Synchronous caregiving from birth to adulthood tunes humans’ social brain

Mammalian young are born with immature brain and rely on the mother’s body and caregiving behavior for maturation of neurobiological systems that sustain adult sociality. While research in animal models indicated the long-term effects of maternal contact and caregiving on the adult brain, little is known about the effects of maternal–newborn contact and parenting behavior on social brain functioning in human adults. We followed human neonates, including premature infants who initially lacked or received maternal–newborn skin-to-skin contact and full-term controls, from birth to adulthood, repeatedly observing mother–child social synchrony at key developmental nodes. We tested the brain basis of affect-specific empathy in young adulthood and utilized multivariate techniques to distinguish brain regions sensitive to others’ distinct emotions from those globally activated by the empathy task. The amygdala, insula, temporal pole (TP), and ventromedial prefrontal cortex (VMPFC) showed high sensitivity to others’ distinct emotions. Provision of maternal–newborn contact enhanced social synchrony across development from infancy and up until adulthood. The experience of synchrony, in turn, predicted the brain’s sensitivity to emotion-specific empathy in the amygdala and insula, core structures of the social brain. Social synchrony linked with greater empathic understanding in adolescence, which was longitudinally associated with higher neural sensitivity to emotion-specific empathy in TP and VMPFC. Findings demonstrate the centrality of synchronous caregiving, by which infants practice the detection and sharing of others’ affective states, for tuning the human social brain, particularly in regions implicated in salience detection, interoception, and mentalization that underpin affect sharing and human attachment.

