Network Localization of Spontaneous Confabulation.

OBJECTIVE: Spontaneous confabulation is a symptom in which false memories are conveyed by the patient as true. The purpose of the study was to identify the neuroanatomical substrate of this complex symptom and evaluate the relationship to related symptoms, such as delusions and amnesia. METHODS: Twenty-five lesion locations associated with spontaneous confabulation were identified in a systematic literature search. The network of brain regions functionally connected to each lesion location was identified with a large connectome database (N=1,000) and compared with networks derived from lesions associated with nonspecific (i.e., variable) symptoms (N=135), delusions (N=32), or amnesia (N=53). RESULTS: Lesions associated with spontaneous confabulation occurred in multiple brain locations, but they were all part of a single functionally connected brain network. Specifically, 100% of lesions were connected to the mammillary bodies (familywise error rate [FWE]-corrected p<0.05). This connectivity was specific for lesions associated with confabulation compared with lesions associated with nonspecific symptoms or delusions (FWE-corrected p<0.05). Lesions associated with confabulation were more connected to the orbitofrontal cortex than those associated with amnesia (FWE-corrected p<0.05). CONCLUSIONS: Spontaneous confabulation maps to a common functionally connected brain network that partially overlaps, but is distinct from, networks associated with delusions or amnesia. These findings lend new insight into the neuroanatomical bases of spontaneous confabulation.

Promoting Growth in Behavioral Neurology: A Path Forward.

Behavioral neurology & neuropsychiatry (BNNP) is a field that seeks to understand brain-behavior relationships, including fundamental brain organization principles and the many ways that brain structures and connectivity can be disrupted, leading to abnormalities of behavior, cognition, emotion, perception, and social cognition. In North America, BNNP has existed as an integrated subspecialty through the United Council for Neurologic Subspecialties since 2006. Nonetheless, the number of behavioral neurologists across academic medical centers and community settings is not keeping pace with increasing clinical and research demand. In this commentary, we provide a brief history of BNNP followed by an outline of the current challenges and opportunities for BNNP from the behavioral neurologist's perspective across clinical, research, and educational spheres. We provide a practical guide for promoting BNNP and addressing the shortage of behavioral neurologists to facilitate the continued growth and development of the subspecialty. We also urge a greater commitment to recruit trainees from diverse backgrounds so as to dismantle persistent obstacles that hinder inclusivity in BNNP-efforts that will further enhance the growth and impact of the subspecialty. With rapidly expanding diagnostic and therapeutic approaches across a range of conditions at the intersection of neurology and psychiatry, BNNP is well positioned to attract new trainees and expand its reach across clinical, research, and educational activities.

Associations among plasma, MRI, and amyloid PET biomarkers of Alzheimer's disease and related dementias and the impact of health-related comorbidities in a community-dwelling cohort.

INTRODUCTION: We evaluated associations between plasma and neuroimaging-derived biomarkers of Alzheimer's disease and related dementias and the impact of health-related comorbidities. METHODS: We examined plasma biomarkers (neurofilament light chain, glial fibrillary acidic protein, amyloid beta [Aß] 42/40, phosphorylated tau 181) and neuroimaging measures of amyloid deposition (Aß-positron emission tomography [PET]), total brain volume, white matter hyperintensity volume, diffusion-weighted fractional anisotropy, and neurite orientation dispersion and density imaging free water. Participants were adjudicated as cognitively unimpaired (CU; N = 299), mild cognitive impairment (MCI; N = 192), or dementia (DEM; N = 65). Biomarkers were compared across groups stratified by diagnosis, sex, race, and APOE ε4 carrier status. General linear models examined plasma-imaging associations before and after adjusting for demographics (age, sex, race, education), APOE ε4 status, medications, diagnosis, and other factors (estimated glomerular filtration rate [eGFR], body mass index [BMI]). RESULTS: Plasma biomarkers differed across diagnostic groups (DEM > MCI > CU), were altered in Aß-PET-positive individuals, and were associated with poorer brain health and kidney function. DISCUSSION: eGFR and BMI did not substantially impact associations between plasma and neuroimaging biomarkers. HIGHLIGHTS: Plasma biomarkers differ across diagnostic groups (DEM > MCI > CU) and are altered in Aß-PET-positive individuals. Altered plasma biomarker levels are associated with poorer brain health and kidney function. Plasma and neuroimaging biomarker associations are largely independent of comorbidities.

