Latent brain state dynamics distinguish behavioral variability, impaired decision-making, and inattention.

Children with Attention Deficit Hyperactivity Disorder (ADHD) have prominent deficits in sustained attention that manifest as elevated intra-individual response variability and poor decision-making. Influential neurocognitive models have linked attentional fluctuations to aberrant brain dynamics, but these models have not been tested with computationally rigorous procedures. Here we use a Research Domain Criteria approach, drift-diffusion modeling of behavior, and a novel Bayesian Switching Dynamic System unsupervised learning algorithm, with ultrafast temporal resolution (490 ms) whole-brain task-fMRI data, to investigate latent brain state dynamics of salience, frontoparietal, and default mode networks and their relation to response variability, latent decision-making processes, and inattention. Our analyses revealed that occurrence of a task-optimal latent brain state predicted decreased intra-individual response variability and increased evidence accumulation related to decision-making. In contrast, occurrence and dwell time of a non-optimal latent brain state predicted inattention symptoms and furthermore, in a categorical analysis, distinguished children with ADHD from controls. Importantly, functional connectivity between salience and frontoparietal networks predicted rate of evidence accumulation to a decision threshold, whereas functional connectivity between salience and default mode networks predicted inattention. Taken together, our computational modeling reveals dissociable latent brain state features underlying response variability, impaired decision-making, and inattentional symptoms common to ADHD. Our findings provide novel insights into the neurobiology of attention deficits in children.

BDNF Val66Met Moderates the Effects of Hypertension on Executive Functioning in Older Adults Diagnosed With aMCI.

OBJECTIVE: To investigate whether the BDNF Val66Met polymorphism influences the associations of hypertension, executive functioning and processing speed in older adults diagnosed with amnestic Mild Cognitive Impairment (aMCI). DESIGN: Secondary data analysis using moderation modeling. SETTING: Veterans Affairs Hospital, Palo Alto, CA. PARTICIPANTS: Sample included 108 community-dwelling volunteers (mean age 71.3 ± 9.2 years) diagnosed with aMCI. MEASUREMENTS: Cognitive performance was evaluated from multiple baseline assessments (Trail Making Test; Stroop Color-Word Test; Symbol Digit Modality Test) and grouped into standardized composite scores representing executive function and processing speed domains. BDNF genotypes were determined from whole blood samples. Hypertension was assessed from resting blood pressures or by self-report. RESULTS: Controlling for age, BDNF Val66Met moderated the effects of hypertension on executive functioning, but added no significant variance to processing speed scores. Specifically, hypertensive carriers of the BDNF Met allele performed significantly below the sample mean on tasks of executive functioning, and evidenced significantly lower scores when compared to Val-Val homozygotes and normotensive participants. CONCLUSIONS: Results posit that the executive functioning of non-demented older adults may be susceptible to interactions between BDNF genotype and hypertension, and Val-Val homozygotes and normotensive older adults may be more resilient to these effects of cognitive change. Further research is needed to understand the underlying processes and to implement strategies that target modifiable risk factors and promote cognitive resilience.

Limited Prediction of Performance Validity Using Embedded Validity Scales of the Neurobehavioral Symptom Inventory in an mTBI Veteran Sample.

OBJECTIVE: To test embedded symptom validity scales of the Neurobehavioral Symptom Inventory (NSI) as predictors of performance validity. SETTING: A Veterans Affairs Level II TBI/Polytrauma outpatient care unit in the Midwestern United States. PARTICIPANTS: Veterans with a history of mild traumatic brain injury undergoing neuropsychological assessment as part of their routine care within the TBI/Polytrauma clinic. DESIGN: Retrospective analysis of the existing clinical data. MAIN MEASURES: The NSI, the b Test, Test of Memory Malingering, Reliable Digit Span, California Verbal Learning Test-II Forced Choice. RESULTS: Embedded NSI validity scales were positively correlated with number of performance validity test failures. Participants identified as invalid responders scored higher on embedded NSI validity scales than participants identified as valid responders. Using receiver operating characteristic analysis, the embedded NSI validity scales showed poor sensitivity and specificity for invalid responding using previously published cutoff scores. Only 1 scale differentiated valid from invalid responders better than chance. CONCLUSION: The embedded NSI validity scales' usefulness in predicting invalid neuropsychological performance validity was limited in this sample. Continued measurement of both symptom and performance validity in clinical settings involving traumatic brain injury treatment is recommended, as the present results support the existing research suggesting symptom validity tests and performance validity tests tap into related but ultimately distinct constructs.