Being born a mammal implies that the brain is immature at birth and develops in the context of the mother’s body, lactation, and caregiving behavior (1). Infants rely on the provisions embedded in the mother’s body, sensory stimuli (2), and the expression of well-adapted caregiving for maturation of neurobiological systems that sustain participation in the social world. Extant research in animal models has shown that breeches in the mother’s continuous presence and variability in the consistency of caregiving carry long-term effects on brain structure and function, particularly on systems that underpin sociality, and these effects are maintained throughout life, altering the adult animal’s capacity to coordinate social bonds, manage hardships, and parent the next generation (3, 4). However, while the human brain is slowest to mature and requires the most extended period of dependence (5), the long-term consequences of caregiving for the human social brain are largely unknown. The current birth-to-adulthood study examines the effects of maternal–newborn skin-to-skin contact (Kangaroo Care, KC) and parent–child social synchrony experienced across development on the brain’s empathic response to others’ emotional states in young adulthood. Social synchrony describes the coordination between the parent’s and child’s nonverbal behavior and communicative signals during social interactions in ways that enhance positivity, reciprocity, and mutual engagement (6, 7), and we tested its longitudinal impact on the brain basis of empathy, a core feature of the social brain.The human social brain integrates activity of subcortical, paralimbic, and cortical structures to sustain human social life, which requires rapid processing of social inputs, top–down regulation of intention and affect, and coordination of the two into the present moment (8). The social brain has undergone massive expansion across primate evolution to support humans’ exquisite social skills, communicative competencies, and mindreading capacities. It has been suggested that Homo sapiens’ success over other hominin owes to their unique empathic abilities, which allow humans to quickly identify and mentally share others’ affective states (9). Such multifaceted empathy, which integrates automatic identification of others’ distinct emotions with the ability to use interoceptive signals to detect others’ specific affect and the capacity to reflect on the changing emotional states of social partners, marks a fundamental achievement of the human social brain. The empathic social brain, in turn, enabled humans to coordinate actions for survival, fine-tune communicative signal systems, and partake in the joys and sorrows of others (10). Yet, while empathy is a core feature of human sociality that is tuned in mammals by patterns of parental care, the relational precursors of the neural empathic response have not been fully explored in human studies.Social synchrony is first observed in the third month of life when parents begin to coordinate with the infant’s nonverbal signals and interactive rhythms. Synchrony continues to mature across childhood and adolescence with the parent’s and child’s increasing reciprocity and adaptation to each other’s verbal and nonverbal communications, affective state, and pace of dialogue and is considered a prototypical experience that prepares children to life with others (11, 12). Through ongoing adaptation first to the infant’s nonverbal cues and then to the older child’s verbal and affective communications, parents orient children to social moments, practice rapid assessment of distinct emotional states, and, over time, enable children to simulate others’ mental states, fine-tuning the social brain and its capacity for empathy (13). Social synchrony undergoes maturation across development and evolves from nonverbal matching to a verbal dialogue that acknowledges others’ emotions, engages multiple perspectives, and reflects on feelings while retaining the interactive rhythms of the familiar dialogue from infancy to adulthood (1). The early experience of synchrony plays a key role in children’s social–emotional development and has been shown to predict the child’s later ability to engage with peers (14, 15), regulate emotions (4), exhibit cognitive control (16), manage stress (17), and display empathic understanding (18), indicating that improvements in mother–infant synchrony during its early stages may have long-term effects on the capacity for empathy and its neural underpinnings.The development of synchrony is highly sensitive to initial conditions. Conditions that compromise maternal–infant bonding bear long-term negative consequences for the development of social synchrony and, consequently, for maturation of human social abilities (19, 20). When infants are born prematurely and full maternal–infant bodily contact is initially lacking, the development of synchrony is halted and socioemotional competencies compromised. Notably, when we provided structured maternal–infant skin-to-skin contact (KC) to premature neonates during the postpartum period, the intervention improved not only social synchrony but also the functioning of regulatory support systems, such as circadian rhythmicity, autonomic maturity, stress responsivity, and exploratory behavior, the same systems that are shaped in young mammals by contact with the mother’s body (17, 18) and consistent presence (21).What may be the effects of maternal–newborn skin-to-skin contact and synchronous caregiving across development on the social brain in young adulthood? Utilizing our unique cohort, we imaged the neural empathic response in three groups of healthy young adults who were recruited at birth: infants born at full-term (FT), preterm infants receiving kangaroo contact (KC), and demographically and medically matched preterm infants receiving standard incubator care (SC) who were followed in our laboratory for two decades (Fig. 1A). We focused on the neural basis of empathy, particularly on the brain’s capacity to detect, affectively share, reflect, and empathize with the different emotions of others (22). Two key hypotheses were tested. First, we expected that the provision of maternal bodily contact in the neonatal period would enhance the expression of social synchrony in infancy and across development. This hypothesis is based on research in animal models which shows that maternal bodily contact, consistent presence, and sensory stimuli improve maternal caregiving and have long-term effects on brain and behavior (21, 23–25). Second, we hypothesized that the experience of synchrony would augment the brain’s capacity to differentiate among others’ emotional states. Synchrony is a dyadic experience by which infants practice the identification and sharing of others’ emotions and, as they develop, learn to imbue others’ feelings with meaning and representations (26). We expected that such practice would tune the brain of young adults to empathize with others’ distinct emotions, particularly in areas that have been linked with parent–child synchrony in the parental brain, the amygdala (27, 28) and insula (29).Open in a separate windowFig. 1.Birth-to-adulthood longitudinal study design and fMRI paradigm. (A) Three cohorts of infants and parents recruited at birth: full-term (FT) infants and two case-matched neurologically intact premature infants assigned to either Kangaroo Care (KC: infants receiving skin-to-skin contact with mother) or matched controls receiving standard incubator care (SC). Mother–child social synchrony was assessed at 4 mo (SD =1.14), 3 y (SD = 1.38), 12 y (SD = 1.62), and 20 y (SD = 2.01). (B) fMRI empathy paradigm. Example illustrates a pseudorandomized design in which participants were presented with an emotional probe followed by four photos depicting this probe. Participants were asked to empathize with the protagonists, and five blocks per condition were presented.Using a longitudinal sample of n = 96 young adults who were followed from infancy, we first examined the neural basis of affect-specific empathy. We employed a validated functional MRI (fMRI) paradigm that exposed participants to others’ distinct emotions (joy, sadness, and distress) and asked them to mentally empathize with the protagonists (30) (Fig. 1B). Consistent with prior imaging studies on the brain regions activated during empathy tasks (31–33), we focused on a network of regions sustaining empathy. This included limbic regions: the amygdala, a key player in emotion detection (34), and the parahippocampal gyrus. Also included were the anterior insula, superior temporal sulcus (STS), and temporal pole (TP) that have been repeatedly implicated in human empathy research (32, 35). We also examined the ventromedial prefrontal cortex (VMPFC), precuneus, and inferior parietal gyrus, known as hubs of the default mode network, which is related to self-referential processing, perspective-taking, and theory of mind tasks (36, 37) and plays a key role in social understanding (38).We used Representational Similarity Analysis (RSA), a multivariate brain pattern analytic technique, to differentiate brain areas that show a distinct neural pattern while empathizing with specific affective states from those generally activated by the empathy task but without a unique response to each emotion. By using RSA, we aimed to compare the distinct neural patterns activated during empathy to different emotions and characterize the brain basis of affect-specific empathy (39). A recent study employing RSA to pinpoint the neural signature of basic emotions indicated that the amygdala, insula, medial prefrontal cortex, frontal pole, and precuneus showed distinct representations for different emotional states (40). Consequently, and in light of research highlighting the role of the amygdala in fear (41) and empathy for negative affective states (42), we focused on the amygdala as a key area that may present differential response during empathy to positive versus negative emotions. Similarly, the insula exhibits similar activations during empathy for physical pain and emotional distress (43, 44), and we expected the insula to show differential activations during empathy to distressing versus nondistressing affective states. Areas including the dorsomedial prefrontal cortex (DMPFC), VMPFC, insula, TP, and precuneus have been shown in research using multivoxel pattern analysis to display specific activation patterns to emotion-related actions and mentalization (36), and we expected these areas to exhibit specific activation patterns during empathy with others’ distinct emotions.     

