Multimodal investigation of neuropathology and neurometabolites in mild cognitive impairment and late-life depression with C-PiB beta-amyloid PET and 7T magnetic resonance spectroscopy.

Positron emission tomography (PET) and magnetic resonance spectroscopy (H-MRS) are complementary techniques that can be applied to study how proteinopathy and neurometabolism relate to cognitive deficits in preclinical stages of Alzheimer's disease (AD)-mild cognitive impairment (MCI) and late-life depression (LLD). We acquired beta-amyloid (Aβ) PET and 7 T H-MRS measures of GABA, glutamate, glutathione, N-acetylaspartate, N-acetylaspartylglutamate, myo-inositol, choline, and lactate in the anterior and posterior cingulate cortices (ACC, PCC) in 13 MCI and 9 LLD patients, and 13 controls. We used linear regression to examine associations between metabolites, Aβ, and cognitive scores, and whether metabolites and Aβ explained cognitive scores better than Aβ alone.

The life-saving benefit of dexamethasone in severe COVID-19 is linked to a reversal of monocyte dysregulation.

Dexamethasone is a life-saving treatment for severe COVID-19, yet its mechanism of action is unknown, and many patients deteriorate or die despite timely treatment initiation. Here, we identify dexamethasone treatment-induced cellular and molecular changes associated with improved survival in COVID-19 patients. We observed a reversal of transcriptional hallmark signatures in monocytes associated with severe COVID-19 and the induction of a monocyte substate characterized by the expression of glucocorticoid-response genes.

Hydroxyurea to prevent brain injury in children with sickle cell disease (HU Prevent)-A randomized, placebo-controlled phase II feasibility/pilot study.

Central nervous system (CNS) injury is common in sickle cell disease (SCD) and occurs early in life. Hydroxyurea is safe and efficacious for treatment of SCD, but high-quality evidence from randomized trials to estimate its neuroprotective effect is scant. HU Prevent was a randomized (1:1), double-blind, phase II feasibility/pilot trial of dose-escalated hydroxyurea vs.

A modified neural circuit framework for semantic memory retrieval with implications for circuit modulation to treat verbal retrieval deficits.

Word finding difficulty is a frequent complaint in older age and disease states, but treatment options are lacking for such verbal retrieval deficits. Better understanding of the neurophysiological and neuroanatomical basis of verbal retrieval function may inform effective interventions. In this article, we review the current evidence of a neural retrieval circuit central to verbal production, including words and semantic memory, that involves the pre-supplementary motor area (pre-SMA), striatum (particularly caudate nucleus), and thalamus.

Verbal retrieval deficits due to traumatic brain injury are associated with changes in event related potentials during a Go-NoGo task.

Objective: Verbal retrieval (VR) deficits often occur after traumatic brain injury (TBI), but the mechanisms remain unclear. We examined how event-related potentials (ERPs) during a Go-NoGo task were associated with VR deficits.

Methods: Sixty veterans with a history of TBI underwent a neuropsychological battery and a Go-NoGo task with concurrent EEG recording.

Cost-Efficient Transcriptomic-Based Drug Screening.

Transcriptomics allows to obtain comprehensive insights into cellular programs and their responses to perturbations. Despite a significant decrease in the costs of library production and sequencing in the last decade, applying these technologies at the scale necessary for drug screening remains prohibitively expensive, obstructing the immense potential of these methods. Our study presents a cost-effective system for transcriptome-based drug screening, combining miniaturized perturbation cultures with mini-bulk transcriptomics.

Chromatin accessibility profiling of targeted cell populations with laser capture microdissection coupled to ATAC-seq.

Spatially resolved omics technologies reveal context-dependent cellular regulatory networks in tissues of interest. Beyond transcriptome analysis, information on epigenetic traits and chromatin accessibility can provide further insights on gene regulation in health and disease. Nevertheless, compared to the enormous advancements in spatial transcriptomics technologies, the field of spatial epigenomics is much younger and still underexplored.

Serotonin Degeneration and Amyloid-β Deposition in Mild Cognitive Impairment: Relationship to Cognitive Deficits.

Background: Neuropathological and neuroimaging studies have demonstrated degeneration of the serotonin system in Alzheimer's disease (AD). Neuroimaging studies have extended these observations to the preclinical stages of AD, mild cognitive impairment (MCI). Serotonin degeneration has been observed also in transgenic amyloid mouse models, prior to widespread cortical distribution of amyloid-β (Aβ).