Transdiagnostic dimensions of anxiety and depression moderate motivation-related brain networks during goal maintenance.

BACKGROUND: Advancing research on the etiology, prevention, and treatment of psychopathology requires the field to move beyond modular conceptualizations of neural dysfunction toward understanding disturbance in key brain networks. Although some studies of anxiety and depression have begun doing so, they typically suffer from several drawbacks, including: (1) a categorical approach ignoring transdiagnostic processes, (2) failure to account for substantial anxiety and depression comorbidity, (3) examination of networks at rest, which overlooks disruption manifesting only when networks are challenged. Accordingly, the present study examined relationships between transdiagnostic dimensions of anxiety/depression and patterns of functional connectivity while goal maintenance was challenged. METHODS: Participants (n = 179, unselected community members and undergraduates selected to be high/low on anxiety/depression) performed a task in which goal maintenance was challenged (color-word Stroop) while fMRI data were collected. Analyses examined moderation by anxiety/depression of condition-dependent coupling between regions of dorsolateral prefrontal cortex (dlPFC) previously associated with approach and avoidance motivation and amygdala/orbitofrontal cortex (OFC). RESULTS: Anxious arousal was positively associated with amygdala↔right dlPFC coupling. Depression was positively associated with OFC↔right dlPFC coupling and negatively associated with OFC↔left dlPFC coupling. CONCLUSIONS: Findings advance the field toward an integrative model of the neural instantiation of anxiety/depression by identifying specific, distinct dysfunctions associated with anxiety and depression in networks important for maintaining approach and avoidance goals. Specifically, findings shed light on potential neural mechanisms involved in attentional biases in anxiety and valuation biases in depression and underscore the importance of examining transdiagnostic dimensions of anxiety/depression while networks are challenged.

Disentangling effects of remote mild traumatic brain injury characteristics and posttraumatic stress on processing speed and executive function in veterans.

Mild traumatic brain injury (mTBI) and posttraumatic stress are prevalent in military service members and share objective and subjective cognitive symptoms, complicating recovery. We investigated the effects of remote mTBI characteristics and current posttraumatic stress symptoms on neuropsychological performance in 152 veterans with a history of remote mTBI and current cognitive concerns. Participants completed clinical neuropsychological evaluations within a Veterans Affairs Level-II TBI/Polytrauma outpatient clinic (i.e. tertiary trauma care center for US military veterans outside of a research or teaching hospital setting). Archival data analysis of mTBI injury characteristics, clinical diagnoses, scores on the Posttraumatic Stress Disorder Checklist-Military Version (PCL-M) and performance on tests of processing speed, attention and executive function was conducted. Hierarchical linear regression demonstrated that elevated PCL-M scores were associated with slower performance on trail making test (TMT) Parts A and B (p < .016). PCL-M symptoms moderated the effect of alteration of consciousness (AOC) on TMT performance, with endorsement of AOC associated with better performance, but only when PCL-M scores were high (p < .005). Follow-up mediation analyses demonstrated that PCL-M score fully mediated the relationship between AOC and TMT-A performance and partially mediated the relationship between AOC and TMT-B performance. Post-hoc analyses meant to separate the impact of processing speed on TMT-B were all non-significant. Remote mTBI characteristics, specifically AOC, were not associated with decrements in cognitive performance. Posttraumatic symptoms were associated with worse processing speed, suggesting that psychological distress and psychopathology are contributing factors in understanding and treating persistent cognitive distress following remote mTBI.

