Faculty Bibliography

The Defense Automated Neurobehavioral Assessment (DANA) is a new neurocognitive assessment tool that includes a library of standardized cognitive and psychological assessments, with three versions that range from a brief 5-minute screen to a 45-minute complete assessment. DANA is written using the Android open-source operating system and is suitable for multiple mobile platforms. This article presents testing of DANA by 224 active duty U.S. service members in five operationally relevant environments (desert, jungle, mountain, arctic, and shipboard). DANA was found to be a reliable instrument and compared favorably to other computer-based neurocognitive assessments. Implications for using DANA in far-forward military settings are discussed.

BACKGROUND:This study examines the effect of initiating medications with anticholinergic activity on the cognitive functions of older persons. METHODS:Participants were 896 older community-dwelling, Catholic clergy without baseline dementia. Medication data was collected annually. The Anticholinergic Cognitive Burden Scale was utilized to identify use of a medication with probable or definite anticholinergic activity. Participants had at least two annual cognitive evaluations. RESULTS:Over a mean follow-up of 10 years, the annual rate of global cognitive function decline for never users, prevalent users, and incident users was -0.062 (SE = 0.005), -0.081(SE = 0.011), and -0.096 (SE = 0.007) z-score units/year, respectively. Compared to never users, incident users had a more rapid decline (difference = -0.034 z-score units/year, SE = 0.008, p<0.001) while prevalent users did not have a significantly more rapid decline (p = 0.1). CONCLUSIONS:Older persons initiating a medication with anticholinergic activity have a steeper annual decline in cognitive functioning than those who are not taking these medications.

BACKGROUND:Computerized neurocognitive testing (NCAT) has been proposed to be useful as a screening tool for post-deployment cognitive deficits in the setting of mild traumatic brain injury (mTBI). We assessed the clinical utility of post-injury/post-deployment Automated Neurocognitive Assessment Metric (ANAM) testing, using a longitudinal design to compare baseline ANAM tests with two post-deployment ANAM tests in a group of Marines who experienced combat during deployment. METHODS AND FINDINGS/RESULTS:Post-deployment cognitive performance and symptom recovery were compared in a subsample of 1324 U.S. Marines with high rates of combat exposure during deployment. Of the sample, 169 Marines had available baseline and twice repeated post-deployment ANAM results. A retrospective analysis of the ANAM data, which consisted of a self-report questionnaire about deployment-related blast exposure, recent history of mTBI, current clinical symptoms, and cognitive performance. Self-reported concussion sustained anytime during deployment was associated with a decrease in cognitive performance measured between 2-8 weeks post-deployment. At the second post-deployment test conducted on average eight months later, performance on the second simple reaction time test, in particular, remained impaired and was the most consistent and sensitive indicator of the cognitive decrements. Additionally, post-concussive symptoms were shown to persist in injured Marines with a self-reported history of concussion for an additional five months after most cognitive deficits resolved. Results of this study showed a measurable deployment effect on cognitive performance, although this effect appears to resolve without lasting clinical sequelae in those without history of deployment-related concussion. CONCLUSIONS:These results highlight the need for a detailed clinical examination for service members with history of concussion and persistent clinical symptoms. Reliance solely upon computerized neurocognitive testing as a method for identifying service members requiring clinical follow-up post-concussion is not recommended, as cognitive functioning only slowly returned to baseline levels in the setting of persistent clinical symptoms.

The current Iraq and Afghanistan conflicts have seen the highest survival rates in US service members ever, despite staggering numbers of traumatic brain injury and limb loss cases. The improvement in survival can be attributed at least in part to advances in far-forward, rapid medical treatment, including the administration of hypertonic saline solutions and decompressive craniectomies to manage elevated intracranial pressure. After evacuation to military hospitals in the continental United States, service members who have had limb loss face extensive rehabilitation. The growing amputee population has led to a burgeoning interest in the treatment of phantom limb pain and in the development of advanced prostheses.

Overactive bladder (OAB) is a common condition, particularly in the elderly. Anticholinergic agents are the mainstay of pharmacological treatment of OAB; however, many anticholinergics can cross the blood-brain barrier (BBB) and may cause central nervous system (CNS) effects, including cognitive deficits, which can be especially detrimental in older patients. Many anticholinergics have the potential to cause adverse CNS effects due to muscarinic (M(1)) receptor binding in the brain. Of note, permeability of the BBB increases with age and can also be affected by trauma, stress, and some diseases and medications. Passive crossing of a molecule across the BBB into the brain is dependent upon its physicochemical properties. Molecular characteristics that hinder passive BBB penetration include a large molecular size, positive or negative ionic charge at physiological pH, and a hydrophilic structure. Active transport across the BBB is dependent upon protein-mediated transporter systems, such as that of permeability-glycoprotein (P-gp), which occurs only for P-gp substrates, such as trospium chloride, darifenacin and fesoterodine. Reliance on active transport can be problematic since genetic polymorphisms of P-gp exist, and many commonly used drugs and even some foods are P-gp inhibitors or are substrates themselves and, due to competition, can reduce the amount of the drug that is actively transported out of the CNS. Therefore, for drugs that are preferred not to cross into the CNS, such as potent anticholinergics intended for the bladder, it is optimal to have minimal passive crossing of the BBB, although it may also be beneficial for the drug to be a substrate for an active efflux transport system. Anticholinergics demonstrate different propensities to cross the BBB. Darifenacin, fesoterodine and trospium chloride are substrates for P-gp and, therefore, are actively transported away from the brain. In addition, trospium chloride has not been detected in cerebrospinal fluid assays and does not appear to have significant CNS penetration. This article reviews the properties of anticholinergics that affect BBB penetration and active transport out of the CNS, discusses issues of increased BBB permeability in patients with OAB, and examines the clinical implications of BBB penetration on adverse events associated with anticholinergics.

