Traumatic brain injury results in altered physiologic, but not subjective responses to emotional stimuli.

BACKGROUND: While the cognitive sequelae of traumatic brain injury (TBI) are well known, emotional impairments after TBI are suboptimally characterized. Lack of awareness of emotional difficulties can make self-report unreliable. However, individuals with TBI demonstrate involuntary changes in heart rate variability which may enable objective quantification of emotional dysfunction. METHODS: Sixteen subjects with chronic TBI and 10 age-matched controls were tested on an emotional function battery during which they watched a series of film clips normed to elicit specific positively and negatively valenced emotions: amusement, sexual amusement, sadness, fear and disgust. Subjective responses to the emotional stimuli were also obtained. Additionally, surface electrodes measured cardiac and respiratory signals to compute heart rate variability (HRV), from which measures of parasympathetic activity, the respiratory frequency area (RFA) and sympathetic activity, the low frequency area (LFA), of the HRV frequency spectrum were derived. The Neurobehavioral Rating Scale-Revised (NRS-R) and the King-Devick (KD) test were administered to assess neurobehavioral dysfunction. RESULTS: The two groups showed no differences in subjective ratings of emotional intensity. Subjects with TBI showed significantly decreased sympathetic activity when viewing amusing stimuli and significantly increased sympathetic activity when viewing sad stimuli compared to controls. Most of the subjects did not show agitation, anxiety, depression, blunted affect, emotional withdrawal, decreased motivation or mental fatiguability on the NRS-R. However, 13/16 subjects with TBI demonstrated attention difficulty on the NRS-R which was positively correlated with the increased sympathetic activity during sad stimuli. Both attention difficulty and abnormal autonomic responses to sad stimuli were correlated with the timing on the KD test, which reflected difficulty with visual attention shifting. CONCLUSIONS: The HRV spectrum may be useful to identify subclinical emotional dysfunction in individuals with TBI. Attention difficulites, specifically impairment in visual attention shifting, may contribute to abnormal reactivity to sad stimuli that may be detected and potentially treated to improve emotional function.

The effect of linguistic background on rapid number naming: implications for native versus non-native English speakers on sideline-focused concussion assessments.

OBJECTIVE: To determine if native English speakers (NES) perform differently compared to non-native English speakers (NNES) on a sideline-focused rapid number naming task. A secondary aim was to characterize objective differences in eye movement behaviour between cohorts. BACKGROUND: The King-Devick (KD) test is a rapid number-naming task in which numbers are read from left-to-right. This performance measure adds vision-based assessment to sideline concussion testing. Reading strategies differ by language. Concussion may also impact language and attention. Both factors may affect test performance. METHODS: Twenty-seven healthy  NNES and healthy NES performed a computerized KD test under high-resolution video-oculography.  NNES also performed a Bilingual Dominance Scale (BDS) questionnaire to weight linguistic preferences (i.e., reliance on non-English language(s)). RESULTS: Inter-saccadic intervals were significantly longer in  NNES (346.3 ± 78.3 ms vs. 286.1 ± 49.7 ms, p = 0.001), as were KD test times (54.4 ± 15.1 s vs. 43.8 ± 8.6 s, p = 0.002). Higher BDS scores, reflecting higher native language dominance, were associated with longer inter-saccadic intervals in  NNES. CONCLUSION: These findings have direct implications for the assessment of athlete performance on vision-based and other verbal sideline concussion tests; these results are particularly important given the international scope of sport. Pre-season baseline scores are essential to evaluation in the event of concussion, and performance of sideline tests in the athlete's native language should be considered to optimize both baseline and post-injury test accuracy.

A Comprehensive and Broad Approach to Resting-State Functional Connectivity in Adult Patients with Mild Traumatic Brain Injury.

