Cortical Correlates of Visuospatial Switching Processes Between Egocentric and Allocentric Frames of Reference: A fNIRS Study.

Human beings represent spatial information according to egocentric (body-to-object) and allocentric (object-to-object) frames of reference. In everyday life, we constantly switch from one frame of reference to another in order to react effectively to the specific needs of the environment and task demands. However, to the best of our knowledge, no study to date has investigated the cortical activity of switching and non-switching processes between egocentric and allocentric spatial encodings. To this aim, a custom-designed visuo-spatial memory task was administered and the cortical activities underlying switching vs non-switching spatial processes were investigated. Changes in concentrations of oxygenated and deoxygenated haemoglobin were measured using functional near-infrared spectroscopy (fNIRS). Participants were asked to memorize triads of geometric objects and then make two consecutive judgments about the same triad. In the non-switching condition, both spatial judgments considered the same frame of reference: only egocentric or only allocentric. In the switching condition, if the first judgment was egocentric, the second one was allocentric (or vice versa). The results showed a generalized activation of the frontal regions during the switching compared to the non-switching condition. Additionally, increased cortical activity was found in the temporo-parietal junction during the switching condition compared to the non-switching condition. Overall, these results illustrate the cortical activity underlying the processing of switching between body position and environmental stimuli, showing an important role of the temporo-parietal junction and frontal regions in the preparation and switching between egocentric and allocentric reference frames.

Between alpha and gamma oscillations: Neural signatures of linguistic predictions and listener's attention to speaker's communication intention.

When listeners hear a message produced by their interlocutor, they can predict upcoming words thanks to the sentential context and their attention can be focused on the speaker's communication intention. In two electroencephalographical (EEG) studies, we investigated the oscillatory correlates of prediction in spoken-language comprehension and how they are modulated by the listener's attention. Sentential contexts which were strongly predictive of a particular word were ended by a possessive adjective either matching the gender of the predicted word or not. Alpha, beta and gamma oscillations were studied as they were considered to play a crucial role in the predictive process. While evidence of word prediction was related to alpha fluctuations when listeners focused their attention on sentence meaning, changes in high-gamma oscillations were triggered by word prediction when listeners focused their attention on the speaker's communication intention. Independently of the endogenous attention to a level of linguistic information, the oscillatory correlates of word predictions in language comprehension were sensitive to the prosodic emphasis produced by the speaker at a late stage. These findings thus bear major implications for understanding the neural mechanisms that support predictive processing in spoken-language comprehension.

Spatial accuracy of the stereotactic Leksell®Vantage™ head frame in comparison with the standard stereotactic Leksell®G Frame for Gamma-Knife.

Purpose. Since January 2021, the Leksell®Vantage head frame (V-frame) is used for Gamma Knife®treatments in addition to the historical Leksell®G-Frame known as the reference. The aim of this study was to compare the spatial accuracy of treatments with these two frames.Methods. Firstly, the constancy of the geometric accuracy of the system according to the Elekta quality assurance process was carried out during sixteen months with V and G-frames' adaptors. Then, End-to-end test was carried out with both V and G-frame using an anthropomorphic phantom and Gafchromic®films. The overall precision of the radiation center was calculated as the displacement vector for a 4 mm collimator shot. Additionally, the Cone Beam Computed Tomography (CBCT) positioning system was used to assess the precision of the Leksell coordinates system defined by V-frames on 64 patients in comparison to G-frames for 46 patients. To ensure that patient's head movement was not possible during treatment with the V-frame, the High Definition Motion Management (HDMM) system was used and a final CBCT was performed at the end of the irradiation.Results. The QA constructor's tests done with the G-frame and V-frame adaptor gave similar results over sixteen months. End-to-end tests demonstrated that the mean positioning accuracy was 0.54 mm (SD of 0.14 mm) and 0.70 mm (SD of 0.14 mm) with V-frame and G-frame respectively. The displacement vector given by CBCT ranged from 0.02 to 1.05 mm with a mean value of 0.38 mm (SD of 0.18 mm) for the 64 V-framed patients and from 0 to 0.92 mm with a mean value of 0.31 mm (SD of 0.18 mm) for the 46 G-framed patients. The mean translation movement between the beginning and the end of the 64 treatments with V-frame was 0.08 mm (SD of 0.04 mm, maximum value of 0.19 mm).Conclusion. We estimated that V-frames are as precise as G-frames with a targeting accuracy of less than 1 mm.

