Abstract:
Transcranial direct current stimulation (tDCS) and electroencephalography (EEG) are integrated, including re-using electrodes to perform both tDCS and EEG, and automatically alternating EEG collection and tDCS application. EEG and tDCS functionalities are integrated into a single headset. Improvements in tDCS include realizing multiple tDCS current flow configurations without repositioning electrodes, and concurrently applying multiple independent tDCS currents to a subject.

Description:
[0001]    This invention was developed under Contract DE-AC04-94AL85000 between Sandia Corporation and the U.S. Department of Energy. The U.S. Government has certain rights in this invention. 
     
    
     FIELD 
       [0002]    The present work relates generally to transcranial direct current stimulation and electroencephalography and, more particularly, to integration of the two. 
       BACKGROUND 
       [0003]    Transcranial direct current stimulation (tDCS) involves applying weak electrical currents to the brain to alter the firing rates of neurons. This is conventionally performed by applying current of 1-2.5 mA between two saline soaked pads positioned in contacting relationship to the scalp, so that current flows over a large portion of the scalp. This technology poses some difficulties. For example, (1) the saline solution tends to drain to the bottom of the pads, causing an uneven current distribution; (2) there is little spatial control; and (3) because of the size of the tDCS pads, there is the possibility that they may stimulate adjacent cortical areas in addition to the intended area. 
         [0004]    Because current density is more critical than total current flow in tDCS, one alternative, referred to as High Definition tDCS (FID-tDCS), uses much smaller electrode pads. Whereas typical electrode pads in standard tDCS have a surface area of around 25˜50 cm 2 , the electrode pads of HD-tDCS have a surface area around 1 cm 2  (diameter under 12 mm). This improves spatial control and helps avoid stimulation of unintended areas. The same current densities achieved with standard tDCS can thus be achieved with significantly smaller currents using HD-tDCS. 
         [0005]    Electroencephalography (EEG) involves the use of electrodes to record electrical activity on the scalp caused by neurons firing in the brain. EEG recordings are typically collected in a laboratory using professional equipment. Combined use of EEG and tDCS technologies is desirable because, for example, it provides the capability of observing brain activity before and after application of tDCS, thereby providing measurement of the brain&#39;s response to tDCS. Conventional approaches to the combination of EEG and to tDCS involve a relatively cumbersome sequence of procedures including placement of the pair of tDCS pads on the scalp, application of tDCS currents, removal of the tDCS pads, placement of EEG electrodes on the scalp, and subsequent observation of EEG activity. 
         [0006]    It is desirable in view of the foregoing to provide for improved integration of EEG and tDCS. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0007]      FIG. 1  illustrates a prior art headset arrangement that uses a plurality of electrodes to collect EEG data. 
           [0008]      FIG. 2  diagrammatically illustrates an apparatus that integrates tDCS and EEG functionalities according to example embodiments of the present work. 
           [0009]      FIG. 3  diagrammatically illustrates a switching element of the switching arrangement of  FIG. 2  according to example embodiments of the present work. 
           [0010]      FIGS. 4 and 5  illustrate respective examples of electrode configurations for tDCS according to the present work. 
           [0011]      FIGS. 6 and 7  diagrammatically illustrate examples of constant current sources that may be used in the system of  FIG. 2  according to the present work. 
           [0012]      FIG. 8  illustrates operations for switching a set of electrodes between tDCS and EEG operating modes according to example embodiments of the present work. 
           [0013]      FIG. 9  illustrates operations for automatic leakage current compensation according to example embodiments of the present work. 
           [0014]      FIG. 10  diagrammatically illustrates an analog-to-digital converter that permits the system of  FIG. 2  to perform automatic leakage current compensation according to example embodiments of the present work. 
           [0015]      FIG. 11  illustrates an example of a graphical user interface implemented by the host computer of  FIG. 2  according to the present work. 
           [0016]      FIG. 12  diagrammatically illustrates a headset that integrates tDCS and EEG functionalities according to example embodiments of the present work. 