BACKGROUND AND PURPOSE: Several recent works using resting-state fMRI suggest possible alterations of resting-state functional connectivity after mild traumatic brain injury. However, the literature is plagued by various analysis approaches and small study cohorts, resulting in an inconsistent array of reported findings. In this study, we aimed to investigate differences in whole-brain resting-state functional connectivity between adult patients with mild traumatic brain injury within 1 month of injury and healthy control subjects using several comprehensive resting-state functional connectivity measurement methods and analyses. MATERIALS AND METHODS: A total of 123 subjects (72 patients with mild traumatic brain injury and 51 healthy controls) were included. A standard fMRI preprocessing pipeline was used. ROI/seed-based analyses were conducted using 4 standard brain parcellation methods, and the independent component analysis method was applied to measure resting-state functional connectivity. The fractional amplitude of low-frequency fluctuations was also measured. Group comparisons were performed on all measurements with appropriate whole-brain multilevel statistical analysis and correction. RESULTS: There were no significant differences in age, sex, education, and hand preference between groups as well as no significant correlation between all measurements and these potential confounders. We found that each resting-state functional connectivity measurement revealed various regions or connections that were different between groups. However, after we corrected for multiple comparisons, the results showed no statistically significant differences between groups in terms of resting-state functional connectivity across methods and analyses. CONCLUSIONS: Although previous studies point to multiple regions and networks as possible mild traumatic brain injury biomarkers, this study shows that the effect of mild injury on brain resting-state functional connectivity has not survived after rigorous statistical correction. A further study using subject-level connectivity analyses may be necessary due to both subtle and variable effects of mild traumatic brain injury on brain functional connectivity across individuals.

Callosal Interhemispheric Communication in Mild Traumatic Brain Injury: A Mediation Analysis on WM Microstructure Effects.

BACKGROUND AND PURPOSE: Because the corpus callosum connects the left and right hemispheres and a variety of WM bundles across the brain in complex ways, damage to the neighboring WM microstructure may specifically disrupt interhemispheric communication through the corpus callosum following mild traumatic brain injury. Here we use a mediation framework to investigate how callosal interhemispheric communication is affected by WM microstructure in mild traumatic brain injury. MATERIALS AND METHODS: Multishell diffusion MR imaging was performed on 23 patients with mild traumatic brain injury within 1 month of injury and 17 healthy controls, deriving 11 diffusion metrics, including DTI, diffusional kurtosis imaging, and compartment-specific standard model parameters. Interhemispheric processing speed was assessed using the interhemispheric speed of processing task (IHSPT) by measuring the latency between word presentation to the 2 hemivisual fields and oral word articulation. Mediation analysis was performed to assess the indirect effect of neighboring WM microstructures on the relationship between the corpus callosum and IHSPT performance. In addition, we conducted a univariate correlation analysis to investigate the direct association between callosal microstructures and IHSPT performance as well as a multivariate regression analysis to jointly evaluate both callosal and neighboring WM microstructures in association with IHSPT scores for each group. RESULTS: Several significant mediators in the relationships between callosal microstructure and IHSPT performance were found in healthy controls. However, patients with mild traumatic brain injury appeared to lose such normal associations when microstructural changes occurred compared with healthy controls. CONCLUSIONS: This study investigates the effects of neighboring WM microstructure on callosal interhemispheric communication in healthy controls and patients with mild traumatic brain injury, highlighting that neighboring noncallosal WM microstructures are involved in callosal interhemispheric communication and information transfer. Further longitudinal studies may provide insight into the temporal dynamics of interhemispheric recovery following mild traumatic brain injury.

Challenges and Lessons Learned for Acute Inpatient Rehabilitation of Persons With COVID-19: Clinical Presentation, Assessment, Needs, and Services Utilization.

