Atypical cortical networks in children at high-genetic risk of psychiatric and neurodevelopmental disorders.

Although many genetic risk factors for psychiatric and neurodevelopmental disorders have been identified, the neurobiological route from genetic risk to neuropsychiatric outcome remains unclear. 22q11.2 deletion syndrome (22q11.2DS) is a copy number variant (CNV) syndrome associated with high rates of neurodevelopmental and psychiatric disorders including autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD) and schizophrenia. Alterations in neural integration and cortical connectivity have been linked to the spectrum of neuropsychiatric disorders seen in 22q11.2DS and may be a mechanism by which the CNV acts to increase risk. In this study, magnetoencephalography (MEG) was used to investigate electrophysiological markers of local and global network function in 34 children with 22q11.2DS and 25 controls aged 10-17 years old. Resting-state oscillatory activity and functional connectivity across six frequency bands were compared between groups. Regression analyses were used to explore the relationships between these measures, neurodevelopmental symptoms and IQ. Children with 22q11.2DS had altered network activity and connectivity in high and low frequency bands, reflecting modified local and long-range cortical circuitry. Alpha and theta band connectivity were negatively associated with ASD symptoms while frontal high frequency (gamma band) activity was positively associated with ASD symptoms. Alpha band activity was positively associated with cognitive ability. These findings suggest that haploinsufficiency at the 22q11.2 locus impacts short and long-range cortical circuits, which could be a mechanism underlying neurodevelopmental and psychiatric vulnerability in this high-risk group.

A data-driven investigation of human action representations.

Understanding actions performed by others requires us to integrate different types of information about people, scenes, objects, and their interactions. What organizing dimensions does the mind use to make sense of this complex action space? To address this question, we collected intuitive similarity judgments across two large-scale sets of naturalistic videos depicting everyday actions. We used cross-validated sparse non-negative matrix factorization to identify the structure underlying action similarity judgments. A low-dimensional representation, consisting of nine to ten dimensions, was sufficient to accurately reconstruct human similarity judgments. The dimensions were robust to stimulus set perturbations and reproducible in a separate odd-one-out experiment. Human labels mapped these dimensions onto semantic axes relating to food, work, and home life; social axes relating to people and emotions; and one visual axis related to scene setting. While highly interpretable, these dimensions did not share a clear one-to-one correspondence with prior hypotheses of action-relevant dimensions. Together, our results reveal a low-dimensional set of robust and interpretable dimensions that organize intuitive action similarity judgments and highlight the importance of data-driven investigations of behavioral representations.

Social-affective features drive human representations of observed actions.

Humans observe actions performed by others in many different visual and social settings. What features do we extract and attend when we view such complex scenes, and how are they processed in the brain? To answer these questions, we curated two large-scale sets of naturalistic videos of everyday actions and estimated their perceived similarity in two behavioral experiments. We normed and quantified a large range of visual, action-related, and social-affective features across the stimulus sets. Using a cross-validated variance partitioning analysis, we found that social-affective features predicted similarity judgments better than, and independently of, visual and action features in both behavioral experiments. Next, we conducted an electroencephalography experiment, which revealed a sustained correlation between neural responses to videos and their behavioral similarity. Visual, action, and social-affective features predicted neural patterns at early, intermediate, and late stages, respectively, during this behaviorally relevant time window. Together, these findings show that social-affective features are important for perceiving naturalistic actions and are extracted at the final stage of a temporal gradient in the brain.

Patient and Family Perspectives on Early Mobilization in Acute Cardiac Care.

BACKGROUND: Emerging evidence indicates that engaging family members in early mobilization may benefit both patients and family members. However, little is known about the effect of patient and family-member experience and perspectives on mobilization in acute cardiac care. Our goal was to assess the perspectives and experience of patients and their family members regarding early mobilization in acute cardiac care, to better understand patient-related barriers to mobilization and assist in the development of mobilization strategies that increase family-member engagement in care. METHODS: Patient and family-member surveys were developed to assess attitudes and knowledge about mobilization, family-members' roles in providing care, and mobilization care the patients received. Surveys were distributed to patients and their family members over a 4-month period. RESULTS: A total of 101 participants completed the survey (patients, n = 78; family members, n = 23). Most patients (n = 54; 69.2%) agreed or strongly agreed that early mobilization should be routinely performed. Of 72 patients who underwent early mobilization, 60 (83.3%) felt that mobilization helped their recovery. The majority of family members were interested in being involved with mobilization (n = 19; 82.6%). One quarter of family members felt that mobilizing their relatives too soon after admission was potentially dangerous (n = 6; 26.1%). CONCLUSIONS: Most patients wish to be mobilized early after admission, and family members want to participate in mobilization efforts. These findings should inform efforts to overcome patient- and family-related barriers to mobilization.

