Assessing the predictors of adaptive and maladaptive Covid-19 preventive behaviours: an application of protection motivation theory.

Despite the high death toll of the COVID-19 pandemic, reported rates of adherence to adaptive preventive health behaviours during the early wave of the pandemic were suboptimal for reducing the risk of disease spread. Additionally, some have adopted practices with the intention of preventing infection that have harmful consequences. Protection Motivation Theory (PMT), consisting of perceived vulnerability, severity, response efficacy, and self-efficacy, has been used to predict intentions to engage in behaviours in past pandemics, and can be extended to the COVID-19 outbreak. Three hundred and thirty-three American adults completed a survey in May 2020 through Amazon's Mechanical Turk. Ten behaviours recommended by the CDC and WHO and two 'maladaptive' behaviours presented in the media were selected for investigation. Binary logistic regressions were conducted to assess the impacts of demographic variables and PMT constructs on behaviour frequency. Perceived severity and vulnerability were not significant predictors of behaviour frequency. Behaviour specific response efficacy and self-efficacy were significant predictors of 11/12 (odds ratios: 2.70-6.22) and 10/12 (odds ratios: 2.59-4.64) behaviours, respectively. Age, gender, education, political ideology, perceived severity, and perceived vulnerability were generally unimportant predictors. Beliefs about the effectiveness of the behaviour and one's ability to carry out that behaviour consistently seem to be more important in predicting how often someone engages in that behaviour than the perceived dangerousness of COVID-19 and one's believed susceptibility to infection. These results suggest that interventions trying to modulate the likelihood of engaging in preventive behaviours should focus on the effectiveness of these behaviours in reducing risk of spread and the individual's ability to engage in these behaviours frequently rather than the dangerousness of the COVID-19 pandemic and the individual's risk of becoming infected.

Technology-Based Approaches for Supporting Perinatal Mental Health.

PURPOSE OF REVIEW: This review explores advances in the utilization of technology to address perinatal mood and anxiety disorders (PMADs). Specifically, we sought to assess the range of technologies available, their application to PMADs, and evidence supporting use. RECENT FINDINGS: We identified a variety of technologies with promising capacity for direct intervention, prevention, and augmentation of clinical care for PMADs. These included wearable technology, electronic consultation, virtual and augmented reality, internet-based cognitive behavioral therapy, and predictive analytics using machine learning. Available evidence for these technologies in PMADs was almost uniformly positive. However, evidence for use in PMADs was limited compared to that in general mental health populations. Proper attention to PMADs has been severely limited by issues of accessibility, affordability, and patient acceptance. Increased use of technology has the potential to address all three of these barriers by facilitating modes of communication, data collection, and patient experience.

Mapping migraine to a common brain network.

Inconsistent findings from migraine neuroimaging studies have limited attempts to localize migraine symptomatology. Novel brain network mapping techniques offer a new approach for linking neuroimaging findings to a common neuroanatomical substrate and localizing therapeutic targets. In this study, we attempted to determine whether neuroanatomically heterogeneous neuroimaging findings of migraine localize to a common brain network. We used meta-analytic coordinates of decreased grey matter volume in migraineurs as seed regions to generate resting state functional connectivity network maps from a normative connectome (n = 1000). Network maps were overlapped to identify common regions of connectivity across all coordinates. Specificity of our findings was evaluated using a whole-brain Bayesian spatial generalized linear mixed model and a region of interest analysis with comparison groups of chronic pain and a neurologic control (Alzheimer's disease). We found that all migraine coordinates (11/11, 100%) were negatively connected (t ≥ ±7, P < 10-6 family-wise error corrected for multiple comparisons) to a single location in left extrastriate visual cortex overlying dorsal V3 and V3A subregions. More than 90% of coordinates (10/11) were also positively connected with bilateral insula and negatively connected with the hypothalamus. Bayesian spatial generalized linear mixed model whole-brain analysis identified left V3/V3A as the area with the most specific connectivity to migraine coordinates compared to control coordinates (voxel-wise probability of ≥90%). Post hoc region of interest analyses further supported the specificity of this finding (ANOVA P = 0.02; pairwise t-tests P = 0.03 and P = 0.003, respectively). In conclusion, using coordinate-based network mapping, we show that regions of grey matter volume loss in migraineurs localize to a common brain network defined by connectivity to visual cortex V3/V3A, a region previously implicated in mechanisms of cortical spreading depression in migraine. Our findings help unify migraine neuroimaging literature and offer a migraine-specific target for neuromodulatory treatment.