       
    
    
     DETAILED DESCRIPTION 
       [0017]    A number of low-cost EEG-like devices have emerged in recent years. One of the most sophisticated of these is the Emotiv EPOC EEG headset, which positions  14  measurement electrodes across the frontal, temporal, and occipital lobes of the brain, and provides four other electrodes for use as references at respective locations. The Emotiv headset, shown in  FIG. 1 , includes a plastic housing that contains pre-positioned electrodes. The housing is made from a Polycarbonate-ABS blend, which is flexible enough to allow the device to accommodate different sized heads while still maintaining sufficient pressure to keep the electrodes in place. The electrodes, which are to approximately  10 . 5  mm in diameter, are connected by wires to an analog board provided within the plastic housing, and located above the subject&#39;s right ear. The Emotiv headset, typically marketed toward garners as an input device for interacting with a game computer, has been shown to function as an effective EEG device for use in neuropsychological experiments. 
         [0018]    Example embodiments of the present work provide a flexible platform integrating tDCS and EEG functionalities. The electrodes provided in various low-cost EEG-like devices (such as the Emotiv headset shown in  FIG. 1 ) are comparable in size to the aforementioned electrode pads used for HD-tDCS. The present work recognizes that this provides an advantageous location to intercept and redirect the electrodes for connection to suitable tDCS circuitry. Some embodiments provide at least two independent precision adjustable constant-current sources, and a plurality of electrodes may be connected to the anodes of the current sources in any tDCS configuration. Some embodiments provide over a billion different electrode configurations for tDCS. The independent current sources permit delivery of matching currents to different electrodes. Some embodiments feature measurement capabilities to verify the tDCS current values and ensure that they are within the voltage compliance of the system. 
         [0019]    Some embodiments provide for observation of brain activity immediately before and after tDCS current application, thereby providing measurement of the brain&#39;s response to tDCS in a heretofore unknown manner. Some embodiments automatically switch between tDCS mode and EEG mode in less than two microseconds, many orders of magnitude faster than prior art techniques. This remarkable improvement in operating speed is achieved virtually independently of the number of electrodes employed, whereas the speed of the prior art techniques is greatly affected by the number of electrode pads used for tDCS. 
         [0020]      FIG. 2  diagrammatically illustrates an apparatus that integrates tDCS and EEG to functionalities, using the same set of electrodes for both tDCS and EEG, according to example embodiments of the present work. A switching arrangement  21  selectively connects either a tDCS drive arrangement  23  or an EEG analyzer  24  to a set of electrodes  22 . A digital controller  26  is coupled to control the switching arrangement  21  via a bus  28 . The tDCS drive arrangement  23  includes m independent constant current sources, collectively designated as CCS. A digital-to-analog converter (DAC)  25  is coupled to control the constant current sources, and the digital controller  26  is coupled to control the DAC  25  via the bus  28 . A host computer  27  controls the digital controller  26  via a host interface  29 . The host computer  27  provides a user interface that receives input from a user and provides output information to the user. 
         [0021]    The switching arrangement  21  includes a plurality of switching elements coupled respectively to the electrodes  22  in one-to-one correspondence.  FIG. 3  diagrammatically illustrates the structure of the individual switching elements  31  within the switching arrangement  21  according to example embodiments of the present work. As shown in  FIG. 3 , each switching element  31  within the switching arrangement  21  includes a plurality of single-pole-single-throw (SPST) switches  33  connected to an associated electrode  32  within the set of electrodes  22 . The switches  33  selectively connect the electrode  32  to respectively associated nodes, designated as EEG, AN 1 , AN 2 , . . . ANm, and CATH. The EEG node is a node of the EEG analyzer  24  normally connected to the associated electrode  32  in an EEG mode of operation. The nodes AN 1 -ANm (see also  FIG. 2 ) are m current sourcing nodes (also referred to as anodes) respectively provided by the m constant current sources CCS of the tDCS drive arrangement  23 . The node CATH is the current sink node (also referred to as the cathode) of the tDCS drive arrangement  23 . 
         [0022]    Each of the switches  33  of a given switching element  31  may be controlled by the controller  26  independently of the other switches  33  of that switching element, and independently of the other switching elements  31 . Thus, the controller  26  may configure to the switching arrangement  21  such that any given electrode  32  is connected by its associated switching element  31  to any of the m+2 nodes shown in  FIG. 3 , independently of how the other electrodes  32  are connected by their respectively associated switching elements  31 . During the EEG mode of operation, all of the electrodes  31  may be connected to their normally associated nodes within the EEG analyzer  24 . During a tDCS mode of operation, the switching elements  31  may re-direct connections of the electrodes  32  away from their normally associated EEG nodes, such that any electrode  32  may be connected to any of the tDCS anodes AN 1 -ANm, or to the tDCS cathode CATH, or may be left unconnected (floating). It is evident that, for example, using an Emotiv headset that has up to  18  electrodes available for tDCS use, the possible electrode configurations for the tDCS mode are manifold. 
