The studies of the Functional Neurosurgery Lab currently test whether neural activity related to the experimental vigilance and conditioned expectation toward pain can be described by interrelated networks in the brain. These two psychological dimensions play an important role in chronic pain syndromes, but their neuroscience is poorly understood. Our studies of spike trains and LFPs utilize an anatomically focused platform with high temporal resolution, which complements fMRI studies surveying the whole brain at lower resolution. This platform to analyze the oscillatory power of structures in the brain, and functional connections (interactions and synchrony and causal interactions) between these structures based upon signals recorded directly from the waking human brain during surgery for epilepsy and movement disorders, e.g. tremor. Our studies have demonstrated that behaviors related to vigilance and expectation are related to electrical signals from the cortex and subcortical structures. These projects are based upon the combined expertise of Dr. Nathan Crone in recordings and clinical management of the patients studied; Dr. Anna Korzeniewska in the analyses of signals recorded from the brain; Drs. Claudia Campbell, Luana Colloca and Rick Gracely in the clinical psychology and cognitive neurology of the expectation of pain and chronic pain; Dr. Joel Greenspan in quantitative sensory testing; and Dr. Martin Lindquist in the statistical techniques. Dr. Lenz has conducted studies of this type for more than thirty years with continuous NIH funding.

The research goals of the Functional Neurosurgery Laboratory include the development of computational models to understand how brain function is affected by neurological conditions and how this abnormal function might be corrected or minimized by neuromodulation through electrical stimulation. The lab uses data collected from patients during epilepsy monitoring or in the operating room during DBS procedures to construct and calibrate the computational models. The models can be manipulated to explore functional changes and treatment possibilities. The other primary goal of the laboratory is the development of a neuromodulation system that applies stimulation pulses at specific phases of brain oscillatory activity. This technique is being explored in the context of Parkinson's disease as well as memory function, and may lead to less invasive therapeutic treatment system with more effective stimulation.

The Hey-Kyoung Lee Lab is interested in exploring the cellular and molecular changes that happen at synapses to allow memory storage. We use various techniques, including electrophysiological recording, biochemical and molecular analysis, and imaging, to understand the cellular and molecular changes that happen during synaptic plasticity. Currently, we are examining the molecular and cellular mechanisms of global homeostatic synaptic plasticity using sensory cortices as model systems. In particular, we found that loss of vision elicits global changes in excitatory synaptic transmission in the primary visual cortex. Vision loss also triggers specific synaptic changes in other primary sensory cortices, which we postulate underlies sensory compensation in the blind. One of our main research goals is to understand the mechanisms underlying such cross-modal synaptic plasticity. We are also interested in elucidating the events that occur in diseased brains. In collaboration with other researchers, we are analyzing various mouse models of Alzheimer's disease, especially focusing on the possible alterations in synaptic plasticity mechanisms.

Dr. Haughey directs a disease-oriented research program that address questions in basic neurobiology, and clinical neurology. The primary research interests of the laboratory are: 1. To identify biomarkers markers for neurodegenerative diseases including HIV-Associated Neurocognitive Disorders, Multiple Sclerosis, and Alzheimer’s disease. In these studies, blood and cerebral spinal fluid samples obtained from ongoing clinical studies are analyzed for metabolic profiles through a variety of biochemical, mass spectrometry and bioinformatic techniques. These biomarkers can then be used in the diagnosis of disease, as prognostic indicators to predict disease trajectory, or as surrogate markers to track the effectiveness of disease modifying interventions. 2. To better understand how the lipid components of neuronal, and glial membranes interact with proteins to regulate signal transduction associated with differentiation, motility, inflammatory signaling, survival, and neuronal excitability. 3. To understand how extracellular vesicles (exosomes) released from brain resident cells regulate neuronal excitability, neural network activity, and peripheral immune responses to central nervous system damage and infections. 4. To develop small molecule therapeutics that regulate lipid metabolism as a neuroprotective and restorative strategy for neurodegenerative conditions.

