Impact of cardiac interoception cues and confidence on voluntary decisions to make or withhold action in an intentional inhibition task

Interoceptive signals concerning the internal physiological state of the body influence motivational feelings and action decisions. Cardiovascular arousal may facilitate inhibition to mitigate risks of impulsive actions. Baroreceptor discharge at ventricular systole underpins afferent signalling of cardiovascular arousal. In a modified Go/NoGo task, decisions to make or withhold actions on ‘Choose’ trials were not influenced by cardiac phase, nor individual differences in heart rate variability. However, cardiac interoceptive awareness and insight predicted how frequently participants chose to act, and their speed of action: Participants with better awareness and insight tended to withhold actions and respond slower, while those with poorer awareness and insight tended to execute actions and respond faster. Moreover, self-reported trait urgency correlated negatively with intentional inhibition rates. These findings suggest that lower insight into bodily signals is linked to urges to move the body, putatively by engendering noisier sensory input into motor decision processes eliciting reactive behaviour

Interoceptive training to target anxiety in autistic adults (ADIE): a single-center, superiority randomized controlled trial

Background This trial tested if a novel therapy, Aligning Dimensions of Interoceptive Experience (ADIE), reduces anxiety in autistic adults. ADIE targets the association of anxiety with mismatch between subjective and behavioral measures of an individual's interoceptive sensitivity to bodily signals, including heartbeats. Methods In this superiority randomized controlled trial, autistic adults (18–65 years) from clinical and community settings in Southern England were randomly assigned (1:1) to receive six sessions of ADIE or an active ‘exteroceptive’ control therapy (emotional prosody identification). Researchers conducting outcome assessments were blind to allocation. ADIE combines two modified heartbeat detection tasks with performance feedback and physical activity manipulation that transiently increases cardiac arousal. Participants were followed-up one-week (T1) and 3-months post-intervention (T2). The primary outcome was Spielberger Trait Anxiety Score (STAI-T) at T2. Outcomes were assessed on an intention-to-treat basis using multiple imputation for dealing with missing values. This trial was registered at International Standard Randomized Controlled Trial Registry, ISRCTN14848787. Findings Between July 01, 2017, and December 31, 2019, 121 participants were randomly allocated to ADIE (n = 61) or prosody (n = 60) intervention groups. Data at T1 was provided by 85 (70%) participants (46 [75%] ADIE; 39 [65%] prosody). Data at T2 was provided by 61 (50%) participants (36 [59%] ADIE; 25 [42%] prosody). One adverse event (cardiac anxiety following ADIE) was recorded. A statistically significant group effect of ADIE on trait anxiety continued at T2 (estimated mean difference 3•23 [95% CI 1•13 to 5•29]; d = 0•30 [95% CI 0•09 to 0•51]; p = 0•005) with 31% of ADIE group participants meeting trial criteria for recovery (compared to 16% in the control group). Interpretation ADIE can reduce anxiety in autistic adults, putatively improving regulatory control over internal stimuli. With little reliance on language and emotional insight, ADIE may constitute an inclusive intervention

Amplified engagement of prefrontal cortex during control of voluntary action in Tourette syndrome

Tourette syndrome is characterized by ‘unvoluntary’ tics, which are compulsive, yet often temporarily suppressible. The inferior frontal gyrus is implicated in motor control, including inhibition of pre-potent actions through influences on downstream subcortical and motor regions. Although tic suppression in Tourette syndrome also engages the inferior frontal gyrus, it is unclear whether such prefrontal control of action is also dysfunctional: Tic suppression studies do not permit comparison with control groups, and neuroimaging studies of motor inhibition can be confounded by the concurrent expression or suppression of tics. Here, patients with Tourette syndrome were directly compared to control participants when performing an intentional inhibition task during functional MRI. Tic expression was recorded throughout for removal from statistical models. Participants were instructed to make a button press in response to Go cues, withhold responses to NoGo cues, and decide whether to press or withhold to ‘Choose’ cues. Overall performance was similar between groups, for both intentional inhibition rates (% Choose-Go) and reactive NoGo inhibition commission errors. A subliminal face prime elicited no additional effects on intentional or reactive inhibition. Across participants, the task activated prefrontal and motor cortices and subcortical nuclei, including pre-supplementary motor area, inferior frontal gyrus, insula, caudate nucleus, thalamus and primary motor cortex. In Tourette syndrome, activity was elevated in the inferior frontal gyrus, insula and basal ganglia, most notably within the right inferior frontal gyrus during voluntary action and inhibition (Choose-Go and Choose-NoGo), and reactive inhibition (NoGo-correct). Anatomically, the locus of this inferior frontal gyrus hyperactivation during control of voluntary action matched that previously reported for tic suppression. In Tourette syndrome, activity within the caudate nucleus was also enhanced during both intentional (Choose-NoGo) and reactive (NoGo-correct) inhibition. Strikingly, despite the absence of overt motor behaviour, primary motor cortex activity increased in patients with Tourette syndrome but decreased in controls during both reactive and intentional inhibition. Additionally, severity of premonitory sensations scaled with functional connectivity of the pre-supplementary motor area to the caudate nucleus, globus pallidus and thalamus when choosing to respond (Choose-Go). Together, these results suggest that patients with Tourette syndrome use equivalent prefrontal mechanisms to suppress tics and withhold non-tic actions, but require greater inferior frontal gyrus engagement than controls to overcome motor drive from hyperactive downstream regions, notably primary motor cortex. Moreover, premonitory sensations may cue midline motor regions to generate tics through interactions with the basal ganglia

