Faculty Bibliography

AIM/OBJECTIVE:To evaluate long-term effects of levodopa-carbidopa intestinal gel on dyskinesia burden. PATIENTS & METHODS/METHODS:Posthoc analysis of the GLORIA registry assessed subgroups of advanced Parkinson's disease patients with <4 and ≥4 h/day of levodopa-induced dyskinesia at baseline. RESULTS & CONCLUSIONS/CONCLUSIONS:Mean dyskinesia duration significantly (p < 0.0001) decreased by 3.5 h in patients with ≥4 h baseline dyskinesia; conversely, dyskinesia duration increased by 1.6 h in patients with <4 h baseline dyskinesia. Quality of life improved in both subgroups. Adverse drug reactions occurred at similar rates in both subgroups. Despite increases in levodopa dose, levodopa-carbidopa intestinal gel treatment led to significant and sustained reductions in dyskinesia time, severity and associated pain in advanced Parkinson's disease patients with high baseline dyskinesia burden.

OBJECTIVE:Localization related epilepsy (LRE) is increasingly accepted as a network disorder. To better understand the network specific characteristics of LRE, we defined individual epilepsy networks and compared them across patients. METHODS:The epilepsy network was defined in the slow cortical potential frequency band in 10 patients using intracranial EEG data obtained during interictal periods. Cortical regions were included in the epilepsy network if their connectivity pattern was similar to the connectivity pattern of the seizure onset electrode contact. Patients were subdivided into frontal, temporal, and posterior quadrant cohorts according to the anatomic location of seizure onset. Jaccard similarity was calculated within each cohort to assess for similarity of the epilepsy network between patients within each cohort. RESULTS:All patients exhibited an epilepsy network in the slow cortical potential frequency band. The topographic distribution of this correlated network activity was found to be unique at the single subject level. CONCLUSIONS:The epilepsy network was unique at the single patient level, even between patients with similar seizure onset locations. SIGNIFICANCE:We demonstrated that the epilepsy network is patient-specific. This is in keeping with our current understanding of brain networks and identifies the patient-specific epilepsy network as a possible biomarker in LRE.

BACKGROUND:There are no clear guidelines on how to treat posttraumatic headache (PTH) or post-concussive symptoms (PCS). However, behavioral interventions such as cognitive behavioral therapy, biofeedback, and relaxation are Level-A evidence-based treatments for headache prevention. To understand how to develop and study further mind-body interventions (MBIs) and behavioral therapies for PTH and PCS, we developed the following question using the PICO framework: Are behavioral therapies and MBIs effective for treating PTH and PCS? METHODS:We conducted a systematic search of 3 databases (Medline, PsycINFO, and EMBASE) for behavioral interventions and MBIs with the subject headings and keywords for PTH, concussion, and traumatic brain injury (TBI). Inclusion criteria were (1) randomized controlled trials, (2) the majority of the intervention had to be behavioral or mind-body therapy focused, (3) the majority of the participants (>50%) had to have had a mild TBI (not a moderate or severe TBI), (4) published in a peer-reviewed publication, and (5) meeting pre-specified primary and/or secondary outcomes. Primary outcome(s): whether there was a significant change in concussion symptom severity (yes/no) based on the symptom severity checklist/scale used, whether there was a 50% reduction in headache days and/or disability; secondary outcome(s): sleep variables, cognitive complaints, depression, and anxiety. The search identified 917 individual studies. Two independent reviewers screened citations and full-text articles independently. Nineteen articles were pulled for full article review. Seven articles met the final inclusion criteria. The systematic review was registered in Prospero (CRD42017070072). RESULTS:Overall, there was vast heterogeneity across the studies, making it difficult to fully assess efficacy. The heterogeneity ranged from differences in patient populations, the timing of when the interventions were initiated, the types of intervention implemented, and the measures used to assess outcomes. Seven studies were identified as meeting final inclusion criteria, resulting in a total of 1108 adult participants ranging from 18 to 80. Sixty-nine percent were male. Of the 7 studies, 3 were focused on military staff (retired and active). Time post-injury for inclusion into the studies varied from 48 hours post-injury to more than 2 years post-injury. One of the 7 studies did not include time post-TBI in the inclusion criteria. Two studies recruited patients who had visited their emergency departments, 4 of the studies recruited subjects through outpatient referrals, and 1 study recruited patients who had been in a prior traffic accident with resulting chronic PTH directly from a headache center. Group cognitive behavioral therapy (CBT) sessions and telephonic counseling or communication were common intervention methods used in the studies, with group CBT being used in 2 of the studies and telephonic counseling being used in 3. Other intervention methods used included individual CBT, cognitive training, psychoeducation, and computer-based and/or therapist-directed cognitive rehabilitation. CONCLUSIONS:Many of the interventions offered vastly different methods of delivery of intervention and doses of intervention. Many of the negative studies were done after an extended duration post-injury (>1-year posttraumatic brain injury [TBI]). In addition, the participants were lumped together regardless of their pre-concussion comorbidities, their mechanism of injury, their symptoms, and the duration from injury to the start of the intervention. The mass heterogeneity found between the studies led to inconclusive findings. Thus, there are various considerations for the design of the intervention for future behavioral/MBI studies for PTH and concussion that must be addressed before the leading question of this review may be effectively answered.