Effects of motor pacing on frontal-hemodynamic responses during continuous upper-limb and whole-body movements.

Advances in timing research advocate for the existence of two timing mechanisms (automatic vs. controlled) that are related to the level of cognitive control intervening for motor behavior regulation. In the present study, we used the functional near-infrared spectroscopy (fNIRS) cutting-edge technique to examine the hypothesis that prefrontal inhibitory control is needed to perform slow motor activities. Participants were asked to perform a sensorimotor-synchronization task at various paces (i.e., slow, close-to-spontaneous, fast). We contrasted upper-limb circle drawing to a more naturalistic behavior that required whole-body movements (i.e., steady-state walking). Results indicated that whole-body movements led to greater brain oxygenation over the motor regions when compared with upper-limb activities. The effect of motor pace was found in the walking task only, with more bilateral orbitofrontal and left dorsolateral activation at slow versus fast pace. Exploratory analyses revealed a positive correlation between the activation of the orbitofrontal and motor areas for the close-to-spontaneous pace in both tasks. Overall, results support the key role of prefrontal cognitive control in the production of slow whole-body movements. In addition, our findings confirm that upper-limb (laboratory-based) tasks might not be representative of those engaged during everyday-life motor behaviors. The fNIRS technique may be a valuable tool to decipher the neurocognitive mechanisms underlying naturalistic, adaptive motor behaviors.

Brain responses to lexical attestedness and phonological well-formedness as revealed by fast periodic visual stimulation.

We investigated the mechanisms underlying the online-processing of phonological constraints using oddball fast-periodic visual stimulation coupled with EEG. We focused on the Sonority Sequencing Principle and examined whether steady-state visual evoked potentials (SSVEPs) are sensitive to the sonority constraint on syllable onsets. Native French speakers were presented with streams of CCVC non-words (C: consonant, V: vowel) at a fixed 6-Hz base rate. We manipulated the phonological well-formedness and lexical attestedness of CC onsets in two conditions. SSVPs were observed at the base rate associated to visual stimuli. As expected, they did not differ between conditions. Oddball SSVEPs were observed at 1.2 Hz (and its harmonics) and differed in the two conditions. These results showed that SSVEPs are sensitive to sublexical features. They also suggest that the processing of phonological constraints rely on mechanisms which could be dissociated from those underlying the processing of statistical properties of the lexicon.

Oscillatory correlates of linguistic prediction and modality effects during listening to auditory-only and audiovisual sentences.

In natural listening situations, understanding spoken sentences requires interactions between several multisensory to linguistic levels of information. In two electroencephalographical studies, we examined the neuronal oscillations of linguistic prediction produced by unimodal and bimodal sentence listening to observe how these brain correlates were affected by the sensory streams delivering linguistic information. Sentence contexts which were strongly predictive of a particular word were ended by a possessive adjective matching or not the gender of the predicted word. Alpha, beta and gamma oscillations were investigated as they were considered to play a crucial role in the predictive process. During the audiovisual or auditory-only listening to sentences, no evidence of word prediction was observed. In contrast, in a more challenging listening situation during which bimodal audiovisual streams switched to unimodal auditory stream, gamma power was sensitive to word prediction based on prior sentence context. Results suggest that prediction spreading from higher sentence levels to lower word levels is optional during unimodal and bimodal sentence listening and is observed when the listening situation is more challenging. Alpha and beta oscillations were found to decrease when semantically constraining sentences were delivered in the audiovisual modality in comparison with the auditory-only modality. Altogether, our findings bear major implications for our understanding of the neural mechanisms that support predictive processing in multimodal language comprehension.

Mask-Based versus Frame-Based Gamma Knife ICON Radiosurgery in Brain Metastases: A Prospective Randomized Trial.

