Frank-Kasper-like network phase from self-assembly of high-χ star-block copolymers.

By taking advantage of the effects of solvent selectivity and topology on high-χ block copolymer (BCP) for self-assembly, network phases with high packing frustration can be formed in self-assembled polystyrene-b-polydimethylsiloxane (PS-b-PDMS). Apart from gyroid with trigonal structure and diamond with tetrahedral structure, a peculiar network phase with space group of [Formula: see text] (Frank-Kasper structure) can be found in six-arm star-block PS-b-PDMS as evidenced by small-angle x-ray scattering. Electron tomography results reveal the network phase with alternating connection of three and four struts. The observed phase behaviors suggest that the network formation is built from the bisectors of dispersive spheres in the Frank-Kasper phase, instead of building connections among them, and thus decipher the origins of complex phase formation due to the adaptive character of malleable mesoatoms.

Taxane-Induced Cutaneous Toxic Effects.

This case report describes dusky red to violaceous lesions with desquamation on the wrists and dorsal surface of both hands and near the Achilles tendon that occurred after intravenous paclitaxel treatment for invasive ductal carcinoma of the breast.

Clinical utility of plasma Aß42/40 ratio by LC-MS/MS in Alzheimer's disease assessment.

Introduction: Plasma Aß42/40 ratio can help predict amyloid PET status, but its clinical utility in Alzheimer's disease (AD) assessment is unclear. Methods: Aß42/40 ratio was measured by LC-MS/MS for 250 specimens with associated amyloid PET imaging, diagnosis, and demographic data, and for 6,192 consecutive clinical specimens submitted for Aß42/40 testing. Results: High diagnostic sensitivity and negative predictive value (NPV) for Aß-PET positivity were observed, consistent with the clinical performance of other plasma LC-MS/MS assays, but with greater separation between Aß42/40 values for individuals with positive vs. negative Aß-PET results. Assuming a moderate prevalence of Aß-PET positivity, a cutpoint was identified with 99% NPV, which could help predict that AD is likely not the cause of patients' cognitive impairment and help reduce PET evaluation by about 40%. Conclusion: High-throughput plasma Aß42/40 LC-MS/MS assays can help identify patients with low likelihood of AD pathology, which can reduce PET evaluations, allowing for cost savings.

The effect of age on alpha rhythms in the human brain derived from source localized resting-state electroencephalography.

With increasing age, peak alpha frequency (PAF) is slowed, and alpha power is reduced during resting-states with eyes closed. These age-related changes are evident across the whole scalp but remained unclear at the source level. The purpose of this study was to determine whether age impacts the power and frequency of the dominant alpha rhythm equally across source generators or whether the impact of age varies across sources. A total of 28 young adults and 26 elderly adults were recruited. High-density EEG was recorded for 10 mins with eyes closed. Single dipoles for each independent component were localized and clustered based on their anatomical label, resulting in 36 clusters. Meta-analyses were then conducted to assess effect sizes for PAF and power at PAF for all 36 clusters. Subgroup analyses were then implemented for frontal, sensorimotor, parietal, temporal, and occipital regions. The results of the meta-analyses showed that the elderly group exhibited slower PAF and less power at PAF compared to the young group. Subgroup analyses revealed age effects on PAF in parietal (g = 0.38), temporal (g = 0.65), and occipital regions (g = 1.04), with the largest effects observed in occipital regions. For power at PAF, age effects were observed in sensorimotor (g = 0.84) and parietal regions (g = 0.80), with the sensorimotor region showing the largest effect. Our findings show that age-related slowing and attenuation of the alpha rhythm manifests differentially across cortical regions, with sensorimotor and occipital regions most susceptible to age effects.

Longitudinal Free-Water Changes in Dementia with Lewy Bodies.

