The Impact of Xanomeline and Trospium Chloride on Cognitive Impairment in Acute Schizophrenia: Replication in Pooled Data From Two Phase 3 Trials.

Objective: Xanomeline and trospium chloride (formerly known as KarXT), a novel M/M muscarinic receptor agonist, demonstrated efficacy across phase 2 and 3 trials as monotherapy for the treatment of inpatients with acute schizophrenia on the Positive and Negative Syndrome Scale total score primary endpoint. In the phase 2 trial, xanomeline/trospium improved performance on a cognitive outcome measure in the subgroup of participants with clinically significant baseline cognitive impairment. The authors sought to confirm this finding using data from two phase 3 trials.

Generalized Slowing of Resting-State Neural Oscillations in People With Schizophrenia.

Background: Recent interest in how neural oscillations reflect the flow of information through the brain has led to partitioning electroencephalography (EEG) recordings into periodic (i.e., oscillatory) and aperiodic (i.

Two neurostructural subtypes: results of machine learning on brain images from 4,291 individuals with schizophrenia.

Machine learning can be used to define subtypes of psychiatric conditions based on shared clinical and biological foundations, presenting a crucial step toward establishing biologically based subtypes of mental disorders. With the goal of identifying subtypes of disease progression in schizophrenia, here we analyzed cross-sectional brain structural magnetic resonance imaging (MRI) data from 4,291 individuals with schizophrenia (1,709 females, age=32.5 years±11.

Limited Consistency and Strength of Neural Oscillations During Sustained Visual Attention in Schizophrenia.

Background: Neural oscillations support perception, attention, and higher-order decision making. Aberrations in the strength or consistency of these oscillations in response to stimuli may underlie impaired visual perception and attention in schizophrenia. Here, we examined the phase and power of alpha oscillations (8-12 Hz) as well as aspects of beta and theta frequency oscillations during a demanding visual sustained attention task.

Thalamocortical connectivity and its relationship with symptoms and cognition across the psychosis continuum.

Background: Coordination between the thalamus and cortex is necessary for efficient processing of sensory information and appears disrupted in schizophrenia. The significance of this disrupted coordination (i.e.

Individual alpha peak frequency is slower in schizophrenia and related to deficits in visual perception and cognition.

The brain at rest generates cycles of electrical activity that have been shown to be abnormal in people with schizophrenia. The alpha rhythm (~ 10 Hz) is the dominant resting state electrical cycle and each person has a propensity toward a particular frequency of oscillation for this rhythm. This individual alpha peak frequency (IAPF) is hypothesized to be central to visual perceptual processes and may have downstream influences on cognitive functions such as attention, working memory, or problem solving.

Smoking Is Related to Reduced Motivation, But Not Global Cognition, in the First Two Years of Treatment for First Episode Psychosis.

Smoking is highly prevalent in people with psychotic disorders, even in the earliest phases of the illness. The neural mechanisms of nicotine dependence and psychosis overlap and may also be linked to deficits in neurocognition and motivation in psychosis. Both neurocognition and motivation are recognized as important clinical targets, though previous research examining the effects of smoking on these features has been inconsistent.

Considerations for Pairing Cognitive Behavioral Therapies and Non-invasive Brain Stimulation: Ignore at Your Own Risk.

Multimodal approaches combining cognitive behavioral therapies (CBT) with non-invasive brain stimulation (NIBS) hold promise for improving the treatment of neuropsychiatric disorders. As this is a relatively new approach, it is a critical time to identify guiding principles and methodological considerations to enhance research rigor. In the current paper, we argue for a principled approach to CBT and NIBS pairings based on synergistic activation of neural circuits and identify key considerations about CBT that may influence pairing with NIBS.

Response to targeted cognitive training may be neuroprotective in patients with early schizophrenia.

Individuals with schizophrenia exhibit widespread cortical thinning associated with illness severity and deficits in cognition. However, intact cortical thickness (CTh) may serve as a protective factor. The current study sought to examine changes in CTh in response to auditory targeted cognitive training (TCT) in individuals with recent onset schizophrenia.

Deficits in Auditory and Visual Sensory Discrimination Reflect a Genetic Liability for Psychosis and Predict Disruptions in Global Cognitive Functioning.