OBJECTIVE: The aim of the study was to present: (1) physiatric care delivery amid the SARS-CoV-2 pandemic, (2) challenges, (3) data from the first cohort of post-COVID-19 inpatient rehabilitation facility patients, and (4) lessons learned by a research consortium of New York and New Jersey rehabilitation institutions. DESIGN: For this clinical descriptive retrospective study, data were extracted from post-COVID-19 patient records treated at a research consortium of New York and New Jersey rehabilitation inpatient rehabilitation facilities (May 1-June 30, 2020) to characterize admission criteria, physical space, precautions, bed numbers, staffing, employee wellness, leadership, and family communication. For comparison, data from the Uniform Data System and eRehabData databases were analyzed. The research consortium of New York and New Jersey rehabilitation members discussed experiences and lessons learned. RESULTS: The COVID-19 patients (N = 320) were treated during the study period. Most patients were male, average age of 61.9 yrs, and 40.9% were White. The average acute care length of stay before inpatient rehabilitation facility admission was 24.5 days; mean length of stay at inpatient rehabilitation facilities was 15.2 days. The rehabilitation research consortium of New York and New Jersey rehabilitation institutions reported a greater proportion of COVID-19 patients discharged to home compared with prepandemic data. Some institutions reported higher changes in functional scores during rehabilitation admission, compared with prepandemic data. CONCLUSIONS: The COVID-19 pandemic acutely affected patient care and overall institutional operations. The research consortium of New York and New Jersey rehabilitation institutions responded dynamically to bed expansions/contractions, staff deployment, and innovations that facilitated safe and effective patient care.

The neural basis for spatial relations.

Studies in semantics traditionally focus on knowledge of objects. By contrast, less is known about how objects relate to each other. In an fMRI study, we tested the hypothesis that the neural processing of categorical spatial relations between objects is distinct from the processing of the identity of objects. Attending to the categorical spatial relations compared with attending to the identity of objects resulted in greater activity in superior and inferior parietal cortices (especially on the left) and posterior middle frontal cortices bilaterally. In an accompanying lesion study, we tested the hypothesis that comparable areas would be necessary to represent categorical spatial relations and that the hemispheres differ in their biases to process categorical or coordinate spatial relations. Voxel-based lesion symptom mapping results were consistent with the fMRI observations. Damage to a network comprising left inferior frontal, supramarginal, and angular gyri resulted in behavioral impairment on categorical spatial judgments. Homologous right brain damage also produced such deficits, albeit less severely. The reverse pattern was observed for coordinate spatial processing. Right brain damage to the middle temporal gyrus produced more severe deficits than left hemisphere damage. Additional analyses suggested that some areas process both kinds of spatial relations conjointly and others distinctly. The left angular and inferior frontal gyrus processes coordinate spatial information over and above the categorical processing. The anterior superior temporal gyrus appears to process categorical spatial information uniquely. No areas within the right hemisphere processed categorical spatial information uniquely. Taken together, these findings suggest that the functional neuroanatomy of categorical and coordinate processing is more nuanced than implied by a simple hemispheric dichotomy.

MULES on the sidelines: A vision-based assessment tool for sports-related concussion.

OBJECTIVE: The Mobile Universal Lexicon Evaluation System (MULES) is a test of rapid picture naming under investigation. Measures of rapid automatic naming (RAN) have been used for over 50 years to capture aspects of vision and cognition. MULES was designed as a series of 54 grouped color photographs (fruits, random objects, animals) that integrates saccades, color perception and contextual object identification. We examined MULES performance in youth, collegiate and professional athletes at pre-season baseline and at the sidelines following concussion. METHODS: Our study teams administered the MULES to youth, collegiate and professional athletes during pre-season baseline testing. Sideline post-concussion time scores were compared to pre-season baseline scores among athletes with concussion to determine degrees and directions of change. RESULTS: Among 681 athletes (age 17 ±â€¯4 years, range 6-37, 38% female), average test times at baseline were 41.2 ±â€¯11.2 s. The group included 280 youth, 357 collegiate and 44 professional athletes; the most common sports were ice hockey (23%), soccer (17%) and football (11%). Age was a predictor of MULES test times, with longer times noted for younger participants (P < .001, linear regression). Consistent with other timed performance measures, significant learning effects were noted for the MULES during baseline testing with trial 1 test times (mean 49.2 ±â€¯13.1 s) exceeding those for trial 2 (mean 41.3 ±â€¯11.2 s, P < .0001, paired t-test). Among 17 athletes with concussion during the sports seasons captured to date (age 18 ±â€¯3 years), all showed increases (worsening) of MULES time scores from pre-season baseline (median increase 11.2 s, range 0.6-164.2, P = .0003, Wilcoxon signed-rank test). The Symptom Severity Score from the SCAT5 Symptom Evaluation likewise worsened from pre-season baseline following injury among participants with concussion (P = .002). CONCLUSIONS: Concussed athletes demonstrate worsening performance on the MULES test compared to their baseline time scores. This test samples a wide network of brain pathways and complements other vision-based measures for sideline concussion assessment. The MULES test demonstrates capacity to identify athletes with sports-related concussion.