INTRODUCTION: De nouvelles données révèlent que la participation des membres de la famille à la mobilisation précoce peut profiter aux patients et aux membres de la famille. Toutefois, on en connaît peu sur les effets de l'expérience des patients et des membres de la famille et les points de vue sur la mobilisation aux soins cardiaques de courte durée. Notre but était d'évaluer les points de vue et l'expérience des patients et des membres de la famille quant à la mobilisation précoce en soins cardiaques de courte durée afin de mieux comprendre les obstacles des patients à l'égard de la mobilisation et de contribuer à l'élaboration de stratégies de mobilisation qui accroissent la participation des membres de la famille aux soins. MÉTHODES: Nous avons élaboré des enquêtes destinées aux patients et aux membres de la famille afin d'évaluer les attitudes et les connaissances à l'égard de la mobilisation, les rôles des membres de la famille dans la prestation des soins et l'expérience des patients quant à la prise en charge de la mobilisation. Nous avons distribué les enquêtes aux patients et aux membres de leur famille au cours d'une période de quatre mois. RÉSULTATS: Un total de 101 participants ont rempli l'enquête (patients, n = 78; membres de la famille, n = 23). La plupart des patients (n = 54; 69,2 %) se disaient d'accord ou tout à fait d'accord avec le fait de pratiquer systématiquement la mobilisation précoce. Parmi les 72 patients qui avaient eu une mobilisation précoce, 60 (83,3 %) percevaient que la mobilisation précoce favorisait leur rétablissement. La majorité des membres de la famille souhaitait participer à la mobilisation (n = 19; 82,6 %). Un quart des membres de la famille percevaient que la mobilisation trop hâtive de leur proche après l'admission était potentiellement dangereuse (n = 6; 26,1 %). CONCLUSIONS: La plupart des patients souhaitent être mobilisés de façon précoce après l'admission, et les membres de la famille veulent participer aux efforts de mobilisation. Ces résultats devraient orienter les efforts visant à surmonter les obstacles des patients et de la famille à l'égard de la mobilisation.

Temporal uncertainty enhances suppression of neural responses to predictable visual stimuli.

Contextual information triggers predictions about the content ("what") of environmental stimuli to update an internal generative model of the surrounding world. However, visual information dynamically changes across time, and temporal predictability ("when") may influence the impact of internal predictions on visual processing. In this magnetoencephalography (MEG) study, we investigated how processing feature specific information ("what") is affected by temporal predictability ("when"). Participants (N = 16) were presented with four consecutive Gabor patches (entrainers) with constant spatial frequency but with variable orientation and temporal onset. A fifth target Gabor was presented after a longer delay and with higher or lower spatial frequency that participants had to judge. We compared the neural responses to entrainers where the Gabor orientation could, or could not be temporally predicted along the entrainer sequence, and with inter-entrainer timing that was constant (predictable), or variable (unpredictable). We observed suppression of evoked neural responses in the visual cortex for predictable stimuli. Interestingly, we found that temporal uncertainty increased expectation suppression. This suggests that in temporally uncertain scenarios the neurocognitive system invests less resources in integrating bottom-up information. Multivariate pattern analysis showed that predictable visual features could be decoded from neural responses. Temporal uncertainty did not affect decoding accuracy for early visual responses, with the feature specificity of early visual neural activity preserved across conditions. However, decoding accuracy was less sustained over time for temporally jittered than for isochronous predictable visual stimuli. These findings converge to suggest that the cognitive system processes visual features of temporally predictable stimuli in higher detail, while processing temporally uncertain stimuli may rely more heavily on abstract internal expectations.

