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.

Funding: This study was funded by a grant from the Army Research Office (grant no. W911NF-11-1-0307) to RPNR and by a grant from the W. M. Keck foundation to AS, CSP, and RPNR ( http://www.arl.army.mil/www/default.cfm?page=181 , http://www.wmkeck.org/grant-programs/research/medical-research-grant-abstracts/science-and-engineering-2014 ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Copyright: © 2014 Rao et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Both of these BBIs rely on stimulation technologies that are either invasive or experimental in humans, and thus are currently confined to animal models. In this paper, we report results from the first non-invasive BBI that can be safely applied to humans. Specifically, we show that it is possible to use EEG to decode motor intentions from a “sender” brain, and TMS to deliver an equivalent motor command to the motor cortex of a “receiver” brain, allowing the receiver to perform the hand movement that was intended by the sender. To test the feasibility and applicability of this procedure, a task was designed that required cooperative information sharing between pairs of participants along the BBI. The rest of the article describes the BBI in detail and presents in-depth results from 6 human participants who played the role of either sender or receiver of information in the BBI. Results from the first demonstration of this BBI were announced in an online report in August 2013 [19] .

Given these advances in BCIs, two recent efforts have addressed the question of whether direct brain-to-brain communication is possible with the technology we have today. Pais-Vieira and colleagues [3] explored the possibility of directly connecting the brains of two awake and behaving rats. In their experiment, cortical microelectrode arrays recorded the neural activity of “encoder” rats performing either a motor task or a tactile stimulation task, and guided the stimulation of motor and sensory areas in the brains of “decoder” rats. Because the actions of “decoder” rats mimicked those of the original “encoder” rats, the authors concluded that information had to have been transferred between their brains. An alternative BBI was proposed by Yoo and colleagues [5] , who successfully demonstrated the transmission of information from a human brain to a rat brain. In this case, visual evoked potentials in the human brain were recorded with EEG and translated into FUS-based stimulation of the part of motor cortex that controlled the tail of the anesthetized rat.

The idea of direct brain-to-brain communication could potentially be achieved using a Brain-to-Brain Interface (BBI) [3] – [5] . A BBI rests on two pillars: the capacity to read (or “decode”) useful information from neural activity and the capacity to write (or “encode”) digital information back into neural activity. In recent years, we have witnessed incredible progress in these two capabilities with the development of Brain-Computer Interfaces, or BCIs [6] , [7] . BCI researchers have demonstrated the possibility of decoding motor [8] , visual [9] and even conceptual information [10] from neural activity via a range of recording techniques such as implanted electrodes [8] , electrocorticography (ECoG, e.g., [11] ), electroencephalography (EEG, e.g., [12] ), functional MRI (e.g., [13] ), and magnetoencephalography (MEG, e.g., [14] ). A variety of stimulation techniques also exist that permit users to encode digital information into neural activity using implanted electrodes [15] , [16] , transcranial magnetic stimulation, (TMS, [17] ) and focused ultrasound (FUS, [18] ). Prominent examples of BCIs that use stimulation include the cochlear implant [15] and deep brain stimulators [16] .

However, most current methods for communicating are still limited by the words and symbols available to the sender and understood by the receiver. Even when they include non-verbal content (as in the case of visual and auditory information), communication constraints can be severe. A great deal of the information that is available to our brain is not introspectively available to our consciousness, and thus cannot be voluntarily put in linguistic form. For instance, knowledge about one’s own fine motor control is completely opaque to the subject [1] , and thus cannot be verbalized. As a consequence, a trained surgeon or a skilled violinist cannot simply “tell” a novice how to exactly position and move the fingers during the execution of critical hand movements. But even knowledge that is introspectively available can be difficult to verbalize. Brilliant teachers may struggle to express abstract scientific concepts in language [2] , and everyone is familiar with the difficulty of putting one’s own feelings into words. Even when knowledge can be expressed in words, one might face the hurdle of translating between the many existing spoken human languages. Can information that is available in the brain be transferred directly in the form of the neural code, bypassing language altogether? We explore this idea in the rest of this article.

Many of the greatest contemporary technological developments have centered on advancing human communication. From the telegraph to the Internet, the primary utility of these game-changing innovations has been to increase the range of audiences that an individual can reach.

Materials and Methods

Human Subjects and Ethics Statement Six participants (aged 21–38; see Table 1) took part in the experiment over the course of three months. All participants were recruited through word of mouth, were fully informed about the experimental procedure and its potential risks and benefits, and gave written consent prior to the beginning of the experiment. They were divided into three pairs, with one participant playing the role of the “sender” and one playing the role of the “receiver.” Because the TMS procedure is inherently more risky than the EEG procedure, participants were allowed to decide which role they wanted to play. To maintain their decision free of any external influence, all participants received monetary compensation that was independent of their role and proportional to the total amount of time devoted to the study. PPT PowerPoint slide

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larger image TIFF original image Download: Table 1. Participant demographics. https://doi.org/10.1371/journal.pone.0111332.t001 Both the experiment and its recruitment procedure were reviewed and approved by the Institutional Review Board of the University of Washington. The individuals in this manuscript have given written informed consent (as outlined in the PLOS consent form) to publish these case details.

