Human Electrophysiology

Division Chief: Donald Robin, Ph.D.

Transcranial Magnetic Stimulation (TMS) Laboratory
Event Related Potentials (ERP) Laboratory

Transcranial Magnetic Stimulation Laboratory

Laboratory Director: Peter Fox, M.D.

The focus of the Transcranial Magnetic Stimulation (TMS) laboratory is to enhance the precision and ease with which TMS can be used for the diagnosis and treatment of neurological and psychiatric disorders and for neuroscience research. TMS is the newest and least invasive form of electrical brain stimulation. It is being developed for clinical application in pre-surgical mapping and in treatment of depression. It is also being used in neuroscientific applications to examine neural connectivity, reversible-lesion cognitive mapping, and chronometry of brain processing. Approximately 4/5 of the studies are in normal subjects; 1/5 of the studies are in patients.

Subject Testing Room: Subjects are tested in a room with a state-of-the-art PC running Neuroscan (for electrophysiology) and E-Prime (for integrated control of TMS stimulus, psychological stimuli, and subjects’ responses), an examination table, color monitor for visual presentation, and headphones.

Cadwell TMS: The RII’s primary human transcranial magnetic stimulation system is a Cadwell High Speed Magnetic Stimulator (HSMS) (Kennewick, Washington). This stimulator uses a B-shaped coil. The peak energy transfer to the coil is 225 joules. The stimulator produces a symmetric bi-phasic pulse with a total duration of about 250 µs. It is capable of delivering pulses at a rapid rate of up to 25 Hz with no reduction in intensity. The maximum rate is 60 Hz at 40% of maximum intensity. We have 2 systems.

Magstim TMS: The RII also has another transcranial magnetic stimulation system, Magstim BiStim Module (The Magstim Co. Ltd. Wales, UK). This stimulator uses a B-shaped coil. The stimulator produces a symmetric mono-phasic pulse with a total duration of about 500 µs. It is capable of delivering pulses at a slow rate of up to 0.25 Hz at maximum intensity. Two small animal coils (2 and 4 loop) are available for use with this system.

NeuroMate Robotic System: The NeuroMate Robotic System includes a five-axis robot arm; robot base and head support frame; and (ActMate) workstation. It was specifically conceived and designed for use by and with humans. It is the only robot approved by the FDA for use in neurosurgical application and the only device of its kind adapted to precise, safe, programmable positioning, with on-line co-referenced spatial coordinate systems. From 1989-1995, over 2500 neurosurgical procedures have been performed with NeuroMate. The NeuroMate Robotic System includes a five-axis robot arm; robot base and head support frame; and (ActMate) workstation. The tool holder contains sensors suitable for monitoring rotational movement of the tool in the holder. The NeuroMate has automatic self-blocking joints, sensor redundancy, and an embedded controller, which are key to its accuracy and safety. All joints are powered by worm gears, making them very stable (for tool holding) and absolutely rigid during power surges and loss. Once positioned, the NeuroMate can be de-powered with no change of position; it does not return to a home position. It is an automatic and extremely accurate positioning device. Its absolute accuracy (positioning 0.75 mm; orientation 0.125°) and repeatability (positioning 0.15 mm; orientation 0.02°) are well suited for accurate positioning of TMS coils at the scalp. Positions are achieved within 45 seconds, directly after trajectory validation on the image planner. The NeuroMate has no geometric limitations due to mechanics. The patient’s head always remains accessible. It has low EM emission, easy cleaning, and ergonomic design appropriate to experimental environment. Its inherent safety features and built-in controls will be efficiently integrated into a 2nd generation TMS- AHRM system in the future.

Microscribe Digitizer: The MicroScribe 3DLX, from Immersion Corp. (San Jose, CA) is a precision mechanical arm used to acquire 3D coordinates (see figure). The arm has five axes with precise encoders, which combine to track the position and orientation of the stylus tip. This particular version of the arm has a spherical workspace of 66" (1.67 meters) and an accuracy of 0.012" (0.30 mm). It supports RS232 serial interface to host computer, and has an internal sampling rate of 1000 per second.

