Research Environment and Resources

The Center for Cognitive Medicine is a multidisciplinary clinical and academic program designed to foster interrelated studies of brain systems supporting affective, cognitive and sensorimotor processes, and to delineate their abnormality in disease states. Our second primary aim is to test the utility of new pharmacological and psychosocial treatments using traditional clinical ratings together with novel biomarker approaches for tracking outcomes and pharmacogenetic approaches to predict beneficial and adverse treatment effects. We have a range of neuropsychological, neurophysiological (EEG and eye movements), psychophysical and neurocognitive assessment protocols active as well as an active MRI research program.

While Center investigators work in several Departments across the University, the majority of the faculty are located in the Neuropsychiatric Institute at the University of Illinois Medical Center. This location facilitates studies because the Neuropsychiatric Institute houses the outpatient services of the Psychiatry, Neurology and Neurosurgery Departments, and is directly connected by overhead bridges to both the inpatient units of the University of Illinois Hospital and the Center for MR Research. A dedicated fiber optic line connects the Center for MR Research to the Center for Cognitive Medicine facilitating rapid transfer of image data. Nine of the faculty have active NIH funding for clinical studies of autism, schizophrenia, bipolar disorder, traumatic brain injury, Parkinson's disease and cognitive disorders of late life. Several industry sponsored trials are being conducted with novel drugs or to evaluate new uses of FDA-approved medications.

Specialized Equipment and Testing Resources

Visual Psychophysics

Subject testing for visual psychophysics and eye movements are carried out in a darkened flat-black room where stimuli are presented on a (72”x96”) seamless rear projection screen via a PC computer controlled CRT projector with high spatial and temporal resolution. An examiner in an adjacent room performs testing using PC computers to control stimulus presentation and digitize eye movement recordings (obtained via scleral reflection and EOG techniques).

Stewart Techplex 150 (72”x96”) seamless rear projection screen with velux frame, Christie Digital Systems Marquee 8500 Ultra projector with 2500x2000 resolution, frequency range 39.5 – 185 Hz with automatic signal locking and open architecture system. It is controlled by a Dell Precision Workstation 330 with Intel Pentium 4 processor/850 chipset; 400Mhz system bus optimized for RDRAM; 1GB PC800 ECC RDRAM (4 RIMMS) with NVIDIA GeForce4 Ti 4200. This workstation is equipped with an nVIDA Quadro2 Pro 64MB VGA/DVI graphics card and a National Instruments DAQ/Counter Timer board PCI 6602. For fMRI studies, we use a Dell laptop with DAQ Di-720 board for A/D sampling of cardiac, respiratory and behavioral measures.

Laboratory Equipment for Eye Movement Studies:

1. Eye-trac Model 310 IR Amplifier from Applied Sciences Laboratory with 2 sets of IR recording spectacles

2. Grass Model 12 Neurodata Acquisition System (4 AC and 4 DC channels for EOG and EEG)

3. Nippon Kogaku Tokyo 907239 lensometer with eyepiece and power drum that provides measurement of the power of lenses in diopters of subjects' eye glasses. This is used to select appropriate “press on” optics (flexible plastic lenses) that are placed on a thin plastic frame attached to the Model 310 spectacle frame to correct vision so all subjects see visual stimuli with similar acuity (verified to be at least 20/40 far acuity).

Computerized Neurophysiological Data Acquisition:

Dell Optiplex GX1P 660Mhz PC records digitized eye movement data equipped with Windaq/Pro+ waveform recording software DataQ Instruments DI205 16-channel A/D converter. Identical systems are in place at the MR Center and at the Center for Cognitive Medicine so that the same stimulus presentations are possible in laboratory and fMRI studies. Windows-based eye movement analysis software developed in this laboratory is based on the REX system developed at the Laboratory for Sensorimotor Research at the National Eye Institute.

Neuropsychological, Cognitive, and Affective Testing

Ten testing rooms are devoted full time for patient testing using paper-and-pencil and computerized neuropsychological tests for our clinical work and research studies. In addition, new neurocognitive tasks designed to probe specific cognitive or emotional processes are developed by our faculty, and programmed by our IT staff using script-driven FLASH software. This software supports movie framework presentation and therefore dynamically moving visual images that can be readily adjusted based on subject performance. A description of our faculty and our clinical and research programs is available at http://ccm.psych.uic.edu.

