Infant attachment does not depend on neonatal amygdala and hippocampal structure and connectivity.

Infant attachment is an antecedent of later socioemotional abilities, which can be adversely affected by preterm birth. The structural integrity of amygdalae and hippocampi may subserve attachment in infancy. We aimed to investigate associations between neonatal amygdalae and hippocampi structure and their whole-brain connections and attachment behaviours at nine months of age in a sample of infants enriched for preterm birth. In 133 neonates (median gestational age 32 weeks, range 22.14-42.14), we calculated measures of amygdala and hippocampal structure (volume, fractional anisotropy, mean diffusivity, neurite dispersion index, orientation dispersion index) and structural connectivity, and coded attachment behaviours (distress, fretfulness, attentiveness to caregiver) from responses to the Still-Face Paradigm at nine months. After multiple comparisons correction, there were no significant associations between neonatal amygdala or hippocampal structure and structural connectivity and attachment behaviours: standardised ß values - 0.23 to 0.18, adjusted p-values > 0.40. Findings indicate that the neural basis of infant attachment in term and preterm infants is not contingent on the structure or connectivity of the amygdalae and hippocampi in the neonatal period, which implies that it is more widely distributed in early life and or that network specialisation takes place in the months after hospital discharge.

Immunohistochemical field parcellation of the human hippocampus along its antero-posterior axis.

The primate hippocampus includes the dentate gyrus, cornu ammonis (CA), and subiculum. CA is subdivided into four fields (CA1-CA3, plus CA3h/hilus of the dentate gyrus) with specific pyramidal cell morphology and connections. Work in non-human mammals has shown that hippocampal connectivity is precisely patterned both in the laminar and longitudinal axes. One of the main handicaps in the study of neuropathological semiology in the human hippocampus is the lack of clear laminar and longitudinal borders. The aim of this study was to explore a histochemical segmentation of the adult human hippocampus, integrating field (medio-lateral), laminar, and anteroposterior longitudinal patterning. We provide criteria for head-body-tail field and subfield parcellation of the human hippocampus based on immunodetection of Rabphilin3a (Rph3a), Purkinje-cell protein 4 (PCP4), Chromogranin A and Regulation of G protein signaling-14 (RGS-14). Notably, Rph3a and PCP4 allow to identify the border between CA3 and CA2, while Chromogranin A and RGS-14 give specific staining of CA2. We also provide novel histological data about the composition of human-specific regions of the anterior and posterior hippocampus. The data are given with stereotaxic coordinates along the longitudinal axis. This study provides novel insights for a detailed region-specific parcellation of the human hippocampus useful for human brain imaging and neuropathology.

Association of Preterm Birth and Socioeconomic Status With Neonatal Brain Structure.

