Faculty Bibliography

BACKGROUND:Young wheat plants are continuously exposed to herbivorous insect attack. To reduce insect damage and maintain their growth, plants evolved different defense mechanisms, including the biosynthesis of deterrent compounds named benzoxazinoids, and/or trichome formation that provides physical barriers. It is unclear whether both of these mechanisms are equally critical in providing an efficient defense for wheat seedlings against aphids-an economically costly pest in cereal production. RESULTS:In this study, we compared the transcriptome, metabolome, benzoxazinoids, and trichome density of three selected wheat genotypes, with a focus on differences related to defense mechanisms. We chose diverse wheat genotypes: two tetraploid wheat genotypes, domesticated durum 'Svevo' and wild emmer 'Zavitan,' and one hexaploid bread wheat, 'Chinese Spring.' The full transcriptomic analysis revealed a major difference between the three genotypes, while the clustering of significantly different genes suggested a higher similarity between the two domesticated wheats than between either and the wild wheat. A pathway enrichment analysis indicated that the genes associated with primary metabolism, as well as the pathways associated with defense such as phytohormones and specialized metabolites, were different between the three genotypes. Measurement of benzoxazinoid levels at the three time points (11, 15, and 18 days after germination) revealed high levels in the two domesticated genotypes, while in wild emmer wheat, they were below detection level. In contrast to the benzoxazinoid levels, the trichome density was dramatically higher in the wild emmer than in the domesticated wheat. Lastly, we tested the bird cherry-oat aphid's (Rhopalosiphum padi) performance and found that Chinese Spring is more resistant than the tetraploid genotypes. CONCLUSIONS:Our results show that benzoxazinoids play a more significant defensive role than trichomes. Differences between the abundance of defense mechanisms in the wild and domesticated plants were observed in which wild emmer possesses high physical defenses while the domesticated wheat genotypes have high chemical defenses. These findings provide new insights into the defense adaptations of wheat plants against aphids.

Cystinosis, a genetic rare disease characterized by cystine accumulation and crystallization, results in significant damage in a multitude of tissues and organs, such as the kidney, thyroid, eye, and brain. While Cystinosis' impact on brain function is relatively mild compared to its effects on other organs, the increased lifespan of this population and thus potential for productive societal contributions have led to increased interest on the effects on brain function. Nevertheless, and despite some evidence of structural brain differences, the neural impact of the mutation is still not well characterized. Here, using a passive duration oddball paradigm (with different stimulus onset asynchronies (SOAs), representing different levels of demand on memory) and high-density electrophysiology, we tested basic auditory processing in a group of 22 children and adolescents diagnosed with Cystinosis (age range: 6-17 years old) and in neurotypical age-matched controls (N = 24). We examined whether the N1 and mismatch negativity (MMN) significantly differed between the groups and if those neural measures correlated with verbal and non-verbal IQ. Individuals diagnosed with Cystinosis presented similar N1 responses to their age-matched peers, indicating typical basic auditory processing in this population. However, whereas both groups showed similar MMN responses for the shortest (450 ms) SOA, suggesting intact change detection and sensory memory, individuals diagnosed with Cystinosis presented clearly reduced responses for the longer (900 ms and 1800 ms) SOAs. This could indicate reduced duration auditory sensory memory traces, and thus sensory memory impairment, in children and adolescents diagnosed with Cystinosis. Future work addressing other aspects of sensory and working memory is needed to understand the underlying bases of the differences described here, and their implication for higher order processing.

BACKGROUND AND PURPOSE/OBJECTIVE:While studies have stratified cardioembolic (CE) stroke risk by qualitative left atrial appendage (LAA) morphology and biomarkers of atrial dysfunction, the quantitative properties that underlie these observations are not well established. Accordingly, we hypothesized that LAA volume and contrast density (attenuation) on computerized tomography (CT) may capture the structural and hemodynamic processes that underlie CE stroke risk. METHODS:Data were collected from a single center prospective ischemic stroke database over 18 months and included all patients with ischemic stroke who previously underwent routine, nongated, contrast enhanced thin-slice (≤2.5 mm) chest CT. Stroke subtype was determined based on the inpatient diagnostic evaluation. LAA volume and attenuation were determined from CT studies performed for various clinically appropriate indications. Univariate and multivariable analyses were performed to determine factors associated with ischemic stroke subtype, including known risk factors and biomarkers, as well as LAA density and morphologic measures. RESULTS:We identified 311 patients with a qualifying chest CT (119 CE subtype, 109 Embolic Stroke of Undetermined Source (ESUS), and 83 non-CE). In unadjusted models, there was an association between CE (versus non-CE) stroke subtype and LAA volume (OR per mL increase 1.15, 95% CI 1.07-1.24, P < .001) and LAA density (4th quartile versus 1st quartile; OR 2.95, 95% CI 1.28-6.80, P = .011), but not with ESUS (versus non-CE) subtype. In adjusted models, only the association between LAA density and CE stroke subtype persisted (adjusted OR 3.71, 95% CI 1.37-10.08, P = .010). CONCLUSION/CONCLUSIONS:The LAA volume and density values on chest CT are associated with CE stroke subtype but not ESUS subtype. Patients with ESUS and increased LAA volume or attenuation may be a subgroup where the mechanism is CE and anticoagulation can be tested for secondary stroke prevention.

