Faculty Bibliography

There are more than two million amputees in the USA, and almost all will experience phantom limb sensations (PLS), describing the missing limb as still present. They may also experience intense pain, known as phantom limb pain (PLP), a considerable factor in poor quality of life. In some upper extremity amputees and following brachial plexus avulsion injury (BPAI), hand digits can be detected and mapped to distinct facial skin areas, termed hand-to-face remapping. In this study, we analysed PLS following brachial plexus anaesthesia (BPA) administered prior to upper limb surgeries. Our 39 participants had planned shoulder, wrist or hand surgery. We sought to determine the time course for the emergence of phantom limb experiences after BPA up to the following 24 hours in participants with intact limbs. We also investigated whether there was hand-to-face remapping, suggesting potential cortical reorganization, or changes in proprioception before and after the induction of BPA. Twenty (54%) participants reported PLS immediately after the onset of BPA (T2), and 28 (72%) participants altered proprioception (AP) after surgery (T3). However, neither PLP nor hand mapping onto the face was reported or evoked. PLS were seen earlier than AP. We conclude that PLS arise rapidly after BPA-induced temporary deafferentation of the upper limb and might serve as a model for the permanent deafferentation experienced in individuals with a major upper limb amputation or BPAI. These results contribute to defining a time course for changes after BPA and increase our understanding of how phantom limb phenomena might arise following limb amputation or BPAI.

Previously, we reported an immediate emergence of new lower jaw input to the anterior forepaw barrel subfield (FBS) in primary somatosensory cortex (SI) following forelimb deafferentation. However, a delay of 7 weeks or more post-amputation results in the presence of this new input to both anterior and posterior FBS. The immediate change suggests pre-existing latent lower jaw input in the FBS, whereas the delayed alteration implies the involvement of alternative sources. One possible source for immediate lower jaw responses is the neighboring lower jaw barrel subfield (LJBSF). We used anatomical tracers to investigate the possible projection of LJBSF to the FBS in normal and forelimb-amputated rats. Our findings are as follows: (1) anterograde tracer injection into LJBSF in normal and amputated rats labeled fibers and terminals exclusively in the anterior FBS; (2) retrograde tracer injection in the anterior FBS in normal and forelimb-amputated rats, heavily labeled cell bodies predominantly in the posterior LJBSF, with fewer in the anterior LJBSF; (3) retrograde tracer injection in the posterior FBS in normal and forelimb-amputated rats, sparsely labeled cell bodies in the posterior LJBSF; (4) retrograde tracer injection in anterior and posterior FBS in normal and forelimb-amputated rats, labeled cells exclusively in ventral posterior lateral (VPL) nucleus and posterior thalamus (PO); (5) retrograde tracer injection in LJBSF-labeled cell bodies exclusively in ventral posterior medial thalamic nucleus and PO. These findings suggest that LJBSF facilitates rapid lower jaw reorganization in the anterior FBS, whereas VPL and/or other subcortical sites provide a likely substrate for delayed reorganization observed in the posterior FBS.

BACKGROUND AND OBJECTIVES/UNASSIGNED:As the population of U.S. service members (SMs) who have sustained concussions and more severe traumatic brain injuries (TBIs) during military service ages, understanding the long-term outcomes associated with such injuries will provide critical information that may promote long-term assessment, support, and rehabilitation following military service. The objective of this research was to examine whether concussion and more severe TBIs are associated with greater risk of precursors to dementia (i.e., mild cognitive impairment, memory loss), early-onset dementia, and any dementia. METHODS/UNASSIGNED: = 1,211,972). Diagnoses of concussion and more severe TBI during active duty service recorded in inpatient settings between 1980 and 2020 and in outpatient settings from 2001 to 2020 were identified. Focal outcomes of interest included memory loss, mild cognitive impairment, Alzheimer's, Lewy Body dementia, frontotemporal dementia, and vascular dementia. Dementia diagnoses before age 65 were labeled early-onset. RESULTS/UNASSIGNED:Those with (vs. without) concussion diagnoses during military service were significantly more likely to be diagnosed with memory loss and mild cognitive impairment and any of the dementias examined. However, they were not at greater risk of being diagnosed with early-onset dementia. DISCUSSION/UNASSIGNED:Military SMs diagnosed with concussion may be at elevated risk for long-term neurodegenerative outcomes including memory loss, mild cognitive impairment, and dementia. As the population of SMs who sustained TBI during the Global War on Terror continue to age, the prevalence of dementia will increase and may bring a unique burden to the VHA.

We used the forepaw barrel subfield (FBS), that normally receives input from the forepaw skin surface, in rat primary somatosensory cortex as a model system to study rapid and delayed lower jaw-to-forepaw cortical reorganization. Single and multi-unit recording from FBS neurons was used to examine the FBS for the presence of "new" lower jaw input following deafferentations that include forelimb amputation, brachial plexus nerve cut, and brachial plexus anesthesia. The major findings are as follows: (1) immediately following forelimb deafferentations, new input from the lower jaw becomes expressed in the anterior FBS; (2) 7-27 weeks after forelimb amputation, new input from the lower jaw is expressed in both anterior and posterior FBS; (3) evoked response latencies recorded in the deafferented FBS following electrical stimulation of the lower jaw skin surface are significantly longer in both rapid and delayed deafferents compared to control latencies for input from the forepaw to reach the FBS or for input from lower jaw to reach the LJBSF; (4) the longer latencies suggest that an additional relay site is imposed along the somatosensory pathway for lower jaw input to access the deafferented FBS. We conclude that different sources of input and different mechanisms underlie rapid and delayed reorganization in the FBS and suggest that these findings are relevant, as an initial step, for developing a rodent animal model to investigate phantom limb phenomena.

