Search

Research on unconscious fear responses has recently been translated into experimental paradigms for reducing fear that bypass conscious awareness of the phobic stimulus and thus do not induce distress. These paradigms stand in contrast to exposure therapies for anxiety disorders, which require direct confrontation of feared situations and thus are distressing. We systematically review these unconscious exposure paradigms. A Preferred Reporting Items for Systematic Reviews and Meta-Analyses-based search yielded 39 controlled experiments based on 10 paradigms that tested whether exposure without awareness can reduce fear-related responses. In randomized controlled trials of phobic participants, unconscious exposure interventions: (a) reduced behavioral avoidance (weighted mean d = 0.77, N = 469) and self-reported fear (d = 0.78, N = 329) during in vivo exposure to feared situations; (b) reduced neurobiological indicators of fear and enhanced such indicators of fear regulation (d = 0.81, N = 205); (c) had significantly stronger effects on reducing symptomatic behaviors and enhancing neurobiological indicators of fear regulation than did conscious exposure (d = 0.78, N = 342); and (d) produced these effects without inducing subjective fear. In fear-conditioned participants, unconscious exposureinduced extinction learning (d = 0.80, N = 420), even during sleep, and yielded somewhat stronger extinction learning than conscious exposure did (d = 0.44, N = 438). We organize these findings within a neuroscientific framework and evaluate alternative mechanisms for unconscious exposure. The use of incommensurate outcome measures across exposure paradigms and nonreporting of relevant statistics limited meta-analyses. Despite steps taken to address publication bias, 25.6% of included studies came from a single laboratory. We propose potential clinical applications of these findings. Future research should clarify underlying mechanisms, use common outcome measures, and explore effects on other anxiety disorders. Public Significance Statement: Phobias are among the most common psychological disorders. Most sufferers avoid or drop out of the frontline treatment, which requires them to directly confront their fears. We report findings supporting the efficacy of a new generation of interventions that address these problems by exposing phobic persons to their feared stimulus without conscious awareness, and thus without causing them to experience distress. If clinical trials support the efficacy of unconscious exposure interventions, their public health impact will be considerable, as they could be widely disseminated online. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions The real‐world effectiveness of exposure‐based therapies for youth depends on the willingness and ability of young people to tolerate confronting their fears, which can be experienced as highly aversive and create problems with treatment engagement and acceptance. Recently, neuroscientific research on the nonconscious basis of fear has been translated into novel exposure interventions that bypass conscious processing of feared stimuli and that thus do not cause phobic youth to experience distress. We present a review of these unconscious exposure interventions.A PRISMA‐based search yielded 20 controlled experiments based on three paradigms that tested if fear‐related responses could be reduced without conscious awareness in highly phobic, transition‐age youth: 14 randomized controlled trials (RCTs), 5 fMRI studies (1 was also an RCT), 4 psychophysiological studies (3 were also RCTs), and 1 ERP study. We conducted meta‐analyses of outcomes where feasible.Unconscious exposure interventions significantly (1) reduced avoidance behavior (range of Cohen's d = 0.51–0.95) and self‐reported fear (d = 0.45–1.25) during in vivo exposure to the feared situation; (2) reduced neurobiological indicators of fear (d = 0.54–0.62) and concomitant physiological arousal (d = 0.55–0.64); (3) activated neural systems supporting fear regulation more strongly than visible exposure to the same stimuli (d = 1.2–1.5); (4) activated regions supporting fear regulation that mediated the reduction of avoidance behavior (d = 0.70); (5) evoked ERPs suggesting encoding of extinction memories (d = 2.13); and (6) had these effects without inducing autonomic arousal or subjective fear.Unconscious exposure interventions significantly reduce a variety of symptomatic behaviors with mostly moderate effect sizes in transition‐age youth with specific phobias. fMRI and physiological findings establish a neurophysiological basis for this efficacy, and suggest it occurs through extinction learning. Unconscious exposure was well tolerated, entirely unassociated with drop out, and is highly scalable for clinical practice. However, a number of limitations must be addressed to assess potential clinical impacts, including combining unconscious exposure with exposure therapy to boost treatment acceptance and efficacy. [ABSTRACT FROM AUTHOR]

