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INTRODUCTION: Studies examining sustained attention abilities typically utilize metrics that quantify performance on vigilance tasks, such as response time and response time variability. However, approaches that assess the duration that an individual can maintain their attention over time are lacking. METHODS: Here we developed an objective attention span metric that quantified the maximum amount of time that a participant continuously maintained an optimal in the zone sustained attention state while performing a continuous performance task. RESULTS: In a population of 262 individuals aged 7-85, we showed that attention span was longer in young adults than in children and older adults. Furthermore, declines in attention span over time during task engagement were related to clinical symptoms of inattention in children. DISCUSSION: These results suggest that quantifying attention span is a unique and meaningful method of assessing sustained attention across the lifespan and in populations with inattention symptoms.

IntroductionExecutive functions (EFs) are linked to positive outcomes across the lifespan. Yet, methodological challenges have prevented precise understanding of the developmental trajectory of their organization.MethodsWe introduce novel methods to address challenges for both measuring and modeling EFs using an accelerated longitudinal design with a large, diverse sample of students in middle childhood (N = 1,286; ages 8 to 14). We used eight adaptive assessments hypothesized to measure three EFs, working memory, context monitoring, and interference resolution. We deployed adaptive assessments to equate EF challenge across ages and a data-driven, network analytic approach to reveal the evolving diversity of EFs while simultaneously accounting for their unity.Results and discussionUsing this methodological paradigm shift brought new precision and clarity to the development of these EFs, showing these eight tasks are organized into three stable components by age 10, but refinement of composition of these components continues through at least age 14.

BackgroundWhile identifying risk factors for adolescent depression is critical for early prevention and intervention, most studies have sought to understand the role of isolated factors rather than across a broad set of factors. Here, we sought to examine multi-level factors that maximize the prediction of depression symptoms in US children participating in the Adolescent Brain and Cognitive Development (ABCD) study.MethodsA total of 7,995 participants from ABCD (version 3.0 release) provided complete data at baseline and 1-year follow-up data. Depression symptoms were measured with the Child Behavior Checklist. Predictive features included child demographic, environmental, and structural and resting-state fMRI variables, parental depression history and demographic characteristics. We used linear (elastic net regression, EN) and non-linear (gradient-boosted trees, GBT) predictive models to identify which set of features maximized prediction of depression symptoms at baseline and, separately, at 1-year follow-up.ResultsBoth linear and non-linear models achieved comparable results for predicting baseline (EN: MAE = 3.757; R2  = 0.156; GBT: MAE = 3.761; R2  = 0.147) and 1-year follow-up (EN: MAE = 4.255; R2  = 0.103; GBT: MAE = 4.262; R2  = 0.089) depression. Parental history of depression, greater family conflict, and shorter child sleep duration were among the top predictors of concurrent and future child depression symptoms across both models. Although resting-state fMRI features were relatively weaker predictors, functional connectivity of the caudate was consistently the strongest neural feature associated with depression symptoms at both timepoints.ConclusionsConsistent with prior research, parental mental health, family environment, and child sleep quality are important risk factors for youth depression. Functional connectivity of the caudate is a relatively weaker predictor of depression symptoms but may represent a biomarker for depression risk.