Our team is focused on understanding how complex movements are normally learned and controlled, and how damage to specific brain areas impairs these processes. We employ several techniques to quantify movement including: 3-dimensional tracking and reconstruction of movement, recordings of muscle activity, force plate recordings, and calculation of joint forces and torques. These techniques allow for very precise measurements of many different types of movements including: walking, reaching, leg movements, hand movements and standing balance. All studies are designed to test specific hypotheses about the function of different brain areas, the cause of specific impairments and/or the effects of different interventions.

Dr. Fridman's research group invents and develops bioelectronics for Neuroengineering and Medical Instrumentation applications. We develop innovative medical technology and we also conduct the necessary biological studies to understand how the technology could be effective and safe for people. Our lab is currently focused on developing the ""Safe Direct Current Stimulation"" technology, or SDCS. Unlike the currently available commercial neural prosthetic devices, such as cochlear implants, pacemakers, or Parkinson's deep brain stimulators that can only excite neurons, SDCS can excite, inhibit, and even sensitize them to input. This new technology opens a door to a wide range of applications that we are currently exploring along with device development: e.g. peripheral nerve stimulation for suppressing neuropathic pain, vestibular nerve stimulation to correct balance disorders, vagal nerve stimulation to suppress an asthma attack, and a host of other neuroprosthetic applications. Medical Instrumentation MouthLab is a ""tricorder"" device that we invented here in the Machine Biointerface Lab. The device currently obtains all vital signs within 60s: Pulse rate, breathing rate, temperature, blood pressure, blood oxygen saturation, electrocardiogram, and FEV1 (lung function) measurement. Because the device is in the mouth, it has access to saliva and to breath and we are focused now on expanding its capability to obtaining measures of dehydration and biomarkers that could be indicative of a wide range of internal disorders ranging from stress to kidney failure and even lung cancer.

The Cognitive Neuropsychiatric Research Laboratory (CNRLab) is part of the Division of Cognitive Neuroscience within the Department of Neurology at the Johns Hopkins University School of Medicine. Its current projects include investigating the motor system's contribution to cognitive function; HIV-related neuroplasticity and attention-to-reward as predictors of real world function; and brain function and cognition in Lyme disease.

We are exploring whether anodal tDCS when administered in combination with spelling, naming, or working memory therapy can improve language performance of PPA and MCI participants at least in the short term more than behavioral therapy alone. We are also investigating whether and how tDCS alters the neuropeptide signature in participants with PPA and MCI. We use proton magnetic resonance spectroscopy (1H-MRS) to monitor neuropeptide concentrations at the areas of stimulation. We hypothesize that tDCS will stabilize the decline of specific neuropeptides, but only in those areas of the brain where tDCS effectively results in more efficient gains in language compared to language therapy alone (with sham tDCS). Study results may help optimize future intervention in individuals with PPA and MCI by providing treatment alternatives in a neurodegenerative condition with no proven effective treatment. A better understanding of the therapeutic and neuromodulatory effects of tDCS in PPA and MCI will offer insight into ways of impeding neurodegeneration that may improve quality of life for individuals with PPA and MCI and may provide insights into the mechanisms of this treatment for augmenting therapy for stroke as well.

The Seth Margolis Laboratory studies the signaling pathways that regulate synapse formation during normal brain development to try to understand how, when these pathways go awry, human cognitive disorders develop. We use Ephexin5 to study the molecular pathways that regulate restriction of excitatory synapse formation and their relevance to the pathophysiology of Angelman syndrome.

The mission of the Stroke Cognitive Outcomes and Recovery (S.C.O.R.E.) Lab is to enhance knowledge of brain mechanisms that allow people recover language, empathy, and other cognitive and communicative functions after stroke, and to improve ways to facilitate recovery of these functions after stroke. We also seek to improve the understanding of neurobiology of primary progressive aphasia., and how to enhance communication in people with this group of clinical syndromes.