BACKGROUND: Radiosurgery is performed with a diversity of instruments relying usually either on a stereotactic frame or a mask for patient head fixation. Comfort and safety efficacy of the 2 systems have never been rigorously evaluated and compared. MATERIAL AND METHOD: Between February 2016 and January 2017, 58 patients presenting with nonsmall cell lung cancer brain metastases have been treated by Gamma Knife radiosurgery (GKS) with random use of a frame or a mask for fixation were included patients older than 18, with <5 brain metastases (at the exclusion of brainstem and optic pathway's locations) and no earlier history of radiotherapy. The primary outcome measure was the pain scale assessment (PSA) at the beginning of the GKS procedure. RESULTS: The PSA at the beginning of the GKS procedure was not different between the 2 groups. The PSA at the day before GKS, before magnetic resonance imaging, just after frame application, and the day after radiosurgery (departure) has shown no difference between the 2 groups. At the end of the radiosurgery itself (just after frame or mask removal) and 1 h after, the mean pain scale was higher in patients treated with the frame (p < 0.05 and p < 0.001, respectively) but 2 patients were not able to tolerate the mask discomfort and had to be treated with frame. Tumor control and morbidity probability were demonstrated to be no difference between the 2 groups in this population of patients with BM not in highly functional area. The median of the extra dose to the body due to the cone-beam computed tomography was 7.5 mGy with a maximum of 35 mGy in patients treated with a mask fixation (null in the others treated with frame). Mask fixation was associated to longer treatment time although the beam on time was not different between the 2 groups. CONCLUSION: In selected patients, with brain oligo-metastases out of critical location, single-dose mask-based GKS can be done with a comfort and a safety efficacy comparable to frame-based GKS. There seems to be no clear patient data that confirm the value of the mask system with regards to comfort.

Toward a comparison and an optimization of CT protocols using new metrics of dose and image quality part I: prediction of human observers using a model observer for detection and discrimination tasks in low-dose CT images in various scanning conditions.

In the context of reducing the patient dose coming from CT scanner examinations without penalizing the diagnosis, the assessment of both patient dose and image quality (IQ) with relevant metrics is crucial. The present study represents the first stage in a larger work, aiming to compare and optimize CT protocols using dose and IQ new metrics. We proposed here to evaluate the capacity of the Non-PreWhitening matched filter with an eye (NPWE) model observer to be a robust and accurate estimation of IQ. We focused our work on two types of clinical tasks: a low contrast detection task and a discrimination task. We designed a torso-shaped phantom, including Plastic Water®slabs with cylindrical inserts of different diameters, sections and compositions. We led a human observer study with 13 human observers on images acquired in multiple irradiation and reconstruction scanning conditions (voltage, pitch, slice thickness, noise level of the reconstruction algorithm, energy level in dual-energy mode and dose), to evaluate the behavior of the model observer compared to the human responses faced to changing conditions. The model observer presented the same trends as the human observers with generally better results. We rescaled the NPWE model on the human responses by scanning conditions (kVp, pitch, slice thickness) to obtain the best agreement between both observer types, estimated using the Bland-Altman method. The impact of some scanning parameters was estimated using the correct answer rate given by the rescaled NPWE model, for both tasks and each insert size. In particular, the comparison between the dual-energy mode at 74 keV and the single-energy mode at 120 kVp showed that, if the 120 kVp voltage provided better results for the smallest insert at the lower doses for both tasks, their responses were equivalent in many cases.

Electrophysiological Mapping During Brain Tumor Surgery: Recording Cortical Potentials Evoked Locally, Subcortically and Remotely by Electrical Stimulation to Assess the Brain Connectivity On-line.

Direct electrical stimulation (DES) is used to perform functional brain mapping during awake surgery and in epileptic patients. DES may be coupled with the measurement of Evoked Potentials (EP) to study the conductive and integrative properties of activated neural ensembles and probe the spatiotemporal dynamics of short- and long-range networks. However, its electrophysiological effects remain by far unknown. We recorded ECoG signals on two patients undergoing awake brain surgery and measured EP on functional sites after cortical stimulations and were the firsts to record three different types of EP on the same patients. Using low-intensity (1-3 mA) to evoke electrogenesis we observed that: (i) "true" remote EPs are attenuated in amplitude and delayed in time due to the divergence of white matter pathways; (ii) "false" remote EPs are attenuated but not delayed: as they originate from the same electrical source; (iii) Singular but reproducible positive components in the EP can be generated when the DES is applied in the temporal lobe or the premotor cortex; and (iv) rare EP can be triggered when the DES is applied subcortically: these can be either negative, or surprisingly, positive. We proposed different activation and electrophysiological propagation mechanisms following DES, based on the nature of activated neural elements and discussed important methodological pitfalls when measuring EP in the brain. Altogether, these results pave the way to map the connectivity in real-time between the DES and the recording sites; to characterize the local electrophysiological states and to link electrophysiology and function. In the future, and in practice, this technique could be used to perform electrophysiological mapping in order to link (non)-functional to electrophysiological responses with DES and could be used to guide the surgical act itself.