Reduced temporal and spatial stability of neural activity patterns predict cognitive control deficits in children with ADHD.

This study explores the neural underpinnings of cognitive control deficits in ADHD, focusing on overlooked aspects of trial-level variability of neural coding. We employed a novel computational approach to neural decoding on a single-trial basis alongside a cued stop-signal task which allowed us to distinctly probe both proactive and reactive cognitive control. Typically developing (TD) children exhibited stable neural response patterns for efficient proactive and reactive dual control mechanisms. However, neural coding was compromised in children with ADHD. Children with ADHD showed increased temporal variability and diminished spatial stability in neural responses in salience and frontal-parietal network regions, indicating disrupted neural coding during both proactive and reactive control. Moreover, this variability correlated with fluctuating task performance and with more severe symptoms of ADHD. These findings underscore the significance of modeling single-trial variability and representational similarity in understanding distinct components of cognitive control in ADHD, highlighting new perspectives on neurocognitive dysfunction in psychiatric disorders.

Developmental Trajectories of Internalizing and Externalizing Symptoms in Youth and Associated Gender Differences: A Directed Network Perspective.

Psychopathology in youth is highly prevalent and associated with psychopathology in adulthood. However, the developmental trajectories of psychopathology symptoms, including potential gender differences, are markedly underspecified. The present study employed a directed network approach to investigate longitudinal relationships and gender differences among eight transdiagnostic symptom domains across three years, in a homogenous age sample of youth participants (n = 6,414; mean baseline age = 10.0 years; 78.6% White; Adolescent Brain Cognitive Development study). Anxious/depressed problems and aggressive behaviors were central symptoms and most predictive of increases in other symptom clusters at later timepoints. Rule-breaking behaviors, aggressive behaviors, and withdrawn/depressed problems emerged as bridge symptoms between externalizing and internalizing problems. Results supported cascade models in which externalizing problems predicted future internalizing problems, but internalizing problems also significantly predicted future externalizing problems, which is contrary to cascade models. Network structure, symptom centrality, and patterns of bridge symptoms differed between female and male participants, suggesting gender differences in the developmental trajectories of youth psychopathology. Results provide new insights into symptom trajectories and associated gender differences that may provide promising pathways for understanding disorder (dis)continuity and co-occurrence. The central and bridge symptoms identified here may have important implications for screening and early intervention for youth psychopathology.

Both reactive and proactive control are deficient in children with ADHD and predictive of clinical symptoms.

Cognitive control deficits are a hallmark of attention deficit hyperactivity disorder (ADHD) in children. Theoretical models posit that cognitive control involves reactive and proactive control processes but their distinct roles and inter-relations in ADHD are not known, and the contributions of proactive control remain vastly understudied. Here, we investigate the dynamic dual cognitive control mechanisms associated with both proactive and reactive control in 50 children with ADHD (16F/34M) and 30 typically developing (TD) children (14F/16M) aged 9-12 years across two different cognitive controls tasks using a within-subject design. We found that while TD children were capable of proactively adapting their response strategies, children with ADHD demonstrated significant deficits in implementing proactive control strategies associated with error monitoring and trial history. Children with ADHD also showed weaker reactive control than TD children, and this finding was replicated across tasks. Furthermore, while proactive and reactive control functions were correlated in TD children, such coordination between the cognitive control mechanisms was not present in children with ADHD. Finally, both reactive and proactive control functions were associated with behavioral problems in ADHD, and multi-dimensional features derived from the dynamic dual cognitive control framework predicted inattention and hyperactivity/impulsivity clinical symptoms. Our findings demonstrate that ADHD in children is characterized by deficits in both proactive and reactive control, and suggest that multi-componential cognitive control measures can serve as robust predictors of clinical symptoms.

Trait motivation moderates neural activation associated with goal pursuit.

