BACKGROUND:The hippocampus plays a central role in post-traumatic stress disorder (PTSD) pathogenesis, and the majority of neuroimaging research on PTSD has studied the hippocampus in its entirety. Although extensive literature demonstrates changes in hippocampal volume are associated with PTSD, fewer studies have probed the relationship between symptoms and the hippocampus' functionally and structurally distinct subfields. We utilized data from a longitudinal study examining post-trauma outcomes to determine whether hippocampal subfield volumes change post-trauma and whether specific subfields are significantly associated with, or prospectively related to, PTSD symptom severity. As a secondary aim, we leveraged our unique study design sample to also investigate reliability of hippocampal subfield volumes using both cross-sectional and longitudinal pipelines available in FreeSurfer v6.0.METHODS:Two-hundred and fifteen traumatically injured individuals were recruited from an urban Emergency Department. Two-weeks post-injury, participants underwent two consecutive days of neuroimaging (time 1: T1, and time 2: T2) with magnetic resonance imaging (MRI) and completed self-report assessments. Six-months later (time 3: T3), participants underwent an additional scan and were administered a structured interview assessing PTSD symptoms. First, we calculated reliability of hippocampal measurements at T1 and T2 (automatically segmented with FreeSurfer v6.0). We then examined the prospective (T1 subfields) and cross-sectional (T3 subfields) relationship between volumes and PTSD. Finally, we tested whether change in subfield volumes between T1 and T3 explained PTSD symptom variability.RESULTS:After controlling for sex, age, and total brain volume, none of the subfield volumes (T1) were prospectively related to T3 PTSD symptoms nor were subfield volumes (T3) associated with current PTSD symptoms (T3). Tl - T2 reliability of all hippocampal subfields ranged from good to excellent (intraclass correlation coefficient (ICC) values > 0.83), with poorer reliability in the hippocampal fissure.CONCLUSION:Our study was a novel examination of the prospective relationship between hippocampal subfield volumes in relation to PTSD in a large trauma-exposed urban sample. There was no significant relationship between subfield volumes and PTSD symptoms, however, we confirmed FreeSurfer v6.0 hippocampal subfield segmentation is reliable when applied to a traumatically-injured sample, using both cross-sectional and longitudinal analysis pipelines. Although hippocampal subfield volumes may be an important marker of individual variability in PTSD, findings are likely conditional on the timing of the measurements (e.g. acute or chronic post-trauma periods) and analysis strategy (e.g. cross-sectional or prospective).

BACKGROUND:The Adolescent Brain Cognitive Development ™ Study (ABCD Study®) is an open-science, multi-site, prospective, longitudinal study following over 11,800 9- and 10-year-old youth into early adulthood. The ABCD Study aims to prospectively examine the impact of substance use (SU) on neurocognitive and health outcomes. Although SU initiation typically occurs during teen years, relatively little is known about patterns of SU in children younger than 12. METHODS:This study aims to report the detailed ABCD Study® SU patterns at baseline (n = 11,875) in order to inform the greater scientific community about cohort's early SU. Along with a detailed description of SU, we ran mixed effects regression models to examine the association between early caffeine and alcohol sipping with demographic factors, externalizing symptoms and parental history of alcohol and substance use disorders (AUD/SUD). PRIMARY RESULTS:At baseline, the majority of youth had used caffeine (67.6 %) and 22.5 % reported sipping alcohol (22.5 %). There was little to no reported use of other drug categories (0.2 % full alcohol drink, 0.7 % used nicotine, <0.1 % used any other drug of abuse). Analyses revealed that total caffeine use and early alcohol sipping were associated with demographic variables (p's<.05), externalizing symptoms (caffeine p = 0002; sipping p = .0003), and parental history of AUD (sipping p = .03). CONCLUSIONS:ABCD Study participants aged 9-10 years old reported caffeine use and alcohol sipping experimentation, but very rare other SU. Variables linked with early childhood alcohol sipping and caffeine use should be examined as contributing factors in future longitudinal analyses examining escalating trajectories of SU in the ABCD Study cohort.