Identifying reliable indicators of cognitive functioning prior to age five has been challenging. Prior studies have shown that maternal cognition, as indexed by intellectual quotient (IQ) and years of education, predict child intelligence at school age. We examined whether maternal full scale IQ, education, and inhibitory control (index of executive function) are associated with newborn brain measures and toddler language outcomes to assess potential indicators of early cognition. We hypothesized that maternal indices of cognition would be associated with brain areas implicated in intelligence in school-age children and adults in the newborn period. Thirty-seven pregnant women and their newborns underwent an MRI scan. T2-weighted images and surface-based morphometric analysis were used to compute local brain volumes in newborn infants. Maternal cognition indices were associated with local brain volumes for infants in the anterior and posterior cingulate, occipital lobe, and pre/postcentral gyrus -- regions associated with IQ, executive function, or sensori-motor functions in children and adults. Maternal education and executive function, but not maternal intelligence, were associated with toddler language scores at 12 and 24 months. Newborn brain volumes did not predict language scores. Overall, the pre/postcentral gyrus and occipital lobe may be unique indicators of early intellectual development in the newborn period. Given that maternal executive function as measured by inhibitory control has robust associations with the newborn brain and is objective, brief, and easy to administer, it may be a useful predictor of early developmental and cognitive capacity for young children. [ABSTRACT FROM AUTHOR]

Context: Correct diagnosis is essential for the appropriate clinical management of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents. Objective: This systematic review provides an overview of the available diagnostic tools. Data sources: We identified diagnostic accuracy studies in 12 databases published from 1980 through June 2023. Study selection: Any ADHD tool evaluation for the diagnosis of ADHD, requiring a reference standard of a clinical diagnosis by a mental health specialist. Data extraction: Data were abstracted and critically appraised by 1 reviewer and checked by a methodologist. Strength of evidence and applicability assessments followed Evidence-based Practice Center standards. Results: In total, 231 studies met eligibility criteria. Studies evaluated parental ratings, teacher ratings, youth self-reports, clinician tools, neuropsychological tests, biospecimen, EEG, and neuroimaging. Multiple tools showed promising diagnostic performance, but estimates varied considerably across studies, with a generally low strength of evidence. Performance depended on whether ADHD youth were being differentiated from neurotypically developing children or from clinically referred children. Limitations: Studies used different components of available tools and did not report sufficient data for meta-analytic models. Conclusions: A valid and reliable diagnosis of ADHD requires the judgment of a clinician who is experienced in the evaluation of youth with and without ADHD, along with the aid of standardized rating scales and input from multiple informants across multiple settings, including parents, teachers, and youth themselves. [ABSTRACT FROM AUTHOR]

Context: Effective treatment of attention-deficit/hyperactivity disorder (ADHD) is essential to improving youth outcomes. Objectives: This systematic review provides an overview of the available treatment options. Data sources: We identified controlled treatment evaluations in 12 databases published from 1980 to June 2023; treatments were not restricted by intervention content. Study selection: Studies in children and adolescents with clinically diagnosed ADHD, reporting patient health and psychosocial outcomes, were eligible. Publications were screened by trained reviewers, supported by machine learning. Data extraction: Data were abstracted and critically appraised by 1 reviewer and checked by a methodologist. Data were pooled using random-effects models. Strength of evidence and applicability assessments followed Evidence-based Practice Center standards. Results: In total, 312 studies reported in 540 publications were included. We grouped evidence for medication, psychosocial interventions, parent support, nutrition and supplements, neurofeedback, neurostimulation, physical exercise, complementary medicine, school interventions, and provider approaches. Several treatments improved ADHD symptoms. Medications had the strongest evidence base for improving outcomes, including disruptive behaviors and broadband measures, but were associated with adverse events. Limitations: We found limited evidence of studies comparing alternative treatments directly and indirect analyses identified few systematic differences across stimulants and nonstimulants. Identified combination of medication with youth-directed psychosocial interventions did not systematically produce better results than monotherapy, though few combinations have been evaluated. Conclusions: A growing number of treatments are available that improve ADHD symptoms and other outcomes, in particular for school-aged youth. Medication therapies remain important treatment options but are associated with adverse events. [ABSTRACT FROM AUTHOR]