         [0023]      FIGS. 4 and 5  illustrate two examples of the multitude of possible electrode configurations for tDCS mode according to the present work. In the example of  FIG. 4 , two electrodes are connected to AN 1 , six electrodes are connected to CATH, and the remaining electrodes are floating. In the example of  FIG. 5 , one electrode is connected to AN 1 , one electrode is connected to AN 2 , six electrodes are connected to CATH, and the remaining electrodes are floating. 
         [0024]      FIGS. 4 and 5  also illustrate an advantage of providing a plurality of constant current sources for tDCS. Referring also to  FIG. 2 , the anodes AN 1 -ANm of the m constant current sources CCS are, for example, capable of delivering matching currents to m different electrodes at  22 . An advantage of this is demonstrated by comparing  FIGS. 4 and 5 . In  FIG. 4 , if AN 1  delivers  1  mA, the currents out of the two electrodes connected to AN 1  may not be evenly split at 500 μA, each, due to variations in contact resistances among the electrodes and/or variations in scalp resistance. With the configuration of  FIG. 5 , however, both AN 1  and AN 2  can be set to deliver 500 μA, which ensures that the currents out of the electrodes connected to AN 1  and AN 2  are equal. The constant current sources driving AN 1  and AN 2  will adjust their respective voltages at AN 1  and AN 2  as necessary so that each anode delivers the desired 500 μA. 
         [0025]      FIG. 6  diagrammatically illustrates in more detail an example of a conventional constant current source  60  suitable for the present work. In some embodiments, m of the  FIG. 6  current sources are provided at CCS in  FIG. 2 . The example constant current source  60  is implemented using the so-called “improved Howland current pump”, which is well-known in the art. The circuit of  FIG. 6  may be understood as a unity-gain differential amplifier that “mirrors” the input voltage to the output voltage. That is, Input+−Input−=Output+−Output−. For example, if Rset=1 kΩ, and Input+−Input−=200 mV, then Output+−Output−=200 mV, so the output (anode) current, Iout, is 200 mV/1000Ω=200 μA. 
         [0026]    The resistor ratios should be appropriately balanced, such that R 11 /(R 12 +R 13 )=R 14 /R 15 . Some embodiments provide, on a printed circuit board where the constant current sources are constructed, several resistor footprints arranged in series and parallel to allow nonstandard trim resistor values to be created using standard SMD resistors. Some embodiments use an LT1991 differential amplifier, conventionally available from Linear Technology Corporation. This amplifier has better than 0.04% matching resistors, and provides sufficient accuracy for keeping the current constant within a few percent without any trimming. When properly tuned, the input voltage to the improved Howland current pump is proportional to the output current, independent of the load impedance, assuming the current source is within its compliance voltage range, and ignoring leakage current through R 12  (discussed below). In some embodiments, R 11 , R 12 , R 14  and R 15  are each 450 kΩ, and R 13  (Rset)=1 kΩ. As shown by broken line in  FIG. 6 , some embodiments provide a suitable filter capacitor C F  across R 15 . Some embodiments also provide a similar filter capacitor across R 12  (not shown in  FIG. 6 ). The load Z L  in  FIG. 6  represents the electrode(s) and the scalp as connected in circuit between the anode and the cathode. 
         [0027]    Based on the aforementioned relatively low currents required for HD-tDCS, the current source of  FIG. 6  may be designed to be precise at low currents (down to 1 μA). The range and resolution of the current source is selectable with the single “set resistor” Rset. For example, in some embodiments, the DAC  25  driving Input+ and Input− is a 16 bit device that outputs from 0 to 2.5V, and Rset is 1 kΩ. This limits Iout to safe levels, e.g., approximately 0-2.5 mA, with resolution of approximately 0.04 μA. If larger currents are required, Rset may be changed to a lower value. For example, in some embodiments, Rset=100Ω, and the resolution is approximately 0.4 μA with a range of approximately of 0-25 mA. 