Mother–child adrenocortical synchrony: Roles of maternal overcontrol and child developmental phase

An increasing amount of empirical attention is focused on adrenocortical synchrony as an index of biobehavioral co-regulation between parent and child in the context of early child development. Working with an ethnically diverse community sample of children (N = 99, 50.5% male, ages 9–12), we collected saliva samples from mother–child dyads prior to and after a laboratory-based performance challenge task, and tested whether maternal overcontrol and child age moderated dyadic synchrony in cortisol. Results revealed that cortisol levels between mothers and children were significantly positively correlated at pretask for dyads with mean age and older children only, at 25-min post-task for all dyads, and at 45-min post-task for all dyads. Higher overcontrol/older child dyads exhibited a unique pattern of cortisol synchrony wherein at pretask, mother–child levels had the strongest positive correlation, whereas at 25 and 45 min, mother–child cortisol levels were significantly inversely correlated. These findings contribute to theory and research on parent–child relationships by examining parenting behavior, developmental stage, and adrenocortical synchrony in tandem.     

Left Ventricular Dyssynchrony and Its Effects on Cardiac Function in Patients with Newly Diagnosed Hypertension

Objectives: Left ventricular (LV) systolic synchrony, defined as simultaneous peak contractions of corresponding cardiac segments, is well documented to be impaired in hypertension but its effect on LV function is not clear. The aim of this study was to assess the impacts of LV systolic dyssynchrony on LV function in newly diagnosed hypertensives. Methods: Forty-eight newly diagnosed hypertensive patients and 33 controls were enrolled. All study population underwent a comprehensive echocardiographic evaluation including tissue synchrony imaging. The time to regional peak systolic tissue velocity (Ts) in LV by 12 segmental models was measured and two parameters of systolic dyssynchrony were computed. Results: Baseline demographic characteristics were similar in both study groups. Dyssynchrony parameters prolonged in newly diagnosed hypertensive patients compared to controls: the standard deviation (SD) of 12 LV segments Ts (40.2 ± 21 vs. 26.2 ± 13.4, P = 0.003); the maximal difference in Ts between any 2 of 12 LV segments (123.3 ± 61.5 vs. 79.8 ± 37.9, P = 0.001). In multivariable analysis, Ts-SD-12 was found to be an independent predictor for systolic function (β=-0.29, P = 0.008). But, both diastolic and global functions were not independently related to Ts-SD-12. Conclusion: LV synchronization is impaired in newly diagnosed hypertensive patients. LV dyssynchrony is one of the independent predictors of systolic function in hypertensive patients.     