Importance: Preterm birth and socioeconomic status (SES) are associated with brain structure in childhood, but the relative contributions of each during the neonatal period are unknown. Objective: To investigate associations of birth gestational age (GA) and SES with neonatal brain morphology by testing 3 hypotheses: GA and SES are associated with brain morphology; associations between SES and brain morphology vary with GA; and associations between SES and brain structure and morphology depend on how SES is operationalized. Design, Setting, and Participants: This cohort study recruited participants from November 2016 to September 2021 at a single center in the United Kingdom. Participants were 170 extremely and very preterm infants and 91 full-term or near-term infants. Exclusion criteria were major congenital malformation, chromosomal abnormality, congenital infection, cystic periventricular leukomalacia, hemorrhagic parenchymal infarction, and posthemorrhagic ventricular dilatation. Exposures: Birth GA and SES, operationalized at the neighborhood level (using the Scottish Index of Multiple Deprivation), the family level (using parental education and occupation), and subjectively (World Health Organization Quality of Life measure). Main Outcomes and Measures: Brain volume (85 parcels) and 5 whole-brain cortical morphology measures (gyrification index, thickness, sulcal depth, curvature, surface area) at term-equivalent age (median [range] age, 40 weeks, 5 days [36 weeks, 2 days to 45 weeks, 6 days] and 42 weeks [38 weeks, 2 days to 46 weeks, 1 day] for preterm and full-term infants, respectively). Results: Participants were 170 extremely and very preterm infants (95 [55.9%] male; 4 of 166 [2.4%] Asian, 145 of 166 [87.3%] White) and 91 full-term or near-term infants (50 [54.9%] male; 3 of 86 [3.5%] Asian, 78 of 86 [90.7%] White infants) with median (range) birth GAs of 30 weeks, 0 days (22 weeks, 1 day, to 32 weeks, 6 days) and 39 weeks, 4 days (36 weeks, 3 days, to 42 weeks, 1 day), respectively. In fully adjusted models, birth GA was associated with a higher proportion of brain volumes (27 of 85 parcels [31.8%]; ß range, -0.20 to 0.24) than neighborhood-level SES (1 of 85 parcels [1.2%]; ß = 0.17 [95% CI, -0.16 to 0.50]) or family-level SES (maternal education: 4 of 85 parcels [4.7%]; ß range, 0.09 to 0.15; maternal occupation: 1 of 85 parcels [1.2%]; ß = 0.06 [95% CI, 0.02 to 0.11] respectively). There were interactions between GA and both family-level and subjective SES measures on regional brain volumes. Birth GA was associated with cortical surface area (ß = 0.10 [95% CI, 0.02 to 0.18]) and gyrification index (ß = 0.16 [95% CI, 0.07 to 0.25]); no SES measure was associated with cortical measures. Conclusions and Relevance: In this cohort study of UK infants, birth GA and SES were associated with neonatal brain morphology, but low GA had more widely distributed associations with neonatal brain structure than SES. Further work is warranted to elucidate the mechanisms underlying the association of both GA and SES with early brain development.

Emotion regulation and cortisol response to the still-face procedure in preterm and full-term infants.

In infancy, stress responses and emotion regulation are often coupled. Both are impacted by prematurity, though their relationship to one another in the case of infants born preterm is not fully understood. We investigated emotion regulation behaviours, cortisol reactivity and recovery and coupling between emotion regulation and cortisol reactivity to and recovery from a stressor in preterm infants. 53 preterm and 67 full-term infants with mean (range) gestational age at birth 29+3 (24+0-31+6) and 39+3 (36+2-42+0) weeks respectively were exposed to a socio-emotional stressor, the still-face (SF) paradigm, at 9 months of age (corrected for prematurity). The duration of negative affect and self-comforting behaviours exhibited in response to the SF, coded from a 10-minute video-taped interaction, were compared between groups. Saliva was collected from a subset (20 preterm, 24 term infants) at three timepoints: pre-SF and 20- and 30-minutes post SF. Cortisol concentrations at each timepoint were compared between groups. Associations between behavioural measures and cortisol concentrations were explored. There was no significant difference in duration of self-comforting behaviour between preterm and term infants. Preterm infants spent a significantly smaller proportion of time in a negative affective state compared to term infants (0.18 vs 0.25 s, p = 0.03). Salivary cortisol concentration was significantly higher in the preterm compared to the term group 30 min post SF (2.85 vs 1.77 nmol/L, p = 0.009), though findings were no longer significant after adjusting for time of day of sampling and socioeconomic deprivation. After controlling for time of day, greater negative affect was correlated with higher cortisol concentration 30 min post SF in the full-term (r = 0.58, p = 0.004) but not the preterm group (r = -0.01, p > 0.05). Our findings suggest altered response to an acute stressor in preterm infants, manifesting as a muted emotional response, and a lack of coupling between endocrine and behavioural stress response. Replication studies in larger samples would help to further understand biological stress repose in preterm infants and its relationship to behaviour, time of day and deprivation.