Following reports on improved test-retest reliability of emotion-modulated startle during a 6-s picture presentation when different pictures are presented at each assessment (Larson et al., 2000) and data suggesting that brief picture presentations also elicit affective blink modulation (Codispoti, Bradley, & Lang, 2001), we assessed test-retest reliability of blink modulation during brief picture presentations. At two acoustic startle sessions (4 weeks apart) subjects viewed different IAPS pictures for either 6 s (long group) or 300 ms (short), with emotion modulation assessed at three different points in time during and following picture viewing. Group ANOVAs revealed emotion modulation for both short and long groups. In addition, comparable and, in some cases, greater stability of emotion modulation was found for short compared to long picture presentations. Stability was generally low for individual probe times for both groups.

Major depression is a heterogeneous condition, and the search for neural correlates specific to clinically defined subtypes has been inconclusive. Theoretical considerations implicate frontostriatal, particularly subgenual prefrontal cortex (PFC), dysfunction in the pathophysiology of melancholia—a subtype of depression characterized by anhedonia—but no empirical evidence has been found yet for such a link. To test the hypothesis that melancholic, but not nonmelancholic depression, is associated with the subgenual PFC impairment, concurrent measurement of brain electrical (electroencephalogram, EEG) and metabolic (positron emission tomography, PET) activity were obtained in 38 unmedicated subjects with DSM-IV major depressive disorder (20 melancholic, 18 nonmelancholic subjects), and 18 comparison subjects. EEG data were analyzed with a tomographic source localization method that computed the cortical three-dimensional distribution of current density for standard frequency bands, allowing voxelwise correlations between the EEG and PET data. Voxel-based morphometry analyses of structural magnetic resonance imaging (MRI) data were performed to assess potential structural abnormalities in melancholia. Melancholia was associated with reduced activity in the subgenual PFC (Brodmann area 25), manifested by increased inhibitory delta activity (1.5–6.0 Hz) and decreased glucose metabolism, which themselves were inversely correlated. Following antidepressant treatment, depressed subjects with the largest reductions in depression severity showed the lowest post-treatment subgenual PFC delta activity. Analyses of structural MRI revealed no group differences in the subgenual PFC, but in melancholic subjects, a negative correlation between gray matter density and age emerged. Based on preclinical evidence, we suggest that subgenual PFC dysfunction in melancholia may be associated with blunted hedonic response and exaggerated stress responsiveness.

Background: The frontal lobe has been crucially involved in the neurobiology of major depression, but inconsistencies among studies exist, in part due to a failure of considering modulatory variables such as symptom severity v, comorbidity with anxiety, and distinct subtypes, as codeterminants for patterns of brain activation in depression.Methods: Resting electroencephalogram was recorded in 38 unmedicated subjects with major depressive disorder and 18 normal comparison subjects, and analyzed with a tomographic source localization method that computes the cortical three-dimensional distribution of current density for standard electroencephalogram frequency, bands. Symptom severity and anxiety were measured via self-report and melancholic features via clinical interview.Results: Depressed subjects showed more excitatory (beta3, 21.5-30.0 Hz) activity in the right superior and inferior frontal lobe (Brodmann's area 9/10/11) than comparison subjects. In melancholic subjects, this effect was particularly pronounced for severe depression, and right frontal activity correlated positively with anxiety. Depressed subjects showed posterior cingulate and precuneus hypoactivity.Conclusions: While confirming prior results implicating right frontal and posterior cingulate regions, this study highlights the importance of depression severity, anxiety, and melancholic features in patterns of brain activity accompanying depression.

It is well known that the eating patterns that restrain chronic dieters (restrained eaters) can be disinhibited by anxiety, which in turn has been associated with relative right frontal brain activity in independent electroencephalographic (EEG) studies. Combining these two lines of evidence, the authors tested the hypothesis that chronic restrained eating is associated with relative right frontal asymmetry. Resting anterior brain asymmetry and self-reported measures of anxiety and depression were collected in 23 restrained and 32 unrestrained eaters. As hypothesized, groups differed in tonic frontal activity, with restrained eaters showing more relative right frontal activity. Furthermore, relative right frontal activity was associated with greater self-reported restraint. Right-sided prefrontal asymmetry may thus represent a diathesis associated with increased vulnerability toward restrained eating.

The present study was undertaken to determine whether aversiveness contributes to startle potentiation in anticipation of affective pictures above and beyond the effects of emotional arousal. Further, participants high in trait anxious apprehension, which is characterized by worry about the future, were expected to show especially pronounced anticipatory startle responses. Startle blink reflex was measured during warning stimuli that predicted the valence of ensuing aversive/unpleasant, pleasant, or neutral pictures. Startle magnitude was larger in anticipation of aversive than of pleasant pictures and smallest in anticipation of neutral pictures. Enhanced startle potentiation was not found in anxious apprehension subjects. These data suggest that the aversive nature of stimuli contribute to the potentiation of startle above and beyond the effects of emotional arousal, which may be a universal phenomenon not modulated by individual differences.