Sensory discrimination thresholds (i.e., the briefest stimulus that can be accurately perceived) can be measured using tablet-based auditory and visual sweep paradigms.

Early- Versus Adult-Onset Schizophrenia as a Predictor of Response to Neuroscience-Informed Cognitive Training.

Background: Developmental stages characterized by greater neural plasticity might be critical periods during which the effects of cognitive training (CT) could theoretically be maximized. However, experiencing a first episode of schizophrenia during childhood or adolescence (ie, early-onset schizophrenia [EOS]) may reduce the brain's ability to benefit from CT. This study examined the effects of EOS versus onset at > 18 years of age (ie, adult-onset schizophrenia [AOS]) as a predictor of response to CT and the relationship between duration of illness and cognitive improvements.

An Activation Likelihood Estimate Meta-analysis of Thalamocortical Dysconnectivity in Psychosis.

Background: Thalamocortical dysconnectivity is hypothesized to underlie the pathophysiology of psychotic disorders, including schizophrenia and bipolar disorder, and individuals at clinical high risk. Numerous studies have examined connectivity networks seeding from the thalamus during rest, revealing a pattern of thalamo-fronto-cerebellar hypoconnectivity and thalamosensory hyperconnectivity. However, given variability in these networks, as well as their relationships with clinical and cognitive symptoms, thalamocortical connectivity's status as a biomarker and treatment target for psychotic disorders remains unclear.

Trait neuroticism and emotion neurocircuitry: Functional magnetic resonance imaging evidence for a failure in emotion regulation.

Though theory suggests that individual differences in neuroticism (a tendency to experience negative emotions) would be associated with altered functioning of the amygdala (which has been linked with emotionality and emotion dysregulation in childhood, adolescence, and adulthood), results of functional neuroimaging studies have been contradictory and inconclusive. We aimed to clarify the relationship between neuroticism and three hypothesized neural markers derived from functional magnetic resonance imaging during negative emotion face processing: amygdala activation, amygdala habituation, and amygdala-prefrontal connectivity, each of which plays an important role in the experience and regulation of emotions. We used general linear models to examine the relationship between trait neuroticism and the hypothesized neural markers in a large sample of over 500 young adults.

Effectiveness of Cognitive Training in an Intensive Outpatient First Episode Psychosis Program.

Despite effective pharmacotherapy for positive symptoms of psychosis, cognitive deficits emerge early and are persistent. Efficacy studies have demonstrated cognitive training can produce improvement in cognition, symptoms, and functional outcomes for psychosis. A chart review of seventy-one first episode psychosis patients in a cognitive training program was designed to determine feasibility and effectiveness of the program in a non-research clinic setting.

Efference copy/corollary discharge function and targeted cognitive training in patients with schizophrenia.

Introduction: During vocalization, efference copy/corollary discharge mechanisms suppress the auditory cortical response to self-generated sounds as reflected in the N1 component of the auditory event-related potential (ERP). N1 suppression during talking is reduced in patients with schizophrenia. We hypothesized that these deficits would recover with auditory training that targets the speech processing system.

Model selection and prediction of outcomes in recent onset schizophrenia patients who undergo cognitive training.

Predicting treatment outcomes in psychiatric populations remains a challenge, but is increasingly important in the pursuit of personalized medicine. Patients with schizophrenia have deficits in cognition, and targeted cognitive training (TCT) of auditory processing and working memory has been shown to improve some of these impairments; but little is known about the baseline patient characteristics predictive of cognitive improvement. Here we use a model selection and regression approach called least absolute shrinkage and selection operator (LASSO) to examine predictors of cognitive improvement in response to TCT for patients with recent onset schizophrenia.

Response to Targeted Cognitive Training Correlates with Change in Thalamic Volume in a Randomized Trial for Early Schizophrenia.

Reduced thalamic volume is consistently observed in schizophrenia, and correlates with cognitive impairment. Targeted cognitive training (TCT) of auditory processing in schizophrenia drives improvements in cognition that are believed to result from functional neuroplasticity in prefrontal and auditory cortices. In this study, we sought to determine whether response to TCT is also associated with structural neuroplastic changes in thalamic volume in patients with early schizophrenia (ESZ).