BACKGROUND: Diffusion-weighted magnetic resonance imaging (dMRI) examines tissue microstructure integrity in vivo. Prior dementia with Lewy bodies (DLB) diffusion tensor imaging studies yielded mixed results. OBJECTIVE: We employed free-water (FW) imaging to assess DLB progression and correlate with clinical decline in DLB. METHODS: Baseline and follow-up MRIs were obtained at 12 and/or 24 months for 27 individuals with DLB or mild cognitive impairment with Lewy bodies (MCI-LB). FW was analyzed using the Mayo Clinic Adult Lifespan Template. Primary outcomes were FW differences between baseline and 12 or 24 months. To compare FW change longitudinally, we included 20 cognitively unimpaired individuals from the Alzheimer's Disease Neuroimaging Initiative. RESULTS: We followed 23 participants to 12 months and 16 participants to 24 months. Both groups had worsening in Montreal Cognitive Assessment (MoCA) and Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) scores. We found significant FW increases at both time points compared to baseline in the insula, amygdala, posterior cingulum, parahippocampal, entorhinal, supramarginal, fusiform, retrosplenial, and Rolandic operculum regions. At 24 months, we found more widespread microstructural changes in regions implicated in visuospatial processing, motor, and cholinergic functions. Between-group analyses (DLB vs. controls) confirmed significant FW changes over 24 months in most of these regions. FW changes were associated with longitudinal worsening of MDS-UPDRS and MoCA scores. CONCLUSIONS: FW increased in gray and white matter regions in DLB, likely due to neurodegenerative pathology associated with disease progression. FW change was associated with clinical decline. The findings support dMRI as a promising tool to track disease progression in DLB. © 2024 International Parkinson and Movement Disorder Society.

Diffusion MRI relates to plasma Aß42/40 in PET negative participants without dementia.

INTRODUCTION: Magnetic resonance imaging (MRI) biomarkers are needed for indexing early biological stages of Alzheimer's disease (AD), such as plasma amyloid-ß (Aß42/40) positivity in Aß positron emission tomography (PET) negative individuals. METHODS: Diffusion free-water (FW) MRI was acquired in individuals with normal cognition (NC) and mild cognitive impairment (MCI) with Aß plasma-/PET- (NC = 22, MCI = 60), plasma+/PET- (NC = 5, MCI = 20), and plasma+/PET+ (AD dementia = 21) biomarker status. Gray and white matter FW and fractional anisotropy (FAt) were compared cross-sectionally and the relationships between imaging, plasma and PET biomarkers were assessed. RESULTS: Plasma+/PET- demonstrated increased FW (24 regions) and decreased FAt (66 regions) compared to plasma-/PET-. FW (16 regions) and FAt (51 regions) were increased in plasma+/PET+ compared to plasma+/PET-. Composite brain FW correlated with plasma Aß42/40 and p-tau181. DISCUSSION: FW imaging changes distinguish plasma Aß42/40 positive and negative groups, independent of group differences in cognitive status, Aß PET status, and other plasma biomarkers (i.e., t-tau, p-tau181, glial fibrillary acidic protein, neurofilament light). HIGHLIGHTS: Plasma Aß42/40 positivity is associated with brain microstructure decline. Plasma+/PET- demonstrated increased FW in 24 total GM and WM regions. Plasma+/PET- demonstrated decreased FAt in 66 total GM and WM regions. Whole-brain FW correlated with plasma Aß42/40 and p-tau181 measures. Plasma+/PET- demonstrated decreased cortical volume and thickness.

Dermoscopic features of pigmented basal cell carcinoma according to size.

