Mechanisms of motor dysfunction in functional neurological disorder: A narrative review.

One of the characteristic presentations of functional neurological disorder (FND) is with motor symptoms, such as weakness and tremor. While these symptoms are both common and disabling, how they arise at a mechanistic level remains unclear. This review provides an up-to-date account of the underpinnings of motor dysfunction in FND by integrating findings from neuroimaging, physiology, genetic, brain stimulation, and behavioral studies.

Subcortical modulation of the salience network during negative emotional processing in mood and anxiety disorders.

Dysfunctional processing of negative emotional events is a key transdiagnostic feature of mood and anxiety disorders. This dysfunction is often associated with aberrant functioning of fronto-insular/cingulate regions involved in salience processing, including the anterior insula, dorsal anterior cingulate cortex, and ventrolateral prefrontal cortex (i.e.

Neural correlates of human fear conditioning and sources of variability in 2199 individuals.

Pavlovian fear conditioning is a fundamental process in both health and disease. We investigate its neural correlates and sources of variability using harmonized functional magnetic resonance imaging data from 2199 individuals across nine countries, including 1888 healthy individuals and 311 with anxiety-related or depressive disorders. Using mega-analysis and normative modeling, we show that fear conditioning consistently engages brain regions within the "central autonomic-interoceptive" or "salience" network.

Shared and distinct alterations in brain structure of youth with internalizing or externalizing disorders: Findings from the ENIGMA Antisocial Behavior, ADHD, MDD, and Anxiety Working Groups.

Background: Externalizing and internalizing disorders are common in youth but are often studied separately, preventing researchers from identifying shared (i.e., transdiagnostic) alterations in brain structure.

Habenula contributions to negative self-cognitions.

Self-related cognitions are integral to personal identity and psychological wellbeing. Persistent engagement with negative self-cognitions can precipitate mental ill health; whereas the ability to restructure them is protective. Here, we leverage ultra-high field 7T fMRI and dynamic causal modelling to characterise a negative self-cognition network centred on the habenula - a small midbrain region linked to the encoding of punishment and negative outcomes.

Multiscale Heterogeneity of White Matter Morphometry in Psychiatric Disorders.

Background: Interindividual variability in the neurobiological and clinical characteristics of mental illnesses are often overlooked by classical group-mean case-control studies. Studies using normative modeling to infer person-specific deviations of gray matter volume have indicated that group means are not representative of most individuals. The extent to which this variability is present in white matter morphometry, which is integral to brain function, remains unclear.

Graded changes in local functional connectivity of the cerebral cortex in young people with depression.

Background: Major depressive disorder (MDD) is marked by significant changes to the local synchrony of spontaneous neural activity across various brain regions. However, many methods for assessing this local connectivity use fixed or arbitrary neighborhood sizes, resulting in a decreased capacity to capture smooth changes to the spatial gradient of local correlations. A newly developed method sensitive to classical anatomo-functional boundaries, Iso-Distant Average Correlation (IDAC), was therefore used to examine depression associated alterations to the local functional connectivity of the brain.

Neural Correlates and Sex-Specific Effects of Affectively Driven Processes Underlying Decision-Making in Adult ADHD.

Aims: Adults with attention-deficit/hyperactivity disorder (ADHD) often exhibit heightened risk-taking behavior due to disadvantageous decision-making. This study investigates the influence of preceding unconscious and affectively driven processes on this behavior, with a focus on sex-specific effects.

Methods: Functional magnetic resonance imaging was used to examine neural activity during the anticipation phase of decision-making in 18 individuals with ADHD (10 females and 8 males) and 20 healthy controls (10 females and 10 males) using a modified version of the Balloon Analogue Risk Task.

Tissue damage-induced axon injury-associated responses in sensory neurons: requirements, prevention, and potential role in persistent post-surgical pain.

Pain resulting from tissue damage, including surgical incision, is often only partially responsive to standard treatments focusing on inflammation, suggesting additional mechanisms are involved. Tissue damage leads to expression in dorsal root ganglion (DRG) sensory neurons of genes associated with axonal injury and regeneration, most notably activating transcription factor 3 (ATF3) and GAP-43. ATF3 expression is associated with sensitization of cellular physiology and enhanced amplitude/duration of a nociceptive reflex.

Classification of Major Depressive Disorder Using Vertex-Wise Brain Sulcal Depth, Curvature, and Thickness with a Deep and a Shallow Learning Model.

Major depressive disorder (MDD) is a complex psychiatric disorder that affects the lives of hundreds of millions of individuals around the globe. Even today, researchers debate if morphological alterations in the brain are linked to MDD, likely due to the heterogeneity of this disorder. The application of deep learning tools to neuroimaging data, capable of capturing complex non-linear patterns, has the potential to provide diagnostic and predictive biomarkers for MDD.

Towards an expanded neurocognitive account of ketamine's rapid antidepressant effects.

Ketamine is an N-methyl-D-aspartate receptor antagonist that has shown effectiveness as a rapidly acting treatment for depression. Although advances have been made in understanding ketamine's antidepressant pharmacological and molecular mechanisms of action, the large-scale neurocognitive mechanisms driving its therapeutic effects are less clearly understood. To help provide such a framework, we provide a synthesis of current evidence linking ketamine treatment to the modulation of brain systems supporting reward processing, interoception, and self-related cognition.

Predicting Antidepressant Treatment Response From Cortical Structure on MRI: A Mega-Analysis From the ENIGMA-MDD Working Group.

