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Concept: Neurotechnology


We present, to our knowledge, the first demonstration that a non-invasive brain-to-brain interface (BBI) can be used to allow one human to guess what is on the mind of another human through an interactive question-and-answering paradigm similar to the “20 Questions” game. As in previous non-invasive BBI studies in humans, our interface uses electroencephalography (EEG) to detect specific patterns of brain activity from one participant (the “respondent”), and transcranial magnetic stimulation (TMS) to deliver functionally-relevant information to the brain of a second participant (the “inquirer”). Our results extend previous BBI research by (1) using stimulation of the visual cortex to convey visual stimuli that are privately experienced and consciously perceived by the inquirer; (2) exploiting real-time rather than off-line communication of information from one brain to another; and (3) employing an interactive task, in which the inquirer and respondent must exchange information bi-directionally to collaboratively solve the task. The results demonstrate that using the BBI, ten participants (five inquirer-respondent pairs) can successfully identify a “mystery item” using a true/false question-answering protocol similar to the “20 Questions” game, with high levels of accuracy that are significantly greater than a control condition in which participants were connected through a sham BBI.

Concepts: Psychology, Brain, Electroencephalography, Visual perception, Mind, Transcranial magnetic stimulation, Problem solving, Neurotechnology


The field of non-pharmacological therapies for treatment resistant depression (TRD) is rapidly evolving and new somatic therapies are valuable options for patients who have failed numerous other treatments. A major challenge for clinicians (and patients alike) is how to integrate the results from published clinical trials in the clinical decision-making process.We reviewed the literature for articles reporting results for clinical trials in particular efficacy data, contraindications and side effects of somatic therapies including electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), vagal nerve stimulation (VNS) and deep brain stimulation (DBS). Each of these devices has an indication for patients with different level of treatment resistance, based on acuteness of illness, likelihood of response, costs and associated risks. ECT is widely available and its effects are relatively rapid in severe TRD, but its cognitive adverse effects may be cumbersome. TMS is safe and well tolerated, and it has been approved by FDA for adults who have failed to respond to one antidepressant, but its use in TRD is still controversial as it is not supported by rigorous double-blind randomized clinical trials. The options requiring surgical approach are VNS and DBS. VNS has been FDA-approved for TRD, however it is not indicated for management of acute illness. DBS for TRD is still an experimental area of investigation and double-blind clinical trials are underway.

Concepts: Clinical trial, Medical terms, Deep brain stimulation, Vagus nerve stimulation, Transcranial magnetic stimulation, Neurotechnology, Electroconvulsive therapy, Treatment-resistant depression


There is increasing interest in using neurostimulation to treat headache disorders. There are now several non-invasive and invasive stimulation devices available with some open-label series and small controlled trial studies that support their use. Non-invasive stimulation options include supraorbital stimulation (Cefaly), vagus nerve stimulation (gammaCore) and single-pulse transcranial magnetic stimulation (SpringTMS). Invasive procedures include occipital nerve stimulation, sphenopalatine ganglion stimulation and ventral tegmental area deep brain stimulation. These stimulation devices may find a place in the treatment pathway of headache disorders. Here, we explore the basic principles of neurostimulation for headache and overview the available methods of neurostimulation.

Concepts: Deep brain stimulation, Vagus nerve, Vagus nerve stimulation, Transcranial magnetic stimulation, Headache, Headaches, Neurotechnology


We describe the first direct brain-to-brain interface in humans and present results from experiments involving six different subjects. Our non-invasive interface, demonstrated originally in August 2013, combines electroencephalography (EEG) for recording brain signals with transcranial magnetic stimulation (TMS) for delivering information to the brain. We illustrate our method using a visuomotor task in which two humans must cooperate through direct brain-to-brain communication to achieve a desired goal in a computer game. The brain-to-brain interface detects motor imagery in EEG signals recorded from one subject (the “sender”) and transmits this information over the internet to the motor cortex region of a second subject (the “receiver”). This allows the sender to cause a desired motor response in the receiver (a press on a touchpad) via TMS. We quantify the performance of the brain-to-brain interface in terms of the amount of information transmitted as well as the accuracies attained in (1) decoding the sender’s signals, (2) generating a motor response from the receiver upon stimulation, and (3) achieving the overall goal in the cooperative visuomotor task. Our results provide evidence for a rudimentary form of direct information transmission from one human brain to another using non-invasive means.