Background(S)-ketamine is a glutamatergic drug with potent and rapid acting effects for the treatment of depression. Little is known about the effectiveness of intranasal (S)-ketamine for treating patients with comorbid depression and post-traumatic stress disorder (PTSD).MethodsWe performed a retrospective case series analysis of clinical outcomes in 35 Veterans with co-morbid depression and PTSD who were treated with intranasal (S)-ketamine treatments at the VA San Diego Neuromodulation Clinic between Jan 2020 and March 2021. Veterans were not randomized or blinded to treatment. The primary outcome measured was a change in patient health questionnaire-9 (PHQ-9) and PTSD Checklist for DSM-5 (PCL-5) scores across the first 8 treatments (induction period) using a repeated measures analysis of variance (ANOVA). In a smaller sub-group (n = 19) of Veterans who received at least 8 additional treatments, we analyzed whether intranasal (S)-ketamine continued to show treatment effects. Finally, we performed a sub-group and correlation analyses to understand how changes in PHQ-9 and PCL-5 scores were related across treatments.FindingsDuring the induction phase of treatment there was an absolute reduction of 5.1 (SEM 0.7) on the patient health questionnaire-9 (PHQ-9) rating scale for depression, from 19.8 (SEM 0.7) at treatment 1 to 14.7 (SEM 0.8) at treatment 8 (week 4) (F(7238) = 8.3, p = 1e-6, partial η2 = 0.2). Five Veterans (14%) showed a clinically meaningful response (50% reduction in PHQ-9 score) at treatment 8. There was an absolute reduction of 15.5 +/- 2.4 on the patient checklist 5 (PCL-5) rating scale for PTSD, from 54.8 (SEM 2) at treatment 1 down to 39.3 (SEM 2.5) at treatment 8 (F(7238) = 15.5, p = 2e-7, partial η2 = 0.31). Sixteen Veterans (46%) showed a clinically meaningful response (reduction in PCL-5 of > 30%) in PTSD. Change in PHQ-9 correlated with change in PCL-5 at treatment 8 (r = 0.47, p = 0.005), but a decrease in PTSD symptoms were observable in some individuals with minimal anti-depressant response.InterpretationsWhile this is an open-label retrospective analysis, our results indicate that both depression and PTSD symptoms in Veterans with dual-diagnoses may improve with repeated intranasal (S)-ketamine treatment. The effects of (S)-ketamine on PTSD symptoms were temporally and individually distinct from those on depression, suggesting potentially different modes of action on the two disorders. This work may warrant formal randomized controlled studies on the effects of intranasal (S)-ketamine for individuals with co-morbid MDD and PTSD.FundingVA Center of Excellence in Stress and Mental Health, VA ORD (Career Development Award to DSR), Burroughs-Wellcome Fund Award (DSR), NIMH (EL).

BackgroundRacemic (R,S)-ketamine is a glutamatergic drug with potent and rapid acting antidepressant effects. An intranasal formulation of (S)-ketamine was recently approved by the US Food and Drug Administration (FDA) to be used in individuals with treatment-resistant depression (TRD). There are no data directly comparing outcomes on depression or other comorbidities between these two formulations of ketamine. However, recent meta-analyses have suggested that IV racemic ketamine may be more potent than IN-(S)-ketamine.MethodsWe retrospectively analyzed clinical outcomes in 15 Veterans with comorbid TRD and post-traumatic stress disorder (PTSD) who underwent ketamine treatment at the VA San Diego Neuromodulation Clinic. All Veterans included in this analysis were given at least 6 intranasal (IN)-(S)-ketamine treatments prior to switching to treatment with IV racemic ketamine.ResultsVeterans receiving ketamine treatment ( across both IN-(S)-ketamine and IV-(R,S)-ketamine) showed significant reductions in both the Patient Health Questionnaire-9 (PHQ-9), a self-report scale measuring depression symptoms (rm ANOVA F(14,42) = 12.6, p

α Oscillations in sensory cortex, under frontal control, desynchronize during attentive preparation. Here, in a selective attention study with simultaneous EEG in humans of either sex, we first demonstrate that diminished anticipatory α synchrony between the mid-frontal region of the dorsal attention network and ventral visual sensory cortex [frontal-sensory synchrony (FSS)] significantly correlates with greater task performance. Then, in a double-blind, randomized controlled study in healthy adults, we implement closed-loop neurofeedback (NF) of the anticipatory α FSS signal over 10 d of training. We refer to this closed-loop experimental approach of rapid NF integrated within a cognitive task as cognitive NF (cNF). We show that cNF results in significant trial-by-trial modulation of the anticipatory α FSS measure during training, concomitant plasticity of stimulus-evoked α/θ responses, as well as transfer of benefits to response time (RT) improvements on a standard test of sustained attention. In a third study, we implement cNF training in children with attention deficit hyperactivity disorder (ADHD), replicating trial-by-trial modulation of the anticipatory α FSS signal as well as significant improvement of sustained attention RTs. These first findings demonstrate the basic mechanisms and translational utility of rapid cognitive-task-integrated NF.SIGNIFICANCE STATEMENT When humans prepare to attend to incoming sensory information, neural oscillations in the α band (8-14 Hz) undergo desynchronization under the control of prefrontal cortex. Here, in an attention study with electroencephalography, we first show that frontal-sensory synchrony (FSS) of α oscillations during attentive preparation significantly correlates with task performance. Then, in a randomized controlled study in healthy adults, we show that neurofeedback (NF) training of this α FSS signal within the attention task is feasible. We show that this rapid cognitive NF (cNF) approach engenders plasticity of stimulus-evoked neural responses, and improves performance on a standard test of sustained attention. In a final study, we implement cNF in children with attention deficit hyperactivity disorder (ADHD), replicating the improvement of sustained attention found in adults.