The Penn computerized neuropsychological battery is used in the laboratory. This battery of tests developed by Ruben Gur at the University of Pennsylvania assesses emotion discrimination acuity as well as cognitive domains such as attention, memory and executive function. COGTEST is also running on office PCs, and we have been an alpha site for the COGTEST ® Inc program since early in the development of the company. Computerized neuropsychological tasks can also be run on laptops, which increases flexibility in testing individuals who may not be able to safely leave the inpatient unit or who need to be tested in their homes. These tests can be used to supplement traditional paper-and-pencil neuropsychological tests. The four laptop computers available include: PC systems (Eurocom T210C Convertible, 1.7 GHz Pentium M Laptop, with touch screen, Dell Latitude D180, Pentium M Processor 750, 1.88 GHz) and Mac systems (Apple 17-inch Powerbook 1.67 GHz PowerPC G4; 13-inch MacBook 2.0 GHz, Intel Core Duo).

Databases are designed and implemented in Microsoft Access to allow ease of data entry, double-entry checks of hand-entered data, and facilitation of importing of data from computerized neuropsychological programs. Once entered, data cannot be modified without permissions of both scientific and data management personnel.

Functional Imaging

Center For Magnetic Resonance (MR) Research

The state-of-the-art MR imaging facility is located on the ground floor of the Outpatient Care Clinic (OCC) of the University of Illinois at Chicago (UIC) Hospital (http://www.uic.edu/com/mrc/). This Center for MR Research is directed by Keith Thulborn, MD, Ph.D. This facility is immediately across the street from the Neuropsychiatric Institute which houses the Center for Cognitive Medicine, and is connected by overhead bridge. It contains the space for imaging systems and MR faculty offices for Drs. Keith Thulborn and X. Joe Zhou. The footprint of the MR Center has been expanded to house a new 9.4T human whole body MRI scanner. The new whole body 9.4T scanner for human brain imaging is now fully installed and operational. The 9.4T scanner operates the latest Paravision software from Bruker Biospin Corp. The MR Center is equipped with human subject preparation, a MR simulator room, electronics laboratory, and a conference room.

There are two 1.5 Tesla clinical scanners (LX Signa, GEMS, Milwaukee ) of which one is the LX CVi system for cardiac and functional brain imaging. The 3.0 Tesla General Electric Signa MR scanner is equipped with the EXCITE and High Definition (HD) technologies, together with a powerful gradient system capable of producing a maximum gradient of 40 mT/m at a slew rate of 150 T/m/s. The 3T scanner is also equipped with a stimulation and control system designed for functional MR experiments. Computers for image analysis are networked to computers maintaining a picture archive and communication system (PACS) in the hospital. A standard single channel transmit/receive coil is available for fMRI studies to ensure homogeneous sensitivity to BOLD effects throughout the brain. In additional to conventional quadrature birdcage head coils, an eight-channel head coil is also available for improved sensitivity and compatibility with parallel imaging. All conventional and echo-planar MR imaging and MR angiographic functions (both phase contrast and time-of-flight methods) are supported at 3T, which operates at the newest version of GE scanner control software. Perfusion and diffusion imaging, and diffusion tensor imaging, are available on this system. The magnet rooms are magnetically, acoustically and RF shielded. Magnet homogeneity is 6Hz over 22 dsv with up to 3 rd order shimming which is automated on the 3.0 Tesla magnet.

Stimulus Presentation and Response Monitoring for fMRI studies: The Center for Cognitive Medicine maintains a synchronization and stimulus control system for presentation of visual stimuli to subjects in the scanner. Identical software is used for stimulus presentation in the testing rooms at the Center for Cognitive Medicine and for fMRI studies at the Center for MR Research. We also maintain an automated synchronization/acquisition of physiological data (respiratory, cardiac) and behavioral data (response times and accuracy via finger switches and eye movement recordings), with image acquisition timing data. An auditory stimulus presentation system is in place. A Cambridge Research Systems MR Eyetracker is available to monitor eye movements during fMRI studies. This system is designed specifically for operation within a MR neuroimaging environment utilizing fiber optic connections and sensors that are constructed from non-ferromagnetic materials. The components do not effect scanner operation or image quality. It has a wide bandwidth (0-500Hz) to allow accurate measurement of saccadic and smooth pursuit metrics as well as good DC stability for measuring direction of gaze and monitoring fixation.

Image Analysis

All research staff are equipped with high-end PCs and large screen monitors linked to our server for image processing as well as the Department of Psychiatry information system servers. CD and DVD writers are used to archive raw image files and final versions of data sets used in analyses.

To support data analysis for fMRI research, the Center for Cognitive Medicine maintains a 46-processor Beowulf cluster used solely for MRI studies. The Beowulf cluster is configured with the master node running dual 933 MHz Pentium III Processors with 256KB cache (coppermine processor), 1GB PC 133 sdram, 2U rackmount case and ps/2 300 watt power supply. There are 8 nodes configured using supermicro 370DER Motherboards with dual 933 MHz Pentium III processors with 256KB cache (coppermine processor), 512MB PC 133 sdram, 1u rackmount case and ps/2 250 watt power supplies. There are 8 other nodes configured using supermicro 370DER Motherboards with dual 1.26 GHz Pentium III processors with 512KB cache (Tualatin processor), 1GB PC 133 sdram, 1u rackmount case and ps/2 250 watt power supplies. There are 7 nodes with dual 3.2GHz Intel Xeon processors with 2MB cache, 1GB DDR 400MHz memory, Dual Gigabit Ethernet controllers, 1u rackmount case and 500 Watt power supply. The nodes are interconnected with a D-Link DGS 1248T gigabit switch.