Network Localization of Unconscious Visual Perception in Blindsight.

OBJECTIVE: Blindsight is a disorder where brain injury causes loss of conscious but not unconscious visual perception. Prior studies have produced conflicting results regarding the neuroanatomical pathways involved in this unconscious perception. METHODS: We performed a systematic literature search to identify lesion locations causing visual field loss in patients with blindsight (n = 34) and patients without blindsight (n = 35). Resting state functional connectivity between each lesion location and all other brain voxels was computed using a large connectome database (n = 1,000). Connections significantly associated with blindsight (vs no blindsight) were identified. RESULTS: Functional connectivity between lesion locations and the ipsilesional medial pulvinar was significantly associated with blindsight (family wise error p = 0.029). No significant connectivity differences were found to other brain regions previously implicated in blindsight. This finding was independent of methods (eg, flipping lesions to the left or right) and stimulus type (moving vs static). INTERPRETATION: Connectivity to the ipsilesional medial pulvinar best differentiates lesion locations associated with blindsight versus those without blindsight. Our results align with recent data from animal models and provide insight into the neuroanatomical substrate of unconscious visual abilities in patients. ANN NEUROL 2022;91:217-224.

When prion disease Isn't suspected: prion disease as the cause of terminal decline in chronic mixed dementia.

Alzheimer's Disease (AD) is the most common cause of dementia, although multiple pathologies are found in nearly half of the cases with clinically diagnosed AD. Prion diseases, such as Creutzfeldt-Jakob disease (CJD), are rare causes of dementia and typically manifest as a rapidly progressive dementia, where symptom onset to dementia most often occurs over the course of months. In this brief report, we describe a patient's typically progressive dementia with a precipitous decline at the end of their life who, on neuropathological evaluation, was found to have multiple neurodegenerative proteinopathies as well as spongiform encephalopathy due to CJD. This case of unsuspected CJD highlights a rare, but epidemiologically important, cause of sudden decline in well-established neurodegenerative dementias.

Neighborhood segregation and cognitive change: Multi-Ethnic Study of Atherosclerosis.

INTRODUCTION: We investigated associations between neighborhood racial/ethnic segregation and cognitive change. METHODS: We used data (n = 1712) from the Multi-Ethnic Study of Atherosclerosis. Racial/ethnic segregation was assessed using Getis-Ord (Gi*) z-scores based on American Community Survey Census tract data (higher Gi* = greater spatial clustering of participant's race/ethnicity). Global cognition and processing speed were assessed twice, 6 years apart. Adjusted multilevel linear regression tested associations between Gi* z-scores and cognition. Effect modification by race/ethnicity, income, education, neighborhood socioeconomic status, and neighborhood social support was tested. RESULTS: Participants were on average 67 years old; 43% were White, 11% Chinese, 29% African American/Black, 17% Hispanic; 40% had high neighborhood segregation (Gi* > 1.96). African American/Black participants with greater neighborhood segregation had greater processing speed decline in stratified analyses, but no interactions were significant. DISCUSSION: Segregation was associated with greater processing speed declines among African American/Black participants. Additional follow-ups and comprehensive cognitive batteries may further elucidate these findings. HIGHLIGHTS: A study of neighborhood racial/ethnic segregation and change in cognition. Study was based on a racially and geographically diverse, population-based cohort of older adults. Racial/ethnic segregation (clustering) was measured by the Getis-ord (Gi*) statistic. We saw faster processing speed decline among Black individuals in segregated neighborhoods.

Blood-based bioenergetic profiling reveals differences in mitochondrial function associated with cognitive performance and Alzheimer's disease.