Effects of Motor Tempo on Frontal Brain Activity: An fNIRS Study.

People are able to modify the spontaneous pace of their actions to interact with their environment and others. This ability is underpinned by high-level cognitive functions but little is known in regard to the brain areas that underlie such temporal control. A salient practical issue is that current neuroimaging techniques (e.g., EEG, fMRI) are extremely sensitive to movement, which renders challenging any investigation of brain activity in the realm of whole-body motor paradigms. Within the last decade, the noninvasive imaging method of functional near-infrared spectroscopy (fNIRS) has become the reference tool for experimental motor paradigms due to its tolerance to motion artefacts. In the present study, we used a continuous-wave fNIRS system to record the prefrontal and motor hemodynamic responses of 16 participants, while they performed a spatial-tapping task varying in motor complexity and externally-paced tempi (i.e., 300 ms, 500 ms, 1200 ms). To discriminate between physiological noise and cerebral meaningful signals, the physiological data (i.e., heart and respiratory rates) were recorded so that frequency bands of such signals could be regressed from the fNIRS data. Particular attention was taken to control the precise position of the optodes in reference to the cranio-cerebral correlates of the NIR channels throughout the experimental session. Results indicated that fast pacing relied on greater activity of the motor areas whereas moving at close-to-spontaneous pace placed a heavier load on posterior prefrontal processes. These results provide new insight concerning the role of frontal cognitive control in modulating the pacing of voluntary motor behaviors.

Network-level causal analysis of set-shifting during trail making test part B: A multimodal analysis of a glioma surgery case.

The trail making test part B (TMT-B) is one of the most widely used task for the assessment of set-shifting ability in patients. However, the set of brain regions impacting TMT-B performance when lesioned is still poorly known. In this case report, we provide a multimodal analysis of a patient operated on while awake for a diffuse low-grade glioma located in the right supramarginal gyrus. TMT-B performance was probed intraoperatively. Direct electrical stimulation of the white matter in the depth of the resection generated shifting errors. Using the recent methodology of axono-cortical-evoked potentials (ACEP), we demonstrated that the eloquent fibers were connected to the posterior end of the middle temporal gyrus (MTG). This was further confirmed by a tractography analysis of the postoperative diffusion MRI. Finally, the functional connectivity maps of this MTG seed were assessed in both pre- and post-operative resting state MRI. These maps matched with the Control network B (13th) and Default B (17th) from the 17-networks parcellation of (Yeo et al., 2011). Last but not least, we showed that the dorsal attention B (6th), the control A & B networks (12th and 13th) and the default A (16th) have been preserved here but disconnected after a more extensive resection in a previous glioma case within the same area, and in whom TMT-B was definitively impaired. Taken together, these data support the need of a network-level approach to identify the neural basis of the TMT-B and point to the Control network B as playing an important role in set-shifting.

Attenuation and Delay of Remote Potentials Evoked by Direct Electrical Stimulation During Brain Surgery.

Direct electrical stimulation (DES) is used to perform functional brain mapping during awake surgery but its electrophysiological effects remain by far unknown. DES may be coupled with the measurement of evoked potentials (EPs) to study the conductive and integrative properties of activated neural ensembles and probe the spatiotemporal dynamics of short- and long-range networks. We recorded ECoG signals on two patients undergoing awake brain surgery and measured EPs on functional sites after cortical stimulations, using combinations of stimulation parameters. EPs were similar in shape but delayed in time and attenuated in amplitude when elicited from a different gyrus or remotely from the recording site. We were able to trigger remote EPs using low stimulation intensities. We propose different activation and electrophysiological propagation mechanisms following DES based on activated neural elements.

Normalization of aberrant pretherapeutic dynamic functional connectivity of extrastriate visual system in patients who underwent thalamotomy with stereotactic radiosurgery for essential tremor: a resting-state functional MRI study.