Concepts: Neuroanatomy, Brain, Human brain, Cerebral cortex, Neurology, Electroencephalography, Transcranial magnetic stimulation, Neurotechnology


Chemotherapy-induced peripheral neuropathy (CIPN) is a significant problem for cancer patients, and there are limited treatment options for this often debilitating condition. Neuromodulatory interventions could be a novel modality for patients trying to manage CIPN symptoms; however, they are not yet the standard of care. This study examined whether electroencephalogram (EEG) neurofeedback (NFB) could alleviate CIPN symptoms in survivors.

Concepts: Epidemiology, Randomized controlled trial, Electroencephalography, Neurotechnology, Peripheral neuropathy, Binaural beats, Neurofeedback, Mind machine


Preoperative functional mapping in children younger than 5 years old remains a challenge. Awake functional MRI (fMRI) is usually not an option for these patients. Except for a description of passive fMRI in sedated patients and magnetoencephalography, no other noninvasive mapping method has been reported as a preoperative diagnostic tool in children. Therefore, invasive intraoperative direct cortical stimulation remains the method of choice. To the authors' knowledge, this is the first case of a young child undergoing preoperative functional motor cortex mapping with the aid of navigated transcranial magnetic stimulation (nTMS). In this 3-year-old boy with a rolandic ganglioglioma, awake preoperative mapping was performed using nTMS. A precise location of Broca area 4 could be established. The surgical approach was planned according to the preoperative findings. Intraoperative direct cortical stimulation verified the location of the nTMS hotspots, and complete resection of the precentral tumor was achieved. Navigated TMS is a precise tool for preoperative motor cortex mapping and is feasible even in very young pediatric patients. In children for whom performing the fMRI motor paradigm is challenging, nTMS is the only available option for functional mapping.

Concepts: Brain, Wernicke's area, Electroencephalography, Medical tests, Transcranial magnetic stimulation, Neurotechnology, Cerebral hemisphere, Functional neuroimaging


Co-registration of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) is a new, promising method for assessing cortical excitability and connectivity. Using this technique, a TMS evoked potential (TEP) can be induced and registered with the EEG. However, the TEP contains an early, short lasting artifact due to the magnetic pulse, and a second artifact, which depends on the location of stimulation and can last up to 40 milliseconds. Different causes for this second artifact have been suggested in literature. In this study, we used principal component analysis (PCA) to suppress both the first and second artifact in TMS-EEG data. Single pulse TMS was applied at the motor and visual cortex in 18 healthy subjects. PCA using singular value decomposition was applied on single trials to suppress the artifactual components. A large artifact suppression was realized after the removal of the first 5 PCA components, thereby revealing early TEP peaks, with only a small suppression of later TEP components. The spatial distribution of the second artifact suggests that it is caused by electrode movement due to activation of the temporal musculature. In conclusion, we showed that PCA can be used to reduce TMS-induced artifacts in EEG, thereby revealing components of the TMS evoked potential.

Concepts: Brain, Electroencephalography, Evoked potential, Principal component analysis, Transcranial magnetic stimulation, Amblyopia, Singular value decomposition, Neurotechnology