Beliefs, attitudes and knowledge of cardiovascular healthcare providers on mobilization.

AIM: To assess the beliefs, attitudes and knowledge of nurses, physicians and physiotherapists in a cardiovascular intensive care unit (CICU) on patient mobilization. DESIGN: Survey of CV healthcare providers in the CICU at two academic tertiary care hospitals. METHODS: The validated Patient Mobilization Attitudes and Beliefs Survey was distributed to CV providers. The survey is a 26-item self-administered questionnaire that assesses providers' perceived barriers in three domains: attitude, behaviour and knowledge. RESULTS: Participants (N = 142) completed the survey (nurses, N = 67, physicians, N = 59 and physiotherapists, N = 16; 155 eligible participants, 91.6% overall completion rate). Nurses had lower overall knowledge, attitude and behaviour barriers to mobilization than physicians, but higher than physiotherapists (all p < .001). The highest barriers to mobilization for nurses were adequate staffing, patient-level and time restraint. These findings should inform efforts to overcome existing barriers and to transform acute cardiovascular mobility culture.

Early Mobilization in People With Acute Cardiovascular Disease.

BACKGROUND: Early mobilization (EM) is recommended in critical care units. However, there is little known about EM in people with acute cardiovascular disease. METHODS: Consecutive admissions to a tertiary-care cardiovascular intensive care unit (CICU) before and after implementation of an EM program were reviewed. The Level of Function (LOF) Mobility Scale, which ranges from 0 (bed immobile) to 5 (able to walk >20 m), was used to measure and guide mobility. The primary outcome was discharge home. RESULTS: There were 1489 patients included in the analysis (preintervention, N = 637; intervention, N = 852). There were no differences in age, sex, or admission for ischemic heart disease (age 68.1 ± 16.1 years; 39.3% female). In the intervention cohort, one-quarter (N = 222; 26.1%) had at least mildly impaired prehospital functional status. The LOF was 4.6 ± 0.7 prehospital, 3.2 ± 1.4 on admission, and 4.2 ± 0.9 on CICU discharge. Half of patients (51.6%) increased their LOF by ≥1 during CICU admission. Nearly all mobility opportunities had a mobility activity (97.0%). The adverse event rate was 0.3% with no life-threatening events, falls, line dislodgements, or health care personnel injuries. The intervention group, compared with the preintervention group, was more likely to be discharged home (83.9% vs 78.3%, P < 0.007) and had a lower rate of in-hospital death (4.2% vs 6.8%; P = 0.04). When adjusted for age, sex, and comorbid illness, admission LOF was a predictor of discharge to health care facility (odds ratio = 0.72; P < 0.001). CONCLUSIONS: EM is safe and feasible in the CICU and effective at increasing discharge home.

Early Mobilization in Older Adults with Acute Cardiovascular Disease.

BACKGROUND: Early mobilization (EM) is beneficial in critical care units and in older hospitalized patients, but little is known about EM in older adults with acute cardiovascular disease. METHODS: Consecutive admissions of adults ≥80 years old to a Cardiac Intensive Care Unit (CICU) prior to and following implementation of a nurse-driven EM program were reviewed. Mobility was measured using the Level of Function (LOF) Mobility Scale, which ranges from 0 (bed immobile) to 5 (able to walk >20 meters). The primary outcome was discharge home. RESULTS: There were 412 patients included (N = 234, intervention; N = 178, preintervention). There was no difference in age between groups (overall 86.3 ± 4.8 years old) or sex (overall female N = 215, 52.2%). In the intervention group, functional impairment was present in 89 patients (38.0%) prehospitalization and in 209 patients (89.3%) on admission. Nearly half of patients (N = 107; 45.7%) improved their LOF by ≥1 during admission. Mobilization occurred during nearly all opportunities (838/850; 98.6%), and most mobility activities were completed (2,207/2,553; 86.4%). Adverse events were rare (5/2,207 activities [0.2% adverse event rate]) and transient. Patients in the intervention group were more likely than patients in the preintervention group to be discharged home (74.4 vs. 65.7%, P = 0.047, respectively) and had a lower rate of in-hospital death (6.4 vs. 14.6%, P = 0.006, respectively). There was no difference in mean length of hospital stay, 30-day emergency department visit or hospital re-admission. CONCLUSION: EM is safe in older adults in the CICU and is associated with reduced discharge to healthcare facility and in-hospital mortality.