Investigating Markers of Rapport in Autistic and Nonautistic Interactions.

Background: Autism is considered to entail a social impairment whereby autistic people experience difficulty interpreting others' mental states. However, recent research has shown that nonautistic people also have difficulty understanding the mental states of autistic people. This mismatch of understanding may explain lower rapport in interactions between autistic and nonautistic people. As mental states can be expressed externally through socially normed signals, it is important to investigate the role of such signals in autistic, nonautistic, and mixed interactions. This study explores variability in two social signals between autistic, nonautistic, and mixed interactions, and how their use may affect rapport within interactions. Methods: Videos from a previous study of autistic, nonautistic, and mixed pair interactions in a diffusion chain context in which participants were aware of others' diagnostic status were video coded for mutual gaze and backchanneling as candidate indicators of interactional rapport. Results: Although use of mutual gaze and backchanneling was lower in mixed pairs than in nonautistic pairs, corresponding to lower ratings of interactional rapport, less backchanneling in autistic pairs of both nonverbal and verbal subtypes corresponded to higher ratings of rapport. Conclusions: We observed differences in the use of candidate rapport markers between autistic, mixed, and nonautistic interactions, which did not map onto patterns of rapport scores, suggesting differences in reliance on these cues between autistic and nonautistic people. These results suggest that visible markers of rapport may vary by neurotype or pairing and give clues to inform future investigations of autistic interaction.

Why is this an important issue?: When someone is autistic, society generally assumes they have difficulty interacting with others. Social difficulties between autistic and nonautistic people are thought to be due to the autistic person not being able to interact using nonautistic social behaviors. This belief can lead to many autistic people feeling alienated. However, recent research supports what autistic people have been saying for a long time: that autistic people are capable of having successful and rewarding interactions with other autistic people. This suggests that social difficulties between autistic and nonautistic people may be due to a mismatch in social norms leading to difficulty for both people, not just the autistic person. What was the purpose of this study?: In this study, we wanted to investigate whether certain social signals are used differently between autistic and nonautistic people. We also questioned whether using these signals helped or hurt the interaction depending on who was involved. What did the researchers do?: We recorded people passing a story down a chain of people, like the game telephone, to see how they interacted with each other. Afterward, people wrote down scores for how much they enjoyed their interaction. We focused on two parts of the interaction: how much people were looking at each other and when they made short verbal responses such as "mhm" to show they were listening (backchanneling). We watched the recordings back and analyzed how long or how many times these actions were occurring. What were the results of the study?: We found that when one autistic and one nonautistic person were interacting, they looked at each other and backchanneled less than two nonautistic people. This seemed to be linked with a less enjoyable interaction for them. However, backchanneling seemed to matter less in interactions between two autistic people. They backchanneled less while still having enjoyable interactions. What do these findings add to what was already known?: Research has previously suggested that different social norms exist between autistic and nonautistic people. This study shows specific examples of this and how they may affect the interaction in a natural setting. What are potential weaknesses in the study?: This study has some weaknesses. For example, we measured when people looked at each other's faces rather than eye contact specifically, which can only be done with an eye tracker. Also, the people in the study knew whether the person they were talking to was autistic. This can be similar to normal life, as people do sometimes know this, although we would also be interested to see what the effect of not knowing would be. How will these findings help autistic adults now or in the future?: This line of research has important implications for how autistic people can be supported in society. Not only will understanding of social differences between autistic and nonautistic people help the way autistic people are perceived, but it will also help nonautistic people better understand and support the autistic people in their lives.

Permeable spaces between glenohumeral ligaments as potential gateways for rapid regional anesthesia of the shoulder.