Loneliness and wisdom have opposing impacts on health and well-being, yet their neuro-cognitive bases have never been simultaneously investigated. In this study of 147 healthy human subjects sampled across the adult lifespan, we simultaneously studied the cognitive and neural correlates of loneliness and wisdom in the context of an emotion bias task. Aligned with the social threat framework of loneliness, we found that loneliness was associated with reduced speed of processing when angry emotional stimuli were presented to bias cognition. In contrast, we found that wisdom was associated with greater speed of processing when happy emotions biased cognition. Source models of electroencephalographic data showed that loneliness was specifically associated with enhanced angry stimulus-driven theta activity in the left transverse temporal region of interest, which is located in the area of the temporoparietal junction (TPJ), while wisdom was specifically related to increased TPJ theta activity during happy stimulus processing. Additionally, enhanced attentiveness to threatening stimuli for lonelier individuals was observed as greater beta activity in left superior parietal cortex, while wisdom significantly related to enhanced happy stimulus-evoked alpha activity in the left insula. Our results demonstrate emotion-context driven modulations in cognitive neural circuits by loneliness versus wisdom.

Childhood adversity has been associated with elevated risk for psychopathology. We investigated whether development of functional brain networks important for executive function (EF) could serve as potential mediators of this association. We analyzed data of 475 adolescents, a subsample of the multisite longitudinal NCANDA (National Consortium on Alcohol and Neurodevelopment in Adolescence) cohort with completed measures of childhood trauma, resting-state functional brain connectivity data, and symptoms of internalizing and externalizing psychopathology at baseline and follow-up years 1-4. Using parallel process latent growth models, we found that childhood adversity was associated with increased risk for externalizing/internalizing behaviors. We specifically investigated whether functional connectivity of the dorsal anterior cingulate cortex (dACC) to brain regions within the cingulo-opercular (CO) network, a well-known EF network that underlies control of attention and self-regulation, mediates the association between adversity and symptoms of psychopathology. We found that childhood adversity, specifically child neglect was negatively associated with functional connectivity of the dACC within the CO network, and that this connectivity mediated the association between neglect and externalizing behaviors. Our study advances a mechanistic understanding of how childhood adversity may impact the development of psychopathology, highlighting the relevance of dACC functional networks particularly for externalizing psychopathology.

Neuro-cognition is our brain’s ability to perform context-appropriate cognitive functions, such as paying attention and maintaining information in working memory, which are associated with specific neural activations. The ability to generate context-appropriate, neuro-cognitively optimal responses to stressful life hardships is a shared aspect of resiliency across all races and ethnicities. We studied how resilience influence neuro-cognitive abilities and if a relationship exists with race and ethnicity. A series of rapid game-like, objective assessments were used to measure internal attention, working memory, distractor processing and emotion processing. We collected demographic characteristics (age, gender, race, ethnicity, socioeconomic status) and measured resilience using the Brief Resilience Scale (BRS). We used generalized linear mixed models to probe the association of demographic factors including race and ethnicity, and resilience with neuro-cognitive performance. Resilience scores alone was not a significant factor contributing to neuro-cognitive performance in these models; however, we found an interaction between multiracial participants and resilience scores for emotional processing consistency. Understanding how race/ethnicity and resilience interact to determine neuro-cognitive abilities can improve the quality of mental healthcare given to diverse Americans, serving to decrease the burden of mental healthcare disparities.