Electrophysiological network alterations in adults with copy number variants associated with high neurodevelopmental risk.

Rare copy number variants associated with increased risk for neurodevelopmental and psychiatric disorders (referred to as ND-CNVs) are characterized by heterogeneous phenotypes thought to share a considerable degree of overlap. Altered neural integration has often been linked to psychopathology and is a candidate marker for potential convergent mechanisms through which ND-CNVs modify risk; however, the rarity of ND-CNVs means that few studies have assessed their neural correlates. Here, we used magnetoencephalography (MEG) to investigate resting-state oscillatory connectivity in a cohort of 42 adults with ND-CNVs, including deletions or duplications at 22q11.2, 15q11.2, 15q13.3, 16p11.2, 17q12, 1q21.1, 3q29, and 2p16.3, and 42 controls. We observed decreased connectivity between occipital, temporal, and parietal areas in participants with ND-CNVs. This pattern was common across genotypes and not exclusively characteristic of 22q11.2 deletions, which were present in a third of our cohort. Furthermore, a data-driven graph theory framework enabled us to successfully distinguish participants with ND-CNVs from unaffected controls using differences in node centrality and network segregation. Together, our results point to alterations in electrophysiological connectivity as a putative common mechanism through which genetic factors confer increased risk for neurodevelopmental and psychiatric disorders.

Spatially and Temporally Distinct Encoding of Muscle and Kinematic Information in Rostral and Caudal Primary Motor Cortex.

The organizing principle of human motor cortex does not follow an anatomical body map, but rather a distributed representational structure in which motor primitives are combined to produce motor outputs. Electrophysiological recordings in primates and human imaging data suggest that M1 encodes kinematic features of movements, such as joint position and velocity. However, M1 exhibits well-documented sensory responses to cutaneous and proprioceptive stimuli, raising questions regarding the origins of kinematic motor representations: are they relevant in top-down motor control, or are they an epiphenomenon of bottom-up sensory feedback during movement? Here we provide evidence for spatially and temporally distinct encoding of kinematic and muscle information in human M1 during the production of a wide variety of naturalistic hand movements. Using a powerful combination of high-field functional magnetic resonance imaging and magnetoencephalography, a spatial and temporal multivariate representational similarity analysis revealed encoding of kinematic information in more caudal regions of M1, over 200 ms before movement onset. In contrast, patterns of muscle activity were encoded in more rostral motor regions much later after movements began. We provide compelling evidence that top-down control of dexterous movement engages kinematic representations in caudal regions of M1 prior to movement production.

Level of function mobility scale for nurse-driven early mobilisation in people with acute cardiovascular disease.

BACKGROUND: There are currently no validated tools that are reliable and easy to use for nurses to assess mobility in people with acute cardiovascular disease in the Cardiovascular Intensive Care Unit (CICU). METHODS: A multidisciplinary team at an academic tertiary care centre developed the Level of Function (LOF) Mobility Scale for use in a nurse-driven early progressive mobilisation in the CICU. To determine inter-rater reliability, the prehospital and admission LOF were assessed independently by two CICU nurses. Pairwise comparisons between raters were evaluated using Cohen's kappa statistic. To determine convergence validity, the LOF and Activity Measure for Post-Acute Care 6-Clicks score upon admission were compared with Spearman's correlation. To determine feasibility, a 9-item mobility scale questionnaire was distributed to CICU nurses with and without experience using the LOF Mobility Scale. The STROBE reporting guidelines were used. RESULTS: The LOF Mobility Scale had good inter-rater reliability for assessment of LOF prior to hospitalisation (N = 131, kappa = 0.66, p < .001) and at the time of CICU admission (N = 131, kappa = 0.71, p < .001). There was a moderate correlation (N = 79 observations; correlation coefficient = 0.525; p < .01) between the bedside nurses LOF and the 6-Clicks score. All nurses surveyed (N = 54; 100%) thought that the LOF Mobility Scale was clear and unambiguous, the LOFs were well-defined and the scale was an appropriate length. Nearly all of the nurses with experience using the scale (N = 22/24; 92%) felt that the scale took less than one minute to complete, compared with about half (N = 14/30; 47%) in the group of nurses without experience using the scale. CONCLUSION: The LOF Mobility Scale is reliable and feasible for mobility assessment in a nurse-driven early progressive mobilisation programme in patients with acute cardiovascular disease in the CICU. RELEVANCE TO CLINICAL PRACTICE: A nurse-driven EM programme can be implemented in the CICU.

