapid action reprogramming. Moreover, the strong virtual lesion effect observed with rTMS over PMd suggest that this area represents a key node for both the suppression of activation based on the precue and response activation based on the response target. [ABSTRACT FROM AUTHOR]

The role of the right hemisphere in aphasia recovery after left hemisphere damage remains unclear. Increased activation of the right hemisphere has been observed after left hemisphere damage. This may simply reflect a release from transcallosal inhibition that does not contribute to language functions. Alternatively, the right hemisphere may actively contribute to language functions by supporting disrupted processing in the left hemisphere via interhemispheric connections. To test this hypothesis, we applied off-line continuous theta burst stimulation (cTBS) over the left inferior frontal gyrus (IFG) in healthy volunteers, then used functional MRI to investigate acute changes in effective connectivity between the left and right hemispheres during repetition of auditory and visual words and pseudowords. In separate sessions, we applied cTBS over the left anterior IFG (aIFG) or posterior IFG (pIFG) to test the anatomic specificity of the effects of cTBS on speech processing. Compared with cTBS over the aIFG, cTBS over the pIFG suppressed activity in the left pIFG and increased activity in the right pIFG during pseudoword vs. word repetition in both modalities. This effect was associated with a stronger facilitatory drive from the right pIFG to the left pIFG during pseudoword repetition. Critically, response became faster as the influence of the right pIFG on left pIFG increased, indicating that homologous areas in the right hemisphere actively contribute to language function after a focal left hemisphere lesion. Our findings lend further support to the notion that increased activation of homologous right hemisphere areas supports aphasia recovery after left hemisphere damage. [ABSTRACT FROM AUTHOR]

Introduction: Continuous theta-burst stimulation (cTBS) has been used as an effective tool in inducing inhibitory aftereffect within a short time periods in the motor cortex; this has been demonstrated in the language network to a limited degree with controversial effect. In this study, we aimed to delineate the offline effect of cTBS-induced changes to the left posterior inferior frontal gyrus (pIFG) in healthy subjects using functional magnetic resonance imaging (fMRI)., Methods: Twenty healthy, normal subjects (mean age: 30.84 years) were recruited. They all were right-handed and had no contra-indications for fMRI or cTBS. They were randomly assigned into the treatment group or the sham control group., Results: ANOVA showed that cTBS had a significant main effect only when the sham treatment was subtracted from the real stimulation in left superior temporal, left inferior frontal gyrus, thalamus, and right insular cortex (uncorrected p < 0.002). The subjects' post-cTBS condition differed significantly from their pre-cTBS condition in the left pIFG (uncorrected p < 0.002). There were interactions in the pIFG, bilateral superior parietal lobules, left superior temporal, left supramarginal, and left cuneus areas. The application of cTBS induced increased BOLD signals in language-related networks by stimulating the left pIFG (BA 44). This implies that inhibiting the pIFG led to increased use of language network resources., Conclusion: This study demonstrated cTBS-induced changes in the language network caused by stimulation of the left pIFG. Based on these findings, future studies on the therapeutic effects of cTBS on the right Broca's homolog area are warranted., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 An, Bashir, Cha, Lee, Ohn, Jung and Yoo.)

Abstract: Theta burst stimulation (TBS) is a novel variant of repetitive transcranial magnetic stimulation (rTMS), which induces changes in neuronal excitability persisting up to 1h. When elicited in the primary motor cortex, such physiological modulations might also have an impact on motor behavior. In the present study, we applied TBS in combination with pseudo continuous arterial spin labeling (pCASL) in order to address the question of whether TBS effects are measurable by means of changes in physiological parameters such as cerebral blood flow (CBF) and if TBS-induced plasticity can modify motor behavior. Twelve right-handed healthy subjects were stimulated using an inhibitory TBS protocol at subthreshold stimulation intensity targeted over the right motor cortex. The control condition consisted of within-subject Sham treatment in a crossover design. PCASL was performed before (pre TBS/pre Sham) and immediately after treatment (post TBS/post Sham). During the pCASL runs, the subjects performed a sequential fingertapping task with the left hand at individual maximum speed. There was a significant increase of CBF in the primary motor cortex after TBS, but not after Sham. It is assumed that inhibitory TBS induced a “local virtual lesion” which leads to the mobilization of more neuronal resources. There was no TBS-specific modulation in motor behavior, which might indicate that acute changes in brain plasticity caused by TBS are immediately compensated. This compensatory reaction seems to be observable at the metabolic, but not at the behavioral level. [Copyright &y& Elsevier]