Mobile Universal Lexicon Evaluation System (MULES) in MS: Evaluation of a new visual test of rapid picture naming.

OBJECTIVE: The Mobile Universal Lexicon Evaluation System (MULES) is a test of rapid picture naming that is under investigation for concussion. MULES captures an extensive visual network, including pathways for eye movements, color perception, memory and object recognition. The purpose of this study was to introduce the MULES to visual assessment of patients with MS, and to examine associations with other tests of afferent and efferent visual function. METHODS: We administered the MULES in addition to binocular measures of low-contrast letter acuity (LCLA), high-contrast visual acuity (VA) and the King-Devick (K-D) test of rapid number naming in an MS cohort and in a group of disease-free controls. RESULTS: Among 24 patients with MS (median age 36 years, range 20-72, 64% female) and 22 disease-free controls (median age 34 years, range 19-59, 57% female), MULES test times were greater (worse) among the patients (60.0 vs. 40.0 s). Accounting for age, MS vs. control status was a predictor of MULES test times (P = .01, logistic regression). Faster testing times were noted among patients with MS who had greater (better) performance on binocular LCLA at 2.5% contrast (P < .001, linear regression, accounting for age), binocular high-contrast VA (P < .001), and K-D testing (P < .001). Both groups demonstrated approximately 10-s improvements in MULES test times between trials 1 and 2 (P < .0001, paired t-tests). CONCLUSION: The MULES test, a complex task of rapid picture naming involves an extensive visual network that captures eye movements, color perception and the characterization of objects. Color recognition, a key component of this novel assessment, is early in object processing and requires area V4 and the inferior temporal projections. MULES scores reflect performance of LCLA, a widely-used measure of visual function in MS clinical trials. These results provide evidence that the MULES test can add efficient visual screening to the assessment of patients with MS.

White Matter Tract Integrity: An Indicator of Axonal Pathology after Mild Traumatic Brain Injury.

We seek to elucidate the underlying pathophysiology of injury sustained after mild traumatic brain injury (mTBI) using multi-shell diffusion magnetic resonance imaging, deriving compartment-specific white matter tract integrity (WMTI) metrics. WMTI allows a more biophysical interpretation of white matter (WM) changes by describing microstructural characteristics in both intra- and extra-axonal environments. Thirty-two patients with mTBI within 30 days of injury and 21 age- and sex-matched controls were imaged on a 3 Tesla magnetic resonance scanner. Multi-shell diffusion acquisition was performed with five b-values (250-2500 sec/mm2) along 6-60 diffusion encoding directions. Tract-based spatial statistics (TBSS) was used with family-wise error (FWE) correction for multiple comparisons. TBSS results demonstrated focally lower intra-axonal diffusivity (Daxon) in mTBI patients in the splenium of the corpus callosum (sCC; p < 0.05, FWE-corrected). The area under the curve value for Daxon was 0.76 with a low sensitivity of 46.9% but 100% specificity. These results indicate that Daxon may be a useful imaging biomarker highly specific for mTBI-related WM injury. The observed decrease in Daxon suggests restriction of the diffusion along the axons occurring shortly after injury.

The new Mobile Universal Lexicon Evaluation System (MULES): A test of rapid picture naming for concussion sized for the sidelines.