OBJECTIVE:The Mobile Universal Lexicon Evaluation System (MULES) is a test of rapid picture naming that captures extensive brain networks, including cognitive, language and afferent/efferent visual pathways. MULES performance is slower in concussion and multiple sclerosis, conditions in which vision dysfunction is common. Visual aspects captured by the MULES may be impaired in Parkinson's disease (PD) including color discrimination, object recognition, visual processing speed, and convergence. The purpose of this study was to compare MULES time scores for a cohort of PD patients with those for a control group of participants of similar age. We also sought to examine learning effects for the MULES by comparing scores for two consecutive trials within the patient and control groups. METHODS:MULES consists of 54 colored pictures (fruits, animals, random objects). The test was administered in a cohort of PD patients and in a group of similar aged controls. Wilcoxon rank-sum tests were used to determine statistical significance for differences in MULES time scores between PD patients and controls. Spearman rank-correlation coefficients were calculated to examine the relation between MULES time scores and PD motor symptom severity (UPDRS). Learning effects were assessed using Wilcoxon rank-sum tests. RESULTS: = 0.37, P = .02). Learning effects were greater among patients with PD (median improvement of 14.8 s between two MULES trials) compared to controls (median 7.4 s, P = .004). CONCLUSION/CONCLUSIONS:The MULES is a complex test of rapid picture naming that captures numerous brain pathways including an extensive visual network. MULES performance is slower in patients with PD and our study suggests an association with the degree of motor impairment. Future studies will determine the relation of MULES time scores to other modalities that test visual function and structure in PD.

PURPOSE:While there is strong evidence supporting the importance of telemedicine in stroke, its role in other areas of neurology is not as clear. The goal of this review is to provide an overview of evidence-based data on the role of teleneurology in the care of patients with neurologic disorders other than stroke. RECENT FINDINGS:Studies across multiple specialties report noninferiority of evaluations by telemedicine compared with traditional, in-person evaluations in terms of patient and caregiver satisfaction. Evidence reports benefits in expediting care, increasing access, reducing cost, and improving diagnostic accuracy and health outcomes. However, many studies are limited, and gaps in knowledge remain. SUMMARY:Telemedicine use is expanding across the vast array of neurologic disorders. More studies are needed to validate and support its use.

INTRODUCTION/BACKGROUND:To demonstrate the broad utility of the remotely supervised transcranial direct current stimulation (RS-tDCS) protocol developed to deliver at-home rehabilitation for individuals with multiple sclerosis (MS). METHODS:Stimulation delivered with the RS-tDCS protocol and paired with adaptive cognitive training was delivered to three different study groups of MS patients to determine the feasibility and tolerability of the protocol. The three studies each used consecutively increasing amounts of stimulation amperage (1.5, 2.0, and 2.5 mA, respectively) and session numbers (10, 20, and 40 sessions, respectively). RESULTS:High feasibility and tolerability of the stimulation were observed for n = 99 participants across three tDCS pilot studies. CONCLUSIONS:RS-tDCS is feasible and tolerable for MS participants. The RS-tDCS protocol can be used to reach those in locations without clinic access and be paired with training or rehabilitation in locations away from the clinic. This protocol could be used to deliver tDCS paired with training or rehabilitation activities remotely to service members and veterans.

: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has become an effective and widely used tool in the treatment of Parkinson's disease (PD). STN-DBS has varied effects on speech. Clinical speech ratings suggest worsening following STN-DBS, but quantitative intelligibility, perceptual, and acoustic studies have produced mixed and inconsistent results. Improvements in phonation and declines in articulation have frequently been reported during different speech tasks under different stimulation conditions. Questions remain about preferred STN-DBS stimulation settings. Seven right-handed, native speakers of English with PD treated with bilateral STN-DBS were studied off medication at three stimulation conditions: stimulators off, 60 Hz (low frequency stimulation-LFS), and the typical clinical setting of 185 Hz (High frequency-HFS). Spontaneous speech was recorded in each condition and excerpts were prepared for transcription (intelligibility) and difficulty judgements. Separate excerpts were prepared for listeners to rate abnormalities in voice, articulation, fluency, and rate. Intelligibility for spontaneous speech was reduced at both HFS and LFS when compared to STN-DBS off. On the average, speech produced at HFS was more intelligible than that produced at LFS, but HFS made the intelligibility task (transcription) subjectively more difficult. Both voice quality and articulation were judged to be more abnormal with DBS on. STN-DBS reduced the intelligibility of spontaneous speech at both LFS and HFS but lowering the frequency did not improve intelligibility. Voice quality ratings with STN-DBS were correlated with the ratings made without stimulation. This was not true for articulation ratings. STN-DBS exacerbated existing voice problems and may have introduced new articulatory abnormalities. The results from individual DBS subjects showed both improved and reduced intelligibility varied as a function of DBS, with perceived changes in voice appearing to be more reflective of intelligibility than perceived changes in articulation.