Using diffusion MRI data acquired with ultra-high gradient strength to improve tractography in routine-quality data.

The development of scanners with ultra-high gradient strength, spearheaded by the Human Connectome Project, has led to dramatic improvements in the spatial, angular, and diffusion resolution that is feasible for in vivo diffusion MRI acquisitions. The improved quality of the data can be exploited to achieve higher accuracy in the inference of both microstructural and macrostructural anatomy. However, such high-quality data can only be acquired on a handful of Connectom MRI scanners worldwide, while remaining prohibitive in clinical settings because of the constraints imposed by hardware and scanning time. In this study, we first update the classical protocols for tractography-based, manual annotation of major white-matter pathways, to adapt them to the much greater volume and variability of the streamlines that can be produced from today's state-of-the-art diffusion MRI data. We then use these protocols to annotate 42 major pathways manually in data from a Connectom scanner. Finally, we show that, when we use these manually annotated pathways as training data for global probabilistic tractography with anatomical neighborhood priors, we can perform highly accurate, automated reconstruction of the same pathways in much lower-quality, more widely available diffusion MRI data. The outcomes of this work include both a new, comprehensive atlas of WM pathways from Connectom data, and an updated version of our tractography toolbox, TRActs Constrained by UnderLying Anatomy (TRACULA), which is trained on data from this atlas. Both the atlas and TRACULA are distributed publicly as part of FreeSurfer. We present the first comprehensive comparison of TRACULA to the more conventional, multi-region-of-interest approach to automated tractography, and the first demonstration of training TRACULA on high-quality, Connectom data to benefit studies that use more modest acquisition protocols.

The effect of heart rate variability biofeedback training on stress and anxiety: a meta-analysis.

BACKGROUND: Some evidence suggests that heart rate variability (HRV) biofeedback might be an effective way to treat anxiety and stress symptoms. To examine the effect of HRV biofeedback on symptoms of anxiety and stress, we conducted a meta-analysis of studies extracted from PubMed, PsycINFO and the Cochrane Library. METHODS: The search identified 24 studies totaling 484 participants who received HRV biofeedback training for stress and anxiety. We conducted a random-effects meta-analysis. RESULTS: The pre-post within-group effect size (Hedges' g) was 0.81. The between-groups analysis comparing biofeedback to a control condition yielded Hedges' g = 0.83. Moderator analyses revealed that treatment efficacy was not moderated by study year, risk of study bias, percentage of females, number of sessions, or presence of an anxiety disorder. CONCLUSIONS: HRV biofeedback training is associated with a large reduction in self-reported stress and anxiety. Although more well-controlled studies are needed, this intervention offers a promising approach for treating stress and anxiety with wearable devices.

Brain connectomics predict response to treatment in social anxiety disorder.

We asked whether brain connectomics can predict response to treatment for a neuropsychiatric disorder better than conventional clinical measures. Pre-treatment resting-state brain functional connectivity and diffusion-weighted structural connectivity were measured in 38 patients with social anxiety disorder (SAD) to predict subsequent treatment response to cognitive behavioral therapy (CBT). We used a priori bilateral anatomical amygdala seed-driven resting connectivity and probabilistic tractography of the right inferior longitudinal fasciculus together with a data-driven multivoxel pattern analysis of whole-brain resting-state connectivity before treatment to predict improvement in social anxiety after CBT. Each connectomic measure improved the prediction of individuals' treatment outcomes significantly better than a clinical measure of initial severity, and combining the multimodal connectomics yielded a fivefold improvement in predicting treatment response. Generalization of the findings was supported by leave-one-out cross-validation. After dividing patients into better or worse responders, logistic regression of connectomic predictors and initial severity combined with leave-one-out cross-validation yielded a categorical prediction of clinical improvement with 81% accuracy, 84% sensitivity and 78% specificity. Connectomics of the human brain, measured by widely available imaging methods, may provide brain-based biomarkers (neuromarkers) supporting precision medicine that better guide patients with neuropsychiatric diseases to optimal available treatments, and thus translate basic neuroimaging into medical practice.

Comparison of psychotherapies for adult depression to pill placebo control groups: a meta-analysis.