OBJECTIVE: The tremor circuitry has commonly been hypothesized to be driven by one or multiple pacemakers within the cerebello-thalamo-cortical pathway, including the cerebellum, contralateral motor thalamus, and primary motor cortex. However, previous studies, using multiple methodologies, have advocated that tremor could be influenced by changes within the right extrastriate cortex, at both the structural and functional level. The purpose of this work was to evaluate the role of the extrastriate cortex in tremor generation and further arrest after left unilateral stereotactic radiosurgery thalamotomy (SRS-T). METHODS: The authors considered 12 healthy controls (HCs, group 1); 15 patients with essential tremor (ET, right-sided, drug-resistant; group 2) before left unilateral SRS-T; and the same 15 patients (group 3) 1 year after the intervention, to account for delayed effects. Blood oxygenation level-dependent functional MRI during resting state was used to characterize the dynamic interactions of the right extrastriate cortex, comparing HC subjects against patients with ET before and 1 year after SRS-T. In particular, the authors applied coactivation pattern analysis to extract recurring whole-brain spatial patterns of brain activity over time. RESULTS: The authors found 3 different sets of coactivating regions within the right extrastriate cortex in HCs and patients with pretherapeutic ET, reminiscent of the "cerebello-visuo-motor," "thalamo-visuo-motor" (including the targeted thalamus), and "basal ganglia and extrastriate" networks. The occurrence of the first pattern was decreased in pretherapeutic ET compared to HCs, whereas the other two patterns showed increased occurrences. This suggests a misbalance between the more prominent cerebellar circuitry and the thalamo-visuo-motor and basal ganglia networks. Multiple regression analysis showed that pretherapeutic standard tremor scores negatively correlated with the increased occurrence of the thalamo-visuo-motor network, suggesting a compensatory pathophysiological trait. Clinical improvement after SRS-T was related to changes in occurrences of the basal ganglia and extrastriate cortex circuitry, which returned to HC values after the intervention, suggesting that the dynamics of the extrastriate cortex had a role in tremor generation and further arrest after the intervention. CONCLUSIONS: The data in this study point to a broader implication of the visual system in tremor generation, and not only through visual feedback, given its connections to the dorsal visual stream pathway and the cerebello-thalamo-cortical circuitry, with which its dynamic balance seems to be a crucial feature for reduced tremor. Furthermore, SRS-T seems to bring abnormal pretherapeutic connectivity of the extrastriate cortex to levels comparable to those of HC subjects.

Pretherapeutic resting-state fMRI profiles are associated with MR signature volumes after stereotactic radiosurgical thalamotomy for essential tremor.

OBJECTIVEEssential tremor (ET) is the most common movement disorder. Drug-resistant ET can benefit from standard stereotactic deep brain stimulation or radiofrequency thalamotomy or, alternatively, minimally invasive techniques, including stereotactic radiosurgery (SRS) and high-intensity focused ultrasound, at the level of the ventral intermediate nucleus (Vim). The aim of the present study was to evaluate potential correlations between pretherapeutic interconnectivity (IC), as depicted on resting-state functional MRI (rs-fMRI), and MR signature volume at 1 year after Vim SRS for tremor, to be able to potentially identify hypo- and hyperresponders based only on pretherapeutic neuroimaging data.METHODSSeventeen consecutive patients with ET were included, who benefitted from left unilateral SRS thalamotomy (SRS-T) between September 2014 and August 2015. Standard tremor assessment and rs-fMRI were acquired pretherapeutically and 1 year after SRS-T. A healthy control group was also included (n = 12). Group-level independent component analysis (ICA; only n = 17 for pretherapeutic rs-fMRI) was applied. The mean MR signature volume was 0.125 ml (median 0.063 ml, range 0.002-0.600 ml). The authors correlated baseline IC with 1-year MR signatures within all networks. A 2-sample t-test at the level of each component was first performed in two groups: group 1 (n = 8, volume < 0.063 ml) and group 2 (n = 9, volume ≥ 0.063 ml). These groups did not statistically differ by age, duration of symptoms, baseline ADL score, ADL point decrease at 1 year, time to tremor arrest, or baseline tremor score on the treated hand (TSTH; p > 0.05). An ANOVA was then performed on each component, using individual subject-level maps and continuous values of 1-year MR signatures, correlated with pretherapeutic IC.RESULTSUsing 2-sample t-tests, two networks were found to be statistically significant: network 3, including the brainstem, motor cerebellum, bilateral thalamus, and left supplementary motor area (SMA) (pFWE = 0.004, cluster size = 94), interconnected with the red nucleus (MNI -2, -22, -32); and network 9, including the brainstem, posterior insula, bilateral thalamus, and left SMA (pFWE = 0.002, cluster size = 106), interconnected with the left SMA (MNI 24, -28, 44). Higher pretherapeutic IC was associated with higher MR volumes, in a network including the anterior default-mode network and bilateral thalamus (ANOVA, pFWE = 0.004, cluster size = 73), interconnected with cerebellar lobule V (MNI -12, -70, -22). Moreover, in the same network, radiological hyporesponders presented with negative IC values.CONCLUSIONSThese findings have clinical implications for predicting MR signature volumes after SRS-T. Here, using pretherapeutic MRI and data processing without prior hypothesis, the authors showed that pretherapeutic network interconnectivity strength predicts 1-year MR signature volumes following SRS-T.