Research has indicated that regions of left and right dorsolateral prefrontal cortex (DLPFC) are involved in integrating the motivational and executive function processes related to, respectively, approach and avoidance goals. Given that sensitivity to pleasant and unpleasant stimuli is an important feature of conceptualizations of approach and avoidance motivation, it is possible that these regions of DLPFC are preferentially activated by valenced stimuli. The present study tested this hypothesis by using a task in which goal pursuit was threatened by distraction from valenced stimuli while functional magnetic resonance imaging data were collected. The analyses examined whether the impact of trait approach and avoidance motivation on the neural processes associated with executive function differed depending on the valence or arousal level of the distractor stimuli. The present findings support the hypothesis that the regions of DLPFC under investigation are involved in integrating motivational and executive function processes, and they also indicate the involvement of a number of other brain areas in maintaining goal pursuit. However, DLPFC did not display differential sensitivity to valence.

Predictive utility of symptom measures in classifying anxiety and depression: A machine-learning approach.

Major depressive disorder (MDD) and generalized anxiety disorder (GAD) are highly prevalent, co-occurring disorders with significant symptom overlap, posing challenges in accurately distinguishing and diagnosing these disorders. The tripartite model proposes that anxious arousal is specific to anxiety and anhedonia is specific to depression, though anxious apprehension may play a greater role in GAD than anxious arousal. The present study tested the efficacy of the Mood and Anxiety Symptom Questionnaire anhedonic depression (MASQ-AD) and anxious arousal (MASQ-AA) scales and the Penn State Worry Questionnaire (PSWQ) in identifying lifetime or current MDD, current major depressive episode (MDE), and GAD using binary support vector machine learning algorithms in an adult sample (n = 150). The PSWQ and MASQ-AD demonstrated predictive utility in screening for and identification of GAD and current MDE respectively, with the MASQ-AD eight-item subscale outperforming the MASQ-AD 14-item subscale. The MASQ-AA did not predict MDD, current MDE, or GAD, and the MASQ-AD did not predict current or lifetime MDD. The PSWQ and MASQ-AD are efficient and accurate screening tools for GAD and current MDE. Results support the tripartite model in that anhedonia is unique to depression, but inclusion of anxious apprehension as a separate dimension of anxiety is warranted.

Factor Structure, Measurement Invariance, and Concurrent Validity of the Penn State Worry Questionnaire Across Development, Psychopathology, and Culture.

The Penn State Worry Questionnaire (PSWQ) is a widely used assessment of excessive worry. American undergraduate samples have predominately been used to evaluate its factor structure, which may not generalize to other developmental, cultural, and psychopathology populations. The present study tested the PSWQ's factor structure across three diverse samples: American undergraduate students (n = 3,243), Dutch high school students (n = 3,906), and American adults with psychopathology (n = 384). Exploratory, confirmatory, and multigroup confirmatory factor analyses were conducted. Measurement invariance and concurrent validity were also tested. Method-factor and two-factor models were largely equivalent and superior to a one-factor model. Invariance tests supported configural and metric invariance but only partial scalar invariance. Positively worded items but not negatively worded items demonstrated concurrent validity with anxiety and depression symptom measures and diagnoses. Overall, the PSWQ appears to measure a unitary construct. Present results warrant further testing of the PSWQ across diverse samples.

Associations of Family Distress, Family Income, and Acculturation on Pediatric Cognitive Performance Using the NIH Toolbox: Implications for Clinical and Research Settings.