Shoulder pain is a highly prevalent condition, often resulting in major life limitations, and requiring effective treatments. In this work, we explore the anatomical basis of a proposed approach to the regional anesthesia of the shoulder through a single injection under the subscapularis muscle. Bilateral experimental injections in shoulders from body donors (Radiolar ® and Methylene-Blue) under the subscapular muscle (n = 11) and cadaveric systematic dissections of other 35 shoulders from body donors were performed. Injectate spread was then qualitatively assessed. Long axis of permeable foramina in the anterior aspect of the shoulder joint capsule was measured in centimeters using a digital caliper. More than 40% of specimens had at least one permeable space (Weitbrech and/or Rouvière foramina) communicating the subscapular bursa and the articular space. We further demonstrate that an ultrasonography-guided injection under the subscapularis muscle allows the spread of the injectate through the anterior, inferior and posterodorsal walls of the articular capsule, the subacromial bursa, and the bicipital groove, as well as into the articular space for some injections. The odds of accidental intraarticular injection decrease when injecting with low volumes. This anatomical study provides a detailed description of foramina between glenohumeral ligaments. Furthermore, the data shown in this work supports, as a proof of concept, a safe alternative for rapid and specific blockade of terminal sensory branches innervating the shoulder joint capsule.

Sex Differences in Cerebral Small Vessel Disease: A Systematic Review and Meta-Analysis.

Background: Cerebral small vessel disease (SVD) is a common cause of stroke, mild cognitive impairment, dementia and physical impairments. Differences in SVD incidence or severity between males and females are unknown. We assessed sex differences in SVD by assessing the male-to-female ratio (M:F) of recruited participants and incidence of SVD, risk factor presence, distribution, and severity of SVD features. Methods: We assessed four recent systematic reviews on SVD and performed a supplementary search of MEDLINE to identify studies reporting M:F ratio in covert, stroke, or cognitive SVD presentations (registered protocol: CRD42020193995). We meta-analyzed differences in sex ratios across time, countries, SVD severity and presentations, age and risk factors for SVD. Results: Amongst 123 relevant studies (n = 36,910 participants) including 53 community-based, 67 hospital-based and three mixed studies published between 1989 and 2020, more males were recruited in hospital-based than in community-based studies [M:F = 1.16 (0.70) vs. M:F = 0.79 (0.35), respectively; p < 0.001]. More males had moderate to severe SVD [M:F = 1.08 (0.81) vs. M:F = 0.82 (0.47) in healthy to mild SVD; p < 0.001], and stroke presentations where M:F was 1.67 (0.53). M:F did not differ for recent (2015-2020) vs. pre-2015 publications, by geographical region, or age. There were insufficient sex-stratified data to explore M:F and risk factors for SVD. Conclusions: Our results highlight differences in male-to-female ratios in SVD severity and amongst those presenting with stroke that have important clinical and translational implications. Future SVD research should report participant demographics, risk factors and outcomes separately for males and females. Systematic Review Registration: [PROSPERO], identifier [CRD42020193995].

Associations between major psychiatric disorder polygenic risk scores and blood-based markers in UK biobank.

Major depressive disorder (MDD), schizophrenia (SCZ), and bipolar disorder (BD) have both shared and discrete genetic risk factors, and are associated with peripheral abnormalities. The relationships between such genetic architectures and blood-based markers are, however, unclear. We investigated relationships between polygenic risk scores (PRS) for these disorders and peripheral markers in the UK Biobank cohort. We calculated polygenic risk scores for n = 367,329 (MDD PRS), n = 366,465 (SCZ PRS), and n = 366,383 (BD PRS) UK Biobank cohort subjects. We then examined associations between disorder PRS and 58 inflammatory/immune, hematological, bone, cardiovascular, hormone, liver, renal and diabetes-associated blood markers using two generalized linear regression models: 'minimally adjusted' controlling for variables such as age and sex, and 'fully adjusted' including additional lifestyle covariates: BMI, alcohol and smoking status, and medication intake. There were 38/58 MDD PRS, 32/58 SCZ PRS, and 20/58 BD PRS-blood marker associations detected for our minimally adjusted model. Of these, 13/38 (MDD PRS), 14/32 (SCZ PRS), and 10/20 (BD PRS) associations remained significant after controlling for lifestyle factors. Many were disorder-specific, with 8/13 unique MDD PRS associations identified. Several disorder-specific associations for MDD and SCZ were immune-related, with mostly positive and negative associations identified for MDD and SCZ PRS respectively. This study suggests that MDD, SCZ and BD have both shared and distinct peripheral markers associated with disorder-specific genetic risk. The results also implicate inflammatory dysfunction in MDD and SCZ, albeit with differences in patterns between the two conditions, and enrich our understanding of potential underlying pathophysiological mechanisms in major psychiatric disorders.