Oscillatory hyperactivity and hyperconnectivity in young APOE-ɛ4 carriers and hypoconnectivity in Alzheimer's disease.

We studied resting-state oscillatory connectivity using magnetoencephalography in healthy young humans (N = 183) genotyped for APOE-ɛ4, the greatest genetic risk for Alzheimer's disease (AD). Connectivity across frequencies, but most prevalent in alpha/beta, was increased in APOE-ɛ4 in a set of mostly right-hemisphere connections, including lateral parietal and precuneus regions of the Default Mode Network. Similar regions also demonstrated hyperactivity, but only in gamma (40-160 Hz). In a separate study of AD patients, hypoconnectivity was seen in an extended bilateral network that partially overlapped with the hyperconnected regions seen in young APOE-ɛ4 carriers. Using machine-learning, AD patients could be distinguished from elderly controls with reasonable sensitivity and specificity, while young APOE-e4 carriers could also be distinguished from their controls with above chance performance. These results support theories of initial hyperconnectivity driving eventual profound disconnection in AD and suggest that this is present decades before the onset of AD symptomology.

Spatial frequency supports the emergence of categorical representations in visual cortex during natural scene perception.

In navigating our environment, we rapidly process and extract meaning from visual cues. However, the relationship between visual features and categorical representations in natural scene perception is still not well understood. Here, we used natural scene stimuli from different categories and filtered at different spatial frequencies to address this question in a passive viewing paradigm. Using representational similarity analysis (RSA) and cross-decoding of magnetoencephalography (MEG) data, we show that categorical representations emerge in human visual cortex at ∼180 ms and are linked to spatial frequency processing. Furthermore, dorsal and ventral stream areas reveal temporally and spatially overlapping representations of low and high-level layer activations extracted from a feedforward neural network. Our results suggest that neural patterns from extrastriate visual cortex switch from low-level to categorical representations within 200 ms, highlighting the rapid cascade of processing stages essential in human visual perception.

Spatiotemporal dynamics in human visual cortex rapidly encode the emotional content of faces.

Recognizing emotion in faces is important in human interaction and survival, yet existing studies do not paint a consistent picture of the neural representation supporting this task. To address this, we collected magnetoencephalography (MEG) data while participants passively viewed happy, angry and neutral faces. Using time-resolved decoding of sensor-level data, we show that responses to angry faces can be discriminated from happy and neutral faces as early as 90 ms after stimulus onset and only 10 ms later than faces can be discriminated from scrambled stimuli, even in the absence of differences in evoked responses. Time-resolved relevance patterns in source space track expression-related information from the visual cortex (100 ms) to higher-level temporal and frontal areas (200-500 ms). Together, our results point to a system optimised for rapid processing of emotional faces and preferentially tuned to threat, consistent with the important evolutionary role that such a system must have played in the development of human social interactions.

Assessment and elimination of the effects of head movement on MEG resting-state measures of oscillatory brain activity.