INTRODUCTION: Despite evidence for systemic mitochondrial dysfunction early in Alzheimer's disease (AD) pathogenesis, reliable approaches monitoring these key bioenergetic alterations are lacking. We used peripheral blood mononuclear cells (PBMCs) and platelets as reporters of mitochondrial function in the context of cognitive impairment and AD. METHODS: Mitochondrial function was analyzed using complementary respirometric approaches in intact and permeabilized cells from older adults with normal cognition, mild cognitive impairment (MCI), and dementia due to probable AD. Clinical outcomes included measures of cognitive function and brain morphology. RESULTS: PBMC and platelet bioenergetic parameters were lowest in dementia participants. MCI platelets exhibited higher maximal respiration than normocognitives. PBMC and platelet respiration positively associated with cognitive ability and hippocampal volume, and negatively associated with white matter hyperintensities. DISCUSSION: Our findings indicate blood-based bioenergetic profiling can be used as a minimally invasive approach for measuring systemic bioenergetic differences associated with dementia, and may be used to monitor bioenergetic changes associated with AD risk and progression. HIGHLIGHTS: Peripheral cell bioenergetic alterations accompanied cognitive decline in older adults with mild cognitive impairment (MCI) and Alzheimer's disease (AD) and related dementia (DEM). Peripheral blood mononuclear cells (PBMC) and platelet glucose-mediated respiration decreased in participants with dementia compared to normocognitive controls (NC). PBMC fatty-acid oxidation (FAO)-mediated respiration progressively declined in MCI and AD compared to NC participants, while platelet FAO-mediated respiration exhibited an inverse-Warburg effect in MCI compared to NC participants. Positive associations were observed between bioenergetics and Modified Preclinical Alzheimer's Cognitive Composite, and bioenergetics and hippocampal volume %, while a negative association was observed between bioenergetics and white matter hyperintensities. Systemic mitochondrial dysfunction is associated with cognitive decline.

Changes in Torque-Angle Profiles of the Hamstrings and Hamstrings-to-Quadriceps Ratio After Two Hamstring Strengthening Exercise Interventions in Female Hockey Players.

Delextrat, A, Bateman, J, Ross, C, Harman, J, Davis, L, Vanrenterghem, J, and Cohen, DD. Changes in torque-angle profiles of the hamstrings and hamstrings-to-quadriceps ratio after two hamstring strengthening exercise interventions in female hockey players. J Strength Cond Res 34(2): 396-405, 2020-The aim of this study was to compare the effects of 2 hamstring strengthening interventions (Nordic hamstrings [NHE] vs. eccentric leg curl [ELC]) on the hamstring torque-angle profiles and functional hamstrings-to-quadriceps ratio (Hecc:Qcon) in female hockey players. Female university-level players were randomly allocated to an NHE group (n = 9, 19.7 ± 1.4 years; 168.4 ± 4.4 cm; 66.2 ± 7.2 kg, 26.0 ± 4.4%), an ELC group (n = 8, 19.5 ± 1.0 years; 168.1 ± 3.4 cm; 66.7 ± 4.5 kg, 24.8 ± 3.5%), or a control (C) group (n = 8, 19.6 ± 1.4 years; 169.9 ± 7.5 cm; 70.7 ± 13.0 kg, 25.9 ± 5.2%). They performed baseline isokinetic concentric strength tests of the quadriceps (Qcon) and eccentric strength of the hamstrings (Hecc) at 120°·s, followed by a 6-week intervention with exercises (NHE or ELC) performed 3 times weekly, before post-tests. Analyses of variance with repeated measures were used to assess the effects of knee position angle (from 90° of knee flexion to 10° close to extension), group, and time on Qcon, Hecc, and Hecc:Qcon. There were no interactions between independent variables. Significant increases in Hecc and Hecc:Qcon were shown after NHE (+29.9 and +27.8%) and ELC (+30.5 and +38.3%) in the nondominant leg only. Furthermore, significant shifts in the hamstring eccentric angle of peak torque toward a longer muscle length were shown in both legs (14.3-28.6%). These findings suggest that NHE and ELC both resulted in significant improvements in peak and muscle-length-specific neuromuscular risk factors in the nondominant (ND) limb, thereby reducing interlimb peak strength asymmetries. Strength and conditioning specialists could therefore use both the NHE and ELC exercises in female hockey players.

The role of PTSD and TBI in post-deployment sleep outcomes.