P3a amplitude to trauma-related stimuli reduced after successful trauma-focused PTSD treatment.

An elevated P3a amplitude to trauma-related stimuli is strongly associated with posttraumatic stress disorder (PTSD), yet little is known about whether this response to trauma-related stimuli is affected by treatment that decreases PTSD symptoms. As an analysis of secondary outcome measures from a randomized controlled trial, we investigated the latency and amplitude changes of the P3a in responses in a three-condition oddball visual task that included trauma-related (combat scenes) and trauma-unrelated (threatening animals) distractors. Fifty-five U.

Differences in electroencephalography oscillations between normal aging and mild cognitive impairment during semantic memory retrieval.

Semantic memory remains relatively stable with normal cognitive aging and declines in early stages of neurodegenerative disease. We measured electroencephalography (EEG) oscillatory correlates of semantic memory retrieval to examine the effects of normal and pathological aging. Twenty-nine cognitively healthy young adults (YA), 22 cognitively healthy aging adults (HA) and 20 patients with mild cognitive impairment (MCI) completed a semantic memory retrieval task with concurrent EEG recording in which they judged whether two words (features of objects) led to retrieval of an object (retrieval) or not (non-retrieval).

Corrigendum: Case report: Improving verbal retrieval deficits with high definition transcranial direct current stimulation targeting the pre-supplementary motor area in a patient with chronic traumatic brain injury.

[This corrects the article DOI: 10.3389/fneur.2021.

Molecular imaging of the association between serotonin degeneration and beta-amyloid deposition in mild cognitive impairment.

Background: Degeneration of the serotonin system has been observed in Alzheimer's disease (AD) and in mild cognitive impairment (MCI). In transgenic amyloid mouse models, serotonin degeneration is detected prior to widespread cortical beta-amyloid (Aβ) deposition, also suggesting that serotonin degeneration may be observed in preclinical AD.

Methods: The differences in the distribution of serotonin degeneration (reflected by the loss of the serotonin transporter, 5-HTT) relative to Aβ deposition was measured with positron emission tomography in a group of individuals with MCI and a group of healthy older adults.

High-definition transcranial direct current stimulation modulates theta response during a Go-NoGo task in traumatic brain injury.

Objective: High Definition transcranial Direct Current Stimulation (HD-tDCS) has been shown to improve cognitive performance in individuals with chronic traumatic brain injury (TBI), although electrophysiological mechanisms remain unclear.

Methods: Veterans with TBI underwent active anodal (N = 15) vs sham (N = 10) HD-tDCS targeting the pre-supplementary motor area (pre-SMA). A Go-NoGo task was conducted simultaneously with electroencephalography (EEG) at baseline and after intervention completion.

Alveolar macrophages in early stage COPD show functional deviations with properties of impaired immune activation.

Despite its high prevalence, the cellular and molecular mechanisms of chronic obstructive pulmonary disease (COPD) are far from being understood. Here, we determine disease-related changes in cellular and molecular compositions within the alveolar space and peripheral blood of a cohort of COPD patients and controls. Myeloid cells were the largest cellular compartment in the alveolar space with invading monocytes and proliferating macrophages elevated in COPD.

A cAMP signalosome in primary cilia drives gene expression and kidney cyst formation.

The primary cilium constitutes an organelle that orchestrates signal transduction independently from the cell body. Dysregulation of this intricate molecular architecture leads to severe human diseases, commonly referred to as ciliopathies. However, the molecular underpinnings how ciliary signaling orchestrates a specific cellular output remain elusive.

Mature neutrophils and a NF-κB-to-IFN transition determine the unifying disease recovery dynamics in COVID-19.

Disease recovery dynamics are often difficult to assess, as patients display heterogeneous recovery courses. To model recovery dynamics, exemplified by severe COVID-19, we apply a computational scheme on longitudinally sampled blood transcriptomes, generating recovery states, which we then link to cellular and molecular mechanisms, presenting a framework for studying the kinetics of recovery compared with non-recovery over time and long-term effects of the disease. Specifically, a decrease in mature neutrophils is the strongest cellular effect during recovery, with direct implications on disease outcome.