'Expedited Interhemispheric Inhibition': A Simple Method to Collect Additional IHI Data in the Same Amount of Time.

Interhemispheric inhibition (IHI) is a dual-site TMS protocol measuring inhibitory interactions between the primary motor cortices (M1). IHI is performed by applying an initial conditioning stimulus followed by a test stimulus to the contralateral M1. Conventionally, the response in the contralateral hand to the conditioning TMS pulse is either not measured, or discarded. The aim of this experiment was to investigate whether MEPs evoked from these conditioning stimuli can be utilised as non-conditioned, or 'baseline', responses, and therefore expedite IHI data collection. We evaluated short-latency (10 ms) and long-latency (40 ms) IHI bidirectionally in 14 healthy participants. There was no difference in MEP amplitudes evoked by conventional single TMS pulses randomly inserted into IHI blocks, and those evoked by the conditioning stimulus. Nor was there any significant difference in IHI magnitude when using single pulse MEPs or conditioning stimulus MEPs as baseline responses. The utilisation of conditioning stimuli dispenses with the need to insert dedicated single TMS pulses into IHI blocks, allowing for additional IHI data to be collected in the same amount of time.

Cortical lesions causing loss of consciousness are anticorrelated with the dorsal brainstem.

Brain lesions can provide unique insight into the neuroanatomical substrate of human consciousness. For example, brainstem lesions causing coma map to a specific region of the tegmentum. Whether specific lesion locations outside the brainstem are associated with loss of consciousness (LOC) remains unclear. Here, we investigate the topography of cortical lesions causing prolonged LOC (N = 16), transient LOC (N = 91), or no LOC (N = 64). Using standard voxel lesion symptom mapping, no focus of brain damage was associated with LOC. Next, we computed the network of brain regions functionally connected to each lesion location using a large normative connectome dataset (N = 1,000). This technique, termed lesion network mapping, can test whether lesions causing LOC map to a connected brain circuit rather than one brain region. Connectivity between cortical lesion locations and an a priori coma-specific region of brainstem tegmentum was an independent predictor of LOC (B = 1.2, p = .004). Connectivity to the dorsal brainstem was the only predictor of LOC in a whole-brain voxel-wise analysis. This relationship was driven by anticorrelation (negative correlation) between lesion locations and the dorsal brainstem. The map of regions anticorrelated to the dorsal brainstem thus defines a distributed brain circuit that, when damaged, is most likely to cause LOC. This circuit showed a slight posterior predominance and had peaks in the bilateral claustrum. Our results suggest that cortical lesions causing LOC map to a connected brain circuit, linking cortical lesions that disrupt consciousness to brainstem sites that maintain arousal.

Neural function in DCC mutation carriers with and without mirror movements.