OBJECTIVE: Measures of rapid automatized naming (RAN) have been used for over 50 years to capture vision-based aspects of cognition. The Mobile Universal Lexicon Evaluation System (MULES) is a test of rapid picture naming under investigation for detection of concussion and other neurological disorders. MULES was designed as a series of 54 grouped color photographs (fruits, random objects, animals) that integrates saccades, color perception and contextual object identification. Recent changes to the MULES test have been made to improve ease of use on the athletic sidelines. Originally an 11 × 17-inch single-sided paper, the test has been reduced to a laminated 8.5 × 11-inch double-sided version. We identified performance changes associated with transition to the new, MULES, now sized for the sidelines, and examined MULES on the sideline for sports-related concussion. METHODS: We administered the new laminated MULES to a group of adult office volunteers as well as youth and collegiate athletes during pre-season baseline testing. Athletes with concussion underwent sideline testing after injury. Time scores for the new laminated MULES were compared to those for the larger version (big MULES). RESULTS: Among 501 athletes and office volunteers (age 16 ±â€¯7 years, range 6-59, 29% female), average test times at baseline were 44.4 ±â€¯14.4 s for the new laminated MULES (n = 196) and 46.5 ±â€¯16.3 s for big MULES (n = 248). Both versions were completed by 57 participants, with excellent agreement (p < 0.001, linear regression, accounting for age). Age was a predictor of test times for both MULES versions, with longer times noted for younger participants (p < 0.001). Among 6 athletes with concussion thus far during the fall sports season (median age 15 years, range 11-21) all showed worsening of MULES scores from pre-season baseline (median 4.0 s, range 2.1-16.4). CONCLUSION: The MULES test has been converted to an 11 × 8.5-inch laminated version, with excellent agreement between versions across age groups. Feasibly administered at pre-season and in an office setting, the MULES test shows preliminary evidence of capacity to identify athletes with sports-related concussion.

Is Kratom the New 'Legal High' on the Block?: The Case of an Emerging Opioid Receptor Agonist with Substance Abuse Potential.

Kratom is an unscheduled opioid receptor agonist that comes in the form of dietary supplements currently being abused by chronic pain patients on prescription opioids. Active alkaloids isolated from kratom such as mitragynine and 7-hydroxymitragynine are thought to act on mu- and delta-opioid receptors as well as alpha-2 adrenergic and 5-HT2A receptors. Animal studies suggest that kratom may be more potent than morphine. Consequently, kratom consumption produces analgesic and euphoric feelings among users. In particular, some chronic pain patients on opioids take kratom to counteract the effects of opioid withdrawal. Although the Food and Drug Administration has banned its use as a dietary supplement, kratom continues to be widely available and easily accessible on the Internet at much less expensive rates than some opioid replacement therapies like buprenorphine. There are no federal regulations monitoring the sale and distribution of this drug, yet kratom has been associated with severe signs and symptoms such as hallucinations, delusions, depressions, myalgias, chills, nausea/vomiting, respiratory hepatoxicity, seizures, coma, and death. A search of the pain literature shows past research has not described the use and potential deleterious effects of this drug. Many pain physicians are not familiar with kratom and as providers who take care of high-risk chronic pain patients using prescribed opioids, knowledge of current unregulated opioid receptor agonists with abuse potential is of paramount importance. The goal of this article is to introduce kratom to pain specialists and to spur a conversation on how pain physicians may take the lead to help curb the opioid abuse and overdose epidemic. Further studies may be required to help better understand the clinical and long-term effects of kratom use among chronic pain patients.Key words: Opioid receptor agonist, Kratom, Mitragynine, opioid overdose, chronic pain, substance abuse.

Mobile Universal Lexicon Evaluation System (MULES) test: A new measure of rapid picture naming for concussion.