OBJECTIVE: There is a growing recognition that the use of conventional norms (e.g., age, sex, years of education, race) as proxies to capture a broad range of sociocultural variability on cognitive performance is suboptimal, limiting sample representativeness. The present study evaluated the incremental utility of family income, family conflict, and acculturation beyond the established associations of age, gender,maternal years of education, and race on cognitive performance. METHOD: Hierarchical linear regressions evaluated the incremental utility of sociocultural factors on National Institutes of Health Toolbox in a nationally representative sample of pre-adolescent children (n = 11,878; Mage = 10.0 years; Adolescent Brain Cognitive Development Study). A regression-based norming procedure was implemented for significant models. Paired sample t-tests were used to compare original and newly created demographically corrected T-scores. RESULTS: Nearly all regression models predicted performance on the NIH-TB subtests and composite scores (p < .005). Greater family income and lower family conflict predicted better performance, although the effect sizes were small by traditional standards. Acculturation scores did not explain additional variance in cognitive performance. Lastly, there were no significant differences between the original and newly created demographically corrected T-scores (Mdiff < 0.50). CONCLUSIONS: The present study highlights that, although family income, family conflict, and acculturation have been shown to routinely influence cognitive performance in preadolescent children, the NIH-TB appears to be highly robust to individual differences in sociocultural factors in children between ages 9 and 10. Contextual and temporal implications of the present results are discussed.

The Structure of Executive Dysfunction in Depression and Anxiety.

BACKGROUND: Although research has demonstrated that depression and anxiety are associated with problematic executive function (EF), results are often inconsistent and underspecified. Delineating specific EF impairments in depression and anxiety has the potential to provide a mechanistic account of symptom presentation and course in these highly co-occurring disorders. The present study evaluated associations between components of EF and symptom dimensions of depression (depressed mood) and anxiety (anxious apprehension, anxious arousal) using factor analyses and structural equation modeling. METHODS: Undergraduates (N = 1,123) completed self-report measures of EF in everyday life and of psychopathology. Based on a three-factor model (Miyake et al., 2000), item-level exploratory (n = 561) and confirmatory (n = 562) factor analyses were conducted on inhibition, shifting, and working memory scales chosen from the EF measure. Structural equation modeling tested the relationship of EF factors to dimensions of psychopathology using the total sample. RESULTS: A three-factor model of EF best fit the data and was replicated via confirmatory factor analysis. Depressed mood and anxious arousal evidenced broad deficits across all EF domains, whereas anxious apprehension evidenced shifting disruptions. LIMITATIONS: Perceived EF may not index the same constructs as performance-based EF tests. Further, the present study was restricted to college students, warranting replication in other samples. CONCLUSIONS: Findings suggest that depressed mood and anxious arousal are characterized by a general disruption in the ability to maintain task goals, whereas anxious apprehension is characterized by cognitive inflexibility. EF impairments are likely contributory factors in the maintenance of affective disorders.

Specificity of anhedonic alterations in resting-state network connectivity and structure: A transdiagnostic approach.

Anhedonia is a prominent characteristic of depression and related pathology that is associated with a prolonged course of mood disturbance and treatment resistance. However, the neurobiological mechanisms of anhedonia are poorly understood as few studies have disentangled the specific effects of anhedonia from other co-occurring symptoms. Here, we take a transdiagnostic, dimensional approach to distinguish anhedonia alterations from other internalizing symptoms on intrinsic functional brain circuits. 53 adults with varying degrees of anxiety and/or depression completed resting-state fMRI. Neural networks were identified through independent components analysis. Dual regression was used to characterize within-network functional connectivity alterations associated with individual differences in anhedonia. Modulation of between-network functional connectivity by anhedonia was tested using region-of-interest to region-of-interest correlational analyses. Anhedonia was associated with visual network hyperconnectivity and expansion of the visual, dorsal attention, and default networks. Additionally, anhedonia was associated with decreased between-network connectivity among default, salience, dorsal attention, somatomotor, and visual networks. Findings suggest that anhedonia is associated with aberrant connectivity and structural alterations in resting-state networks that contribute to impairments in reward learning, low motivation, and negativity bias characteristic of depression. Results reveal dissociable effects of anhedonia on resting-state network dynamics, characterizing possible neurocircuit mechanisms for intervention.

Co-occurring anxiety influences patterns of brain activity in depression.

