Formal Innovations to Clinical Cognitive Science and Assessment

Mathematical modeling is increasingly driving progress in clinical cognitive science and assessment. Mathematical modeling is essential for detecting certain effects of psychopathology – mental disturbance--through comprehensive understanding of tell-tale cognitive variables such as workload capacity and efficiency in using capacity, and their contrast under quantitative measurement. The research paradigm guiding this formal clinical science is outlined. An example using a distinctive cognitive abnormality in schizophrenia – taking longer to cognitively represent encountered stimulation – provides an illustration of a quantitative framework for studying intricate mental health-impairing phenomena. Added benefits of formal developments, among others, include symptom description and prediction, new methods of cognitive- and statistical-science grounded clinical assessment over time, both for individuals and treatment regimens, and refinement of the cognitive-function side of clinical functional neuroimaging

Moral wounds run deep: exaggerated midbrain functional network connectivity across the default mode network in posttraumatic stress disorder

Background: A moral injury occurs when a deeply held moral code has been violated, and it can lead to the development of symptoms of posttraumatic stress disorder (PTSD). However, the neural correlates that differentiate moral injury and PTSD remain largely unknown. Intrinsic connectivity networks such as the default mode network (DMN) appear to be altered in people with PTSD who have experienced moral injury. However, brainstem, midbrain and cerebellar systems are rarely integrated into the intrinsic connectivity networks; this is a critical oversight, because these systems display marked differences in people with PTSD and are thought to underlie strong moral emotions such as shame, guilt and betrayal. Methods: We conducted an independent component analysis on data generated during script-driven memory recall of moral injury in participants with military-or law enforcement–related PTSD (n = 28), participants with civilian-related PTSD (n = 28) and healthy controls exposed to a potentially morally injurious event (n = 18). We conducted group-wise comparisons of functional network connectivity differences across a DMN-correlated independent component, with a particular focus on brainstem, midbrain and cerebellar systems. Results: We found stronger functional network connectivity in the midbrain periaqueductal grey (t71 = 4.95, pFDR = 0.028, k = 39) and cerebellar lobule IX (t71 = 4.44, pFDR = 0.046, k = 49) in participants with civilian-related PTSD as compared to healthy controls. We also found a trend toward stronger functional network connectivity in the midbrain periaqueductal grey (t71 = 4.22, pFDR = 0.076, k = 60) in participants with military-or law enforcement–related PTSD as compared to healthy controls. Limitations: The significant clusters were large, but resolution is generally lower for subcortical structures. Conclusion: In PTSD, the DMN appears to be biased toward lower-level, midbrain systems, which may drive toxic shame and related moral emotions that are common in PTSD, highlighting the depth at which moral injuries are represented neurobiologically

Differential mechanisms of posterior cingulate cortex downregulation and symptom decreases in posttraumatic stress disorder and healthy individuals using real-time fMRI neurofeedback

Background: Intrinsic connectivity networks, including the default mode network (DMN), are frequently disrupted in individuals with posttraumatic stress disorder (PTSD). The posterior cingulate cortex (PCC) is the main hub of the posterior DMN, where the therapeutic regulation of this region with real-time fMRI neurofeedback (NFB) has yet to be explored. Methods: We investigated PCC downregulation while processing trauma/stressful words over 3 NFB training runs and a transfer run without NFB (total n = 29, PTSD n = 14, healthy controls n = 15). We also examined the predictive accuracy of machine learning models in classifying PTSD versus healthy controls during NFB training. Results: Both the PTSD and healthy control groups demonstrated reduced reliving symptoms in response to trauma/stressful stimuli, where the PTSD group additionally showed reduced symptoms of distress. We found that both groups were able to downregulate the PCC with similar success over NFB training and in the transfer run, although downregulation was associated with unique within-group decreases in activation within the bilateral dmPFC, bilateral postcentral gyrus, right amygdala/hippocampus, cingulate cortex, and bilateral temporal pole/gyri. By contrast, downregulation was associated with increased activation in the right dlPFC among healthy controls as compared to PTSD. During PCC downregulation, right dlPFC activation was negatively correlated to PTSD symptom severity scores and difficulties in emotion regulation. Finally, machine learning algorithms were able to classify PTSD versus healthy participants based on brain activation during NFB training with 80% accuracy. Conclusions: This is the first study to investigate PCC downregulation with real-time fMRI NFB in both PTSD and healthy controls. Our results reveal acute decreases in symptoms over training and provide converging evidence for EEG-NFB targeting brain networks linked to the PCC

