Neurobehavioral Research Unit (NBRU)

The NBRU, located at Kennedy Krieger Institute, is one of four research units of the Johns Hopkins General Clinical Research Center (GCRC). The GCRC program was established in 1960 to create and sustain specialized institutional resources in which clinical investigators can observe and study human physiology, as well as study and treat disease with innovative approaches. Centers operate as discrete, multi-departmental, multi-categorical resources where scientists from many departments complement their laboratory studies with carefully controlled clinical investigations and analyses. The Johns Hopkins University has one of the largest, most comprehensive GCRCs in the United States.

The NBRU offers three major service components: neurobehavioral assessment, neuroimaging and inpatient beds. The NBRU is uniquely suited to provide clinical management, neuroimaging and neurobehavioral assessment, especially to pediatric populations who have rare brain disorders. These research resources have become available as of January 1999, and complement -- rather than compete with -- the existing scientific capabilities of the Hopkins GCRC. Enhancing the major service components of the NBRU, and also located in the facility, are the audiology department and the Center for Movement Studies. Available to all Hopkins faculty and collaborating scientists at other research centers, the NBRU provides not only a local, but a needed national research resource.

Neurobehavioral Assessment:

Neurobehavioral assessment resources include the full range of neuropsychological assessments, operant performance testing using equipment and paradigms appropriate for use with subjects of any intellectual level, including profound intellectual disabilities, and any level of behavior disorder, including children with autism and post-traumatic brain injury. These services will be provided by the Departments of Behavioral Psychology and Neuropsychology at the Kennedy Krieger Institute.

• Neuropsychological Assessment: Experienced psychologists are available to assist with research design and selection of measures for neuropsychological variables of interest. These variables might include aspects of intelligence, attention, memory and other executive functions, language, visual-spatial skills, personality, behavior, emotion and academic achievement. Once a study has been approved, the Neuropsychology Research Lab also offers testing services for specific research protocols. These assessments are performed by psychologists and psychology associates with expertise in neuropsychological testing and with considerable experience working with children at a variety of developmental levels. For more information on the types of services available and how to access services, please consult the Neuropsychology Research Lab website.

• Operant Performance Measures: Direct observation of behavior conducted in areas that simulate naturalistic settings is accomplished by the use of desktop and laptop computers with accompanying customized software that allows for the simultaneous recording of up to twenty behaviors for real time analysis, including conditional probability calculations.

• Customized Assessments: Specialized, or customized, testing of behavioral characteristics, performances and learning repertoires is available in the NBRU. In addition to both MAC and IBM desktop and laptop computers, resources include touch screens, scanners, voice synthesizers and input devices appropriate for use with children and adolescents with disabilities. There are also video cameras, recorders and monitors for direct observation and data coding, computer peripherals for customizing video displays for stimulus presentation and commercially available or custom designed software applications to implement computerized standard learning and performance tasks.

Neuroimaging:

Neuroimaging resources include structural and functional magnetic resonance imaging, spectroscopic and diffusion analysis, fiber track mapping, fMRI protocol development and training of pediatric and brain/behavior disordered subjects to cooperate with research protocols, including motion control during scans. The F.M. Kirby Research Center for Functional Brain Imaging is dedicated to brain research using functional MRI technologies and is specifically designed to provide a uniquely comfortable scanning environment for studies in children, the elderly and subjects with neurological and psychiatric disorders. The center opened in May 1999 with a 1.5 Tesla scanner, and was upgraded in early 2002 with the addition of a 3.0 Tesla scanner (both from Philips Medical Systems). Both magnets are unique in that they have very short bores -- for example, the 1.5T scanner has the shortest bore available of all 1.5T scanners. The special design of the Center includes enhanced MRI signal-to-noise and temporal stability, integration of dedicated equipment for stimulus provision and subject monitoring and a second radio-frequency channel to allow heteronuclear and homonuclear MR spectroscopy interleaved with fast imaging. The Center was established through the combined efforts of neuroscientists, physicists and radiologists at KKI and Johns Hopkins University, who concluded that functional neuroimaging would thrive in a resource dedicated to brain research where newly developed methods could be applied directly to neuroscience. MRI techniques available and being developed include imaging of brain blood flow and oxygen consumption, imaging of brain metabolite levels and metabolic activity and imaging of axonal connections. In addition, an MRI-compatible electroencephalogram (EEG) and high-resolution evoked potential (EP) system has been obtained to complement the Phillips functional MRI systems. This EEG system is intended for studies that will permit correlation of fMRI data with neurophysiological monitoring and should provide investigators with a system for high-resolution EEG-EP acquisition and analysis and spatial co-registration of the EEG/EP data with fMRI. More information about the Kirby Center may be found on-line at mri.kennedykrieger.org.