The purpose of this study was to evaluate the main and interaction effects of PTSD and TBI on sleep outcomes in veterans. Post-deployment combat veterans (N = 293, 87.37% male) completed clinical interviews to determine diagnosis and severity of PTSD and deployment TBI history, as well as subjective measures of sleep quality, sleep duration, and restedness. Sleep-related medical diagnoses were extracted from electronic medical records for all participants. PTSD and TBI were each associated with poorer ratings of sleep quality, restedness, shorter sleep duration, and greater incidence of clinically diagnosed sleep disorders. Analyses indicated main effects of PTSD on sleep quality (p < .001), but no main effects of TBI. PTSD severity was significantly associated with poorer sleep quality (p < .001), restedness (p = .018), and shorter sleep duration (p = .015). TBI severity was significantly associated with restedness beyond PTSD severity (p = .036). There were no interaction effects between diagnostic or severity variables. PTSD severity is a driving factor for subjective ratings of sleep disturbance beyond PTSD diagnosis as well as TBI diagnosis and severity. Despite this, poor sleep was apparent throughout the sample, which suggests post-deployment service members may globally benefit from routine screening of sleep problems and increased emphasis on sleep hygiene.

Aprosodia and prosoplegia with right frontal neurodegeneration.

Affective prosody and facial expression are essential components of human communication. Aprosodic syndromes are associated with focal right cerebral lesions that impair the affective-prosodic aspects of language, but are rarely identified because affective prosody is not routinely assessed by clinicians. Inability to produce emotional faces (affective prosoplegia) is a related and important aspect of affective communication has overlapping neuroanatomic substrates with affective prosody. We describe a patient with progressive aprosodia and prosoplegia who had right greater than left perisylvian and temporal atrophy with an anterior predominance. We discuss the importance of assessing affective prosody and facial expression to arrive at an accurate clinical diagnosis.

Acute Pharmacological Management of Behavioral and Emotional Dysregulation Following a Traumatic Brain Injury: A Systematic Review of the Literature.

BACKGROUND: Traumatic brain injury (TBI) is an increasingly common cause of behavioral and emotional dysregulation among hospitalized patients. While consultation-liaison psychiatrists are often called to help manage these behaviors, acute pharmacological management guidelines are limited. OBJECTIVE: Conduct a systematic review to determine which pharmacological measures are supported by the literature for targeting agitation and aggression in the acute time period following a TBI. METHODS: In a systematic review of MEDLINE, Embase, PsycInfo, ClinicalTrials.gov and the Cochrane Library, we identified and then analyzed publications that investigated the pharmacological management of behavioral and emotional dysregulation following a TBI during the acute time period following injury. RESULTS: There were a limited number of high quality studies that met our inclusion criteria, including only five randomized controlled trials. The majority of the literature identified consisted of case reports or case series. Trends identified in the literature reviewed suggested that amantadine, propranolol, and anti-epileptics were the best supported medications to consider. For many medication classes, the time of medication initiation and duration of treatment, relative to the time of injury, may impact the effect observed. CONCLUSIONS: The pharmacological management of agitated patients immediately following a TBI is still an area of much-needed research, as there is limited data-driven guidance in the literature.

Experimental Realization of a Thermal Squeezed State of Levitated Optomechanics.

We experimentally squeeze the thermal motional state of an optically levitated nanosphere by fast switching between two trapping frequencies. The measured phase-space distribution of the center of mass of our particle shows the typical shape of a squeezed thermal state, from which we infer up to 2.7 dB of squeezing along one motional direction. In these experiments the average thermal occupancy is high and, even after squeezing, the motional state remains in the remit of classical statistical mechanics. Nevertheless, we argue that the manipulation scheme described here could be used to achieve squeezing in the quantum regime if preceded by cooling of the levitated mechanical oscillator. Additionally, a higher degree of squeezing could, in principle, be achieved by repeating the frequency-switching protocol multiple times.

Interferometric Laser Cooling of Atomic Rubidium.