Interactional synchrony and negative symptoms: An outcome study of body-oriented psychotherapy for schizophrenia

Objective: We sought to assess the efficacy of a manualized body-oriented psychotherapy (BPT) intervention for schizophrenia, by focusing on improvement of negative symptoms and on changes in interactional synchrony. We also explored aspects of a phenomenological theory of schizophrenia, which states that negative symptoms should be understood within an encompassing disturbance of subjectivity and intersubjectivity. Method: Sixteen persons with schizophrenia participated in 10 weeks of BPT. General psychiatric symptomatology and negative symptoms were assessed before and after therapy. Interactional synchrony was assessed via cross-correlations of movements between patient and interviewer in interviews conducted before and after therapy. Results: Psychiatric symptomatology and negative symptoms significantly improved with a medium effect size. We also demonstrated a significant increase in interactional synchrony with a strong effect size. Post hoc analyses showed a significant increase only with open-ended interviews conducted by the same interviewer. Furthermore, we explored the correlation between negative symptoms and interactional synchrony, finding a large inverse relationship. Conclusions: BPT for schizophrenia may effectively reduce patients’ negative symptoms and psychiatric symptomatology. Moreover, it may yield some recovery of pre-reflective social relations. Further evidence of the specific relation between negative symptoms and interactional synchrony would support a phenomenologically informed holistic view of schizophrenia.     

Neural oscillations in antipsychotic-naïve patients with a first psychotic episode

Objectives: In chronic schizophrenic psychoses, oscillatory abnormalities predominantly occur in prefrontal cortical regions and are associated with reduced communication across cortical areas. Nevertheless, it remains unclear whether similar alterations can be observed in patients with a first episode of psychosis (FEP), a state characterised by pathological features occurring in both late prodromal patients and initial phases of frank schizophrenic psychoses. Methods: We assessed resting-state electroencephalographic data of 31 antipsychotic-naïve FEP patients and 29 healthy controls (HC). We investigated the three-dimensional (3D) current source density (CSD) distribution and lagged phase synchronisation (LPS) of oscillations across small-scale and large-scale brain networks. We additionally investigated LPS relationships with clinical symptoms using linear mixed-effects models. Results: Compared to HC, FEP patients demonstrated abnormal CSD distributions in frontal areas of the brain; while decreased oscillations were found in the low frequencies, an increase was reported in the high frequencies (P?<?0.01). Patients also exhibited deviant LPS in the high frequencies, whose dynamics changed over increasing 3D cortico-cortical distances and increasing psychotic symptoms. Conclusions: These results indicate that in addition to prefrontal cortical abnormalities, altered synchronised neural oscillations are also present, suggesting possible disruptions in cortico-cortical communications. These findings provide new insights into the pathophysiological mechanisms of emerging schizophrenic psychoses.     

Widespread spatial integration in primary somatosensory cortex

Tactile discrimination depends on integration of information from the discrete receptive fields (RFs) of peripheral sensory afferents. Because this information is processed over a hierarchy of subcortical nuclei and cortical areas, the integration likely occurs at multiple levels. The current study presents results indicating that neurons across most of the extent of the hand representation in monkey primary somatosensory cortex (area 3b) interact, even when these neurons have separate RFs. We obtained simultaneous recordings by using a 100-electrode array implanted in the hand representation of primary somatosensory cortex of two anesthetized owl monkeys. During a series of 0.5-s skin indentations with single or dual probes, the distance between electrodes from which neurons with synchronized spike times were recorded exceeded 2 mm. The results provide evidence that stimuli on different parts of the hand influence the degree of synchronous firing among a large population of neurons. Because spike synchrony potentiates the activation of commonly targeted neurons, synchronous neural activity in primary somatosensory cortex can contribute to discrimination of complex tactile stimuli.     

From the Cover: Synchronizing theta oscillations with direct-current stimulation strengthens adaptive control in the human brain