OBJECTIVE: Recently identified mutations of the axon guidance molecule receptor gene, DCC, present an opportunity to investigate, in living human brain, mechanisms affecting neural connectivity and the basis of mirror movements, involuntary contralateral responses that mirror voluntary unilateral actions. We hypothesized that haploinsufficient DCC+/- mutation carriers with mirror movements would exhibit decreased DCC mRNA expression, a functional ipsilateral corticospinal tract, greater "mirroring" motor representations, and reduced interhemispheric inhibition. DCC+/- mutation carriers without mirror movements might exhibit some of these features. METHODS: The participants (n = 52) included 13 DCC+/- mutation carriers with mirror movements, 7 DCC+/- mutation carriers without mirror movements, 13 relatives without the mutation or mirror movements, and 19 unrelated healthy volunteers. The multimodal approach comprised quantitative real time polymerase chain reaction, transcranial magnetic stimulation (TMS), functional magnetic resonance imaging (fMRI) under resting and task conditions, and measures of white matter integrity. RESULTS: Mirror movements were associated with reduced DCC mRNA expression, increased ipsilateral TMS-induced motor evoked potentials, increased fMRI responses in the mirroring M1 and cerebellum, and markedly reduced interhemispheric inhibition. The DCC+/- mutation, irrespective of mirror movements, was associated with reduced functional connectivity and white matter integrity. INTERPRETATION: Diverse connectivity abnormalities were identified in mutation carriers with and without mirror movements, but corticospinal effects and decreased peripheral DCC mRNA appeared driven by the mirror movement phenotype. ANN NEUROL 2019;85:433-442.

Network localization of cervical dystonia based on causal brain lesions.

Cervical dystonia is a neurological disorder characterized by sustained, involuntary movements of the head and neck. Most cases of cervical dystonia are idiopathic, with no obvious cause, yet some cases are acquired, secondary to focal brain lesions. These latter cases are valuable as they establish a causal link between neuroanatomy and resultant symptoms, lending insight into the brain regions causing cervical dystonia and possible treatment targets. However, lesions causing cervical dystonia can occur in multiple different brain locations, leaving localization unclear. Here, we use a technique termed 'lesion network mapping', which uses connectome data from a large cohort of healthy subjects (resting state functional MRI, n = 1000) to test whether lesion locations causing cervical dystonia map to a common brain network. We then test whether this network, derived from brain lesions, is abnormal in patients with idiopathic cervical dystonia (n = 39) versus matched controls (n = 37). A systematic literature search identified 25 cases of lesion-induced cervical dystonia. Lesion locations were heterogeneous, with lesions scattered throughout the cerebellum, brainstem, and basal ganglia. However, these heterogeneous lesion locations were all part of a single functionally connected brain network. Positive connectivity to the cerebellum and negative connectivity to the somatosensory cortex were specific markers for cervical dystonia compared to lesions causing other neurological symptoms. Connectivity with these two regions defined a single brain network that encompassed the heterogeneous lesion locations causing cervical dystonia. These cerebellar and somatosensory regions also showed abnormal connectivity in patients with idiopathic cervical dystonia. Finally, the most effective deep brain stimulation sites for treating dystonia were connected to these same cerebellar and somatosensory regions identified using lesion network mapping. These results lend insight into the causal neuroanatomical substrate of cervical dystonia, demonstrate convergence across idiopathic and acquired dystonia, and identify a network target for dystonia treatment.

Parents' Perceptions of Internalizing and Externalizing Features in Childhood OCD.

Although obsessive-compulsive disorder (OCD) has often been characterized as an internalizing disorder, some children with OCD exhibit externalizing behaviors that are specific to their OCD. This study sought to demonstrate that parents perceive both internalizing and externalizing behaviors in childhood OCD by examining the factor structure of the Child Obsessive-Compulsive Externalizing/Internalizing Scale (COCEIS), a parent-report questionnaire intended to measure these constructs. This study also investigated clinical correlates of internalizing and externalizing factors in the COCEIS. A factor analysis of questionnaire responses from 122 parents of youth with OCD revealed both externalizing and internalizing factors in the COCEIS. Externalizing behaviors in childhood OCD were associated with other, co-occurring externalizing behavior problems, while both factors were positively correlated with OCD severity and co-occurring internalizing symptoms. They were positively associated with each other at a trend level, and neither showed a significant relationship with insight. Sixty-two percent of parents endorsed "often" or "always" to at least one externalizing item, though modal responses to items suggested that each individual feature captured by the COCEIS may be relatively uncommon. Mean responses were significantly greater for internalizing items. This study provides evidence for distinct but related externalizing and internalizing behaviors specific to childhood OCD. Treatment for children with OCD presenting with more externalizing behaviors may require a greater emphasis on behavioral parent training and motivational enhancement.