Voice hearing in borderline personality disorder across perceptual, subjective, and neural dimensions

BACKGROUND: Auditory verbal hallucinations (AVH) commonly occur in the context of borderline personality disorder (BPD) yet remain poorly understood. AVH are often perceived by patients with BPD as originating from inside the head and hence viewed clinically as "pseudohallucinations," but they nevertheless have a detrimental impact on well-being. METHODS: The current study characterized perceptual, subjective, and neural expressions of AVH by using an auditory detection task, experience sampling and questionnaires, and functional neuroimaging, respectively. RESULTS: Perceptually, reported AVH correlated with a bias for reporting the presence of a voice in white noise. Subjectively, questionnaire measures indicated that AVH were significantly distressing and persecutory. In addition, AVH intensity, but not perceived origin (i.e., inside vs outside the head), was associated with greater concurrent anxiety. Neurally, fMRI of BPD participants demonstrated that, relative to imagining or listening to voices, periods of reported AVH induced greater blood oxygenation level-dependent activity in anterior cingulate and bilateral temporal cortices (regional substrates for language processing). AVH symptom severity was associated with weaker functional connectivity between anterior cingulate and bilateral insular cortices. CONCLUSION: In summary, our results indicate that AVH in participants with BPD are (1) underpinned by aberrant perceptual-cognitive mechanisms for signal detection, (2) experienced subjectively as persecutory and distressing, and (3) associated with distinct patterns of neural activity that inform proximal mechanistic understanding. Our findings are like analogous observations in patients with schizophrenia and validate the clinical significance of the AVH experience in BPD, often dismissed as "pseudohallucinations." These highlight a need to reconsider this experience as a treatment priority

Revealing hidden species distribution with pheromones: the case of Synanthedon vespiformis (Lepidoptera: Sesiidae) in Sweden

Synanthedon vespiformis L. (Lepidoptera: Sesiidae) is considered a rare insect in Sweden, discovered in 1860, with only a few observations recorded until a sex pheromone attractant became available recently. This study details a national survey conducted using pheromones as a sampling method for this species. Through pheromone trapping we captured 439 specimens in Southern Sweden at 77 sites, almost tripling the number of previously reported records for this species. The results suggest that S. vespiformis is truly a rare species with a genuinely scattered distribution, but can be locally abundant. Habitat analyses were conducted in order to test the relationship between habitat quality and the number of individuals caught. In Sweden, S. vespiformis is thought to be associated with oak hosts, but our attempts to predict its occurrence by the abundance of oaks yielded no significant relationships. We therefore suggest that sampling bias and limited knowledge on distribution may have led to the assumption that this species is primarily reliant on oaks in the northern part of its range, whereas it may in fact be polyphagous, similar to S. vespiformis found as an agricultural pest in Central and Southern Europe. We conclude that pheromones can massively enhance sampling potential for this and other rare lepidopteran species. Large-scale pheromone-based surveys provide a snapshot of true presences and absences across a considerable part of a species national distribution range, and thus for the first time provide a viable means of systematically assessing changes in distribution over time with high spatiotemporal resolution

Horizontal transfer of an adaptive chimeric photoreceptor from bryophytes to ferns

Ferns are well known for their shade-dwelling habits. Their ability to thrive under low-light conditions has been linked to the evolution of a novel chimeric photoreceptor-neochrome-that fuses red-sensing phytochrome and blue-sensing phototropin modules into a single gene, thereby optimizing phototropic responses. Despite being implicated in facilitating the diversification of modern ferns, the origin of neochrome has remained a mystery. We present evidence for neochrome in hornworts (a bryophyte lineage) and demonstrate that ferns acquired neochrome from hornworts via horizontal gene transfer (HGT). Fern neochromes are nested within hornwort neochromes in our large-scale phylogenetic reconstructions of phototropin and phytochrome gene families. Divergence date estimates further support the HGT hypothesis, with fern and hornwort neochromes diverging 179 Mya, long after the split between the two plant lineages (at least 400 Mya). By analyzing the draft genome of the hornwort Anthoceros punctatus, we also discovered a previously unidentified phototropin gene that likely represents the ancestral lineage of the neochrome phototropin module. Thus, a neochrome originating in hornworts was transferred horizontally to ferns, where it may have played a significant role in the diversification of modern ferns

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin