Cortical α4β2-nicotinic acetylcholine receptors and cognitive decline in Parkinson's disease.

Background: Autopsy and molecular imaging studies suggest altered binding of the α4β2-nicotinic cholinergic receptor (α4β2-nAChR) with cognitive dysfunction in Parkinson's disease (PD).

Objective: To determine the relationship between cortical and hippocampal binding of the α4β2-nAChR with [F]XTRA PET, a high-affinity radiotracer that enables quantification of α4β2-nAChR in these regions, and cognitive function in individuals with PD.

Methods: Individuals with PD (N = 32) and age-similar, controls without PD or dementia (N = 10) completed a cognitive assessment and one 90-min, [F]XTRA PET scan.

Pro-cognitive reshaping of neuronal dynamics by a human CSF-based factor.

Neuronal connection dysfunction is a convergent cause of cognitive deficits in mental disorders. Cognitive processes are finely regulated at the synaptic level by membrane proteins, some of which are shed and detectable in patients' cerebrospinal fluid (CSF). However, whether these soluble synaptic proteins can harnessed as innovative pro-cognitive factors to treat brain disorders remains unclear.

Imaging the translocator protein 18 kDa within cognitive control and declarative memory circuits in virally suppressed people with HIV.

Objectives: Virally suppressed people with HIV (VS-PWH) show heterogeneity in patterns of cognitive dysfunction. To better understand the relationship between the neuroimmune response and cognition, we used PET to image the translocator protein 18 kDa (TSPO). The study examined HIV-serostatus differences in TSPO as well as associations between regional TSPO and select cognitive processes defined using the Research Domain Criteria (RDoC) framework.

Intact HIV Reservoir in Monocytes Is Associated With Cognitive Function in Virally Suppressed Women With HIV.

Background: Monocytes are susceptible to human immunodeficiency virus (HIV) infection, form HIV reservoirs, and contribute to central nervous system complications (eg, cognitive impairment) in virally suppressed women with HIV (vsWWH). However, it remains unknown if the quality and/or quantity of the monocyte reservoir contributes to cognition in vsWWH.

Methods: Sixty-two vsWWH (mean age = 56.

Hippocampal Availability of the α7 Nicotinic Acetylcholine Receptor in Recent-Onset Psychosis.

Importance: Studies using human postmortem tissue and imaging with positron emission tomography (PET) support a low hippocampal availability of the α7 nicotinic acetylcholine receptor (α7-nAChR) in psychotic conditions, particularly in schizophrenia or schizoaffective disorder (nonaffective psychosis). If validated further, the finding may have implications for clinical diagnosis and treatment.

Objective: To test for lower availability of the α7-nAChR in the hippocampus of individuals with recent-onset psychosis compared with healthy control individuals and its association with lower cognitive performance or higher psychotic symptom burden within recent-onset psychosis.

Neuroimaging alterations and relapse in early-stage psychosis.

Background: Recent reports have indicated that symptom exacerbation after a period of improvement, referred to as relapse, in early-stage psychosis could result in brain changes and poor disease outcomes. We hypothesized that substantial neuroimaging alterations may exist among patients who experience relapse in early-stage psychosis.

Methods: We studied patients with psychosis within 2 years after the first psychotic event and healthy controls.

Reduction of N-acetyl aspartate (NAA) in association with relapse in early-stage psychosis: a 7-Tesla MRS study.

Understanding the biological underpinning of relapse could improve the outcomes of patients with psychosis. Relapse is elicited by multiple reasons/triggers, but the consequence frequently accompanies deteriorations of brain function, leading to poor prognosis. Structural brain imaging studies have recently been pioneered to address this question, but a lack of molecular investigations is a knowledge gap.

Imaging Brain Injury in Former National Football League Players.

Importance: Pilot studies that involved early imaging of the 18 kDa translocator protein (TSPO) using positron emission tomography (PET) indicated high levels of TSPO in the brains of active or former National Football League (NFL) players. If validated further in larger studies, those findings may have implications for athletes involved in collision sport.

Objective: To test for higher TSPO that marks brain injury and repair in a relatively large, unique cohort of former NFL players compared with former elite, noncollision sport athletes.