Electromyography (EMG): The TMS lab has a Neuroscan SynAmps 32 channel EEG/ERP system running Scan 4.3 acquisition and analysis software that is used to record EMG. In addition there is a custom 8-channel double differential surface EMG (sEMG) system (Motion Lab Systems, Baton Rouge, LA). The TMS lab also has SML-10 strain gauges and a 9840 intelligent indicator (Interface, www.interfaceforce.com) to provide constant feedback of the muscle forces.

E-Field Measurement: Currently we measure the electric field using both a custom-made dipole probe and a custom-made coil probe. The output from these probes is measured using a Tektronix TDS 320 100 MHz, 2-channel digital oscilloscope. We have calculated and verified comprehensive 3-D E-Field maps for all TMS coils.

 

Behavioral Apparatus: RII investigators also conduct psychological experiments to develop the behavioral paradigms that serve as the basis for PET and TMS experiments, as well as for fMRI and ERP studies. In these experiments, a computer presents visual or auditory stimuli and collects either verbal, button-press, or joystick responses from a subject, which then can be analyzed for accuracy, reaction times, or other behavioral parameters. These computer experiments are conducted using either E-Prime (Psychology Software Tools, Inc.) on PC platform, SuperLab (Cedrus, Inc.) on an Apple or PC platform. Further the laboratory has audio and video recording capabilities during motor and speech studies.

 

TMS Funded Grants:

1. “Mechanisms of Action of TMS-Induced Performance Enhancement.” VA Merit award. PI: Peter T. Fox.

The overall goal of this project is 1) to determine the mechanisms of action of short-term (single stimulation session) TMS-induced performance enhancement. 2) To determine the mechanisms of action of long-term (multiple stimulation sessions) TMS-induced performance enhancement.

2. “Image-Guided Robotically-Positioned TMS System.” 1 R41 MH074278-01. PI: Jack L. Lancaster.

The overall goals for Phase I are: 1) incorporate current irTMS treatment planning and delivery control software, 2) add hardware specific for the new robot, and 3) test the new irTMS system by comparison with the current irTMS system.

3. “Imaging and Modeling Therapeutic Mechanisms of Action.” R21 NS43738. PI: Peter T. Fox.

The major goals of this project are to develop system-level modeling strategies for neuroimaging and to apply these novel strategies to mechanisms of action of motor learning.

4. “Imaging Mechanisms of Action in Motor Learning.” BCS- 0225711. PI: Jinhu Xiong

The major goals of this project are to develop system-level modeling strategies for neuroimaging and to apply these novel strategies to mechanisms of action of motor learning.

5. “Robotic Image-Guided Transcranial Magnetic Stimulation.” R01 MH60246-03. PI: Peter T. Fox.

The major goal of this project is to enhance the precision and ease with which transcranial magnetic stimulation (TMS) can be used for the diagnosis and treatment of neurological and psychiatric disorders and for neuroscience research.


Event Related Potentials Laboratory

Laboratory Director: Nicole Y. Y. Wicha, Ph.D.

Contact Marshall Naylor for information. Phone - (210) 567-8165

The focus of the Electrophysiological Imaging Division is spatio-temporal mapping of information processing in the human brain in health and disease. Event-related potentials (ERPs) are the most frequently performed type of electrophysiological study. ERPs are scalp-recorded voltage fluctuations resulting from evoked neural activity. These are extracted from the background EEG by time-locked selective averaging and provide very high temporal resolution reflection of the patterns of neuronal activity evoked by sensory, cognitive or motor events. Roughly 3/4 of the studies are in normal subjects and 1/4 in patients.

Facilities: The ERP lab consists of two audiometric examinations rooms, a preparation room and a workstation room. The examination rooms are custom installed double-wall insulated, sound-attenuating, RF-shielded testing chambers (Industrial Acoustics) measuring 8’8”w x 8’6”l x 6’6”h and 9’0”w x 7’0”l x 6’6”h. The larger testing room can comfortably seat two participants for any studies involving real-time human feedback or interaction. Each testing room is equipped with adjustable interior lighting and a monitoring window (the integrity of the RF shielding is protected in all cases), as well as a participant chair, adjustable table and an intercom system communicating to outside the chamber. Both chambers can be used as auditory recording booths, or for behavioral testing when a sound-attenuated environment is needed. The prep room includes locking storage cabinets for supplies and sensitive materials (e.g., completed consent forms) and a large sink for cleaning and disinfecting recording equipment. The workstation room houses computers for experimental design and testing, and data processing and analysis. In addition, engineers with access to mechanical and electronic workshop facilities for repair of ERP equipment or construction of custom-built equipment are available at the Research Imaging Institute.