A striking observation among veterans returning from the recent conflicts in Iraq and Afghanistan has been the co-occurrence of blast-related mild traumatic brain injury (mTBI) and post-traumatic stress disorder (PTSD). PTSD and mTBI might coexist due to additive effects of independent psychological and physical traumas experienced in a war zone. Alternatively blast injury might induce PTSD-related traits or damage brain structures that mediate responses to psychological stressors, increasing the likelihood that PTSD will develop following a subsequent psychological stressor. Rats exposed to repetitive low-level blasts consisting of three 74.5 kilopascal exposures delivered once daily for three consecutive days develop a variety of anxiety and PTSD-related behavioral traits that are present for at least 9 months after blast exposure. A single predator scent challenge delivered 8 months after the last blast exposure induces additional anxiety-related changes that are still present 45 days later. Because the blast injuries occur under general anesthesia, it appears that blast exposure in the absence of a psychological stressor can induce chronic PTSD-related traits. The reaction to a predator scent challenge delivered many months after blast exposure suggests that blast exposure in addition sensitizes the brain to react abnormally to subsequent psychological stressors. The development of PTSD-behavioral related traits in the absence of a psychological stressor suggests the existence of blast-induced "PTSD". Findings that PTSD-related behavioral traits can be reversed by BCI-838, a group II metabotropic glutamate receptor antagonist offers insight into pathogenesis and possible treatment options for blast-related brain injury.

OBJECTIVE:Current brain-computer interface (BCI) studies demonstrate the potential to decode neural signals obtained from structured and trial-based tasks to drive actuators with high performance within the context of these tasks. Ideally, to maximize utility, such systems will be applied to a wide range of behavioral settings or contexts. Thus, we explore the potential to augment such systems with the ability to decode abstract behavioral contextual states from neural activity. APPROACH/METHODS:To demonstrate the feasibility of such context decoding, we used electrocorticography (ECoG) and stereo-electroencephalography (sEEG) data recorded from the cortical surface and deeper brain structures, respectively, continuously across multiple days from three subjects. During this time, the subjects were engaged in a range of naturalistic behaviors in a hospital environment. Behavioral contexts were labeled manually from video and audio recordings; four states were considered: engaging in dialogue, rest, using electronics, and watching television. We decode these behaviors using a factor analysis and support vector machine (SVM) approach. MAIN RESULTS/RESULTS:We demonstrate that these general behaviors can be decoded with high accuracies of 73% for a four-class classifier for one subject and 71% and 62% for a three-class classifier for two subjects. SIGNIFICANCE/CONCLUSIONS:To our knowledge, this is the first demonstration of the potential to disambiguate abstract naturalistic behavioral contexts from neural activity recorded throughout the day from implanted electrodes. This work motivates further study of context decoding for BCI applications using continuously recorded naturalistic activity in the clinical setting.

Neuropsychiatric symptoms (NPS) are common in Alzheimer's disease (AD)-associated neurodegeneration. However, NPS lack a consistent relationship with AD pathology. It is unknown whether any common neural circuits can link these clinically disparate while mechanistically similar features with AD pathology. Here, we explored the neural circuits of NPS in AD-associated neurodegeneration using multivariate pattern analysis (MVPA) of resting-state functional MRI data. Data from 98 subjects (70 amnestic mild cognitive impairment and 28 AD subjects) were obtained. The top 10 regions differentiating symptom presence across NPS were identified, which were mostly the fronto-limbic regions (medial prefrontal cortex, caudate, etc.). These 10 regions' functional connectivity classified symptomatic subjects across individual NPS at 69.46-81.27%, and predicted multiple NPS (indexed by Neuropsychiatric Symptom Questionnaire-Inventory) and AD pathology (indexed by baseline and change of beta-amyloid/pTau ratio) all above 70%. Our findings suggest a fronto-limbic dominated neural circuit that links multiple NPS and AD pathology. With further examination of the structural and pathological changes within the circuit, the circuit may shed light on linking behavioral disturbances with AD-associated neurodegeneration.

Tuberculosis is the leading infectious cause of death globally and extra-pulmonary disease occurs in 15% of incident cases annually. Tuberculous meningitis (TBM) is arguably the most lethal form of tuberculosis and requires prompt diagnosis and initiation of treatment to prevent death and serious neurological disability. The development of rapid diagnostic tests using polymerase chain reaction (PCR) technology for the detection of Mycobacterium tuberculosis (MTB), including the World Health Organization (WHO) - endorsed Xpert MTB/RIF Ultra assay, has allowed earlier definite diagnosis of TBM than conventional culture methods which usually take two weeks or longer for positive identification of MTB. Detection of MTB in cerebrospinal fluid (CSF) using PCR assays requires special attention to the collection, handling, and processing of CSF. Herein we present best practices guidance to maximize the detection rate of MTB in CSF using Xpert MTB/RIF Ultra.