Implementation and Preliminary Outcomes of an Exposure-Based Summer Camp for Pediatric OCD and Anxiety.

Despite the high prevalence of anxiety disorders in children and adolescents and the existence of effective evidence-based treatments for them, access to psychological care remains a major public health concern. Summer camps may provide an effective treatment avenue for youth who might not otherwise have access to care. This study describes the design and implementation of Fear Facers, a semistructured, 5-day, daytime exposure-therapy-based summer camp designed for youth with a primary diagnosis of obsessive-compulsive disorder (OCD), social anxiety, separation anxiety, or a specific phobia. Preliminary data regarding feasibility and patient outcomes is also reported. Among 52 children and adolescents aged 7 to 16 who attended one of six camp sessions between 2018 and 2021, significant reductions in anxiety (d = 0.54) and OCD symptoms (d = 0.57) were observed from pre-camp to immediately post-camp. A subset of campers who were followed for an additional 3 months post-camp (n = 22) showed maintenance of treatment gains. Retention rates for the intervention were high. Our investigation provides further support for the use of a camp-based design for cognitive-behavioral approaches, and may provide a unique setting to maximize elements of inhibitory learning in exposures. We also discuss a number of elements regarding feasibility that need consideration for those hoping to develop similar interventions.

An examination of obsessive-compulsive symptom domains, depression, and quality of life within an online survey sample.

Obsessive-compulsive disorder (OCD) is a heterogeneous and highly impairing disorder that is frequently comorbid with other conditions. Participants in this study were 212 individuals recruited through Mechanical Turk who filled out validated measures of obsessive-compulsive symptoms, quality of life (QoL), generalized anxiety, and depressive symptoms. Analyses examined the influences of each symptom variable on QoL and the mediating role of depression as an indirect link between unacceptable thoughts (UT) and QoL. Depressive symptoms had a significant negative relationship with multiple domains of functioning. Generalized anxiety was not significant. Higher endorsement of UT symptoms was related to lower physical, emotional, and social QoL. Depression partially mediated the relationship between UT symptoms and physical, emotional, and social health. Depressive symptoms are important to consider in clinical work surrounding OCD. The significant associations between UT symptoms and QoL in a nonclinical population illustrate a relevant area for future intervention, public awareness, and education.

Distinct Symptom-Specific Treatment Targets for Circuit-Based Neuromodulation.

OBJECTIVE: Treatment of different depression symptoms may require different brain stimulation targets with different underlying brain circuits. The authors sought to identify such targets, which could improve the efficacy of therapeutic brain stimulation and facilitate personalized therapy. METHODS: The authors retrospectively analyzed two independent cohorts of patients who received left prefrontal transcranial magnetic stimulation (TMS) for treatment of depression (discovery sample, N=30; active replication sample, N=81; sham replication sample, N=87). Each patient's TMS site was mapped to underlying brain circuits using functional connectivity MRI from a large connectome database (N=1,000). Circuits associated with improvement in each depression symptom were identified and then clustered based on similarity. The authors tested for reproducibility across data sets and whether symptom-specific targets derived from one data set could predict symptom improvement in the other independent cohort. RESULTS: The authors identified two distinct circuit targets effective for two discrete clusters of depressive symptoms. Dysphoric symptoms, such as sadness and anhedonia, responded best to stimulation of one circuit, while anxiety and somatic symptoms responded best to stimulation of a different circuit. These circuit maps were reproducible, predicted symptom improvement in independent patient cohorts, and were specific to active compared with sham stimulation. The maps predicted symptom improvement in an exploratory analysis of stimulation sites from 14 clinical TMS trials. CONCLUSIONS: Distinct clusters of depressive symptoms responded better to different TMS targets across independent retrospective data sets. These symptom-specific targets can be prospectively tested in a randomized clinical trial. This data-driven approach for identifying symptom-specific targets may prove useful for other disorders and facilitate personalized neuromodulation therapy.