BACKGROUND: The effects of antidepressants for treating depressive disorders have been overestimated because of selective publication of positive trials. Reanalyses that include unpublished trials have yielded reduced effect sizes. This in turn has led to claims that antidepressants have clinically insignificant advantages over placebo and that psychotherapy is therefore a better alternative. To test this, we conducted a meta-analysis of studies comparing psychotherapy with pill placebo. METHOD: Ten 10 studies comparing psychotherapies with pill placebo were identified. In total, 1240 patients were included in these studies. For each study, Hedges' g was calculated. Characteristics of the studies were extracted for subgroup and meta-regression analyses. RESULTS: The effect of psychotherapy compared to pill placebo at post-test was g = 0.25 [95% confidence interval (CI) 0.14-0.36, I² = 0%, 95% CI 0-58]. This effect size corresponds to a number needed to treat (NNT) of 7.14 (95% CI 5.00-12.82). The psychotherapy conditions scored 2.66 points lower on the Hamilton Depression Rating Scale (HAMD) than the placebo conditions, and 3.20 points lower on the Beck Depression Inventory (BDI). Some indications for publication bias were found (two missing studies). We found no significant differences between subgroups of the studies and in meta-regression analyses we found no significant association between baseline severity and effect size. CONCLUSIONS: Although there are differences between the role of placebo in psychotherapy and pharmacotherapy research, psychotherapy has an effect size that is comparable to that of antidepressant medications. Whether these effects should be deemed clinically relevant remains open to debate.

Comment on Lundh (2023).

In this commentary of Lundh's (2023) article, we point to an individualized process-based approach for the future of psychotherapy. The traditional nomothetic research paradigm is limiting our understanding of processes of change, oversimplifying psychological phenomena, and neglecting individual dynamics. In contrast, a process-based approach calls for ideographic methodologies, departing from the latent-disease paradigm toward process-based interventions. Process-based research promises avenues for enhancing intervention science and a deeper comprehension about psychopathology and therapeutic mechanisms, in a comprehensive, personalized, and holistic manner.

The Human Connectome Project of adolescent anxiety and depression dataset.

This article describes primary data and resources available from the Boston Adolescent Neuroimaging of Depression and Anxiety (BANDA) study, a novel arm of the Human Connectome Project (HCP). Data were collected from 215 adolescents (14-17 years old), 152 of whom had current diagnoses of anxiety and/or depressive disorders at study intake. Data include cross-sectional structural (T1- and T2-weighted), functional (resting state and three tasks), and diffusion-weighted magnetic resonance images. Both unprocessed and HCP minimally-preprocessed imaging data are available within the data release packages. Adolescent and parent clinical interview data, as well as cognitive and neuropsychological data are also included within these packages. Release packages additionally provide data collected from self-report measures assessing key features of adolescent psychopathology, including: anxious and depressive symptom dimensions, behavioral inhibition/activation, exposure to stressful life events, and risk behaviors. Finally, the release packages include 6- and 12-month longitudinal data acquired from clinical measures. Data are publicly accessible through the National Institute of Mental Health Data Archive (ID: #2505).

The natural course of social anxiety disorder among adolescents and young adults.

OBJECTIVE: To examine the natural course of social anxiety disorder (SAD) in the community and to explore predictors for adverse long-term outcomes. METHOD: A community sample of N = 3021 subjects aged 14-24 was followed-up over 10 years using the DSM-IV/M-CIDI. Persistence of SAD is based on a composite score reflecting the proportion of years affected since onset. Diagnostic stability is the proportion of SAD subjects still affected at follow-up. RESULTS: SAD reveals considerable persistence with more than half of the years observed since onset spent with symptoms. 56.7% of SAD cases revealed stability with at least symptomatic expressions at follow-up; 15.5% met SAD threshold criteria again. 15.1% were completely remitted (no SAD symptoms and no other mental disorders during follow-up). Several clinical features (early onset, generalized subtype, more anxiety cognitions, severe avoidance and impairment, co-occurring panic) and vulnerability characteristics (parental SAD and depression, behavioural inhibition, harm avoidance) predicted higher SAD persistence and - less impressively - diagnostic stability. CONCLUSION: A persistent course with a considerable degree of fluctuations in symptom severity is characteristic for SAD. Both consistently meeting full threshold diagnostic criteria and complete remissions are rare. Vulnerability and clinical severity indicators predict poor prognosis and might be helpful markers for intervention needs.