 

Data Acquisition: The ERP chamber is equipped with a BioSemi ActiveTwo EEG/ERP system, which uses “active” electrode technology, with a preamplifier located at each recording electrode to increase the signal-to-noise ratio. The electrodes snap into an elastic cap (Electrocap) with preset labeled holes, and are connected directly to a battery-powered analog-to-digital conversion box (AD-box). Additional external electrodes for monitoring eye movement or physiological activity (e.g., GSR) can also be used. Each AD-box channel consists of a low-noise DC-coupled post-amplifier, with a first order anti-aliasing filter, followed by a Delta-Sigma modulator with an over-sampling rate of 64, and decimation filter with a steep fifth order sinc response and high resolution 24-bit output. The digital outputs of all the AD converters (capacity for up to 256 channels of data) are digitally multiplexed and sent to a PC via a single optical fiber without any data compression or reduction. The amplifiers have 4 user-adjustable sampling rates (2, 4, 8 or 16 kHz per channel). A receiver unit converts the optical data coming from the AD-box to an USB2 output. In addition, the USB2 receiver has a trigger port with 16 independent trigger inputs and 16 independent trigger outputs. This setup keeps the complete stimulation setup galvanically isolated from the subject. The trigger output signals can be controlled with an independent LabVIEW thread integrated in the BioSemi acquisition software. The trigger inputs allow easy setup of EP/ERP measurements, and event logging. Digital EEG/ERP data is stored on a PC running Windows XP and ActiView acquisition software (based on Labview). ActiView is a free open-source complete acquisition program designed to display all ActiveTwo channels on screen during recording and save all the data to (network) disk in BioSemi Data Format (BDF).

 

Stimulus Generation and Behavioral Responses: Stimulus generation will be accomplished using Presentation software running on a Windows XP platform PC. Presentation has the capacity to display the stimulus, both to the participant in the chamber and the experimenter outside the chamber using a video splitter, as well as continuous real-time monitoring of performance (e.g., behavioral responses such as button press) and upcoming stimuli (using a script dialog). Presentation reports precise timing for each stimulus and response event (critical for ERP research) to the digitization computer and interfaces with standard low cost input devices (e.g., mouse, joy-stick or serial response box). Presentation has a powerful scripting language that allows ample flexibility for experiment design and stimulus generation. This chamber will be equipped with a 21-inch CRT color monitor with low distortion and high refresh rate for visual-stimulus presentation, headphones for auditory-stimulus presentation, an ergonomic finger-response pad and a table-mounted video camera connected to a monitor outside the chamber. A monitor switch is used to switch between stimulus presentation and real time data acquisition on the participant monitor when necessary. For psychophysical-level control of the stimuli in auditory experiments, the computer-generated acoustic stimuli will be funneled through additional equipment in an auditory rack containing special filters, a mixer and decibel-precision attenuators.

 

Data Processing and Analysis: A Linux platform (Red Hat Enterprise) PC runs EEG/ERP analysis software, including ERPSS (free open source software from the Hillyard lab at UCSD), which has sophisticated programs for artifact rejection, selective averaging to extract the ERPs, data manipulation, calculating topographic contour plots of both the voltage potentials and reference-free current-source densities (CSDs), and plotting of both the ERP waveforms and the various types of contour plots. We are acquiring EEGLab (free open source software from the Makeig Lab at UCSD; Delorme and Makeig, 2004), another powerful software package that provides complimentary analysis tools to ERPSS using Independent Components for source localization, time/frequency for dynamic brain activity analysis and other methods. The lab also owns the Brain Electrical Source Analysis (BESA) software (M. Scherg) for dipole source localization. Additional software and strategies have been developed in-house to integrate the ERP data with data sets from the other brain imaging technologies at the center (i.e., structural MRI, functional MRI, and PET).

 

Scalp 3-D Spatial Digitization: The ERP lab is acquiring a handheld Polhemus Patriot 3D Digitizer system with stylus, for spatial mapping of the scalp electrodes. These spatial coordinates will be used when overlapping data collected from other imaging techniques, such as fMRI, for the same individual. Scalp mapping is currently done using equipment in the TMS laboratory at the Research Imaging Institute.