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).

[F]FNDP PET neuroimaging test-retest repeatability and whole-body dosimetry in humans.

Purpose: Soluble epoxide hydrolase (sEH) is an enzyme that shapes immune signaling through its role in maintaining the homeostasis of polyunsaturated fatty acids and their related byproducts. [F]FNDP is a radiotracer developed for use with positron emission tomography (PET) to image sEH, which has been applied to imaging sEH in the brains of healthy individuals. Here, we report the test-retest repeatability of [F]FNDP brain PET binding and [F]FNDP whole-body dosimetry in healthy individuals.

Exploring [C]CPPC as a CSF1R-targeted PET Imaging Marker for Early Parkinson's Disease Severity.

Neuroinflammation through enhanced innate immunity is thought play a role in the pathogenesis of Parkinson's disease (PD). Methods for monitoring neuroinflammation in living patients with PD are currently limited to positron emission tomography (PET) ligands that lack specificity in labeling immune cells in the nervous system. The colony stimulating factor 1 receptor (CSF1R) plays a crucial role in microglial function, an important cellular contributor to the nervous system's innate immune response.

Pilot imaging of the colony stimulating factor 1 receptor in the brains of virally-suppressed individuals with HIV.

Objective: Neuroimmune activation is a putative driver of cognitive impairment in people with HIV (PWH), even in the age of modern antiretroviral therapy. Nevertheless, imaging of the microglial marker, the 18 kDa translocator protein (TSPO), with positron emission tomography (PET) in treated PWH has yielded inconclusive findings. One potential reason for the varied TSPO results is a lack of cell-type specificity of the TSPO target.

Imaging of Brain Structural and Functional Effects in People With Human Immunodeficiency Virus.

Before the introduction of antiretroviral therapy, human immunodeficiency virus (HIV) infection was often accompanied by central nervous system (CNS) opportunistic infections and HIV encephalopathy marked by profound structural and functional alterations detectable with neuroimaging. Treatment with antiretroviral therapy nearly eliminated CNS opportunistic infections, while neuropsychiatric impairment and peripheral nerve and organ damage have persisted among virally suppressed people with HIV (PWH), suggesting ongoing brain injury. Neuroimaging research must use methods sensitive for detecting subtle HIV-associated brain structural and functional abnormalities, while allowing for adjustments for potential confounders, such as age, sex, substance use, hepatitis C coinfection, cardiovascular risk, and others.

First-in-human imaging using [C]MDTC: a radiotracer targeting the cannabinoid receptor type 2.

Purpose: We report findings from the first-in-human study of [C]MDTC, a radiotracer developed to image the cannabinoid receptor type 2 (CB2R) with positron emission tomography (PET).

Methods: Ten healthy adults were imaged according to a 90-min dynamic PET protocol after bolus intravenous injection of [C]MDTC. Five participants also completed a second [C]MDTC PET scan to assess test-retest reproducibility of receptor-binding outcomes.

Variability and magnitude of brain glutamate levels in schizophrenia: a meta and mega-analysis.

Glutamatergic dysfunction is implicated in schizophrenia pathoaetiology, but this may vary in extent between patients. It is unclear whether inter-individual variability in glutamate is greater in schizophrenia than the general population. We conducted meta-analyses to assess (1) variability of glutamate measures in patients relative to controls (log coefficient of variation ratio: CVR); (2) standardised mean differences (SMD) using Hedges g; (3) modal distribution of individual-level glutamate data (Hartigan's unimodality dip test).

First-in-human use of C-CPPC with positron emission tomography for imaging the macrophage colony-stimulating factor 1 receptor.

Purpose: Study of the contribution of microglia to onset and course of several neuropsychiatric conditions is challenged by the fact that these resident immune cells often take on different phenotypes and functions outside the living brain. Imaging microglia with radiotracers developed for use with positron emission tomography (PET) allows researchers to study these cells in their native tissue microenvironment. However, many relevant microglial imaging targets such as the 18 kDa translocator protein are also expressed on non-microglial cells, which can complicate the interpretation of PET findings.

Generation of Digital Brain Phantom for Machine Learning Application of Dopamine Transporter Radionuclide Imaging.