In the motor system, transcranial magnetic stimulation (TMS) has proved an invaluable tool to study the organisation and interaction of the cortical motor areas. In this review I describe some of the ways in which TMS has been used to map out the major topographical features of the motor output and to test how these change in response motor learning or after peripheral (e.g. amputation) or central (e.g. stroke) injury. More recent work has shown that longer periods of repeated TMS involving several hundred to a thousand pulses can lead to lasting changes in motor cortex excitability that are thought to involve changes in the efficacy of intracortical synapses equivalent to LTP and LTP in slice preparations. These are accompanied by changes in the rate of motor learning and are presently being trialled as potential treatments to speed recovery from stroke. [ABSTRACT FROM AUTHOR]

A commonly held view is that, when delivered during the performance of a task, repetitive TMS (rTMS) influences behavior by producing transient “virtual lesions” in targeted tissue. However, findings of rTMS-related improvements in performance are difficult to reconcile with this assumption. With regard to the mechanism whereby rTMS influences concurrent task performance, a combined rTMS/EEG study conducted in our lab has revealed a complex set of relations between rTMS, EEG activity, and behavioral performance, with the effects of rTMS on power in the alpha band and on alpha:gamma phase synchrony each predicting its effect on behavior. These findings suggest that rTMS influences performance by biasing endogenous task-related oscillatory dynamics, rather than creating a “virtual lesion”. To further differentiate these two alternatives, in the present study we compared the effects of 10 Hz rTMS on neural activity with the results of an experiment in which rTMS was replaced with 10 Hz luminance flicker. We reasoned that 10 Hz flicker would produce widespread entrainment of neural activity to the flicker frequency, and comparison of these EEG results with those from the rTMS study would shed light on whether the latter also reflected entrainment to an exogenous stimulus. Results revealed pronounced evidence for “entrainment noise” produced by 10 Hz flicker—increased oscillatory power and inter-trial coherence (ITC) at the driving frequency, and increased alpha:gamma phase synchronization—that were nonetheless largely uncorrelated with behavior. This contrasts markedly with 10-Hz rTMS, for which the only evidence for stimulation-induced noise, elevated ITC at 30 Hz, differed qualitatively from the flicker results. Simultaneous recording of the EEG thus offers an important means of directly testing assumptions about how rTMS exerts its effects on behavior. [ABSTRACT FROM AUTHOR]

Transcranial magnetic stimulation (TMS) produces a direct causal effect on brain activity that can now be studied by new approaches that simultaneously combine TMS with neuroimaging methods, such as functional magnetic resonance imaging (fMRI). In this review we highlight recent concurrent TMS–fMRI studies that illustrate how this novel combined technique may provide unique insights into causal interactions among brain regions in humans. We show how fMRI can detect the spatial topography of local and remote TMS effects and how these may vary with psychological factors such as task-state. Concurrent TMS–fMRI may furthermore reveal how the brain adapts to so-called virtual lesions induced by TMS, and the distributed activity changes that may underlie the behavioural consequences often observed during cortical stimulation with TMS. We argue that combining TMS with neuroimaging techniques allows a further step in understanding the physiological underpinnings of TMS, as well as the neural correlated of TMS-evoked consequences on perception and behaviour. This can provide powerful new insights about causal interactions among brain regions in both health and disease that may ultimately lead to developing more efficient protocols for basic research and therapeutic TMS applications. [ABSTRACT FROM AUTHOR]

The article discusses the study which estimates the impact of strawberry leaf scorch on photosynthesis and physiological-lesion size in Canada. The impact of strawberry leaf scorch on net carbon dioxide assimilation and transpiration rates was determined for both greenhouse-grown and field-grown plants. Photosynthesis measurements on individual leaflets of greenhouse-grown plants were taken in a biotron under saturating light conditions.