Brain function and clinical characterization in the Boston adolescent neuroimaging of depression and anxiety study.

We present a Human Connectome Project study tailored toward adolescent anxiety and depression. This study is one of the first studies of the Connectomes Related to Human Diseases initiative and is collecting structural, functional, and diffusion-weighted brain imaging data from up to 225 adolescents (ages 14-17 years), 150 of whom are expected to have a current diagnosis of an anxiety and/or depressive disorder. Comprehensive clinical and neuropsychological evaluations and longitudinal clinical data are also being collected. This article provides an overview of task functional magnetic resonance imaging (fMRI) protocols and preliminary findings (N = 140), as well as clinical and neuropsychological characterization of adolescents. Data collection is ongoing for an additional 85 adolescents, most of whom are expected to have a diagnosis of an anxiety and/or depressive disorder. Data from the first 140 adolescents are projected for public release through the National Institutes of Health Data Archive (NDA) with the timing of this manuscript. All other data will be made publicly-available through the NDA at regularly scheduled intervals. This article is intended to serve as an introduction to this project as well as a reference for those seeking to clinical, neurocognitive, and task fMRI data from this public resource.

Electrophysiological evidence of attentional biases in social anxiety disorder.

BACKGROUND: Previous studies investigating attentional biases in social anxiety disorder (SAD) have yielded mixed results. Recent event-related potential (ERP) studies using the dot-probe paradigm in non-anxious participants have shown that the P1 component is sensitive to visuospatial attention towards emotional faces. We used a dot-probe task in conjunction with high-density ERPs and source localization to investigate attentional biases in SAD. METHOD: Twelve SAD and 15 control participants performed a modified dot-probe task using angry-neutral and happy-neutral face pairs. The P1 component elicited by face pairs was analyzed to test the hypothesis that SAD participants would display early hypervigilance to threat-related cues. The P1 component to probes replacing angry, happy or neutral faces was used to evaluate whether SAD participants show either sustained hypervigilance or decreased visual processing of threat-related cues at later processing stages. RESULTS: Compared to controls, SAD participants showed relatively (a) potentiated P1 amplitudes and fusiform gyrus (FG) activation to angry-neutral versus happy-neutral face pairs; (b) decreased P1 amplitudes to probes replacing emotional (angry and happy) versus neutral faces; and (c) higher sensitivity (d') to probes following angry-neutral versus happy-neutral face pairs. SAD participants also showed significantly shorter reaction times (RTs) to probes replacing angry versus happy faces, but no group differences emerged for RT. CONCLUSIONS: The results provide electrophysiological support for early hypervigilance to angry faces in SAD with involvement of the FG, and reduced visual processing of emotionally salient locations at later stages of information processing, which might be a manifestation of attentional avoidance.

[Saving psychoanalysis. At any cost?]. / Die Psychoanalyse soll gerettet werden. Mit allen Mitteln?

Although long-term psychoanalysis has been criticized due to lacking scientific efficacy, a meta-analysis by Leichsenring and Rabung concludes it is even more effective than other psychological interventions and follows a dose:response relationship (i.e. the longer the better). We reassessed this meta-analysis and find that its conclusions are not warranted. First, major parts of them are not based on the included randomised clinical trials (11) but on observational studies (12), which are known to be subject to investigator bias. The definition of long-term psychoanalysis included mainly randomised clinical trials with fewer than 50 treatment sessions, which is untypically short for this kind of intervention. Comparison groups were misclassified (especially the classification "cognitive interventions"). Important disorders were not clearly defined, hindering any interpretation of which treatment is to be indicated. Moreover the authors did not consider the lack of acceptance and attrition rates, nor did they include intention-to-treat data sets. For some of the studies only 45% of samples were included in the meta-analysis. We conclude that a few of the included randomised clinical trials using psychodynamic short-term interventions truly are promising and of high quality; however these do not justify generalizations on long-term psychoanalysis, and the presented meta-analysis is clearly biased.

[Conclusion: How should a meaningful meta-analysis of long-term psychodynamic psychotherapy be designed?]. / Schlusswort: Wie müsste eine aussagekräftige Metaanalyse zur psychodynamischen Langzeittherapie gestaltet sein?