Predicting patterns of service utilization within children\u27s mental health agencies

Background: Some children with mental health (MH) problems have been found to receive ongoing care, either continuously or episodically. We sought to replicate patterns of MH service use over extended time periods, and test predictors of these patterns. Methods: Latent class analyses were applied to 4 years of visit data from five MH agencies and nearly 6000 children, 4-to 13-years-old at their first visit. Results: Five patterns of service use were identified, replicating previous findings. Overall, 14% of cases had two or more episodes of care and 23% were involved for more than 2 years. Most children (53%) were seen for just a few visits within a few months. Two patterns represented cases with two or more episodes of care spanning multiple years. In the two remaining patterns, children tended to have just one episode of care, but the number of sessions and length of involvement varied. Using discriminant function analyses, we were able to predict with just over 50% accuracy children\u27s pattern of service use. Severe externalizing behaviors, high impairment, and high family burden predicted service use patterns with long durations of involvement and frequent visits. Conclusions: Optimal treatment approaches for children seen for repeated episodes of care or for care lasting multiple years need to be developed. Children with the highest level of need (severe pathology, impairment, and burden) are probably best served by providing high intensity services at the start of care

Search for charginos in e+e- interactions at sqrt(s) = 189 GeV

An update of the searches for charginos and gravitinos is presented, based on a data sample corresponding to the 158 pb^{-1} recorded by the DELPHI detector in 1998, at a centre-of-mass energy of 189 GeV. No evidence for a signal was found. The lower mass limits are 4-5 GeV/c^2 higher than those obtained at a centre-of-mass energy of 183 GeV. The (\mu,M_2) MSSM domain excluded by combining the chargino searches with neutralino searches at the Z resonance implies a limit on the mass of the lightest neutralino which, for a heavy sneutrino, is constrained to be above 31.0 GeV/c^2 for tan(beta) \geq 1.Comment: 22 pages, 8 figure

Search for composite and exotic fermions at LEP 2

A search for unstable heavy fermions with the DELPHI detector at LEP is reported. Sequential and non-canonical leptons, as well as excited leptons and quarks, are considered. The data analysed correspond to an integrated luminosity of about 48 pb^{-1} at an e^+e^- centre-of-mass energy of 183 GeV and about 20 pb^{-1} equally shared between the centre-of-mass energies of 172 GeV and 161 GeV. The search for pair-produced new leptons establishes 95% confidence level mass limits in the region between 70 GeV/c^2 and 90 GeV/c^2, depending on the channel. The search for singly produced excited leptons and quarks establishes upper limits on the ratio of the coupling of the excited fermio

Search for lightest neutralino and stau pair production in light gravitino scenarios with stau NLSP

Promptly decaying lightest neutralinos and long-lived staus are searched for in the context of light gravitino scenarios. It is assumed that the stau is the next to lightest supersymmetric particle (NLSP) and that the lightest neutralino is the next to NLSP (NNLSP). Data collected with the Delphi detector at centre-of-mass energies from 161 to 183 \GeV are analysed. No evidence of the production of these particles is found. Hence, lower mass limits for both kinds of particles are set at 95% C.L.. The mass of gaugino-like neutralinos is found to be greater than 71.5 GeV/c^2. In the search for long-lived stau, masses less than 70.0 to 77.5 \GeVcc are excluded for gravitino masses from 10 to 150 \eVcc . Combining this search with the searches for stable heavy leptons and Minimal Supersymmetric Standard Model staus a lower limit of 68.5 \GeVcc may be set for the stau mas

Hadronization properties of b quarks compared to light quarks in e+e- -> q qbar from 183 to 200 GeV