• Single-pulse TMS over the STG was used to disrupt pain memory encoding. • Real, but not sham TMS, prevented exaggerated pain unpleasantness memories. • No effects were noted for pain intensity and non-painful memories. • Neurostimulation can affect pain memories, suggesting new avenues for chronic pain. Past studies have shown that pain memories are often inaccurate, a phenomenon known as mnemonic pain bias. Pain memories are thought to play an important role on how future pain is felt. Recent evidence from our laboratory suggests that individuals who exaggerate past pain display increased superior temporal gyrus (STG) activity during the encoding of experimental painful stimulations, suggesting that this brain structure plays an important role in pain memories. /hypothesis. To determine whether a virtual lesion paradigm, targeting the STG during pain encoding, can affect long-lasting pain memories. We hypothesized that interfering with the activity of the STG would attenuate mnemonic bias. Randomized double-blind study with two parallel groups. Participants received either sham (n = 21) or real (n = 21) transcranial magnetic stimulation (TMS - virtual lesion paradigm) over the STG during pain encoding (milliseconds after the administration of a painful stimuli). Pain intensity and unpleasantness were evaluated using a visual analog scale (VAS; 0 to 10) immediately after the painful event, and at recall, 2 months later. The mnemonic pain bias (calculated by subtracting the pain scores obtained at recall from the pain score obtained during encoding) was compared between the two groups for both pain intensity and unpleasantness. Participants in both groups did not differ in terms of age and gender (real TMS = 27 years ± 9, 43% female; sham TMS = 25 years ± 4, 49% female; p > 0.64). The mnemonic bias related to pain intensity was similar in both groups (p = 0.83). However, the mnemonic bias related to pain unpleasantness was lower in the real TMS group (p = 0.04). Our results provide the first evidence that the STG, is causally involved in the formation of biased memories of pain unpleasantness. [ABSTRACT FROM AUTHOR]

Objectives: The significance of pre-motor (PMC) corticospinal projections in a frontoparietal motor network remains elusive. Temporal activation patterns can provide valuable information about a region's engagement in a hierarchical network. Navigated transcranial magnetic stimulation (nTMS)-induced virtual lesions provide an excellent method to study cortical physiology by disrupting ongoing activity at high temporal resolution and anatomical precision. We use nTMS-induced virtual lesions applied during an established behavioral task demanding pre-motor activation to clarify the temporal activation pattern of pre-motor corticospinal projections. Materials and Methods: Ten healthy volunteers participated in the experiment (4 female, mean age 24 ± 2 years, 1 left-handed). NTMS was used to map Brodmann areae 4 and 6 for primary motor (M1) and PMC corticospinal projections. We then determined the stimulator output intensity required to elicit a 1 mV motor evoked potential (1 mV-MT) through M1 nTMS. TMS pulse were randomly delivered at distinct time intervals (40, 60, 80, 100, 120, and 140 ms) at 1 mV-MT intensity to M1, PMC and the DLPFC (dorsolateral pre-frontal cortex; control condition) before participants had to perform major changes of their trajectory of movement during a tracing task. Each participant performed six trials (20 runs per trial). Task performance and contribution of regions under investigation was quantified through calculating the tracing error induced by the stimulation. Results: A pre-motor stimulation hotspot could be identified in all participants (16.3 ± 1.7 mm medial, 18.6 ± 1.4 mm anterior to the M1 hotspot). NTMS over studied regions significantly affected task performance at discrete time intervals ( F (10, 80) = 3.25, p = 0.001). NTMS applied over PMC 120 and 140 ms before changes in movement trajectory impaired task performance significantly more than when applied over M1 ( p = 0.021 and p = 0.003) or DLPFC ( p = 0.017 and p < 0.001). Stimulation intensity did not account for error size ( β = -0.0074, p = 1). Conclusions: We provide novel evidence that the role of pre-motor corticospinal projections extends beyond that of simple corticospinal motor output. Their activation is crucial for task performance early in the stage of motor preparation suggesting a significant role in shaping voluntary movement. Temporal patterns of human pre-motor activation are similar to that observed in intracortical electrophysiological studies in primates., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Fleischmann, Triller, Brandt and Schmidt.)