The Medicare Parts C and D Star Ratings system was established to improve care quality in Medicare. Previous studies reported racial/ethnic disparities in the calculation of medication adherence measures of Star Ratings in patients with diabetes, hypertension, and hyperlipidemia. This study aimed to identify possible racial/ethnic disparities in the calculation of adherence measures of Medicare Part D Star Ratings among patients with Alzheimer's disease and related dementias (ADRD) and diabetes, hypertension, or hyperlipidemia. This retrospective study analyzed the 2017 Medicare data and Area Health Resources Files. Non-Hispanic White (White) patients were compared to Black, Hispanic, Asian/Pacific Islander (Asian), and other patients on their likelihood of being included in the calculation of adherence measures for diabetes, hypertension, and/or hyperlipidemia. To adjust for the individual/community characteristics, logistic regression was used when the outcome is the inclusion in the calculation of one adherence measure; multinomial regression was used when examining the inclusion in the calculation of multiple adherence measures. Analyzing the data of 1438,076 Medicare beneficiaries with ADRD, this study found that Black (adjusted odds ratio, or OR = 0.79, 95% confidence interval, or 95% CI = 0.73-0.84) and Hispanic (OR = 0.82, 95% CI = 0.75-0.89) patients were less likely than White patients to be included in the calculation of adherence measure for diabetes medications. Further, Black patients were less likely to be included in the calculation of the adherence measure for hypertension medications than White patients (OR = 0.81, 95% CI = 0.78-0.84). All minorities were less likely to be included in calculating the adherence measure for hyperlipidemia medications than Whites. The ORs for Black, Hispanic, and Asian patients were 0.57 (95% CI = 0.55-0.58), 0.69 (95% CI = 0.64-0.74), and 0.83 (95% CI = 0.76-0.91), respectively. Minority patients were generally likely to be included in the measure calculation of fewer measures than White patients. Racial/ethnic disparities were observed in the calculation of Star Ratings measures among patients with ADRD and diabetes, hypertension, and/or hyperlipidemia. Future studies should explore possible causes of and solutions to these disparities.

Purpose of Review: This article focuses on a review of the non-surgical treatment options for patients with phantom limb pain (PLP). Recent Findings: Based on a review of the published literature over the past 5 years, the most promising evidenced-based therapies involve sensory feedback to the user through either visual or tactile stimulation. Summary: Of these, the most effective therapies include mirror therapy, phantom motor imagery, and phantom motor execution and, therefore, should be considered when treating individuals with PLP.

OBJECTIVE/UNASSIGNED:Older patients with Alzheimer's disease (AD) are challenged with adhering to complex medication regimens. We examined effects of Comprehensive Medication Review (CMR), a required Medicare Part D Medication Therapy Management (MTM) program component, on medication adherence among AD patients. METHODS/UNASSIGNED:This retrospective study analyzed 100% of 2016-2017 Medicare claims covering the entire United States, linked to Area Health Resources Files. Medicare beneficiaries aged ≥65 years were included. Propensity score matching identified comparable intervention and comparison groups with the intervention defined as receiving a CMR in 2017. A difference-in-differences analysis included in multivariate logistic regressions an interaction term between CMR receipt and year 2017. The outcome measured was nonadherence to diabetes, hypertension and hyperlipidemia medications, with nonadherence defined as proportion of days covered <80% for study medications. RESULTS/UNASSIGNED:Unadjusted comparisons indicated the proportion of nonadherence for intervention group members decreased from 2016 to 2017 but increased for the comparison group. In adjusted analyses, reduction in medication nonadherence among the intervention group remained higher: odds ratios for the interaction term were 0.62 (95% confidence interval [CI] = 0.54-0.71), 0.54 (95% CI = 0.50-0.58) and 0.50 (95% CI = 0.47-0.53) respectively for diabetes, hypertension and hyperlipidemia medications. This suggests that the likelihood of nonadherence in the intervention group was respectively reduced by 38%, 46% and 50% more than the comparison group. CONCLUSIONS/UNASSIGNED:CMR was found to reduce nonadherence to diabetes, hypertension and hyperlipidemia medications among older Medicare beneficiaries with AD. This provides evidence that the MTM program is effective for a population with unique medication compliance challenges.

Barrel subfields in rodent primary somatosensory cortex (SI) are important model systems for studying cortical organization and reorganization. During cortical reorganization that follows limb deafferentation, neurons in deafferented forelimb SI become responsive to previously unexpressed inputs from the lower jaw. Although the lower jaw barrel subfield (LJBSF) is a likely source of the input, this subfield has received little attention. Our aim was to describe the structural and functional organization of the normal LJBSF. To investigate LJBSF organization, a nomenclature for lower jaw skin surface was developed, cytochrome oxidase (CO) was used to label flattened-cut LJBSF sections, microelectrodes were used to map the lower jaw skin surface representation in SI, and electrolytic lesions, recovered from electrode penetrations, were used to align the physiological map to the underlying barrel map. LJBSF is a tear-shaped subfield containing approximately 24 barrels, arranged in eight mediolateral rows and a barrel-free zone capping the anterior border. The representation of the lower jaw skin consisting of chin vibrissae and microvibrissae embedded in common fur is somatotopically organized in a single map in the contralateral SI. This physiological map shows that the activity from the vibrissae aligns with the CO-staining of the underlying LJBSF. LJBSF barrels receive topographically ordered barrel-specific input from individual vibrissa and microvibrissae in the lower jaw but not from trident whiskers. The barrel-free zone receives topographically ordered input from the lower lip. These data demonstrating that the LJBSF is a highly organized subfield are essential for understanding its possible role in cortical reorganization.