Background: Brain bases and progression of methotrexate-associated neurotoxicity and cognitive disturbances remain unknown. We tested whether brain abnormalities worsen in proportion to intrathecal methotrexate(IT-MTX) doses., Methods: In this prospective, longitudinal study, we recruited 19 patients with newly diagnosed acute lymphoblastic leukemia 4-to-20 years of age and 20 matched controls. We collected MRI and neuropsychological assessments at a pre-methotrexate baseline and at week 9, week 22, and year 1 during treatment., Results: Patients had baseline abnormalities in cortical and subcortical gray matter(GM), white matter(WM) volumes and microstructure, regional cerebral blood flow, and neuronal density. Abnormalities of GM, blood flow, and metabolites worsened in direct proportions to IT-MTX doses. WM abnormalities persisted until week 22 but normalized by year 1. Brain injuries were localized to dorsal and ventral attentional and frontoparietal cognitive networks. Patients had cognitive deficits at baseline that persisted at 1-year follow-up., Conclusions: Baseline abnormalities are likely a consequence of neuroinflammation and oxidative stress. Baseline abnormalities in WM microstructure and volumes, and blood flow persisted until week 22 but normalized by year 1, likely due to treatment and its effects on reducing inflammation. The cytotoxic effects of IT-MTX, however, likely contributed to continued, progressive cortical thinning and reductions in neuronal density, thereby contributing to enduring cognitive deficits., Impact: Brain abnormalities at a pre-methotrexate baseline likely are due to acute illness. The cytotoxic effects of intrathecal MTX contribute to progressive cortical thinning, reductions in neuronal density, and enduring cognitive deficits. Baseline white matter abnormalities may have normalized via methotrexate treatment and decreasing neuroinflammation. Corticosteroid and leucovorin conferred neuroprotective effects. Our findings suggest that the administration of neuroprotective and anti-inflammatory agents should be considered even earlier than they are currently administered. The neuroprotective effects of leucovorin suggest that strategies may be developed that extend the duration of this intervention or adapt it for use in standard risk patients., (© 2024. The Author(s).)

Prior regional Cerebral Blood Flow (rCBF) studies in Major Depressive Disorder (MDD) have been limited by small, highly selective, non-representative samples that have yielded variable and poorly replicated findings. The aim of this study was to compare rCBF measures in a large, more representative community sample of adults with MDD and healthy control participants. This is a cross-sectional, retrospective multi-site cohort study in which clinical data from 338 patients 18-65 years of age with a primary diagnosis of MDD were retrieved from a central database for 8 privately owned, private-pay outpatient psychiatric centers across the United States. Two 99m Tc-HMPAO SPECT brain scans, one at rest and one during performance of a continuous performance task, were acquired as a routine component of their initial clinical evaluation. In total, 103 healthy controls, 18-65 years old and recruited from the community were also assessed and scanned. Depressed patients had significantly higher rCBF in frontal, anterior cingulate, and association cortices, and in basal ganglia, thalamus, and cerebellum, after accounting for significantly higher overall CBF. Depression severity associated positively with rCBF in the basal ganglia, hippocampus, cerebellum, and posterior white matter. Elevated rCBF was especially prominent in women and older patients. Elevated rCBF likely represents pathogenic hypermetabolism in MDD, with its magnitude in direct proportion to depression severity. It is brain-wide, with disproportionate increases in cortical and subcortical attentional networks. Hypermetabolism may be a reasonable target for novel therapeutics in MDD., (© 2024. The Author(s).)