Magnetoencephalography (MEG) is increasingly being used to study brain function because of its excellent temporal resolution and its direct association with brain activity at the neuronal level. One possible cause of error in the analysis of MEG data comes from the fact that participants, even MEG-experienced ones, move their head in the MEG system. Head movement can cause source localization errors during the analysis of MEG data, which can result in the appearance of source variability that does not reflect brain activity. The MEG community places great importance in eliminating this source of possible errors as is evident, for example, by recent efforts to develop head casts that limit head movement in the MEG system. In this work we use software tools to identify, assess and eliminate from the analysis of MEG data any possible correlations between head movement in the MEG system and widely-used measures of brain activity derived from MEG resting-state recordings. The measures of brain activity we study are a) the Hilbert-transform derived amplitude envelope of the beamformer time series and b) functional networks; both measures derived by MEG resting-state recordings. Ten-minute MEG resting-state recordings were performed on healthy participants, with head position continuously recorded. The sources of the measured magnetic signals were localized via beamformer spatial filtering. Temporal independent component analysis was subsequently used to derive resting-state networks. Significant correlations were observed between the beamformer envelope time series and head movement. The correlations were substantially reduced, and in some cases eliminated, after a participant-specific temporal high-pass filter was applied to those time series. Regressing the head movement metrics out of the beamformer envelope time series had an even stronger effect in reducing these correlations. Correlation trends were also observed between head movement and the activation time series of the default-mode and frontal networks. Regressing the head movement metrics out of the beamformer envelope time series completely eliminated these correlations. Additionally, applying the head movement correction resulted in changes in the network spatial maps for the visual and sensorimotor networks. Our results a) show that the results of MEG resting-state studies that use the above-mentioned analysis methods are confounded by head movement effects, b) suggest that regressing the head movement metrics out of the beamformer envelope time series is a necessary step to be added to these analyses, in order to eliminate the effect that head movement has on the amplitude envelope of beamformer time series and the network time series and c) highlight changes in the connectivity spatial maps when head movement correction is applied.

Assessing symptoms during comprehensive interventions for young children with autism spectrum disorder: Development and preliminary analysis of the Autism Behaviour Coding System (ABCS).

The aims of this paper are to present the Autism Behaviour Coding System (ABCS), a novel, video-based observational instrument for assessing core autism symptoms during intensive early interventions in autism spectrum disorder (ASD), to provide preliminary data on its psychometric characteristics and to discuss its clinical utility. Video recordings of child-therapist interactions during the 'Frühintervention bei autistischen Störungen' (FIAS) were coded by treatment-independent raters who were blind with respect to the temporal order of the sequences. We assessed inter-rater reliability using intra-class correlations (ICCs). Mean ICCs ranged from 0.85 to 0.90. We analysed the sensitivity of the ABCS to change by comparing the change in ABCS scores with the change in a validated external measure of level of functioning (Developmental Disorder-Child-Global Assessment of functioning Scale, DD-C-GAS) in a sample of 15 children who received intensive treatment. Both the ABCS and DD-C-GAS indicated that the intervention improved symptoms. The ABCS has promise as a research instrument and has good to excellent inter-rater agreement and sensitivity to intervention-related changes. This pilot study suggests that the ABCS may be useful as an objective method of assessing the proximal effects of therapy in young children with ASD.

Become Related: FIAS, an Intensive Early Intervention for Young Children with Autism Spectrum Disorders.

BACKGROUND: In autism spectrum disorders (ASDs), impairments in fundamental social abilities and a lack of interest in social stimuli become apparent early in life. These impairments are thought to negatively affect further brain and behavioural development. Early intensive interventions can help to attenuate social-development and other risk factors and, thus, to ameliorate the deficits associated with ASDs. We present FIAS, an intensive early intervention approach for young children with ASD, which aims at developing children's social motivation. During 18 days, therapists work continuously for 6 h a day with the affected child, involving the whole family in a day care setting. Follow-up care at home over 1 year as well as fresh-up interventions and inclusion in kindergarten or a play group should stabilise the effects and help to respond to further challenges. MATERIAL AND METHODS: Here, we present observations from the first 12 patients (25-48 months of age) treated according to the FIAS approach. We evaluated changes in core autistic symptoms and level of functioning after the 18 days of intensive intervention. Beyond standardised assessment, two innovative video-based instruments (Autism Behaviour Coding System and Evaluationsfragebogen) have been developed to assess autistic symptoms and interaction parameters during intervention. RESULTS: Improvements were noted in most core autistic symptom domains, with the highest effect sizes in domains like eye contact, communication, repetitive behaviour, imitation, motivation and reciprocity. In addition, the level of functioning significantly improved. CONCLUSIONS: The first evaluation of the FIAS approach shows promising results, as the FIAS intervention appears to improve core autistic symptom domains as well as the level of everyday functioning. Limitations of this study are the small sample size and the lack of a control group. A more comprehensive and longitudinal evaluation is in progress; this will focus on the stability of the observed effects and will attempt to identify potential predictors of treatment response. © 2015 S. Karger AG, Basel.