OBJECTIVE:Drawing on two different populations, Israeli police and Hungarian civilians, the present study assessed the ability of individuals with posttraumatic stress disorder (PTSD) to generalize previous learning to novel situations. Past neuroimaging studies have demonstrated diminished medial temporal lobe (MTL) activation and/or reduced hippocampal volume in individuals with PTSD. Our earlier computational models of cortico-hippocampal function and subsequent experimental tests of these models in MTL-impaired clinical populations argue that even mild hippocampal dysfunction may result in subtle impairments in generalization. Therefore, we predicted that individuals with PTSD would show impaired generalization. METHOD/METHODS:We compared the performance of five groups from two countries, including 19 Israeli police with PTSD and 22 trauma-exposed police without PTSD, and 22 Hungarian civilians with PTSD, 25 trauma-exposed civilians without PTSD, and 25 individuals without PTSD unexposed to the same trauma. Participants were tested on a two-phase learning paradigm, the Acquired Equivalence Task, which measures the ability to generalize past learning to novel situations. RESULTS:We found that both PTSD and non-PTSD participants were capable of learning the initial stimulus-outcome associations, F(4, 108) = 1.79, p = .14. However, as predicted, only individuals with PTSD showed a selective deficit in generalization of this learning to novel situations (F(4, 108) = 8.35, p < .001, Partial η2 = 0.26). CONCLUSIONS:Individuals with PTSD show a selective impairment in generalization of past learning similar to other clinical populations with MTL/hippocampal dysfunction. This is consistent with an emerging view of PTSD as being not only an anxiety disorder but also a learning disorder.

Patients face two major difficulties following limb loss: phantom limb pain (PLP) in the residual limb and limited functionality in the prosthetic limb. Many studies have focused on decreasing PLP with mirror therapy, yet few have examined the same visual ameliorating effect with a virtual or prosthetic limb. Our study addresses the following key questions: (1) does PLP decrease through observation of a 3D limb in a virtual integration environment (VIE) and (2) can consistent surface electromyography (sEMG) signals from the VIE drive an advanced modular prosthetic limb (MPL)? Recorded signals from the residual limb were correlated to the desired motion of the phantom limb, and changes in PLP were scored during each VIE session. Preliminary results show an overall reduction in PLP and a trend toward improvement in signal-to-motion accuracy over time. These signals allowed MPL users to perform a wide range of hand motions.

OBJECTIVE:This study evaluated usage of the Army Knowledge Online (AKO) Telemedicine Consultation Program for neurology and traumatic brain injury (TBI) cases in remote overseas areas with limited access to subspecialists. We performed a descriptive analysis of quantity of consults, response times, sites where consults originated, military branches that benefitted, anatomic locations of problems, and diagnoses. METHODS:This was a retrospective analysis that searched electronic databases for neurology consults from October 2006 to December 2010 and TBI consults from March 2008 to December 2010. RESULTS:A total of 508 consults were received for neurology, and 131 consults involved TBI. For the most part, quantity of consults increased over the years. Meanwhile, response times decreased, with a mean response time of 8 hours, 14 minutes for neurology consults and 2 hours, 44 minutes for TBI consults. Most neurology consults originated in Iraq (67.59%) followed by Afghanistan (16.84%), whereas TBI consults mainly originated from Afghanistan (40.87%) followed by Iraq (33.91%). The most common consultant diagnoses were headaches, including migraines (52.1%), for neurology cases and mild TBI/concussion (52.3%) for TBI cases. In the majority of cases, consultants recommended in-theater management. After receipt of consultant's recommendation, 84 known neurology evacuations were facilitated, and 3 known neurology evacuations were prevented. CONCLUSIONS:E-mail-based neurology and TBI subspecialty teleconsultation is a viable method for overseas providers in remote locations to receive expert recommendations for a range of neurologic conditions. These recommendations can facilitate medically necessary patient evacuations or prevent evacuations for which on-site care is preferable.

In their recent paper, Goldstein et al. show murine brain tau neuropathology after explosive blast with head rotation but do not present additional evidence that would delineate whether this neuropathology was principally caused by blast exposure alone or by blast exposure plus head rotational injury.

The Revolutionizing Prosthetics 2009 program conducted by the Defense Advanced Research Projects Agency (DARPA) has resulted in a Virtual Integration Environment (VIE) that provides a common development platform for researchers and clinicians that design, model and build prosthetic limbs and then integrate and test them with patients. One clinical need that arose during the VIE development was a feature to easily create and model animations that represent patient activities of daily living (ADLs) and simultaneously capture real-time surface EMG activity from the residual limb corresponding to the ADLs. An application of this feature is being made by the Walter Reed Military Amputee Research Program (MARP) where they are utilizing the VIE to investigate methods of reducing upper extremity amputee phantom limb pain (PLP).