Accurately predicting individual antidepressant treatment response could expedite the lengthy trial-and-error process of finding an effective treatment for major depressive disorder (MDD). We tested and compared machine learning-based methods that predict individual-level pharmacotherapeutic treatment response using cortical morphometry from multisite longitudinal cohorts. We conducted an international analysis of pooled data from six sites of the ENIGMA-MDD consortium (n = 262 MDD patients; age = 36.

Sex differences in physiological correlates of affectively driven decision-making behavior in adult ADHD.

Background: Sex differences in the symptomatology of adults with attention-deficit/hyperactivity disorder (ADHD) have often been overlooked when studying behavioral abnormalities. However, it is known that women exhibit considerably more stronger symptoms related to emotional competence than men. Since affective functions significantly influence the processing of risky decision-making and risk-engagement, we assume that risky behavior in ADHD is affected by sex differences.

Pavlovian safety learning: An integrative theoretical review.

Safety learning involves associating stimuli with the absence of threats, enabling the inhibition of fear and anxiety. Despite growing interest in psychology, psychiatry, and neuroscience, safety learning lacks a formal consensus definition, leading to inconsistent methodologies and varied results. Conceptualized as a form of inhibitory learning (conditioned inhibition), safety learning can be understood through formal learning theories, such as the Rescorla-Wagner and Pearce-Hall models.

Multiscale heterogeneity of white matter morphometry in psychiatric disorders.

Background: Inter-individual variability in neurobiological and clinical characteristics in mental illness is often overlooked by classical group-mean case-control studies. Studies using normative modelling to infer person-specific deviations of grey matter volume have indicated that group means are not representative of most individuals. The extent to which this variability is present in white matter morphometry, which is integral to brain function, remains unclear.

Using electrodermal activity to estimate fear learning differences in anxiety: A multiverse analysis.

Meta-analyses indicate differences in Pavlovian fear responses between anxious and non-anxious individuals using electrodermal activity (EDA). Recent research, however, has cast doubt on whether these effects are robust to different analytic choices. Using the multiverse approach conceived by Steegen et al.

Brain-age prediction: Systematic evaluation of site effects, and sample age range and size.

Structural neuroimaging data have been used to compute an estimate of the biological age of the brain (brain-age) which has been associated with other biologically and behaviorally meaningful measures of brain development and aging. The ongoing research interest in brain-age has highlighted the need for robust and publicly available brain-age models pre-trained on data from large samples of healthy individuals. To address this need we have previously released a developmental brain-age model.

Major depressive disorder associated alterations in the effective connectivity of the face processing network: a systematic review.

Major depressive disorder (MDD) is marked by altered processing of emotional stimuli, including facial expressions. Recent neuroimaging research has attempted to investigate how these stimuli alter the directional interactions between brain regions in those with MDD; however, methodological heterogeneity has made identifying consistent effects difficult. To address this, we systematically examined studies investigating MDD-associated differences present in effective connectivity during the processing of emotional facial expressions.

Altered task-related decoupling of the rostral anterior cingulate cortex in depression.

Dysfunctional activity of the rostral anterior cingulate cortex (rACC) - an extensively connected hub region of the default mode network - has been broadly linked to cognitive and affective impairments in depression. However, the nature of aberrant task-related rACC suppression in depression is incompletely understood. In this study, we sought to characterize functional connectivity of rACC activity suppression ('deactivation') - an essential feature of rACC function - during external task engagement in depression.

Multi-site benchmark classification of major depressive disorder using machine learning on cortical and subcortical measures.

Machine learning (ML) techniques have gained popularity in the neuroimaging field due to their potential for classifying neuropsychiatric disorders. However, the diagnostic predictive power of the existing algorithms has been limited by small sample sizes, lack of representativeness, data leakage, and/or overfitting. Here, we overcome these limitations with the largest multi-site sample size to date (N = 5365) to provide a generalizable ML classification benchmark of major depressive disorder (MDD) using shallow linear and non-linear models.

Normative Modeling of Brain Morphometry Across the Lifespan Using CentileBrain: Algorithm Benchmarking and Model Optimization.

We present an empirically benchmarked framework for sex-specific normative modeling of brain morphometry that can inform about the biological and behavioral significance of deviations from typical age-related neuroanatomical changes and support future study designs. This framework was developed using regional morphometric data from 37,407 healthy individuals (53% female; aged 3-90 years) following a comparative evaluation of eight algorithms and multiple covariate combinations pertaining to image acquisition and quality, parcellation software versions, global neuroimaging measures, and longitudinal stability. The Multivariate Factorial Polynomial Regression (MFPR) emerged as the preferred algorithm optimized using nonlinear polynomials for age and linear effects of global measures as covariates.

A brain model of altered self-appraisal in social anxiety disorder.

The brain's default mode network has a central role in the processing of information concerning oneself. Dysfunction in this self-referential processing represents a key component of multiple mental health conditions, particularly social anxiety disorder (SAD). This case-control study aimed to clarify alterations to network dynamics present during self-appraisal in SAD participants.

Frontoamygdalar Effective Connectivity in Youth Depression and Treatment Response.

Background: Emotion regulation deficits are characteristic of youth depression and are underpinned by altered frontoamygdalar function. However, the causal dynamics of frontoamygdalar pathways in depression and how these dynamics relate to treatment prognosis remain unexplored. This study aimed to assess frontoamygdalar effective connectivity during cognitive reappraisal in youths with depression and to test whether pathway dynamics are predictive of individual response to combined cognitive behavioral therapy plus treatment with fluoxetine or placebo.