INTRODUCTION
With growing globalization, interconnectedness, and complexity of our societies, “soft skills” have become increasingly important. Social competences, such as empathy, compassion, and taking the perspective of another person, allow for a better understanding of others’ feelings and different beliefs and are crucial for successful cooperation. Previous research has shown a reciprocal relationship between social abilities, mental health (
1,
2), and altruistic behavior (
3), suggesting that cultivating these capacities may have therapeutic and social benefits. Despite extensive research on the neural mechanisms underlying social skills such as empathy, compassion, and cognitive perspective-taking [Theory of Mind (ToM)] in healthy and clinical populations (
4–
24), it remains unknown whether training these capacities can induce structural brain changes. Plasticity research, despite its tradition and relevance to neuroscience, has, so far, mainly focused on learning-dependent brain reorganization of sensory, motor, and memory systems in animals and humans (
25–
33).
Recent mental training and mindfulness research in humans (
34–
38) has begun to address changes in gray matter volume after the training of higher-level skills, such as present-moment attention and mindfulness based on contemplative practices (
38–
41). However, most studies have been cross-sectional, focusing on meditation practitioners and not directly assessing training-related plasticity within training-naïve subjects (
42). The few published longitudinal training studies on structural plasticity to date have mainly assessed the effects of cultivating a rather broad range of mindfulness-related capacities, including attention, acceptance, and interoceptive awareness (
39–
41). Notably, samples in these studies were relatively small, and studies often lacked active control groups; furthermore, testing intervals were short, providing neither generalizable and robust estimates of brain change nor information about the effects of different types of mental practices on plasticity (
38–
41).
An increasing body of social cognitive neuroscience research suggests that we can distinguish at least two major routes of interpersonal understanding: a socio-affective route encompassing social emotions and motivation, such as empathy [the sharing of affect with others (
4)] and compassion [the concern for others and motivation to benefit the welfare of another (
5)]. Conversely, there is also evidence for socio-cognitive mechanisms that enable an individual to understand others’ beliefs and intentions [also referred to as ToM, mentalizing, or cognitive perspective-taking (
6,
7)]. Functional neuroimaging supported this distinction by revealing dissociable brain substrates underlying these processes. For socio-affective processing, studies have consistently identified a network, including limbic/paralimbic cortical areas, such as the anterior insula (AI) and anterior cingulate cortex (ACC) for empathy (
8,
9,
20,
21), together with lateral areas involved in emotion regulation, such as the dorsolateral prefrontal cortex (dlPFC) and supramarginal gyrus (SMG) (
19,
24,
43). Compassion further involves orbitofrontal cortices and ACC, as well as subcortical structures such as the ventral striatum and ventral tegmental area (
18,
22,
23). In contrast, cognitive perspective-taking or ToM is primarily supported by a network that includes the medial PFC, temporoparietal junction (TPJ), superior temporal gyrus/superior temporal sulcus (STS), and posterior midline regions such as the precuneus (
7–
17). Individual differences in empathizing and ToM competences have been found to show only a little correlation and to instead differentially relate to the function and structure of these networks (
5,
11–
13). Despite evidence of two dissociable functional networks supporting our capacity not only to empathize with and have compassion for others but also to infer their thoughts and beliefs, it is unknown whether these two functions can be differentially targeted by mental training and whether this intervention would result in changes in brain structure.