Transcranial Magnetic Stimulation and its Imaging Features in Patients With Depression, Post-traumatic Stress Disorder, and Traumatic Brain Injury.

Transcranial magnetic stimulation (TMS) is a type of noninvasive neurostimulation used increasingly often in clinical medicine. While most studies to date have focused on TMS's ability to treat major depressive disorder, it has shown promise in several other conditions including post-traumatic stress disorder (PTSD) and traumatic brain injury (TBI). As different treatment protocols are often used across studies, the ability to predict patient outcomes and evaluate immediate and long-term changes using imaging becomes increasingly important.

Regional amyloid correlates of cognitive performance in ageing and mild cognitive impairment.

Beta-amyloid deposition is one of the earliest pathological markers associated with Alzheimer's disease. Mild cognitive impairment in the setting of beta-amyloid deposition is considered to represent a preclinical manifestation of Alzheimer's disease. imaging studies are unique in their potential to advance our understanding of the role of beta-amyloid deposition in cognitive deficits in Alzheimer's disease and in mild cognitive impairment.

Positron emission tomography imaging of serotonin degeneration and beta-amyloid deposition in late-life depression evaluated with multi-modal partial least squares.

Depression in late-life is associated with increased risk of cognitive decline and development of all-cause dementia. The neurobiology of late-life depression (LLD) may involve both neurochemical and neurodegenerative mechanisms that are common to depression and dementia. Transgenic amyloid mouse models show evidence of early degeneration of monoamine systems.

Baseline delayed verbal recall predicts response to high definition transcranial direct current stimulation targeting the superior medial frontal cortex.

Anodal high definition transcranial direct current stimulation (HD-tDCS) targeting the pre-supplementary motor area/dorsal anterior cingulate cortex (pre-SMA/dACC) has recently been shown to improve verbal retrieval deficits in veterans with chronic traumatic brain injury (TBI) (Motes et al., 2020), but predictors of treatment response are unclear. We hypothesized that baseline delayed verbal recall, a sensitive measure for post-TBI chronic cognitive decline, would predict therapeutic effects of HD-tDCS targeting the pre-SMA/dACC for verbal retrieval deficits.

Case Report: Improving Verbal Retrieval Deficits With High Definition Transcranial Direct Current Stimulation Targeting the Pre-Supplementary Motor Area in a Patient With Chronic Traumatic Brain Injury.

We report a patient who has cognitive sequalae including verbal retrieval deficits after severe traumatic brain injury (TBI). The cortico-caudate-thalamic circuit involving the pre-Supplementary Motor Area (pre-SMA) has been proposed to underlie verbal retrieval functions. We hypothesized that High Definition-transcranial Direct Current Stimulation (HD-tDCS) targeting the pre-SMA would selectively modulate this circuit to remediate verbal retrieval deficits.

Swarm Learning for decentralized and confidential clinical machine learning.

Fast and reliable detection of patients with severe and heterogeneous illnesses is a major goal of precision medicine. Patients with leukaemia can be identified using machine learning on the basis of their blood transcriptomes. However, there is an increasing divide between what is technically possible and what is allowed, because of privacy legislation.

Auditory N2 Correlates of Treatment Response in Posttraumatic Stress Disorder.

Emotional processing and cognitive control are implicated as being dysfunctional in posttraumatic stress disorder (PTSD) and targeted in cognitive processing therapy (CPT), a trauma-focused treatment for PTSD. The N2 event-related potential has been interpreted in the context of emotional processing and cognitive control. In this analysis of secondary outcome measures from a randomized controlled trial, we investigated the latency and amplitude changes of the N2 in responses to task-relevant target tones and task-irrelevant distractor sounds (e.

Molecular imaging of beta-amyloid deposition in late-life depression.

Late-life depression (LLD) is associated with an increased risk of all-cause dementia and may involve Alzheimer's disease pathology. Twenty-one LLD patients who met the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria for a current major depressive episode and 21 healthy controls underwent clinical and neuropsychological assessments, magnetic resonance imaging to measure gray matter volumes, and high-resolution positron emission tomography to measure beta-amyloid (Aβ) deposition. Clinical and neuropsychological assessments were repeated after 10-12 weeks of Citalopram or Sertraline treatment (LLD patients only).