Experimental Task During each experimental session, two participants had to carry out a specific task in the form of a series of consecutive trials of a computer game. The game was designed so that the two participants had to play cooperatively, and the required cooperation could only be achieved through direct brain-to-brain communication (Figure 1A). The goal of the game (Figure 1B) was to defend a city (located beyond the left visible part of the screen) from enemy rockets fired by a pirate ship on the lower right portion of the screen (represented by a skull-and-bones insignia). The rockets followed an arc trajectory, traversing the screen from the lower right to the upper left corner of the screen. A cannon, located in the lower center portion of the screen, tracked the rocket as it crossed the screen. To defend the city, the subjects had to fire the cannon by pressing a touchpad. If the cannon was fired before the moving rocket reached the city, the rocket was destroyed and the city was saved. In 50% of the trials, a friendly “supply airplane” flew across the screen instead of a pirate rocket. In such trials, participants had to avoid firing the cannon to let the supply airplane enter the city. Note that this task stresses the real-time nature of our BBI because the participants have to destroy the rocket before it crosses the screen for the trial to be successful. PPT PowerPoint slide

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larger image TIFF original image Download: Figure 1. Experimental Set-Up. (A) Schematic diagram of set-up. Brain signals from one participant (the “Sender”) were recorded using EEG. When imagined hand movements were detected by the computer, a “Fire” command was transmitted over the internet to the TMS machine, which caused an upward movement of the right hand of a second participant (the “Receiver”), resulting in a press by the hand on a touchpad. This press triggered the firing of the cannon in the game seen by the Sender. Red lines mark the part of the architecture that corresponds to the direct brain-to-brain interface. (B) Screen shot from the game. In 50% of the trials, the pirate ship on the right side (skull-and-bones) shoots a rocket (top center) towards a city on the left. The Sender engages in motor imagery to move the white cursor on the left to hit the blue circular target in order to fire the cannon (bottom center) and destroy the rocket before it reaches the city. In the other 50% of the trials, a supply airplane moves from the right to the left side of the screen (not shown). The Sender rests in this case and refrains from imagery in order to avoid hitting the target. https://doi.org/10.1371/journal.pone.0111332.g001

Brain-to-Brain Collaboration Between the Two Participants The two participants were given different and complementary roles. One participant (henceforth, the “Sender”) was able to see the game on a computer screen, but was not provided with any input device to control the cannon (Figure 2, Sender watching the game screen, which is not shown). The second participant (henceforth, the “Receiver”) could use his/her right hand to press a touchpad, but could not see the game. The two participants were located in separate buildings on the University of Washington’s campus. Specifically, the Sender side was stationed in the Computer Science & Engineering building while the Receiver side was stationed in the Psychology building. The two buildings were located approximately 1 mile apart. The two participants could only communicate with each other through a brain-to-brain communication channel. PPT PowerPoint slide

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larger image TIFF original image Download: Figure 2. EEG Set-Up. EEG signals being recorded from a subject (the “Sender”) as the subject watches the computer game (the game screen is to the left and not shown in the picture). The larger screen displays EEG signals processed by the BCI2000 software. The smaller laptop screen placed further away is from the live Skype session and shows a “Receiver” subject in the TMS lab across the University of Washington campus. (Image from the pilot study referred to in the text). https://doi.org/10.1371/journal.pone.0111332.g002 The brain-to-brain communication channel was built using two existing technologies: EEG for non-invasively recording brain signals from the scalp and TMS for non-invasively stimulating the brain (Figure 1A). During rocket trials, the sender conveyed the intent to fire the cannon by engaging in right hand motor imagery. Electrical brain activity from the Sender was recorded using EEG, and the resultant signal was used to control the vertical movement of a cursor (Figure 1B) – this allowed the subject to get continuous feedback about imagery performance. When the cursor hit the “Fire” target (a large blue circle) located at the top of the screen, the Sender’s computer transmitted a signal over the Internet to the Receiver’s computer. The two computers communicated using the standard hypertext transfer protocol (HTTP). The Receiver’s computer was connected through a custom-made serial cable to a TMS machine. Whenever the Receiver’s computer received a fire command, a TMS pulse was delivered to a pre-selected region of the Receiver's brain. The stimulation caused a quick upward jerk of the Receiver's right hand, which was positioned above the touchpad. This up-down movement of the hand typically resulted in enough force to trigger a “click” event on the touchpad, causing the cannon in the computer game to be fired as requested by the Sender. In successful “supply airplane” trials, the Sender would rest and refrain from motor imagery, allowing the cursor to drift towards the bottom of the screen; in such trials, no signal was sent to the Receiver’s computer. An analysis of the log times revealed that the transmission of information across the internet took approximately 10 ms, the activation of the TMS machine occurred approximately 1.4 ms later, the generation of the electromagnetic pulse occurred approximately 4.0 ms later, and the receiver’s entire motor response (corresponding the end of the downward trajectory of the hand, following the upward movement generated by the TMS) occurred on average 627.1 ms afterwards. Thus, the transmission of the signal along the BBI channel took ∼650 ms.