Brain activation associated with anhedonic depression and co-occurring anxious arousal and anxious apprehension was measured by fMRI during performance of an emotion word Stroop task. Consistent with EEG findings, depression was associated with rightward frontal lateralization in the dorsolateral prefrontal cortex (DLPFC), but only when anxious arousal was elevated and anxious apprehension was low. Activity in the right inferior frontal gyrus (IFG) was also reduced for depression under the same conditions. In contrast, depression was associated with more activity in the anterior cingulate cortex (dorsal ACC and rostral ACC) and the bilateral amygdala. Results imply that depression, particularly when accompanied by anxious arousal, may result in a failure to implement top-down processing by appropriate brain regions (left DLPFC, right IFG) due to increased activation in regions associated with responding to emotionally salient information (right DLPFC, amygdala).

Effects of adult attachment and emotional distractors on brain mechanisms of cognitive control.

Using data from 34 participants who completed an emotion-word Stroop task during functional magnetic resonance imaging, we examined the effects of adult attachment on neural activity associated with top-down cognitive control in the presence of emotional distractors. Individuals with lower levels of secure-base-script knowledge--reflected in an adult's inability to generate narratives in which attachment-related threats are recognized, competent help is provided, and the problem is resolved--demonstrated more activity in prefrontal cortical regions associated with emotion regulation (e.g., right orbitofrontal cortex) and with top-down cognitive control (left dorsolateral prefrontal cortex, anterior cingulate cortex, and superior frontal gyrus). Less efficient performance and related increases in brain activity suggest that insecure attachment involves a vulnerability to distraction by attachment-relevant emotional information and that greater cognitive control is required to attend to task-relevant, nonemotional information. These results contribute to the understanding of mechanisms through which attachment-related experiences may influence developmental adaptation.

Anxiety and Stress Alter Decision-Making Dynamics and Causal Amygdala-Dorsolateral Prefrontal Cortex Circuits During Emotion Regulation in Children.

BACKGROUND: Anxiety and stress reactivity are risk factors for the development of affective disorders. However, the behavioral and neurocircuit mechanisms that potentiate maladaptive emotion regulation are poorly understood. Neuroimaging studies have implicated the amygdala and dorsolateral prefrontal cortex (DLPFC) in emotion regulation, but how anxiety and stress alter their context-specific causal circuit interactions is not known. Here, we use computational modeling to inform affective pathophysiology, etiology, and neurocircuit targets for early intervention. METHODS: Forty-five children (10-11 years of age; 25 boys) reappraised aversive stimuli during functional magnetic resonance imaging scanning. Clinical measures of anxiety and stress were acquired for each child. Drift-diffusion modeling of behavioral data and causal circuit analysis of functional magnetic resonance imaging data, with a National Institute of Mental Health Research Domain Criteria approach, were used to characterize latent behavioral and neurocircuit decision-making dynamics driving emotion regulation. RESULTS: Children successfully reappraised negative responses to aversive stimuli. Drift-diffusion modeling revealed that emotion regulation was characterized by increased initial bias toward positive reactivity during viewing of aversive stimuli and increased drift rate, which captured evidence accumulation during emotion evaluation. Crucially, anxiety and stress reactivity impaired latent behavioral dynamics associated with reappraisal and decision making. Anxiety and stress increased dynamic casual influences from the right amygdala to DLPFC. In contrast, DLPFC, but not amygdala, reactivity was correlated with evidence accumulation and decision making during emotion reappraisal. CONCLUSIONS: Our findings provide new insights into how anxiety and stress in children impact decision making and amygdala-DLPFC signaling during emotion regulation, and uncover latent behavioral and neurocircuit mechanisms of early risk for psychopathology.

Effects of prior hypoglycemia and hyperglycemia on cognition in children with type 1 diabetes mellitus.