OBJECTIVE: This study introduces a rapid picture naming test, the Mobile Universal Lexicon Evaluation System (MULES), as a novel, vision-based performance measure for concussion screening. The MULES is a visual-verbal task that includes 54 original photographs of fruits, objects and animals. We piloted MULES in a cohort of volunteers to determine feasibility, ranges of picture naming responses, and the relation of MULES time scores to those of King-Devick (K-D), a rapid number naming test. METHODS: A convenience sample (n=20, age 34±10) underwent MULES and K-D (spiral bound, iPad versions). Administration order was randomized; MULES tests were audio-recorded to provide objective data on temporal variability and ranges of picture naming responses. RESULTS: Scores for the best of two trials for all tests were 40-50s; average times required to name each MULES picture (0.72±0.14s) was greater than those needed for each K-D number ((spiral: 0.33±0.05s, iPad: 0.36±0.06s, 120 numbers), p<0.0001, paired t-test). MULES scores showed the greatest degree of improvement between trials (9.4±4.8s, p<0.0001 for trials 1 vs. 2), compared to K-D (spiral 1.5±3.3s, iPad 1.8±3.4s). Shorter MULES times demonstrated moderate and significant correlations with shorter iPad but not spiral K-D times (r=0.49, p=0.03). CONCLUSION: The MULES test is a rapid picture naming task that may engage more extensive neural systems than more commonly used rapid number naming tasks. Rapid picture naming may require additional processing devoted to color perception, object identification, and categorization. Both tests rely on initiation and sequencing of saccadic eye movements.

Art produced by a patient with Parkinson's disease.

Artists with neurological diseases sometimes produce remarkably appealing art. Here we present the art of a patient with Parkinson's disease, who demonstrated remarkable creativity and productivity well into the course of his disease. Despite his manifest motor impairments, he produced paintings and drawings with fluid sinuous movements. He also became preoccupied with his art in an unprecedented way, raising the possibility that his disease and medications were contributing to his creative drive.

Pain in the Geriatric Patient with Advanced Chronic Disease.

The World Health Organization, one of the leading authorities on pain management, stressed the need for further guidelines to help manage pain in patients with chronic disease. In light of the impact of pain on morbidity and quality of life, this article summarizes current knowledge about pain experienced by older adults in 3 advanced non-cancer-related chronic diseases (ie, congestive heart failure, end-stage renal disease, and stroke) in which pain is common but not typically a primary focus of disease management. This article examines the data on the prevalence of pain, co-occurring symptoms, and challenges in managing pain in these conditions.

Ultrasound Guidance for Technically Challenging Intrathecal Baclofen Pump Refill: Three Cases and Procedure Description.

Intrathecal baclofen (ITB) therapy is a common treatment used to reduce spasticity due to neurologic disorders and injuries. A variety of factors can increase the difficulty of ITB pump refill. Excess subcutaneous fat overlying the pump, spasticity, suboptimal positioning, pump rotation or inversion, and scar formation over the reservoir fill port can create challenges during pump refill. As a result, multiple unsuccessful attempts at accessing the reservoir fill port can be painful and increase the risk of infection, particularly when repeat skin puncture is required. Blind attempts to refill a pump in challenging cases may also result in subcutaneous injection or pocket fill, resulting in a potentially fatal baclofen withdrawal syndrome. We describe 3 successful ITB pump refills in technically challenging cases when using ultrasound guidance. This represents an innovative approach to using ultrasound guidance to facilitate ITB refill in adults with intractable spasticity. We present these new clinical data with a literature review of potential complications related to inaccurate pump refill procedures and discuss the utility of ultrasound guidance for preventing such adverse events.

Language, perception, and the schematic representation of spatial relations.

Schemas are abstract nonverbal representations that parsimoniously depict spatial relations. Despite their ubiquitous use in maps and diagrams, little is known about their neural instantiation. We sought to determine the extent to which schematic representations are neurally distinguished from language on the one hand, and from rich perceptual representations on the other. In patients with either left hemisphere damage or right hemisphere damage, a battery of matching tasks depicting categorical spatial relations was used to probe for the comprehension of basic spatial concepts across distinct representational formats (words, pictures, and schemas). Left hemisphere patients underperformed right hemisphere patients across all tasks. However, focused residual analyses using voxel-based lesion-symptom mapping (VLSM) suggest that (1) left hemisphere deficits in the representation of categorical spatial relations are difficult to distinguish from deficits in naming these relations and (2) the right hemisphere plays a special role in extracting schematic representations from richly textured pictures.