To study structural plasticity of attentional and social capacities in adulthood, we designed a secular mental training program that lasted over 9 months—the ReSource Project (
44). The main goal was to investigate the effects of three different mental training modules (Presence, Affect, and Perspective; each lasting 3 months) on magnetic resonance imaging (MRI)–based markers of cortical morphology and to relate those to behavioral indices. The first module (Presence) focused on cultivating present-moment attention and interoception. This module resembled well-known mindfulness interventions (
37,
45). On the basis of previous research, we expected increases in thickness in both attention-related networks in PFC, ACC, and parietal cortices (
46,
47), as well as interoceptive regions, such as AI (
48,
49). With respect to the two social intersubjective training modules (Affect and Perspective), we made predictions in line with the abovementioned literature showing dissociable networks underlying socio-emotional processes, such as empathy and compassion (
8,
9,
18–
23), and ToM (
7–
17). We expected that the socio-cognitive Perspective Module would result in changes in ToM networks, including the medial PFC, ventrolateral PFC, precuneus, temporal neocortices, and TPJ (
7–
17). We expected that the Affect Module would primarily target the structure of regions implicated in socio-emotional processing, such as AI, ACC, and orbital frontal regions, as well as the SMG and lateral PFC, the latter playing an important role in emotion regulation (
8,
9,
18–
24). Conversely, we expected that the socio-cognitive Perspective Module would result in changes in ToM networks, including the medial PFC, ventrolateral PFC, precuneus, temporal neocortices, and TPJ (
7–
17). Module-specific changes in morphology were expected to correlate with training-related behavioral changes in the same individuals, assessed via markers matched to the main functions trained in a module [that is, attention for Presence, compassion for Affect, and ToM for Perspective (
8,
44,
47,
50)].
For details on cohort selection, training content, behavioral phenotyping, image processing, and analysis, see the Supplementary Materials. Briefly, two randomly assigned training cohorts (TC1 and TC2) underwent three distinct 3-month modules with weekly instructed group sessions at the testing sites and daily exercises completed via smartphone and internet platforms (
Fig. 1, A and B, and table S1). Both cohorts underwent these three modules in alternating order (TC1: Presence→Affect→Perspective; TC2: Presence→Perspective→Affect), each serving as “active” control group for the other. In addition, we studied a matched retest control cohort (RCC) that did not undergo any training but followed the same measures as the training cohorts. Last, a third training cohort (TC3) completed only the Affect Module for 3 months, specifically to be compared to the first 3-month Presence training module.
Because the Presence Module fostered present-moment attention and interoception as abilities that may also support further practices (
51), it was administered first in line with the sequencing of other contemplative traditions and secular mindfulness programs (
37,
45). We subsequently opted for a crossover design that trained Affect and Perspective Modules in different order in our two closely matched training cohorts (TC1 and TC2), allowing for direct comparison between both social capacity trainings while accounting for sequence effects. To test for the effects of the Presence Module, we added another control group (TC3) undergoing a 3-month Affect training (TC3) without a preceding Presence Module. This design enabled the assessment of specific effects of a module against the others, both within and between cohorts. Notably, it offered control over unspecific effects associated with engaging in group training, teacher effects, and test-retest.
Whereas the Presence Module aimed at calming and stabilizing the mind using classical meditative practices, Affect and Perspective Modules targeted intersubjective capacities by training socio-affective or socio-cognitive skills, using classical meditation–based and dyadic interpersonal exercises. The latter dyads were practiced with another partner for 10 min daily via a smartphone application or in person during the weekly group sessions [for details, see Singer
et al. (
44) and Kok and Singer (
52)].
Participants were tested at baseline (T
0) and after each 3-month module (T
1, T
2, and T
3) using 3-T MRI and behavioral measures. Moreover, although all participants were scanned on the same MRI platform in Leipzig, participants were recruited and trained at two different sites (Berlin and Leipzig), with site-based subcohorts being matched for gender, age, education, and several socio-emotional trait markers (
44). Assessing these subcohorts separately allowed for the testing of consistency across sites.
Extensive quality control by two independent raters (S.L.V. and B.C.B.) corrected for segmentation faults and excluded cases with MRI artifacts by consensus (table S1). Surface extractions underwent manual corrections (
11,
53,
54). At the time of study initialization (2013), emerging techniques to prospectively control for so-called micromotion in structural MRI data were not yet fully established (
55–
58). However, by means of a parallel-acquired resting-state functional MRI (fMRI) acquisition in the same session, we assessed overall head motion as a proxy for the tendency of a subject to move in the scanner (
59,
60) and evaluated whether the effects were consistent after regressing out this surrogate marker. For details on quality control, sample selection, and analysis, see Materials and Methods. Longitudinal changes in the brain structure were assessed using mixed-effects analysis of MRI-based cortical thickness (
61), and data were smoothed at 20-mm full width at half maximum (FWHM). Results were corrected for multiple comparisons using random field theory (see Materials and Methods for details).