BACKGROUND: Basal cell carcinoma (BCC), the most common skin cancer in humans, requires early detection. Dermoscopy enhances diagnostic accuracy through a noninvasive approach. Pigmented BCC (pBCC) is characterized by distinctive dermoscopic features, including the presence of pigmented globules or nests. While dermoscopic features of large pBCC (size >6 mm) have been extensively studied, limited data are available on small pBCC (size ≤6 mm) and its relationship with tumor progression. METHODS: Dermoscopic images of histologically proven pBCCs were collected between 2014 and 2022 at Hualien Tzu Chi Hospital. Each image was analyzed for patterns of pigmentation, vasculature, and epidermal and dermal structures. Statistical analysis was performed to compare the differences according to the size and the trend during tumor progression. RESULTS: In total, 135 pBCCs (48 small and 87 large) were included. Pigment structures were present in all cases. Short fine telangiectasia and small erosions constituted over 85% of the cases, showing no significant distinction between small and large pBCCs, nor any specific pattern correlating with tumor enlargement. The number of arborizing vessels, ulcerations, and shiny white structures showed an increasing trend associated with size progression. Arborizing vessels appeared when tumor size exceeded 6 mm. CONCLUSIONS: This study provides a dynamic interpretation of the dermoscopic features of pBCC according to size enlargement. Short fine telangiectasia and small erosions are highly important features for the early diagnosis of small pBCCs. Arborizing vessels, ulceration, and shiny white structures are more frequent in large pBCCs, and they increase in association with tumor progression.

Plasma Alzheimer's biomarkers and brain amyloid in Hispanic and non-Hispanic older adults.

INTRODUCTION: Alzheimer's disease studies often lack ethnic diversity. METHODS: We evaluated associations between plasma biomarkers commonly studied in Alzheimer's (p-tau181, GFAP, and NfL), clinical diagnosis (clinically normal, amnestic MCI, amnestic dementia, or non-amnestic MCI/dementia), and Aß-PET in Hispanic and non-Hispanic older adults. Hispanics were predominantly of Cuban or South American ancestry. RESULTS: Three-hundred seventy nine participants underwent blood draw (71.9 ± 7.8 years old, 60.2% female, 57% Hispanic of which 88% were Cuban or South American) and 240 completed Aß-PET. P-tau181 was higher in amnestic MCI (p = 0.004, d = 0.53) and dementia (p < 0.001, d = 0.97) than in clinically normal participants and discriminated Aß-PET[+] and Aß-PET[-] (AUC = 0.86). P-tau181 outperformed GFAP and NfL. There were no significant interactions with ethnicity. Among amnestic MCI, Hispanics had lower odds of elevated p-tau181 than non-Hispanic (OR = 0.41, p = 0.006). DISCUSSION: Plasma p-tau181 informs etiological diagnosis of cognitively impaired Hispanic and non-Hispanic older adults. Hispanic ethnicity may relate to greater likelihood of non-Alzheimer's contributions to memory loss. HIGHLIGHTS: Alzheimer's biomarkers were measured in Hispanic and non-Hispanic older adults. Plasma p-tau181 related to amnestic cognitive decline and brain amyloid burden. AD biomarker associations did not differ between Hispanic and non-Hispanic ethnicity. Hispanic individuals may be more likely to have non-Alzheimer causes of memory loss.

Flexible Block Copolymer Metamaterials Featuring Hollow Ordered Nanonetworks with Ultra-High Porosity and Surface-To-Volume Ratio.

By utilizing bicontinuous and nanoporous ordered nanonetworks, such as double gyroid (DG) and double diamond (DD), metamaterials with exceptional optical and mechanical properties can be fabricated through the templating synthesis of functional materials. However, the volume fraction range of DG in block copolymers is significantly narrow, making it unable to vary its porosity and surface-to-volume ratio. Here, the theoretically limited structural volume of the DG phase in coil-coil copolymers is overcome by enlarging the conformational asymmetry through the association of mesogens, providing fast access to achieving flexible structured materials of ultra-high porosities. The new materials design, dual-extractable nanocomposite, is created by incorporating a photodegradable block with a solvent-extractable mesogen (m) into an accepting block, resulting in a new hollow gyroid (HG) with the largely increased surface-to-volume ratio and porosity of 77 vol%. The lightweight HG exhibits a low refractive index of 1.11 and a very high specific reduced modulus, almost two times that of the typical negative gyroid (porosity≈53%) and three times that of the positive gyroid (porosity≈24%). This novel concept can significantly extend the DG phase window of block copolymers and the corresponding surface-to-volume ratio, being applicable for nanotemplate-synthesized nanomaterials with a great gain of mechanical, catalytic, and optoelectronic properties.

Lower individual alpha frequency in individuals with chronic low back pain and fear of movement.