A Procom Network Attached Storage Device (NAS) storage system with 3.0 TB of storage space was designed with dual fiber channel data paths and multiple power supplies for fault tolerance. Two additional NAS systems (Dell EMC AX100i) each have 2.2 TB of disk space, resulting in a total storage capacity of 7.4 Gb. Backup is accomplished with a 36 tape Accent DLT tape changer, but all studies are immediately written to CD/DVD after they are completed. Current versions of SPM, AFNI and FIASCO software are operational on this system for image analysis.

Mock Scanner to Prepare Subjects for MRI Studies: Preparation for MRI studies in a mock MRI scanner that replicates the sound and noise of an actual MRI scanner can improve patient comfort with the experience. Biofeedback training during the MRI simulation can teach patients to minimize head movement by progressively lowing tolerated head movement, and thus reduce head motion artifact during image acquisition. Biofeedback approaches are also in place for reducing anxiety prior to scan sessions. In this way, simulation can help prepare subjects for the confinement and noise in ways that reduce anxiety-related fluctuations in physiological parameters such as heart and respiratory rate. This increases compliance with scan procedures and representativeness of study samples.

For this reason, we constructed a mock scanner at the Center for Cognitive Medicine. We have manualized a training protocol that incorporates standards for training and requirements for establishing minimal head motion over the duration of time required by image acquisition protocols. The mock scanner closely resembles the physical dimensions of the real scanner. This system provides subjects with the opportunity to examine the size of the bore from the outside and ask questions regarding the process of both feedback training and the MRI scan. Volunteers use a step stool with a handle bar (also used in the 3.0 T scanner) to get on to a table-like gurney that slides into the scanner bore. The table has a Tempur-medic mattress and standard pillow for leg comfort. Once lying on the table, a mock head coil is fitted in place to mimic the scanner environment. The mock head coil was custom designed to closely approximate the head coil used for MR studies by the UIC campus Scientific Instrument Shop. The top half slides forward and backward like a MRI head coil. The head coil is attached to the table using Velcro and, therefore, can be interchanged with other mock head coils as needed. A Patriot (Polhemus) 3D motion sensor is attached to the patient's forehead. It relays three-dimensional head motion information to a Dell computer. Motion information is displayed to both the trainer via computer monitor, and the volunteer via a small LCD screen affixed to the top of the bore. Levels of acceptable motion allowance are gradually reduced to 1 mm from start position while the patient either rests in the bore or performs tasks that will be administered during fMRI studies. The goal of this biofeedback training is to help subjects remain a stationary head position for the time course of a planned MR study. Visual and auditory feedback is provided when volunteers exceed the designated tolerance limit. Through successive steps, tolerance limits are reduced to 1 mm of movement over a 10-20-minute period. Sensory details of the scanning experience are also incorporated to approximate the demands of specific protocols, including ear plugs, a mock pulse oximeter placed on the fingertip, and other specialized devices such as button boxes.

The cylindrical bore of the mock scanner is the same length and circumference as that of our 3T scanner bore, and provides volunteers the opportunity to experience the confinement of that space. Once inside, they are presented digitally recorded scan sounds that are associated with the planned image acquisition protocol. The sounds of all the scan sequences we use are recorded directly from the 3.0 T scanner. These sounds are played with Windows Media Player through an AudioSource AMP300 stereo amplifier with a bridged dual-channel output that drives a Tactile Sound (Clark Synthesis) transducer bolted underneath the mock scanner table. This not only delivers the scanner sounds but also adds physical vibrations to the entire table, simulating both the decibel level of the scanner and the vibrations patients will experience during MRI studies. The overall effect of training in the mock scanner is to reduce distress, leave subjects in a more stable physiologic state throughout the actual scanning session, and improve the quality of data by minimizing head motion artifact.

Ovidio DeLeon , MD , a faculty member of the Center for Cognitive Medicine, directs a 37-bed general psychiatry inpatient service at the University of Illinois Hospital, Department of Psychiatry. Two of the four teams are directed by physicians working in the Center for Cognitive Medicine. The inpatient unit supports research studies, with an allocation from state funds of 200 bed days per year for medication washout periods and to allow studies to be completed before beginning treatment and after treatment has been completed. Unit staff are specially trained in implementing research procedures and maintaining patients off medications for clinical research studies.