Electrophysiological Activity Evoked by Direct Electrical Stimulation of the Human Brain: Interest of the P0 Component.

Direct electrical stimulation (DES) at 60 Hz is used clinically to perform real-time functional mapping of the brain and guide tumor resection during wide-awake neurosurgery. The electrophysiological effects of DES remain by far unknown, both locally and remotely. In this study, by lowering the DES frequency to 9 Hz and by using differential recording of electro-corticographic signals to improve the focality, we were able to observe that the amplitude of the initial P0 component of the direct cortical response increased when the inter-electrode distance was increased and the pulse width was decreased. This result strongly suggests that larger neural elements, including somas and axons of pyramidal neurons buried in deeper layers of the cortical column, are activated. Their activation produce the observed P0 component, which results from the synchronized summation of action potentials triggered by DES. Interestingly, the early P0 component was not observed during the usual 60 Hz DES. The study of the P0 component and subsequent evoked potentials may help decipher the effects of DES on the stimulated cortical column and identify the activation of underlying white matter fibers. This is crucial to better understand the electrophysiological diffusion of DES, especially at higher frequencies (e.g., 60 Hz).

Effect of Cosmetic Ceramics on Fracture Toughness of All-Ceramic Restorations.

OBJECTIVES: The use of zirconia as a framework for prosthetic restorations is increasing due to its favorable mechanical properties. Zirconia also has remarkable aesthetic properties when used as a framework and covered with a layer of cosmetic ceramic. The aim of this study was to compare the fracture toughness of three types of aesthetic ceramics, namely VITA VM®9, ceraMotion® Zr, and IPS e.max® Ceram. MATERIALS AND METHODS: Three groups of aesthetic ceramics (n=10) were subjected to three-point bending tests. The force leading to fracture was recorded for each sample to measure the impact of the ceramic type on the solidity of the framework. The type of fracture has not been studied in this work. One-way analysis of variance (ANOVA) was used to statistically analyze the results. RESULTS: The statistical analysis showed significantly different fracture toughness values among the three groups. IPS e.max® showed the lowest fracture toughness (25.42 MPa) compared to VITA VM®9 and ceraMotion® Zr (respectively 40.39 MPa; P<0.001, and 48.78 MPa; P<0.005). CONCLUSIONS: Within the limitations of the present study, it can be concluded that aesthetic ceramics play an important role in the fracture toughness of all-ceramic restorations.

The difference between electrical microstimulation and direct electrical stimulation - towards new opportunities for innovative functional brain mapping?

Both electrical microstimulation (EMS) and direct electrical stimulation (DES) of the brain are used to perform functional brain mapping. EMS is applied to animal fundamental neuroscience experiments, whereas DES is performed in the operating theatre on neurosurgery patients. The objective of the present review was to shed new light on electrical stimulation techniques in brain mapping by comparing EMS and DES. There is much controversy as to whether the use of DES during wide-awake surgery is the 'gold standard' for studying the brain function. As part of this debate, it is sometimes wrongly assumed that EMS and DES induce similar effects in the nervous tissues and have comparable behavioural consequences. In fact, the respective stimulation parameters in EMS and DES are clearly different. More surprisingly, there is no solid biophysical rationale for setting the stimulation parameters in EMS and DES; this may be due to historical, methodological and technical constraints that have limited the experimental protocols and prompted the use of empirical methods. In contrast, the gap between EMS and DES highlights the potential for new experimental paradigms in electrical stimulation for functional brain mapping. In view of this gap and recent technical developments in stimulator design, it may now be time to move towards alternative, innovative protocols based on the functional stimulation of peripheral nerves (for which a more solid theoretical grounding exists).