ABSTRACT: Significant progress has been made in linking measures of individual alpha frequency (IAF) and pain. A lower IAF has been associated with chronic neuropathic pain and with an increased sensitivity to pain in healthy young adults. However, the translation of these findings to chronic low back pain (cLBP) are sparse and inconsistent. To address this limitation, we assessed IAFs in a cohort of 70 individuals with cLBP, implemented 3 different IAF calculations, and separated cLBP subjects based on psychological variables. We hypothesized that a higher fear movement in cLBP is associated with a lower IAF at rest. A total of 10 minutes of resting data were collected from 128 electroencephalography channels. Our results offer 3 novel contributions to the literature. First, the high fear group had a significantly lower peak alpha frequency. The high fear group also reported higher pain and higher disability. Second, we calculated individual alpha frequency using 3 different but established methods; the effect of fear on individual alpha frequency was robust across all methods. Third, fear of movement, pain intensity, and disability highly correlated with each other and together significantly predicted IAF. Our findings are the first to show that individuals with cLBP and high fear have a lower peak alpha frequency.

Case Report: Ribociclib-induced phototoxicity presented as dyschromia with subsequent bullae formation.

Ribociclib, a cyclin-dependent kinase 4/6 inhibitor, is a novel targeted therapy for advanced-stage breast cancer. Although ribociclib-induced cutaneous side effects have been previously noted, they have not been well documented. Herein, we present a case of ribociclib-induced phototoxicity, which manifested as dyschromia over sun-exposed forearms and neck initially and as bullae formation subsequently. A 71-year-old woman with metastatic breast cancer developed dyschromia after daily treatment with ribociclib (600 mg) for 7 months. Skin biopsy of the pigmented lesion revealed interface dermatitis with melanin incontinence and dyskeratotic cells and ballooning keratinocytes with loss of melanocytes in the basal layer. Further, clefting at the basal layer of epidermis was noted in a more hyperpigmented field. Fontana-Masson staining revealed melanophages in the dermis. Human Melanoma Black-45 staining revealed decreased melanocyte numbers in the epidermis above the cleft. Immunohistochemical analyses revealed activated CD1a+ epidermal Langerhans cells and infiltrating CD4+ and CD8+ T cells in the epidermis and dermis, thereby indicating type IV hypersensitivity that was associated with damage to keratinocytes and melanocytes. To prevent progression of bullous dermatitis, we advised the patient to discontinue ribociclib and prescribed oral and topical prednisolone. Due to the risk of phototoxicity, we educated the patient on sun-protection strategies. The patient's skin lesions subsided during the 2 months of treatment. Phototoxicity with dyschromia is a rare but significant ribociclib-induced cutaneous side effect. Early diagnosis, rapid ribociclib withdrawal, protection from sunlight, and prompt treatment are critical for preventing subsequent severe bullous dermatosis.

Distinct cortical and subcortical predictors of Purdue Pegboard decline in Parkinson's disease and atypical parkinsonism.

Objective measures of disease progression are critically needed in research on Parkinson's disease (PD) and atypical Parkinsonism but may be hindered by both practicality and cost. The Purdue Pegboard Test (PPT) is objective, has high test-retest reliability, and has a low cost. The goals of this study were to determine: (1) longitudinal changes in PPT in a multisite cohort of patients with PD, atypical Parkinsonism, and healthy controls; (2) whether PPT performance reflects brain pathology revealed by neuroimaging; (3) quantify kinematic deficits shown by PD patients during PPT. Parkinsonian patients showed a decline in PPT performance that correlated with motor symptom progression, which was not seen in controls. Neuroimaging measures from basal ganglia were significant predictors of PPT performance in PD, whereas cortical, basal ganglia, and cerebellar regions were predictors for atypical Parkinsonism. Accelerometry in a subset of PD patients showed a diminished range of acceleration and irregular patterns of acceleration, which correlated with PPT scores.

Imaging features of small vessel disease in cerebral amyloid angiopathy among patients with Alzheimer's disease.