         [0028]    Note that some leakage current flows through resistor R 12  instead of into the load. However, if resistors R 11 , R 12 , R 14  and R 15  are much larger than Rset in  FIG. 6 , the leakage current flowing through R 12  is negligible.  FIG. 7  illustrates an alternative embodiment that provides a unity gain buffer  71  (with picoampere leakage current) feeding R 12  from the Output− node, so that lout is virtually equal to the current through Rset. 
         [0029]    Because the output of the differential amplifier  61  (Output+ in  FIG. 6 ) cannot go all the way to ground with a single power supply, some embodiments compensate by using the DAC  25  to maintain the cathode voltage (CATH in  FIGS. 2 ,  6  and  7 ) slightly above ground (so the anode can be dropped to meet the cathode voltage). An output of the DAC  25  thus functions as the cathode (sinking current into the DAC). In some embodiments, the cathode voltage is set to approximately 100 mV. 
         [0030]    Note also that the outputs of the DAC  25  may not go all the way to ground when the DAC is set to zero scale, due to the zero scale offset of the DAC. This prevents the output current lout from going all the way to zero. (Hence the current range would be 1 μA-2.5 mA for lout in the foregoing example with Rset=1 kΩ if the DAC has a zero scale offset of 1 mV.) For applications that may require Iout to go all the way to zero, the input reference voltage, Input−, may be set slightly higher than ground, for example, using an output of DAC  25  to drive Input− to some small positive voltage (e.g., a few mV). This is shown by broken line in  FIG. 6 . 
         [0031]    Referring again to  FIG. 2 , in some embodiments, the host interface  29  is a conventional USB bus, and the bus  28  is a conventional SPI bus, with the digital controller  26  acting as the SPI master, and the switching arrangement  21  and DAC  25  acting as SPI slaves. In some embodiments, the digital controller  26  is implemented with the FT4232H High-Speed Quad USB UART IC available from Future Technology Devices International Ltd., the switching arrangement  21  is implemented with a suitable number of the ADG1414 (Serially-Controlled Octal SPST Switches) available from Analog Devices, Inc., and the DAC  25  is implemented with a suitable number of the AD5668 Octal 16-bit DAC available from Analog Devices, Inc. The FT4232H has a defined API for executing commands over an SPI bus. In some embodiments, software on the host computer  27  permits a user to configure the electrodes  22  and control the tDCS currents, by using the USB bus  29  to communicate with the controller  26 , which in turn controls the switching arrangement  21  and DAC  25  via the SPI bus  28 . 
         [0032]    In some embodiments, the digital controller  26 , constant current sources CCS, DAC  25  and switching arrangement  21  are provided on a first printed circuit board (also referred to a the tDCS board) similar in size to a second printed circuit board (also referred to as the EEG board) that contains the EEG components of the aforementioned Emotiv headset. The EEG board, located above the wearer&#39;s ear in  FIG. 1 , generally corresponds to the EEG analyzer  24  of  FIG. 2 . Suitable openings are cut into the housing around the EEG board to permit mounting the tDCS board to the EEG board using suitable conventional techniques. Jumper wires are used to insert the switching arrangement  21  electrically between the headset electrodes and the EEG board. This to results in a modified headset that conforms electrically to  FIG. 2 , and has a physical structure similar to that of the Emotiv headset shown in  FIG. 1 . 
         [0033]      FIG. 12  diagrammatically illustrates the above-described arrangement wherein the tDCS board  121  (containing the digital controller  26 , constant current sources CCS, DAC  25  and switching arrangement  21  of  FIG. 2 ) is mounted to the EEG board  122  by suitable mounting structure  123  that extends through openings in the housing  125  that surrounds the EEG board  122 . Jumper wires  126  connect the Emotiv electrode cabling  128  to the tDCS board  121 , and jumper wires  127  connect the tDCS board  121  to the EEG board  122 . In some embodiments, the host computer  27  (see also  FIG. 2 ) is connected to the tDCS board  121  by a USB cable, and the tDCS board  121  is powered by connection to a suitable power supply, such as a 9V or 18V battery. 
         [0034]    Various embodiments use various combinations of scalp electrodes and EEG analyzers. For example, in some embodiments, the electrodes  22  of  FIG. 2  are provided by a commercially available, disposable headset, and the EEG analyzer  24  is provided by a laboratory-grade EEG apparatus. 