In their answer to our critical evaluation of their meta-analysis about long-term psychodynamic psychotherapy (LTPP), Leichsenring and Rabung claim that all our critical points could be rejected. This is surprising, as the authors already confirmed different shortcomings of their analysis. Our major criticism is that the meta-analysis is based on very few high-quality studies (including follow-up assessments), but on many studies with poor quality and/or observational studies resulting in serious publication bias. Neither the treatment of interest (LTPP) nor the target group is sufficiently circumscribed, but the very few studies are misinterpreted as if confirming efficacy of all psychodynamic interventions for nearly all psychiatric groups. Superior efficacy over other effective psychological interventions is mentioned, although not justified by data. Patient selection bias which is a major issue in long-term treatments is not addressed adequately and led to erroneous conclusions that the more treatment people receive, the higher the benefit. To conclude, the authors try to suggest far-reaching conclusions which are only based on a few studies with poor data quality.

D-cycloserine to enhance extinction of cue-elicited craving for alcohol: a translational approach.

Cue-elicited craving for alcohol is well established but extinction-based treatment to extinguish this response has generated only modest positive outcomes in clinical trials. Basic and clinical research suggests that D-cycloserine (DCS) enhances extinction to fear cues under certain conditions. However, it remains unclear whether DCS would also accelerate extinction of cue-elicited craving for alcohol. The goal of the current study was to examine whether, compared with placebo (PBO), DCS enhanced extinction of cue-elicited craving among treatment-seeking individuals with alcohol use disorders (AUDs). Participants were administered DCS (50 mg) or PBO 1 h before an alcohol extinction paradigm in a simulated bar environment on two occasions. The extinction procedures occurred 1 week apart and were fully integrated into outpatient treatment. Subjective craving for alcohol was the primary variable of interest. Follow-up cue reactivity sessions were conducted 1 week and 3 weeks later to ascertain persisting DCS effects. Drinking outcomes and tolerability were also examined. DCS was associated with augmented reductions in alcohol craving to alcohol cues during the first extinction session and these effects persisted through all subsequent sessions, suggesting facilitation of extinction. Participants in the DCS condition reported significant short-term reductions in drinking, although these did not persist to follow-up, and found the medication highly tolerable. These findings provide evidence that DCS enhances extinction of cue-elicited craving for alcohol in individuals with AUDs in the context of outpatient treatment. The potential clinical utility of DCS is discussed, including methodological considerations and context-dependent learning.

Pretreatment attrition in a comparative treatment outcome study on panic disorder.

OBJECTIVE: Whereas the fact of attrition during the course of treatment is well documented, little is known about the factors that affect sample selection before the beginning of a study ("pretreatment attrition"). The present study reports on the degree and sources of pretreatment attrition at two sites of a multicenter study on panic disorder that compared treatment outcomes for imipramine and cognitive behavior therapy. METHOD: Data were collected at two clinical research sites, one with a pharmacological treatment orientation (N = 420) and one with a psychosocial treatment orientation (N = 208). RESULTS: The main source of pretreatment attrition was participant refusal. At both research sites, eligible patients most often refused participation because they were either unwilling to start treatment with imipramine (30.6% and 47.4%, respectively) or discontinue their current medication (22.6% and 35.1%, respectively). CONCLUSIONS: Results from comparative treatment outcome studies are limited not only to people who meet the study criteria but also to those who are willing to begin a medication treatment and discontinue their current medication.

Information processing in social phobia: a critical review.

This review critically discusses the empirical evidence for information-processing biases in social phobia. Distortions in attention, interpretation, and memory processes are analyzed as they apply to individuals with social phobia. The literature provides evidence for a specific attentional bias towards socially threatening stimuli and a specific interpretational/judgment bias towards self-relevant social information. However, there is little evidence to suggest that social phobia is associated with a memory bias for socially threatening stimuli. Furthermore, the relationship between the empirical evidence from information processing studies and the cognitive model of social phobia by Clark and Wells (1995) will be discussed.

Psychophysiological differences between subgroups of social phobia.