BACKGROUND AND PURPOSE: Cerebral small vessel disease biomarkers including white matter hyperintensities (WMH), lacunes, and enlarged perivascular spaces (ePVS) are under investigation to identify those specific to cerebral amyloid angiopathy (CAA). In subjects with Alzheimer's disease (AD), we assessed characteristic features and amounts of WMH, lacunes, and ePVS in four CAA categories (no, mild, moderate and severe CAA) and correlated these with Clinical Dementia Rating sum of boxes (CDRsb) score, ApoE genotype, and neuropathological changes at autopsy. METHODS: The study included patients with a clinical diagnosis of dementia due to AD and neuropathological confirmation of AD and CAA in the National Alzheimer's Coordinating Center (NACC) database. The WMH, lacunes, and ePVS were evaluated using semi-quantitative scales. Statistical analyses compared the WMH, lacunes, and ePVS values in the four CAA groups with vascular risk factors and AD severity treated as covariates, and to correlate the imaging features with CDRsb score, ApoE genotype, and neuropathological findings. RESULTS: The study consisted of 232 patients, of which 222 patients had FLAIR data available and 105 patients had T2-MRI. Occipital predominant WMH were significantly associated with the presence of CAA (p = 0.007). Among the CAA groups, occipital predominant WMH was associated with severe CAA (ß = 1.22, p = 0.0001) compared with no CAA. Occipital predominant WMH were not associated with the CDRsb score performed at baseline (p = 0.68) or at follow-up 2-4 years after the MRI (p = 0.92). There was no significant difference in high grade ePVS in the basal ganglia (p = 0.63) and centrum semiovale (p = 0.95) among the four CAA groups. The WMH and ePVS on imaging did not correlate with the number of ApoE ε4 alleles but the WMH (periventricular and deep) correlated with the presence of infarcts, lacunes and microinfarcts on neuropathology. CONCLUSION: Among patients with AD, occipital predominant WMH is more likely to be found in patients with severe CAA than in those without CAA. The high-grade ePVS in centrum semiovale were common in all AD patients regardless of CAA severity.

Mediation of Reduced Hippocampal Volume by Cerebral Amyloid Angiopathy in Pathologically Confirmed Patients with Alzheimer's Disease.

BACKGROUND: Hippocampal atrophy in cerebral amyloid angiopathy (CAA) has been reported to be similar to that in Alzheimer's disease (AD). OBJECTIVE: To evaluate if CAA pathology partly mediates reduced hippocampal volume in patients with AD. METHODS: Patients with a clinical diagnosis of AD and neuropathological confirmation of AD+/-CAA in the National Alzheimer's Coordinating Center database were included in the study. The volumes of temporal lobe structures were calculated on T1-weighted imaging (T1-MRI) using automated FreeSurfer software, from images acquired on average 5 years prior to death. Multivariate regression analysis was performed to compare brain volumes in four CAA groups. The hippocampal volume on T1-MRI was correlated with Clinical Dementia Rating sum of boxes (CDRsb) score, apolipoprotein E (APOE) genotype, and hippocampal atrophy at autopsy. RESULTS: The study included 231 patients with no (n = 45), mild (n = 70), moderate (n = 67), and severe (n = 49) CAA. Among the four CAA groups, patients with severe CAA had a smaller mean left hippocampal volume (p = 0.023) but this was not significant when adjusted for APOE ɛ4 (p = 0.07). The left hippocampal volume on MRI correlated significantly with the hippocampal atrophy grading on neuropathology (p = 0.0003). Among patients with severe CAA, the left hippocampal volume on T1-MRI: (a) decreased with an increase in the number of APOE ɛ4 alleles (p = 0.04); but (b) had no evidence of correlation with CDRsb score (p = 0.57). CONCLUSION: Severe CAA was associated with smaller left hippocampal volume on T1-MRI up to five years prior to death among patients with neuropathologically confirmed AD. This relationship was dependent on APOE ɛ4 genotype.

Association of longitudinal cognitive decline with diffusion MRI in Gray Matter, Amyloid, and Tau deposition.