Language is sustained by large-scale networks in the human brain. Stroke often severely affects function and network dynamics. However, the adaptive potential of the brain to compensate for lesions is poorly understood. A key question is whether upregulation of the right hemisphere is adaptive for language recovery. Targeting the potential for short-term reorganization in the lesioned brain, we applied 'virtual lesions' over left anterior or posterior inferior frontal gyrus (IFG) in post-stroke patients with left temporo-parietal lesions prior to functional neuroimaging. Perturbation of the posterior IFG selectively delayed phonological decisions and decreased phonological activity. The individual response delay was correlated with the upregulation of the lesion homologue, likely reflecting compensation. Moreover, stronger individual tract integrity of the right superior longitudinal fascicle was associated with lesser disruption. Our results provide evidence for functional and structural underpinnings of plasticity in the lesioned language network, and a compensatory role of the right hemisphere., Competing Interests: GH, AS, LC, MW, JK, KW, HO, DS No competing interests declared, (© 2020, Hartwigsen et al.)

Sentence comprehension requires the rapid analysis of semantic and syntactic information. These processes are supported by a left hemispheric dominant fronto-temporal network, including left posterior inferior frontal gyrus (pIFG) and posterior superior temporal gyrus/sulcus (pSTG/STS). Previous electroencephalography (EEG) studies have associated semantic expectancy within a sentence with a modulation of the N400 and syntactic gender violations with increases in the LAN and P600. Here, we combined focal perturbations of neural activity by means of short bursts of transcranial magnetic stimulation (TMS) with simultaneous EEG recordings to probe the functional relevance of pIFG and pSTG/STS for sentence comprehension. We applied 10 Hz TMS bursts of three pulses at verb onset during auditory presentation of short sentences. Verb-based semantic expectancy and article-based syntactic gender requirement were manipulated for the sentence final noun. We did not find any TMS effect at the noun. However, TMS had a short-lasting impact at the mid-sentence verb that differed for the two stimulation sites. Specifically, TMS over pIFG elicited a frontal positivity in the first 200 msec post verb onset whereas TMS over pSTG/STS was limited to a parietal negativity at 200-400 msec post verb onset. This indicates that during verb processing in sentential context, frontal brain areas play an earlier role than temporal areas in predicting the upcoming noun. The short-living perturbation effects at the mid-sentence verb suggest a high degree of online compensation within the language system since the sentence final noun processing was unaffected., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Transcranial magnetic stimulation (TMS) is a safe and noninvasive means of electrically stimulating the brain by electromagnetic induction. TMS is capable of probing intracortical circuits and modulating cortical activity in humans; as such it has been instrumental to studying the neurophysiology and functional neuroanatomy of the frontal lobes. For example, using TMS to induce "virtual lesions"-transient disruption of function in the targeted brain region-has yielded important insights into the functional organization of the prefrontal cortex (PFC) with respect to working memory, language, and other core cognitive functions. Whereas neuroimaging is typically limited to observing correlations between brain function and behavior, TMS, by interacting with neural circuits, can lead to causal inferences that bridge human, nonhuman primate, and other model system studies. Applied repetitively in trains of stimuli, TMS is also capable of normalizing aberrant patterns of cortical activity in the treatment of neurologic and psychiatric disorders. The earliest and most well-established clinical use of repetitive TMS is in the treatment of medication-resistant depression with high-frequency stimulation of the left dorsolateral PFC. Research efforts to identify other promising clinical applications-such as for stroke and Alzheimer's disease-are rapidly expanding; however, the majority of these indications have yet to have devices cleared by the FDA for on-label use., (Copyright © 2019 Elsevier B.V. All rights reserved.)