The DELPHI detector at LEP has collected 54 pb^{-1} of data at a centre-of-mass energy around 183 GeV during 1997, 158 pb^{-1} around 189 GeV during 1998, and 187 pb^{-1} between 192 and 200 GeV during 1999. These data were used to measure the average charged particle multiplicity in e+e- -> b bbar events, _{bb}, and the difference delta_{bl} between _{bb} and the multiplicity, _{ll}, in generic light quark (u,d,s) events: delta_{bl}(183 GeV) = 4.55 +/- 1.31 (stat) +/- 0.73 (syst) delta_{bl}(189 GeV) = 4.43 +/- 0.85 (stat) +/- 0.61 (syst) delta_{bl}(200 GeV) = 3.39 +/- 0.89 (stat) +/- 1.01 (syst). This result is consistent with QCD predictions, while it is inconsistent with calculations assuming that the multiplicity accompanying the decay of a heavy quark is independent of the mass of the quark itself.Comment: 13 pages, 2 figure

Neuroimaging-based classification of PTSD using data-driven computational approaches: A multisite big data study from the ENIGMA-PGC PTSD consortium

Background: Recent advances in data-driven computational approaches have been helpful in devising tools to objectively diagnose psychiatric disorders. However, current machine learning studies limited to small homogeneous samples, different methodologies, and different imaging collection protocols, limit the ability to directly compare and generalize their results. Here we aimed to classify individuals with PTSD versus controls and assess the generalizability using a large heterogeneous brain datasets from the ENIGMA-PGC PTSD Working group. Methods: We analyzed brain MRI data from 3,477 structural-MRI; 2,495 resting state-fMRI; and 1,952 diffusion-MRI. First, we identified the brain features that best distinguish individuals with PTSD from controls using traditional machine learning methods. Second, we assessed the utility of the denoising variational autoencoder (DVAE) and evaluated its classification performance. Third, we assessed the generalizability and reproducibility of both models using leave-one-site-out cross-validation procedure for each modality. Results: We found lower performance in classifying PTSD vs. controls with data from over 20 sites (60 % test AUC for s-MRI, 59 % for rs-fMRI and 56 % for D-MRI), as compared to other studies run on single-site data. The performance increased when classifying PTSD from HC without trauma history in each modality (75 % AUC). The classification performance remained intact when applying the DVAE framework, which reduced the number of features. Finally, we found that the DVAE framework achieved better generalization to unseen datasets compared with the traditional machine learning frameworks, albeit performance was slightly above chance. Conclusion: These results have the potential to provide a baseline classification performance for PTSD when using large scale neuroimaging datasets. Our findings show that the control group used can heavily affect classification performance. The DVAE framework provided better generalizability for the multi-site data. This may be more significant in clinical practice since the neuroimaging-based diagnostic DVAE classification models are much less site-specific, rendering them more generalizable

Greater involvement of action simulation mechanisms in emotional vs cognitive empathy

Empathy is crucial for successful interpersonal interactions, and it is impaired in many psychiatric and neurological disorders. Action-perception matching, or action simulation mechanisms, has been suggested to facilitate empathy by supporting the simulation of perceived experience in others. However, this remains unclear, and the involvement of the action simulation circuit in cognitive empathy (the ability to adopt another\u27s perspective) vs emotional empathy (the capacity to share and react affectively to another\u27s emotional experience) has not been quantitatively compared. Presently, healthy adults completed a classic cognitive empathy task (false belief), an emotional empathy task and an action simulation button-pressing task during functional magnetic resonance imaging. Conjunction analyses revealed common recruitment of the inferior frontal gyrus (IFG), thought to be critical for action-perception matching, during both action simulation and emotional, but not cognitive, empathy. Furthermore, activation was significantly greater in action simulation regions in the left IFG during emotional vs cognitive empathy, and activity in this region was positively correlated with mean feeling ratings during the emotional empathy task. These findings provide evidence for greater involvement of action simulation mechanisms in emotional than cognitive empathy. Thus, the action simulation circuit may be an important target for delineating the pathophysiology of disorders featuring emotional empathy impairments