Extracellular amyloid plaques in gray matter are the earliest pathological marker for Alzheimer's disease (AD), followed by abnormal tau protein accumulation. The link between diffusion changes in gray matter, amyloid and tau pathology, and cognitive decline is not well understood. We first performed cross-sectional analyses on T1-weighted imaging, diffusion MRI, and amyloid and tau PETs from the ADNI 2/3 database. We evaluated cortical volume, free-water, fractional anisotropy (FA), and amyloid and tau SUVRs in 171 cognitively normal, 103 MCI, and 44 AD individuals. When the 3 groups were combined, increasing amyloid burden was associated with reduced extracellular free-water in the entorhinal cortex and hippocampus in those with amyloid-negative status whereas increasing tau burden was associated with increased extracellular free-water regardless of amyloid status. Next, we found that for the MCI subjects, diffusion measures (free-water, FA) alone predicted MMSE score 2 years later with a high r-square value (87%), as compared to tau SUVRs (27%), T1 volume (36%), and amyloid SUVRs (75%). Diffusion measures represent a potent non-invasive marker for predicting cognitive decline.

Successful treatment of extremely large Bowen's disease lesion by topical photodynamic therapy and imiquimod: Using optical coherence tomography to detect early recurrence loci and validate the cure.

Bowen's disease, a form of skin cancer, is an intraepithelial carcinoma involving keratinocytes. It is associated with a risk of developing invasive squamous cell carcinoma in 3-5% of cases. Ultraviolet exposure, arsenic, human papillomavirus infection, immunosuppression, and genetic factors have been reported to be the causes. Clinically, it presents as symptomless and slowly growing, well-demarcated, irregular erythematous patches or plaques with scaly or crusted surfaces. Surgical excision remains common; however, for large (>20 mm) or multiple Bowen's disease lesions, alternative therapies need to be considered. Here, we present a case of extremely large Bowen's disease lesions in the lower extremities successfully treated with combination therapy using topical aminolevulinic acid-based photodynamic therapy followed by topical 5% imiquimod cream. Optical coherence tomography revealed disorganized and uneven nuclei of keratinocytes in the recurrent lesions, which became relatively small and uniform upon resolution. We demonstrated that photodynamic therapy provides a generally safe and effective strategy for treating large Bowen's disease lesions and optical coherence tomography provides a useful and noninvasive diagnosis of early Bowen's disease recurrence.

Clinical utility of plasma Aß42/40 ratio by LC-MS/MS in Alzheimer's disease assessment.

INTRODUCTION: Plasma Aß42/40 ratio can be used to help predict amyloid PET status, but its clinical utility in Alzheimer's disease (AD) assessment is unclear. METHODS: Aß42/40 ratio was measured by LC-MS/MS in 250 specimens with associated amyloid PET imaging, diagnosis, and demographic data, and 6,192 consecutive clinical specimens submitted for Aß42/40 testing. RESULTS: High diagnostic sensitivity and negative predictive value (NPV) for Aß-PET positivity were observed, consistent with the clinical performance of other plasma LC-MS/MS assays, but with greater separation between Aß42/40 values for individuals with positive vs negative Aß-PET results. Assuming a moderate prevalence of Aß-PET positivity, a cutpoint was identified with 99% NPV, which could help predict that AD is likely not the cause of patients' cognitive impairment and help reduce PET evaluation by about 40%. DISCUSSION: Using high-throughput plasma Aß42/40 LC-MS/MS assays can help reduce PET evaluations in patients with low likelihood of AD pathology, allowing for cost savings.

Neurophysiology of movement inhibition during full body reaching.

Our current understanding of response inhibition comes from go/no-go studies that draw conclusions based on the overt movement of single limbs (i.e., a single finger pushing a button). In general, go/no-go paradigms have found that an individual's ability to correctly inhibit the motor system is indicative of a healthy central nervous system. However, measuring inhibition by an overt behavioral response may lack the sensitivity to conclude whether the motor system is completely inhibited. Therefore, our goal was to use behavioral and neurophysiological measures to investigate inhibition of the motor system during a full-body reaching task. When directly comparing neurophysiological and behavioral measures, we found that neurophysiological measures were associated with a greater number of errors during no-go trials and faster onset times during go trials. Further analyses revealed a negative correlation between errors and onset times, such that the muscles that activated the earliest during go trials also had the greatest number of errors during no-go trials. Together, our observations show that the absence of an overt behavioral response does not always translate to total inhibition of the motor system.