To assess structural change following each of the three training modules and to test for behavioral and functional specificities, we applied three canonical analyses: (i) We compared thickness change of each training module against the other modules and RCC; (ii) correlated individual differences in training-related thickness change with training-related behavioral change in markers of attention (Presence), compassion (Affect), and ToM (Perspective); (iii) and assessed the overlap between functional brain activation maps measured in these tasks at baseline and the observed structural change after training.
RESULTS
By investigating changes over the 9-month period of testing in the RCC, we observed only decreases in cortical thickness in lateral frontal regions [family-wise error (FWE) <0.025] (
Fig. 1C and table S2), consistent with findings showing aging-related cortical atrophy (
62,
63). Conversely, examining both training cohorts (TC1 and TC2) over the same 9 months revealed increases in thickness in right lateral and medial frontal regions (FWE <0.001), together with focal decreases in the right lingual gyrus (FWE <0.025) (fig. S1 and table S3).
To assess changes specific to the different mental practices, we compared longitudinal thickness changes between the training modules (
Fig. 1). For Presence (targeting interoception and attention), we observed thickness increases in the right PFC extending to ACC (FWE <0.001) and in bilateral occipital regions extending to inferior temporal cortices [FWE <0.05 (left) and <0.001 (right)] in both training cohorts relative to Affect and Perspective Modules (
Fig. 1D and table S2). These findings were consistent across training cohorts (
Fig. 1E), clusters (fig. S2), sites (that is, Berlin and Leipzig; fig. S3 and table S2), and when comparing TC1 and TC2 undergoing Presence to RCC (fig. S4 and table S4). Affect (socio-affective training) induced increases in a cluster extending from the right SMG to the insular-opercular regions and dlPFC (FWE <0.001), left mid/posterior cingulate (FWE <0.001), and bilateral parahippocampal areas [FWE <0.005 (left) and <0.025 (right)] (
Fig. 1D and table S2). Patterns were again consistent across cohorts (
Fig. 1E), clusters (fig. S2), and sites (fig. S3). A similar pattern was observed when testing Affect versus Perspective within-subjects only (TC1 and TC2; fig. S5 and table S5). Last, Perspective (socio-cognitive training) resulted in increases in thickness of the left ventrolateral PFC (FWE <0.05), left occipital regions (FWE < 0.025), and right middle temporal gyrus (FWE <0.05) (
Fig. 1D and table S2). These findings were again consistent in both cohorts (
Fig. 1E), clusters (fig. S2), and when testing Perspective versus Affect within-subjects only (fig. S5 and table S5).
In addition to assessing differential plasticity induced by the three modules, we were also interested in how changes would relate to improvements in targeted behavioral capacities. We developed and adapted behavioral tasks assessing components of attention (
47), as well as compassion and ToM (
8), each being a target outcome of one of the three training modules (
Fig. 1B). In a related publication (
50), we showed that the Perspective Module increased performance in the interactive video task assessing ToM, whereas Affect led to increased compassion ratings after watching neutral and emotionally distressing videos. Moreover, the Presence Module was associated with improvements in attention (
50). Here, we tested whether individual differences in training-related cortical thickness increases correlated with those in attention (after Presence), compassion (after Affect), and ToM (after Perspective) in the same individuals. Our analyses revealed that improvements in attentional scores during Presence related to increased thickness in left middle temporal regions (T
0→T
1; TC1,
r = 0.46; TC2,
r = 0.19;
Fig. 2A and table S6). Conversely, compassion increases after Affect training were associated with thickness increases of the right insula extending to the temporal pole, with findings consistent across all cohorts undergoing Affect training [TC1, T
1→T
2 (
r = 0.37); TC2, T
2→T
3 (
r = 0.28); TC3, T
0→T
1 (
r = 0.31);
Fig. 2A and table S6]. Last, enhanced ToM performance after Perspective training was related to increased thickness in left parietal regions [TC1, T
2→T
3 (
r = 0.32); TC2, T
1→T
2 (
r = 0.32);
Fig. 2A and table S6] and right TPJ [TC1, T
1→T
2 (
r = 0.44); TC2, T
2→T
3 (
r = 0.24);
Fig. 2A and table S6], with findings again being consistent across cohorts.