While machine learning (ML) methods may significantly improve image quality for SPECT imaging for the diagnosis and monitoring of Parkinson's disease (PD), they require a large amount of data for training. It is often difficult to collect a large population of patient data to support the ML research, and the ground truth of lesion is also unknown. This paper leverages a generative adversarial network (GAN) to generate digital brain phantoms for training ML-based PD SPECT algorithms.

Brain regions associated with olfactory dysfunction in first episode psychosis patients.

Objectives: Olfactory dysfunction is reproducibly reported in psychotic disorders, particularly in association with negative symptoms. The superior frontal gyrus (SFG) has been frequently studied in patients with psychotic disorders, in particular with their associations with negative symptoms. The relationship between olfactory functions and brain structure has been studied in healthy controls (HCs).

Sex-specific involvement of the Notch-JAG pathway in social recognition.

Under the hypothesis that olfactory neural epithelium gene expression profiles may be useful to look for disease-relevant neuronal signatures, we examined microarray gene expression in olfactory neuronal cells and underscored Notch-JAG pathway molecules in association with schizophrenia (SZ). The microarray profiling study underscored JAG1 as the most promising candidate. Combined with further validation with real-time PCR, downregulation of NOTCH1 was statistically significant.

Real-time facial emotion recognition deficits across the psychosis spectrum: A B-SNIP Study.

Affective and non-affective psychotic disorders are associated with variable levels of impairment in affective processing, but this domain typically has been examined via presentation of static facial images. We compared performance on a dynamic facial expression identification task across six emotions (sad, fear, surprise, disgust, anger, happy) in individuals with psychotic disorders (bipolar with psychotic features [PBD] = 113, schizoaffective [SAD] = 163, schizophrenia [SZ] = 181) and healthy controls (HC; n = 236) derived from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP). These same individuals with psychotic disorders were also grouped by B-SNIP-derived Biotype (Biotype 1 [B1] = 115, Biotype 2 [B2] = 132, Biotype 3 [B3] = 158), derived from a cluster analysis applied to a large biomarker panel that did not include the current data.

A biomarker-authenticated model of schizophrenia implicating NPTX2 loss of function.

Schizophrenia is a polygenetic disorder whose clinical onset is often associated with behavioral stress. Here, we present a model of disease pathogenesis that builds on our observation that the synaptic immediate early gene NPTX2 is reduced in cerebrospinal fluid of individuals with recent onset schizophrenia. NPTX2 plays an essential role in maintaining excitatory homeostasis by adaptively enhancing circuit inhibition.

Face processing of social cognition in patients with first episode psychosis: Its deficits and association with the right subcallosal anterior cingulate cortex.

The clinical importance of social cognition is well acknowledged in patients with psychosis, in particular those with first episode psychosis (FEP). Nevertheless, its brain substrates and circuitries remain elusive, lacking precise analysis between multimodal brain characteristics and behavioral sub-dimensions within social cognition. In the present study, we examined face processing of social cognition in 71 FEP patients and 77 healthy controls (HCs).

A multimodal study of a first episode psychosis cohort: potential markers of antipsychotic treatment resistance.

Treatment resistant (TR) psychosis is considered to be a significant cause of disability and functional impairment. Numerous efforts have been made to identify the clinical predictors of TR. However, the exploration of molecular and biological markers is still at an early stage.

Higher circulating intermediate monocytes are associated with cognitive function in women with HIV.

BACKGROUNDIdentifying a quantitative biomarker of neuropsychiatric dysfunction in people with HIV (PWH) remains a significant challenge in the neuroHIV field. The strongest evidence to date implicates the role of monocytes in central nervous system (CNS) dysfunction in HIV, yet no study has examined monocyte subsets in blood as a correlate and/or predictor of neuropsychiatric function in virally suppressed PWH.METHODSIn 2 independent cohorts of virologically suppressed women with HIV (vsWWH; n = 25 and n = 18), whole blood samples were obtained either in conjunction with neuropsychiatric assessments (neuropsychological [NP] test battery, self-report depression and stress-related symptom questionnaires) or 1 year prior to assessments.