We report the 1D cooling of ^{85}Rb atoms using a velocity-dependent optical force based upon Ramsey matter-wave interferometry. Using stimulated Raman transitions between ground hyperfine states, 12 cycles of the interferometer sequence cool a freely moving atom cloud from 21 to 3 µK. This pulsed analog of continuous-wave Doppler cooling is effective at temperatures down to the recoil limit; with augmentation pulses to increase the interferometer area, it should cool more quickly than conventional methods and be more suitable for species that lack a closed radiative transition.

Compact, high-pulse-energy, high-power, picosecond master oscillator power amplifier.

We report a compact, stable, gain-switched-diode-seeded master oscillator power amplifier (MOPA), employing direct amplification via conventional Yb(3+)-doped fibers, to generate picosecond pulses with energy of 17.7 µJ and 97-W average output power (excluding amplified spontaneous emission) at 5.47-MHz repetition frequency in a diffraction-limited and single-polarization beam. A maximum peak power of 197 kW is demonstrated. Such a high-energy, high-power, MHz, picosecond MOPA is of great interest for high-throughput material processing. With 13.8-µJ pulse energy confined in the 0.87-nm 3-dB spectral bandwidth, this MOPA is also a promising source for nonlinear frequency conversion to generate high-energy pulses in other spectral regions. We have explored the pulse energy scaling until the stimulated Raman Scattering (SRS) becomes significant (i.e. spectral peak intensity exceeds 1% of that of the signal).

Scalable spatial superresolution using entangled photons.

N00N states-maximally path-entangled states of N photons-exhibit spatial interference patterns sharper than any classical interference pattern. This is known as superresolution. However, even given perfectly efficient number-resolving detectors, the detection efficiency of all previous measurements of such interference would decrease exponentially with the number of photons in the N00N state, often leading to the conclusion that N00N states are unsuitable for spatial measurements. A technique known as the "optical centroid measurement" has been proposed to solve this and has been experimentally verified for photon pairs; here we present the first extension beyond two photons, measuring the superresolution fringes of two-, three-, and four-photon N00N states. Moreover, we compare the N00N-state interference to the corresponding classical superresolution interference. Although both provide the same increase in spatial frequency, the visibility of the classical fringes decreases exponentially with the number of detected photons. Our work represents an essential step forward for quantum-enhanced measurements, overcoming what was believed to be a fundamental challenge to quantum metrology.

Biopsychosocial contexts influence adult cognitive function concurrently and longitudinally.

Background: Cognitive aging is a complex process that impacts human behavior. Identifying the factors that preserve cognitive functioning is a public health priority, given that 20% of the US population will be at least 65 years old in the next decade. Biopsychosocial determinants of cognitive decline across the lifespan are often examined as ecological factors that independently moderate cognitive aging, despite the known complexity surrounding these relationships. Objective: We aimed to address this gap by exploring the synergistic and simultaneous relationship between risk and protective factors on cognitive functioning. Method: Using the MIDUS study datasets, we examined the relationships among physiological markers, friendship quality, and global cognition functioning, concurrently and longitudinally over ten years. Our participants included 929 healthy (417 men, 512 women) adults (average age at Time 1: 54.6 ± 11.6 years). Exploratory analyses examining the effects of racial minority status were also conducted. Results: Cross-sectionally, age, and friendship quality moderated the relationship between vagally-mediated heart rate variability (vm-HRV) and cognition such that younger adults with greater friendship quality had a negative relationship between vm-HRV and cognitive performance; our unexpected finding suggests the heart-brain relationship is sensitive to the biopsychosocial environment. Longitudinally, higher IL-6 levels at Time 1 predicted poorer cognitive performance a decade later, but only among those with greater levels of friendship quality, especially for white-identifying individuals. Conclusions: The relationships among physiological risk factors, social protective factors and cognitive functioning appear to be temporally different during mid-adulthood. Given many of the whole sample findings were not replicated within the racial minority subgroup, we suggest that these relationships should be examined in a larger and more diverse racial minority sample to determine whether this study lacked the power necessary to detect a relationship or if the relationships are in fact different by racial minority sub-group. In addition, future research should overcome the study's reliance on healthy adults and self-report measures of friendship quality by including adults with pre-existing cognitive impairments, and employing more real-time measures of friendship quality, such as daily diary or ecological momentary assessment.