OBJECTIVEThe anterior cingulate cortex has been implicated in depression. Results are best interpreted by considering anatomic and cytoarchitectonic subdivisions. Evidence suggests depression is characterized by hypoactivity in the dorsal anterior cingulate, whereas hyperactivity in the rostral anterior cingulate is associated with good response to treatment. The authors tested the hypothesis that activity in the rostral anterior cingulate during the depressed state has prognostic value for the degree of eventual response to treatment. Whereas prior studies used hemodynamic imaging, this investigation used EEG.METHODThe authors recorded 28-channel EEG data for 18 unmedicated patients with major depression and 18 matched comparison subjects. Clinical outcome was assessed after nortriptyline treatment. Of the 18 depressed patients, 16 were considered responders 4-6 months after initial assessment. A median split was used to classify response, and the pretreatment EEG data of patients showing better (N=9) and worse (N=9) responses were analyzed with low-resolution electromagnetic tomography, a new method to compute three-dimensional cortical current density for given EEG frequency bands according to a Talairach brain atlas.RESULTSThe patients with better responses showed hyperactivity (higher theta activity) in the rostral anterior cingulate (Brodmann's area 24/32). Follow-up analyses demonstrated the specificity of this finding, which was not confounded by age or pretreatment depression severity.CONCLUSIONSThese results, based on electrophysiological imaging, not only support hemodynamic findings implicating activation of the anterior cingulate as a predictor of response in depression, but they also suggest that differential activity in the rostral anterior cingulate is associated with gradations of response.

Test-retest reliability of resting regional cerebral metabolic rate of glucose (rCMR) was examined in selected subcortical structures: the amygdala, hippocampus, thalamus, and anterior caudate nucleus. Findings from previous studies examining reliability of rCMR suggest that rCMR in small subcortical structures may be more variable than in larger cortical regions. We chose to study these subcortical regions because of their particular interest to our laboratory in its investigations of the neurocircuitry of emotion and depression. Twelve normal subjects (seven female, mean age = 32.42 years, range 21-48 years) underwent two FDG-PET scans separated by approximately 6 months (mean = 25 weeks, range 17-35 weeks). A region-of-interest approach with PET-MRI coregistration was used for analysis of rCMR reliability. Good test-retest reliability was found in the left amygdala, right and left hippocampus, right and left thalamus, and right and left anterior caudate nucleus. However, rCMR in the right amygdala did not show good test-retest reliability. The implications of these data and their import for studies that include a repeat-test design are considered.

Despite the prominence of emotional dysfunction in psychopathology, relatively few experiments have explicitly studied emotion regulation in adults. The present study examined one type of emotion regulation: voluntary regulation of short-term emotional responses to unpleasant visual stimuli. In a sample of 48 college students, both eyeblink startle magnitude and corrugator activity were sensitive to experimental manipulation. Instructions to suppress negative emotion led to both smaller startle eyeblinks and decreased corrugator activity. Instructions to enhance negative emotion led to larger startle eyeblinks and increased corrugator activity. Several advantages of this experimental manipulation are discussed, including the use of both a suppress and an enhance emotion condition, independent measurement of initial emotion elicitation and subsequent regulation of that emotion, the use of a completely within-subjects design, and the use of naturalistic emotion regulation strategies.

In the present study, we examined the stability of one measure of emotion, the emotion-modulated acoustic startle response, in an undergraduate sample. Using the acoustic startle paradigm on two different occasions, we measured stability of affective modulation of the startle response during and following the presentation of pictures selected to be of positive, negative, or neutral emotional valence. The two assessments were separated by 4 weeks. Two groups of subjects were compared: one group that viewed the same pictures at each assessment and a second group that viewed different pictures at the second assessment. We found that viewing different pictures at two assessments separated by 4 weeks yielded moderate stability of the emotion modulation of startle magnitude, whereas subjects who viewed the same pictures at both assessments showed poor stability. Furthermore, this difference was due to the stability of responses to high versus low arousal pictures, not to differences in valence.