• Protocol Development: The NBRU will assist investigators in the development of research protocols, including neuroimaging paradigms, customized assessments and operant performance tasks.

• Behavior Training: Staff of the NBRU will train research subjects to cooperate with protocols, which is especially important with pediatric subjects and subjects with behavior and compliance problems. fMRI protocol development will be based on the activation criteria specified by investigators and the abilities of subjects to cooperate with special tasks. Specifically, behavioral protocols will be designed based on the specific fMRI acquisition goals of the study and the abilities of NBRU staff to train subjects to cooperate with the protocol. The end product will be a neuroimaging paradigm that addresses each investigator's hypothesis and specifies the behavioral performance and cortical activation tasks and related procedures that ensure the needed subject cooperation, response acquisition, motion control, etc.

Inpatient Beds:

The NBRU will have the capability to manage acute medical problems while accommodating patients (including children of all ages) with visual, auditory, communication and behavioral disorders.

• On the Neurobehavioral Unit (NBU), for those persons who cannot be accommodated on Osler 5 or the PCRU at Johns Hopkins (because of behaviors associated with brain disorders, including self-injurious behavior)

• On the Brain Injury Unit (BIU), for those persons requiring intensive neurorehabilitation as the result of acute head injury, including patients in coma. This unit is the regional acute brain injury resource and because of the close proximity to the neuroimaging center two floors below, imaging studies with this population can be safely carried out.

The Audiology Department:

The Audiology Department has a wide variety of procedures available for assessment of peripheral and central auditory function. The department has experience in administration of auditory evoked potentials, including the auditory brainstem response, middle latency response, long latency response and mismatch negativity. Behavioral audiometric procedures include audiological screenings, comprehensive audiological evaluations and central auditory processing evaluations. The department has the capability to assess middle ear function utilizing conventional procedures as well as multi-frequency and high-frequency tympanometry. Measurements of otoacoustic emissions can be made utilizing transient evoked otoacoustic emissions, as well as distortion product otoacoustic emissions. The department also has a number assessment procedures and capabilities available for various populations.

The department has state-of-the-art hardware for psychoacoustic and speech research involving older children based upon Tucker-Davis Technologies modular hardware (described in detail at www.tdt.com). The software available enables simple and complex non-speech, as well as natural and synthetic speech to be presented under computer control with automated recording of patient responses. The software may be of potential use in assessing the auditory discrimination abilities of children with a variety of language learning difficulties.

Center for Movement Studies:

The Center for Movement Studies was built for quantitative, whole-body movement assessments and is located on the ground floor of the Kennedy Krieger Institute. Several techniques are used to quantify movement, including three-dimensional tracking and reconstruction of movement kinematics, force plate recordings, recordings of muscle activity and calculation of joint forces and torques. The laboratory is equipped with an Optotrak motion measurement system (Northern Digital Inc.) with two infrared 3-D position sensors. These sensors allow researchers to track infrared markers placed on the joints of the body, bilaterally. Using the Optotrak system, we can make very precise measurements of natural movements, including (but not limited to) walking, reaching, leg movements, hand movements and standing balance. The laboratory houses two Kistler force plates, which allow us to measure the forces exerted on the floor by a person standing, walking or running. In addition, we have equipment to record surface muscle activity (electromyography or EMG). We have also purchased a custom treadmill that allows us to control the two legs independently (split-belt treadmill).

There are several active projects in the Center for Movement Studies at this time. Most of the work is focused on understanding motor disorders in adults and children who have damage or disease of the central nervous system. The main goals of these studies are to understand the mechanisms of different types of motor disorders and determine how and why different treatments improve movement. Ongoing studies are also aimed at determining how new movements are learned and what the course of movement recovery following different types brain damage is. One specific focus of the laboratory is determining how cerebellar damage causes limb and gait ataxia. This work is funded by the National Institutes of Health. Other active studies in the laboratory address the movement disorders and treatments associated with cerebral palsy, adrenomyeloneuropathy and Parkinson's disease. Overall, the quantitative information that can be obtained from the Center for Movement Studies will provide a better understanding of the mechanisms of movement deficits and allow investigators to detect very small changes in movement performance over time or with treatment.