A human memory circuit derived from brain lesions causing amnesia.

Human memory is thought to depend on a circuit of connected brain regions, but this hypothesis has not been directly tested. We derive a human memory circuit using 53 case reports of strokes causing amnesia and a map of the human connectome (n = 1000). This circuit is reproducible across discovery (n = 27) and replication (n = 26) cohorts and specific to lesions causing amnesia. Its hub is at the junction of the presubiculum and retrosplenial cortex. Connectivity with this single location defines a human brain circuit that incorporates > 95% of lesions causing amnesia. Lesion intersection with this circuit predicts memory scores in two independent datasets (N1 = 97, N2 = 176). This network aligns with neuroimaging correlates of episodic memory, abnormalities in Alzheimer's disease, and brain stimulation sites reported to enhance memory in humans.

A Human Depression Circuit Derived From Focal Brain Lesions.

BACKGROUND: Focal brain lesions can lend insight into the causal neuroanatomical substrate of depression in the human brain. However, studies of lesion location have led to inconsistent results. METHODS: Five independent datasets with different lesion etiologies and measures of postlesion depression were collated (N = 461). Each 3-dimensional lesion location was mapped to a common brain atlas. We used voxel lesion symptom mapping to test for associations between depression and lesion locations. Next, we computed the network of regions functionally connected to each lesion location using a large normative connectome dataset (N = 1000). We used these lesion network maps to test for associations between depression and connected brain circuits. Reproducibility was assessed using a rigorous leave-one-dataset-out validation. Finally, we tested whether lesion locations associated with depression fell within the same circuit as brain stimulation sites that were effective for improving poststroke depression. RESULTS: Lesion locations associated with depression were highly heterogeneous, and no single brain region was consistently implicated. However, these same lesion locations mapped to a connected brain circuit, centered on the left dorsolateral prefrontal cortex. Results were robust to leave-one-dataset-out cross-validation. Finally, our depression circuit derived from brain lesions aligned with brain stimulation sites that were effective for improving poststroke depression. CONCLUSIONS: Lesion locations associated with depression fail to map to a specific brain region but do map to a specific brain circuit. This circuit may have prognostic utility in identifying patients at risk for poststroke depression and therapeutic utility in refining brain stimulation targets.

Prospective Validation That Subgenual Connectivity Predicts Antidepressant Efficacy of Transcranial Magnetic Stimulation Sites.

BACKGROUND: The optimal target in the dorsolateral prefrontal cortex for treating depression with repetitive transcranial magnetic stimulation (rTMS) remains unknown. Better efficacy has been associated with stimulation sites that are 1) more anterior and lateral and 2) more functionally connected to the subgenual cingulate. Here we prospectively test whether these factors predict response in individual patients. METHODS: A primary cohort (Boston, n = 25) with medication-refractory depression underwent conventional open-label rTMS to the left dorsolateral prefrontal cortex. A secondary cohort (Michigan, n = 16) underwent 4 weeks of sham followed by open-label rTMS for nonresponders (n = 12). In each patient, the location of the stimulation site was recorded with frameless stereotaxy. Connectivity between each patient's stimulation site and the subgenual cingulate was assessed using resting-state functional connectivity magnetic resonance imaging from a cohort of healthy subjects (n = 1000) and confirmed using connectivity from patients with depression (n = 38). RESULTS: In our primary cohort, antidepressant efficacy was predicted by stimulation sites that were both more anterolateral (r = .51, p < .01) and more negatively correlated with the subgenual cingulate (r = -.55, p < .005). However, subgenual connectivity was the only independent predictor of response and the only factor to predict response to active (r = -.52, p < .05) but not sham rTMS in our secondary cohort. CONCLUSIONS: This study provides prospective validation that functional connectivity between an individual's rTMS cortical target and the subgenual cingulate predicts antidepressant response. Implications for improving the cortical rTMS target for depression are discussed.