Association of Cognitive Impairment With Free Water in the Nucleus Basalis of Meynert and Locus Coeruleus to Transentorhinal Cortex Tract.

BACKGROUND AND OBJECTIVES: The goal of this work was to determine the relationship between diffusion microstructure and early changes in Alzheimer disease (AD) severity as assessed by clinical diagnosis, cognitive performance, dementia severity, and plasma concentrations of neurofilament light chain. METHODS: Diffusion MRI scans were collected on cognitively normal participants (CN) and patients with early mild cognitive impairment (EMCI), late mild cognitive impairment, and AD. Free water (FW) and FW-corrected fractional anisotropy were calculated in the locus coeruleus to transentorhinal cortex tract, 4 magnocellular regions of the basal forebrain (e.g., nucleus basalis of Meynert), entorhinal cortex, and hippocampus. All patients underwent a battery of cognitive assessments; neurofilament light chain levels were measured in plasma samples. RESULTS: FW was significantly higher in patients with EMCI compared to CN in the locus coeruleus to transentorhinal cortex tract, nucleus basalis of Meynert, and hippocampus (mean Cohen d = 0.54; p fdr < 0.05). FW was significantly higher in those with AD compared to CN in all the examined regions (mean Cohen d = 1.41; p fdr < 0.01). In addition, FW in the hippocampus, entorhinal cortex, nucleus basalis of Meynert, and locus coeruleus to transentorhinal cortex tract positively correlated with all 5 cognitive impairment metrics and neurofilament light chain levels (mean r 2 = 0.10; p fdr < 0.05). DISCUSSION: These results show that higher FW is associated with greater clinical diagnosis severity, cognitive impairment, and neurofilament light chain. They also suggest that FW elevation occurs in the locus coeruleus to transentorhinal cortex tract, nucleus basalis of Meynert, and hippocampus in the transition from CN to EMCI, while other basal forebrain regions and the entorhinal cortex are not affected until a later stage of AD. FW is a clinically relevant and noninvasive early marker of structural changes related to cognitive impairment.

Cortical dynamics of movement-evoked pain in chronic low back pain.

KEY POINTS: Cortical activity underlying movement-evoked pain is not well understood, despite being a key symptom of chronic musculoskeletal pain. We combined high-density electroencephalography with a full-body reaching protocol in a virtual reality environment to assess cortical activity during movement-evoked pain in chronic low back pain. Movement-evoked pain in individuals with chronic low back pain was associated with longer reaction times, delayed peak velocity and greater movement variability. Movement-evoked pain was associated with attenuated disinhibition in prefrontal motor areas, as evidenced by an attenuated reduction in beta power in the premotor cortex and supplementary motor area. ABSTRACT: Although experimental pain alters neural activity in the cortex, evidence of changes in neural activity in individuals with chronic low back pain (cLBP) remains scarce and results are inconsistent. One of the challenges in studying cLBP is that the clinical pain fluctuates over time and often changes during movement. The goal of the present study was to address this challenge by recording high-density electroencephalography (HD-EEG) data during a full-body reaching task to understand neural activity during movement-evoked pain. HD-EEG data were analysed using independent component analyses, source localization and measure projection analyses to compare neural oscillations between individuals with cLBP who experienced movement-evoked pain and pain-free controls. We report two novel findings. First, movement-evoked pain in individuals with cLBP was associated with longer reaction times, delayed peak velocity and greater movement variability. Second, movement-evoked pain was associated with an attenuated reduction in beta power in the premotor cortex and supplementary motor area. Our observations move the field forward by revealing attenuated disinhibition in prefrontal motor areas during movement-evoked pain in cLBP.