Procedure Each experiment consisted of two experimental blocks and two control blocks (see below), the order of which was randomized prior to the beginning of the experiment. The length of each block was initially set to 10 trials for Pair 1 to make sure that the experimental session could be completed within 1 hour, so as to minimize the discomfort for the TMS participant. Since the setup procedure was significantly faster than what we had initially estimated (based on our 2013 pilot study), the length of each block was extended to 16 trials for Pairs 2 and 3. Participants were told in advance of the presence of two conditions, but were not told to which condition each block belonged. Trials were separated by 2 seconds of set-up time plus a 20 second visual countdown. This large pause prevented two consecutive TMS pulses from being delivered less than 20 seconds apart, thus reducing the maximum amount of magnetic stimulation delivered to the Receiver to a level well below the strictest safety guidelines [20], and setting the upper limit of information throughput to 0.05 bits per second. During experimental blocks, the non-invasive brain-to-brain channel was fully operational. However, during control blocks the brain-to-brain channel was made non-operational by changing the coil position so that the TMS pulse could not cause the desired movement of the right hand. Note that the electromagnetic pulse was still delivered at the same intensity, thus making the two conditions identical but for the target location. As will be clear in the discussion of the results, the control condition affects the performance of the receiver but does not have detectable effects on the sender’s behavior.

EEG Procedure Participants playing the role of the Sender came in for two consecutive sessions: a training session and the BBI experimental session. During both sessions, electrical signals were recorded at a frequency of 512 Hz from the Sender's scalp via a 64-channel Ag/AgCl electrode cap (actiCAP, Brain Products GmBH, Gilching, Germany) and amplified using gUSBamps (Guger Technologies, Austria). A Laplacian spatial filter [7] was used to reduce artifacts common to nearby electrodes and emphasize local activity. Signal processing and data storage were managed through the BCI2000 software package. Changes in the “mu” band (typically 8–12 Hz) have long been linked to motor imagery signals and used in BCIs (for an introduction, see [6], [7]). During the training session, subjects learned to control the vertical movement of a 1-D cursor by imagining right hand movement. The power in a low frequency band (the “mu” band) was computed across the electrodes and the electrode most correlated with the subject's motor imagery during an initial training period was selected as the control electrode for the task. The computer translated the power in the mu band to vertical movement of a cursor, which provided visual feedback to the sender. Specifically, the decrease in power that accompanied right hand motor imagery was mapped to upward movement of the cursor, while a lack of suppression in the mu band caused downward cursor movement (see Figure 3 for an example). All the participants underwent the same amount of training. Although participants differ in their response to training, and it is reasonable to assume that increased training may improve a Sender’s subsequent performance, we did not make any attempt to optimize or manipulate the duration of the training sessions. PPT PowerPoint slide

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larger image TIFF original image Download: Figure 3. EEG Traces during the Two Trial Types and Timing of Information Transfer from Sender to Receiver during a Rocket Trial. EEG signal during one rocket trial (red trace) and one airplane trial (blue trace) from the Sender in Pair 1 is shown. The traces demonstrate suppression of power in the mu control band (11–13 Hz) during the rocket trial due to motor imagery. Dashed vertical lines mark timestamps of key events in the transfer of information in the BBI from Sender to Receiver during the rocket trial. https://doi.org/10.1371/journal.pone.0111332.g003 During the BBI experimental session, a monitor displayed both the cursor window and the cannon game (Figure 1B). Depending on the type of projectile in each trial, the Sender modulated activity in the mu band to guide the cursor to either the “Fire” target at the top of the screen or towards the bottom of the screen. Note that this procedure tracks the Sender’s intention of moving the right hand and not the hand movement itself, which was, in fact, not necessary to trigger the remote action. Motor imagery is frequently adopted in BCIs developed for disabled patients, who have retained control of such imagery but whose motor activity is disrupted [6], [7]. Imagery is central to the demonstration of brain-to-brain communication, as the movement intention that is initially imagined in the Sender’s brain is remotely executed by the Receiver’s brain.