Individuals meeting criteria of the revised third edition of Diagnostic and Statistical Manual for Mental Disorders (American Psychiatric Association, 1987) for social phobia with a fear of speaking in front of people were subdivided into those with (n = 16) and without (n = 14) avoidant personality disorder (APD). These individuals and nonanxious controls (n = 22) spoke in front of a small audience while speaking time, subjective anxiety, fearful thoughts, and electrocardiographic and respiratory measures were recorded. Controls spoke for longer than either social phobia group. Those with social phobia and APD reported more subjective anxiety and more fear cognitions than the other two groups; phobic individuals without APD showed greater heart rates in the phobic situation than either social phobics with APD or controls. The latter two groups did not differ in heart rate. These results indicate incongruent subjective and heart rate responses to the feared situation. A similar pattern of results was found when participants were divided into generalized and specific social phobia groups.

Self-focused attention before and after treatment of social phobia.

It has been hypothesized that effective psychological treatment for social phobia changes the person's representation of the self in a more positive direction. In order to test this hypothesis, we analyzed 506 thoughts that were endorsed by 23 social phobic individuals while anticipating socially stressful situations before and after exposure therapy. Treatment efficacy was assessed with the Social Phobia and Anxiety Inventory (SPAI) [Turner, S. M., Beidel, D. C., Dancu, C. V., & Stanley M. A. (1989) An empirically derived inventory to measure social fears and anxiety: the Social Phobia and Anxiety Inventory. Psychological Assessment, 1, 35-40)]. Subjects endorsed significantly fewer negative self-focused thoughts after treatment (on average 8.7% of the thoughts) than before treatment (26.5%, p < 0.005). These changes were highly correlated with pre-post difference scores in the social phobia subscale of the SPAI (r = 0.74, p < 0.0001). Implications of the results for the cognitive model of social phobia will be discussed.

Conditioning theory: a model for the etiology of public speaking anxiety?

To study the etiology of public speaking anxiety (speech phobia), 30 Ss with the fear of public speaking, and 24 controls without this fear were asked about past public speaking experiences, their beliefs about the main reason for their phobia, and their concerns in the feared situation. All speech phobics met the DSM-III-R criteria for social phobia. Results showed that traumatic external events, vicarious and informational learning--the causes for phobia that fit in best with Rachman's conditioning theory--were notably uncommon among these phobics, who attributed their fear most often to panic attacks. Yet it was not clear whether panic attacks were causes or consequences of phobia.

Speech disturbances and gaze behavior during public speaking in subtypes of social phobia.

Twenty-four social phobics with public speaking anxiety and 25 nonphobic individuals (controls) gave a speech in front of two people. Subjective anxiety, gaze behavior, and speech disturbances were assessed. Based on subjects' fear ratings of social situations, phobics and controls were divided into the generalized and nongeneralized subtype. Results showed that generalized phobics reported the most, and nongeneralized controls the least anxiety during public speaking. All subjects had longer and more frequent eye contact when delivering a speech than when talking with an experimenter or sitting in front of an audience. Phobics showed more filled pauses, had longer silent pauses, paused more frequently, and spent more time pausing than controls when giving a speech. Generalized phobics spent more time pausing during their speech than the other subgroups (nongeneralized controls, generalized controls, and nongeneralized phobics). These results suggest that generalized phobics tended to shift attentional resources from speech production to other cognitive tasks.

How specific are specific phobias?

To study the generality of fears among specific phobic individuals and controls, 31 individuals with a DSM-IV diagnosis of specific phobia (natural environmental type: n = 13; blood-injection-injury type: n = 10; and situational type: n = 8) and 33 never mentally ill control subjects participated in an interview and questionnaire study. Based on subjects' fear ratings on the Fear Survey Schedule, subjects were classified as either positive or negative with regard to fear categories that correspond to the five diagnostic subtypes of specific phobia. Phobics showed overall a more generalized form of fear than controls. Furthermore, situational fears were more common among specific phobics who did not meet criteria for specific phobia, situational type, than among controls. These results add to the literature on the functional relationship among different fears and suggest that specific phobias are not as "specific" as is implied by the current diagnostic system.

An instrument to assess self-statements during public speaking: scale development and preliminary psychometric properties.

Public speaking is the most commonly reported fearful social situation. Although a number of contemporary theories emphasize the importance of cognitive processes in social anxiety, there is no instrument available to assess fearful thoughts experienced during public speaking. The Self-Statements During Public Speaking (SSPS) scale is a 10-item questionnaire consisting of two 5-item subscales, the "Positive Self-Statements" (SSPS-P) and the "Negative Self-Statements" subscale (SSPS-N). Four studies report on the development and the preliminary psychometric properties of this instrument.