Executive control and flexible adjustment of behavior following errors are essential to adaptive functioning. Loss of adaptive control may be a biomarker of a wide range of neuropsychiatric disorders, particularly in the schizophrenia spectrum. Here, we provide support for the view that oscillatory activity in the frontal cortex underlies adaptive adjustments in cognitive processing following errors. Compared with healthy subjects, patients with schizophrenia exhibited low frequency oscillations with abnormal temporal structure and an absence of synchrony over medial-frontal and lateral-prefrontal cortex following errors. To demonstrate that these abnormal oscillations were the origin of the impaired adaptive control in patients with schizophrenia, we applied noninvasive dc electrical stimulation over the medial-frontal cortex. This noninvasive stimulation descrambled the phase of the low-frequency neural oscillations that synchronize activity across cortical regions. Following stimulation, the behavioral index of adaptive control was improved such that patients were indistinguishable from healthy control subjects. These results provide unique causal evidence for theories of executive control and cortical dysconnectivity in schizophrenia.Networks involving frontal cortex allow us to adapt our actions to dynamic environments and adjust information processing following errors (1). This adaptive control is a hallmark of healthy goal-directed behavior, but it is dysfunctional in a variety of psychiatric and neurological disorders (2–4). In particular, the adaptive-control deficits that are a central feature of schizophrenia are highly predictive of poor functioning in daily life (5). In the laboratory, a canonical signature of adaptive control is the magnitude of posterror slowing of reaction time (RT), in which healthy subjects respond more slowly after making an error (6, 7). Patients with schizophrenia show an impaired ability to slow down their responses after errors (4, 8–13, but also 14, 15), providing a laboratory index that captures the rigid, perseverative, and maladaptive behavior that is characteristic of the disorder (8, 16).Adaptive control in the healthy brain is hypothesized to depend partly on the low-frequency EEG oscillations measured over medial-frontal cortex. The low-frequency oscillations are thought to reflect coordinated activity across the diverse set of brain areas recruited to perform a task (1, 17–22). In addition, medial-frontal theta (4–8 Hz) oscillations appear to signal the need for adaptive control across a variety of tasks and situations. Situations that call for adaptive control include stimulus novelty, response conflict, negative feedback, and behavioral errors, with all of these situations sharing a common medial-frontal spectral signature in the theta band (21). However, the functional significance of medial-frontal theta may be much broader than simply functioning as an alarm for the adaptive-control system. Theta oscillations have been hypothesized to serve as the temporal code that coordinates neuronal populations involved in implementing control (1, 19–21), with medial-frontal cortex working in concert with dorsolateral prefrontal areas to support flexible, adaptive behavior (1, 23–26). For example, when an error occurs, network-level oscillations allow executive mechanisms to adjust subordinate cognitive mechanisms (e.g., perceptual attention, response-selection thresholds). In the present study, we examined whether the executive-control deficits in patients with schizophrenia arise from communication and coordination failures among the cognitive subsystems flexibly linked through low-frequency oscillatory activity (3, 27, 28).We recorded EEG oscillations from outpatients with schizophrenia and demographically matched healthy controls (Table S1) while they performed a two-alternative forced-choice target discrimination task with response deadlines and interleaved stop-signal trials sufficient to produce errors (similar to a go/no-go task) (Fig. 1A). We reasoned that if temporal structured medial-frontal theta activity underlies normal adaptive control, the patients should exhibit abnormal medial-frontal theta provided that they show abnormal posterror slowing.Open in a separate windowFig. 1.tDCS model, task, and the behavioral and spectral signatures of adaptive control. (A) Target discrimination task requiring subjects to report the color of the target (red vs. blue, magenta vs. green, or purple vs. yellow) by pressing one of two buttons on a handheld gamepad. (B) Mean posterror RT slowing and mean intertrial phase coherence shown across stimulation conditions and subject groups. HC, healthy controls; SZ, patients with schizophrenia. (C) Mean total power and mean evoked power as in B. (D) Intertrial phase coherence (Left), total power (Middle), and evoked power (Right) at Cz on error minus correct trials shown across subject groups in the sham condition. Topographies show spatial distribution from the selected time-frequency measurement windows (green rectangles). (Far Left) Source estimate of intertrial phase coherence centered on Cz peak activity for healthy subjects in the sham condition is shown across sagittal, coronal, and axial MRI slices. A, anterior; L, left; P, posterior; R, right. (E) Schematic of tDCS montage and the modeled distribution of current during active tDCS on top and front views of a 3D reconstruction of the cortical surface. (F) Response-related time-frequency representations and topographies as in D shown across subject groups in the anodal tDCS condition. The analytical window for intertrial phase coherence and total power analyses was 4–8 Hz, −50 to 300 ms periresponse. The analytical window for evoked power analyses was 4–8 Hz, 0–100 ms postresponse. Data were scalp Laplacian-transformed.