OBJECTIVE: Despite the general consensus that youth with type 1 diabetes mellitus (T1DM) can experience modest cognitive impairment, debate continues over the role of severe hypoglycemia (Hypo) and/or hyperglycemia (Hyper) in producing such impairment. Our aim was to determine how Hypo and Hyper experienced during brain development predict patterns of subsequent cognitive performance in youth with T1DM. METHODS: We tested youth aged 5-16 yr (T1DM, n = 117; non-diabetic sibling controls, n = 58) on cognitive tasks (verbal and spatial intelligence, verbal and spatial memory, and processing speed). T1DM participants were categorized as having experienced 0, 1-2, or 3 or more (3+) Hypo episodes, as having their first Hypo episode before or after 5 yr of age and as having early (before age 5) or late (after age 5) diabetes onset. Hyper exposure was estimated with median hemoglobin A1c, adjusted for diabetes duration for each subject. RESULTS: The group with T1DM had lower estimated verbal intelligence than sibling controls. Within the T1DM group, verbal intelligence was reduced with increased exposure to Hyper, not to Hypo. In contrast, spatial intelligence and delayed recall were reduced only with repeated Hypo, particularly when Hypo episodes occurred before the age of 5 yr. Age of onset did not explain these results. CONCLUSIONS: Hypo and Hyper have qualitatively different effects on cognitive function in T1DM that depend in part on the timing of exposure during development, independent of onset age. This information extends the known benefits of avoiding both Hypo and chronic Hyper during childhood to include preservation of specific cognitive skills.

Frequency and timing of severe hypoglycemia affects spatial memory in children with type 1 diabetes.

OBJECTIVE: Repeated severe hypoglycemia has been reported to reduce long-term spatial memory in children with type 1 diabetes. Early exposure to hypoglycemia may be more damaging to cognitive function than later exposure. Our goal was to determine whether the age at which severe hypoglycemia occurs modulates the impact of severe hypoglycemia frequency on long-term spatial memory. RESEARCH DESIGN AND METHODS: We combined data from three independent studies to obtain a sample of children aged 6-18 years with type 1 diabetes (n = 103) and nondiabetic control subjects (n = 60). Each study evaluated previous severe hypoglycemia and tested short (5 s)- and long (60 s)-delay spatial memory with the spatial delayed response task. Type 1 diabetic participants were categorized as having zero, one to two, or three or more severe hypoglycemic episodes and as having their first severe hypoglycemic episode before or after 5 years of age. Information on chronic hyperglycemia (HbA1c values) was also collected. RESULTS: We found that repeated severe hypoglycemia (more than three episodes) reduced long-delay spatial delayed response performance, particularly when severe hypoglycemic episodes began before the age of 5 years. Age of type 1 diabetes onset and estimates of chronic hyperglycemia did not influence performance. CONCLUSIONS: High frequency of and early exposure to severe hypoglycemia during development negatively affects spatial long-term memory performance.

Executive function deficits associated with current and past major depressive symptoms.

BACKGROUND: Although there has been extensive research showing that depression is associated with executive function (EF) deficits, the nature of these deficits is not clearly delineated. Specifically, previous reviews on this topic have yielded different conclusions about the particular domains of EF that are disrupted in depressed individuals. Further, research on whether these deficits persist after depressed mood has remitted is less prevalent and not consistent. METHODS: In two independent samples of college students, we examined associations between clinical ratings of current and past symptoms of a Major Depressive Episode (MDE) and difficulties in two domains of EF: inhibition and shifting. In Study 1 (n=162), EF was measured using behavioral tasks shown to index these two domains. In Study 2 (n=95), EF was measured using a self-report questionnaire believed to capture EF difficulties experienced in daily life. RESULTS: In both studies, past MDE symptoms were associated with worse shifting. In contrast, current MDE symptoms were associated with worse inhibition, though only on the behavioral measure (in Study 1). LIMITATIONS: Both studies used college samples and retrospective assessments of past symptoms. Further, only two domains of EF were examined, and the EF measures employed in each study have their own unique methodological limitations. CONCLUSIONS: Findings suggest that inhibition deficits vary as a function of current symptoms and thus may be a by-product of distress rather than a causal contributor. In contrast, shifting deficits associated with depression appear to be more enduring, suggesting that they could contribute to risk for depression.