Serotonergic innervation of the striatum in a nonhuman primate model of Parkinson's disease.

Parkinson's disease (PD) is characterized by dopaminergic neurodegeneration in the substantia nigra and dopamine depletion in the striatum. Non-dopaminergic systems are also affected, including the serotonergic system. Enhanced striatal serotonergic innervation is a proposed compensatory mechanism for the dopaminergic deficit. Meanwhile a serotonergic deficit has been suggested as preceding the nigrostriatal dopaminergic pathology in PD. Our aim was to assess the serotonergic innervation of the striatum in a model of progressive experimental parkinsonism in macaques, from pre-symptomatic to symptomatic stages. The neurotoxin 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) was administered to adult macaque monkeys using a slow intoxication protocol. The intoxicated animals were classified into asymptomatic, recovered, moderate and severe parkinsonian, based on their motor behavior. The serotonergic innervation was studied by immunohistochemistry against serotonin (5-HT). In the striatum, the density of 5-HT-immunoreactive (5-HT+) axons was estimated with stereology. Images of the striatum in the immunostained sections were taken to compare the distribution patterns of the serotonergic innervation between groups. These patterns were apparently similar among the groups. Axonal density estimations showed no differences in striatal 5-HT+ innervation between the intoxicated groups and the control group. Accordingly, this study fails to find significant changes in the striatal serotonergic axonal innervation in MPTP-treated monkeys, coinciding with previous biochemical findings in our model. However, it is possible that alterations in the serotonergic system in PD could be independent of axonal density changes. Consequently, the proposed role for striatal serotonin serving as a compensatory mechanism for dopaminergic denervation merits further study. This article is part of the special issue entitled 'Serotonin Research: Crossing Scales and Boundaries'.

Ultrasonography-guided anterior approach for axillary nerve blockade: An anatomical study.

Combined ultrasound (US)-guided blockade of the suprascapular and axillary nerves (ANs) has been proposed as an alternative to interscalene blockade for pain control in shoulder joint pathology or postsurgical care. This technique could help avoid respiratory complications and/or almost total upper limb palsy. Nowadays, the AN blockade is mostly performed using an in-plane caudal-to-cephalic approach from the posterior surface of the shoulder, reaching the nerve immediately after it exits the neurovascular quadrangular space (part of the spatium axillare). Despite precluding most respiratory complications, this approach has not made postsurgical pain relief any better than an interscalene blockade, probably because articular branches of the AN are not blocked.Cephalic-to-caudal methylene blue injections were placed in the first segment of the AN of six Thiel-embalmed cadavers using an US-guided anterior approach in order to compare the distribution with that produced by a posterior approach to the contralateral AN in the same cadaver. Another 21 formalin-fixed cadavers were bilaterally dissected to identify the articular branches of the AN.We found a good spread of the dye on the AN and a constant relationship of this nerve with the subscapularis muscle. The dye reached the musculocutaneous nerve, which also contributes to shoulder joint innervation. We describe the anatomical landmarks for an ultrasonography-guided anterior AN blockade and hypothesize that this anterior approach will provide better pain control than the posterior approach owing to complete blocking of the joint nerve. Clin. Anat. 33:488-499, 2020. © 2019 Wiley Periodicals, Inc.