         [0035]      FIG. 8  illustrates operations that may be performed according to example embodiments of the present work. In some embodiments, the operations of  FIG. 8  are performed by the system of  FIG. 2  automatically, under control of the digital controller  26  and host  27 . At  81 , with the electrodes connected for EEG mode operation, the electrodes are monitored for EEG purposes as is conventional. At  82 , the electrode connections are switched to a desired configuration (see also  FIGS. 3 and 4 ) for tDCS mode operation. At  83 , one or more selected tDCS currents are driven to one or more of the electrodes by one or more constant current sources for a desired interval of time. Various embodiments use various tDCS current drive intervals. As one example, the tDCS current drive interval is 15 minutes in some embodiments. When the tDCS current drive operation is completed at  83 , the electrode connections are immediately switched to back to EEG mode at  84 . As mentioned above, some embodiments switch from tDCS mode to EEG mode in less than two microseconds. After the switch to EEG mode at  84 , the electrodes are again monitored for EEG purposes at  81 . 
         [0036]    In some embodiments, the application of tDCS current includes ramping the output current up to the desired value. In some embodiments, the tDCS current is similarly ramped down to zero. Various embodiments employ various waveforms to effect application and removal of tDCS current. 
         [0037]    Some embodiments provide capability to compensate automatically for the aforementioned leakage current that flows through resistor R 12  in  FIG. 6 . To compensate for the leakage current, the anode voltage (at Output−) is measured, and the amount of leakage current flowing to the differential amplifier is calculated as 
         [0000]      [(Output−)−(Input+)]/900 k (for  R 11 and  R 12 of 450 kΩ).
 
         [0038]    The set point of the input voltage (Input+−Input−) is then adjusted such that the corresponding output current is equal to the sum of the desired load current and the calculated leakage current. The current flowing into the load then matches the desired current. In some embodiments, the automatic leakage current compensation is updated once per second. Various embodiments update the leakage current compensation at various rates. 
         [0039]      FIG. 9  illustrates an example of the aforementioned automatic leakage current compensation according to the present work. The operations of  FIG. 9  may be integrated into the tDCS current drive operation  83  of  FIG. 8 . The operations at  91  and  92  drive the desired output current(s) at  91  until it is determined at  92  that an update interval has expired. When the update interval expires, the anode voltage is measured at  93 , after which the leakage current is calculated at  94 . At  95 , the set point of the input voltage is adjusted such that the corresponding output current is equal to the sum of the desired load current and the calculated leakage current. This adjustment accommodates the effect of the leakage current on the load current. 
         [0040]      FIG. 10  diagrammatically illustrates an analog-to-digital converter (ADC)  101  that is cooperable with the digital controller  26  via bus  28  (see also  FIG. 2 ) for implementing automatic leakage current compensation according to example embodiments of the present work. The ADC  101  communicates with the controller  26  on bus  28 , and receives the anode voltages AN 1 -ANm as analog inputs to permit measurement of those voltages. The controller  26  of  FIG. 2  periodically reads an anode voltage measurement as provided on bus  28  by ADC  101 , calculates the leakage current based on the measurement, and appropriately updates the input voltage set point via the DAC  25 . In some embodiments, the ADC  101  is implemented with the LTC1867LA 16-bit, 8-channel ADC available from Linear Technology Corporation. 
         [0041]    As also shown in  FIG. 10 , some embodiments use the ADC  101  to measure the voltage on both sides of Rset. The controller  26  may then divide the voltage difference by the value of Rset to produce an estimate of the current through Rset. In some embodiments, the ADC  101  also measures the cathode voltage CATH. In some embodiments, the controller  26  uses available anode and cathode voltage measurements, together with the selected output current and Ohm&#39;s Law, to produce a rough calculation of the resistance between any two subsets of the electrodes. In some embodiments, the ADC  101  measures the battery voltage. 
         [0042]    In some embodiments, the host  27  (see also  FIG. 2 ) implements a graphical user interface (GUI) that provides a user with convenient access to set points, measurements and electrode configurations. An example of such a GUI is shown in  FIG. 11 . 
         [0043]    Although example embodiments of the present work are described above in detail, this does not limit the scope of the present work, which can be practiced in a variety of embodiments.