High-frequency subthalamic nucleus (STN) deep brain stimulation (DBS) is used to treat the movement disorders Parkinson’s disease and dystonia. However, the therapeutic mechanisms of DBS are not well understood. Electroencephalographic (EEG) studies in ...

Combination therapies are being developed to improve memory in cases of mild cognitive impairment and early stage Alzheimer’s. To this end, we followed changes in brain activity caused by a serotonin receptor antagonist given alone or in combination wit...

Emerging technologies allow whole brain imaging and electrophysiology of the living brain. Results are changing our concepts of how various brain regions integrate for coordinated processing to produce emotional states evidenced by behavior. Manganese-e...

Background: ThinkRx, an intensive, 60+ hour, clinician delivered, one-on-one, multi-construct cognitive rehabilitation training program, has been shown to remediate cognitive skill deficits resulting from acquired and traumatic brain injury. In previous...

Background: The earliest brain changes in Alzheimer’s disease (AD) occur in the locus coeruleus (LC), the major noradrenergic nucleus of the brain. The LC plays an integral role in the regulation of arousal, cognitive and autonomic function, thus degene...

Serotonin and serotonin 1A (5-HT1A) receptors play a direct role in neuronal development, cell proliferation, and dendritic branching. We hypothesized that variability in 5-HT1A density can affect cortical thickness, and may account for a subtype of maj...

Continuous intrathecal (IT) delivery of morphine sulfate (MS) for 28 days can produce aseptic subdural inflammatory masses (granulomas) localized at the catheter tip. The rate at which these IT masses develop, and if they regress after MS infusions are terminated are unknown. To assess this, we performed serial MRI scans with gadolinium (Gd) enhancement in dogs. Beagle dogs were implanted with chronic IT lumbar catheters and were infused at 0.96 ml/day for 28 days. Dogs received a 100% granuloma inducing concentration of MS (12.5 mg/ml), the maximum tolerable concentration of fentanyl HCl (2 mg/ml) or the mu specific peptide DAMGO (2 mg/ml). Before MS infusions, MRI scans were obtained with a Siemens Symphony 1.5 Tesla system while dogs were anesthetized with propofol. Dogs had repeated MRI scans at intervals ranging from 3 to 14 days, for up to 45 days, with IV Gd (Optimark, 0.2 mmol/kg). One group of dogs had saline substituted for MS at the first appearance of a mass by MRI. A second group of dogs conti...

Prior MRI studies have shown cortical gray matter increases in bipolar patients treated with lithium, but it is unknown whether this is related to the disease process. We studied serial structural MRI brain scans (3D SPGR, 1.5 mm slices) from 13 healthy subjects (6F/7M; mean age: 25.5 yrs.+/-10.0SD, scan interval: 4 weeks) treated with 0.5-1.5 mEq/L lithium (a therapeutic dose). To map 3D patterns of local tissue changes over time, an intensity-based elastic registration algorithm deformed the follow-up to the baseline scan by maximizing the mutual information. A tissue change map (the Jacobian of the deformation), for each individual, was nonlinearly normalized to the anatomical space of a reference subject. Mean lithium effects were established by voxel-wise averaging the log-transformed Jacobian maps. Significant tissue hypertrophy was detected. A 2-4% average volume increase was detected in primary sensorimotor and superior frontal regions, consistent with tissue gains localized in prior cortical mappi...

MRI studies have shown dramatic age-associated changes in grey and white matter volume, but typically use univariate analyses that do not explicitly test the interrelationship among brain regions. The current study employed a multivariate approach to identify covariance patterns of grey and white matter tissue density to distinguish older from younger adults. A second aim was to examine whether the expression of these age-associated covariance topographies is related to performance on cognitive tests affected by normal aging. Methods: 84 young (M age=24.0) and 29 older (M age=73.1) participants were scanned with a 1.5 T MRI and assessed with a cognitive battery. Images were spatially normalized and segmented to produce grey and white matter density maps. A multivariate covariance technique, based on the Subprofile Scaling Model, was used to capture sources of between- and within-group variation and to produce a series of principal components (PCs). The analysis identified a linear combination of the PCs th...

Our day-to-day life depends on the expression of high level motor skills (e.g. typing, driving, etc). Prior work has shown that local activity and the network connections of cognitive control regions in the dorsolateral prefrontal cortex (DLPFC) show ma...