No abstract

A mechanistic understanding of the pathology of psychiatric disorders has been hampered by extensive heterogeneity in biology, symptoms, and behavior within diagnostic categories that are defined subjectively. We investigated whether leveraging individual differences in information-processing impairments in patients with post-traumatic stress disorder (PTSD) could reveal phenotypes within the disorder. We found that a subgroup of patients with PTSD from two independent cohorts displayed both aberrant functional connectivity within the ventral attention network (VAN) as revealed by functional magnetic resonance imaging (fMRI) neuroimaging and impaired verbal memory on a word list learning task. This combined phenotype was not associated with differences in symptoms or comorbidities, but nonetheless could be used to predict a poor response to psychotherapy, the best-validated treatment for PTSD. Using concurrent focal noninvasive transcranial magnetic stimulation and electroencephalography, we then identified alterations in neural signal flow in the VAN that were evoked by direct stimulation of that network. These alterations were associated with individual differences in functional fMRI connectivity within the VAN. Our findings define specific neurobiological mechanisms in a subgroup of patients with PTSD that could contribute to the poor response to psychotherapy.

Repetitive transcranial magnetic stimulation (rTMS) is a commonly-used treatment for major depressive disorder (MDD). However, our understanding of the mechanism by which TMS exerts its antidepressant effect is minimal. Furthermore, we lack brain signals that can be used to predict and track clinical outcome. Such signals would allow for treatment stratification and optimization. Here, we performed a randomized, sham-controlled clinical trial and measured electrophysiological, neuroimaging, and clinical changes before and after rTMS. Patients (N = 36) were randomized to receive either active or sham rTMS to the left dorsolateral prefrontal cortex (dlPFC) for 20 consecutive weekdays. To capture the rTMS-driven changes in connectivity and causal excitability, resting fMRI and TMS/EEG were performed before and after the treatment. Baseline causal connectivity differences between depressed patients and healthy controls were also evaluated with concurrent TMS/fMRI. We found that active, but not sham rTMS elicited (1) an increase in dlPFC global connectivity, (2) induction of negative dlPFC-amygdala connectivity, and (3) local and distributed changes in TMS/EEG potentials. Global connectivity changes predicted clinical outcome, while both global connectivity and TMS/EEG changes tracked clinical outcome. In patients but not healthy participants, we observed a perturbed inhibitory effect of the dlPFC on the amygdala. Taken together, rTMS induced lasting connectivity and excitability changes from the site of stimulation, such that after active treatment, the dlPFC appeared better able to engage in top-down control of the amygdala. These measures of network functioning both predicted and tracked clinical outcome, potentially opening the door to treatment optimization.

Concurrent single-pulse TMS-EEG (spTMS-EEG) is an emerging noninvasive tool for probing causal brain dynamics in humans. However, in addition to the common artifacts in standard EEG data, spTMS-EEG data suffer from enormous stimulation-induced artifacts, posing significant challenges to the extraction of neural information. Typically, neural signals are analyzed after a manual time-intensive and often subjective process of artifact rejection. Here we describe a fully automated algorithm for spTMS-EEG artifact rejection. A key step of this algorithm is to decompose the spTMS-EEG data into statistically independent components (ICs), and then train a pattern classifier to automatically identify artifact components based on knowledge of the spatio-temporal profile of both neural and artefactual activities. The autocleaned and hand-cleaned data yield qualitatively similar group evoked potential waveforms. The algorithm achieves a 95% IC classification accuracy referenced to expert artifact rejection performance, and does so across a large number of spTMS-EEG data sets (n = 90 stimulation sites), retains high accuracy across stimulation sites/subjects/populations/montages, and outperforms current automated algorithms. Moreover, the algorithm was superior to the artifact rejection performance of relatively novice individuals, who would be the likely users of spTMS-EEG as the technique becomes more broadly disseminated. In summary, our algorithm provides an automated, fast, objective, and accurate method for cleaning spTMS-EEG data, which can increase the utility of TMS-EEG in both clinical and basic neuroscience settings.

No abstract

There is limited research exploring attachment style and defenses in adolescents. The purpose of the current research is to explore the relationship between adolescent attachment style and development of defense mechanisms, as well as attachment style and problem behaviors. A total of 1487 students from two California high-schools completed three self-report questionnaires to establish defense mechanisms, psychiatric symptoms, and attachment style. Attachment styles characterized by a positive selfimage predict greater levels of mature defense mechanisms, and lower levels of immature defense mechanisms, both in the interpersonal and intrapsychic domains. Relationships between insecure attachment styles and psychopathology were mediated by greater levels of immature defense mechanisms. These results provide initial compelling evidence that: a) attachment style is an important determinant of the type of defense mechanisms utilized by the individual to maintain psychological stability; and b) defense mechanisms serve to transmit the detrimental effects of insecure attachment style on psychological health.

When exposed to others' emotional responses, people often make rapid decisions as to whether these others are members of their group or not. These group categorization decisions have been shown to be extremely important to understanding group behavior. Yet, despite their prevalence and importance, we know very little about the attributes that shape these categorization decisions. To address this issue, we took inspiration from ensemble coding research and developed a task designed to reveal the influence of the mean and variance of group members' emotions on participants' group categorization. In Study 1, we verified that group categorization decreases when the group's mean emotion is different from the participant's own emotional response. In Study 2, we established that people identify a group's mean emotion more accurately when its variance is low rather than high. In Studies 3 and 4, we showed that participants were more likely to self-categorize as members of groups with low emotional variance, even if their own emotions fell outside of the range of group emotions they saw, and that this preference is seen for judgments of both positive and negative group emotions. In Study 5, we showed that this unique preference for low group emotional variance is special to group categorization and does not appear in a more basic face categorization task. Our studies reveal unexplored and important tendencies in group categorization based on group emotions.

Objective: A major challenge in understanding and treating posttraumatic stress disorder (PTSD) is its clinical heterogeneity, which is likely determined by various neurobiological perturbations. This heterogeneity likely also reduces the effectiveness of standard group comparison approaches. The authors tested whether a statistical approach aimed at identifying individual-level neuroimaging abnormalities that are more prevalent in case subjects than in control subjects could reveal new clinically meaningful insights into the heterogeneity of PTSD.