For ages, we have been looking for ways to enhance our physical and cognitive capacities in order to augment our security. One potential way to enhance our capacities may be to externally stimulate the brain. Methods of non-invasive brain stimulation (NIBS), such as repetitive transcranial magnetic stimulation (rTMS) and transcranial electrical stimulation (tES), have been recently developed to modulate brain activity. Both techniques are relatively safe and can transiently modify motor and cognitive functions outlasting the stimulation period. The purpose of this paper is to review data suggesting that NIBS can enhance motor and cognitive performance in healthy volunteers. We frame these findings in the context of whether they may serve security purposes. Specifically, we review studies reporting that NIBS induces paradoxical facilitation in motor (precision, speed, strength, acceleration endurance, and execution of daily motor task) and cognitive functions (attention, impulsive behavior, risk-taking, working memory, planning, and deceptive capacities). Although transferability and meaningfulness of these NIBS-induced paradoxical facilitations into real-life situations are not clear yet, NIBS may contribute at improving training of motor and cognitive functions relevant for military, civil, and forensic security services. This is an enthusiastic perspective that also calls for fair and open debates on the ethics of using NIBS in healthy individuals to enhance normal functions.

Concepts: Psychology, Cognitive neuroscience, Transcranial magnetic stimulation, Neurotechnology


Episodic memory retrieval is assumed to rely on the rapid reactivation of sensory information that was present during encoding, a process termed “ecphory.” We investigated the functional relevance of this scarcely understood process in two experiments in human participants. We presented stimuli to the left or right of fixation at encoding, followed by an episodic memory test with centrally presented retrieval cues. This allowed us to track the reactivation of lateralized sensory memory traces during retrieval. Successful episodic retrieval led to a very early (∼100-200 ms) reactivation of lateralized alpha/beta (10-25 Hz) electroencephalographic (EEG) power decreases in the visual cortex contralateral to the visual field at encoding. Applying rhythmic transcranial magnetic stimulation to interfere with early retrieval processing in the visual cortex led to decreased episodic memory performance specifically for items encoded in the visual field contralateral to the site of stimulation. These results demonstrate, for the first time, that episodic memory functionally relies on very rapid reactivation of sensory information.

Concepts: Brain, Memory, Hippocampus, Sensory system, Transcranial magnetic stimulation, Episodic memory, Amnesia, Neurotechnology


Cortical excitability, as measured by transcranial magnetic stimulation combined with electromyography, is a potential biomarker for the diagnosis and follow-up of epilepsy. We report on long-interval intracortical inhibition data measured in four different centres in healthy controls (n = 95), subjects with refractory genetic generalized epilepsy (n = 40) and with refractory focal epilepsy (n = 69). Long-interval intracortical inhibition was measured by applying two supra-threshold stimuli with an interstimulus interval of 50, 100, 150, 200 and 250 ms and calculating the ratio between the response to the second (test stimulus) and to the first (conditioning stimulus). In all subjects, the median response ratio showed inhibition at all interstimulus intervals. Using a mixed linear-effects model, we compared the long-interval intracortical inhibition response ratios between the different subject types. We conducted two analyses; one including data from the four centres and one excluding data from Centre 2, as the methods in this centre differed from the others. In the first analysis, we found no differences in long-interval intracortical inhibition between the different subject types. In all subjects, the response ratios at interstimulus intervals 100 and 150 ms showed significantly more inhibition than the response ratios at 50, 200 and 250 ms. Our second analysis showed a significant interaction between interstimulus interval and subject type (P = 0.0003). Post hoc testing showed significant differences between controls and refractory focal epilepsy at interstimulus intervals of 100 ms (P = 0.02) and 200 ms (P = 0.04). There were no significant differences between controls and refractory generalized epilepsy groups or between the refractory generalized and focal epilepsy groups. Our results do not support the body of previous work that suggests that long-interval intracortical inhibition is significantly reduced in refractory focal and genetic generalized epilepsy. Results from the second analysis are even in sharper contrast with previous work, showing inhibition in refractory focal epilepsy at 200 ms instead of facilitation previously reported. Methodological differences, especially shorter intervals between the pulse pairs, may have contributed to our inability to reproduce previous findings. Based on our results, we suggest that long-interval intracortical inhibition as measured by transcranial magnetic stimulation and electromyography is unlikely to have clinical use as a biomarker of epilepsy.

Concepts: Ratio, Perception, Harshad number, Transcranial magnetic stimulation, Neurophysiology, Neurotechnology, Euclid's Elements, Renaissance music