To finally explore whether areas showing training-associated thickness increases that were related to behavioral performance overlapped with postulated functional networks, we overlaid a significant structural change with fMRI activations at baseline in the same participants during tasks probing attention, socio-affective, or socio-cognitive processing (
8,
47). Functional networks overlapped with module-specific structure-behavior modulations: Compassion-related AI increases overlapped with activations during the socio-affective task, whereas ToM performance–related increases in TPJ thickness overlapped with functional activations observed during the socio-cognitive task (
Fig. 2B). However, attention-related thickness increases did not overlap with functional activation during the attention task at baseline.
DISCUSSION
MRI and behavioral results derived from a 9-month longitudinal mental training study, the ReSource Project (
44), provide evidence for structural plasticity of the social brain in healthy adults between 20 and 55 years of age. We demonstrated a training-specific change in cortical morphology after three different mental training modules focusing on improving mindfulness-based attention (Presence), socio-affective skills (Affect), and socio-cognitive capacities (Perspective). Notably, module-specific thickness increases correlated with individual improvements in attention, compassion, and ToM in respective behavioral markers after training and, in part, overlapped with functional networks obtained from tasks targeting module-specific functions at baseline before training.
After 3 months of Presence training, our two independently matched cohorts (that is, TC1 and TC2) showed increases in thickness in the anterior PFC extending to ACC relative to RCC. This finding is in accordance with meta-analytical synthesis of cross-sectional studies reporting altered PFC/ACC morphology in expert mindfulness meditators relative to controls (
42,
64). To capture attention-related increases after Presence training in the ReSource Project, a measure of executive attention/conflict resolution was selected (
47,
50). Consistent with these findings, we observed improved attention after Presence training. However, significant correlations between training-related thickness changes and attentional improvements did not lie within the functional network classically linked to executive attention, including the lateral PFC and ACC (
47,
65), but rather in inferior temporal regions. Arguably, the applied task may not have tapped into the full content of the Presence Module, which also encompassed interoception and metacognitive awareness (
44). Monitoring and meta-awareness–related processing could be in line with thickening in the medial PFC, a region suggested by cross-sectional studies to participate in these functions (
66–
68).
Our results revealed evidence that two further mental training modules focusing on socio-affective and socio-cognitive capacities induced structural plasticity in nonoverlapping brain networks. A priori, the Affect Module was expected to result in changes primarily in affect-relevant cortices, such as AI, midcingulate, and orbital frontal regions, as well as the subgenual ACC, SMG, and dlPFC (
8,
9,
18–
24). For Perspective, we primarily expected changes in ToM networks including the medial PFC, ventrolateral PFC, precuneus, temporal neocortices, and TPJ (
7–
17). Contrary to mindfulness-based Presence training, Affect training resulted in structural increases in regions implicated in empathy and emotion regulation (
8,
9,
18–
24,
43). Notably, changes following Affect overlapped partially with functional activations associated with empathy and compassion at baseline (
8). Affect training–related right anterior to mid-insula thickening was associated with enhanced compassion ratings after training. This supports a role of insular cortex in representing and integrating interoceptive and affective signals into feeling states (
21,
48) and for social emotions such as empathy (
21,
69) and compassion (
18,
70). By comparing Affect-only training (in TC3) with the 3-month Presence module in TC1 and TC2, we observed increases in SMG and sensorimotor regions extending to the insular cortex in the former, whereas TC1 and TC2 showed medial PFC thickening after Presence. This raises the possibility to target socio-affective functions without prior training in stabilizing the mind, which is to be addressed in future work.
In contrast to Affect training, Perspective aimed at improving metacognitive skills and perspective-taking on one’s own thoughts, aspects of the self, and the mental states of others (ToM). Relative to the other modules, it resulted in increased thickness of the middle temporal gyrus, a region reliably associated with ToM (
7–
10), and left ventrolateral PFC. The latter has been related to self-perspective inhibition, an executive control process supporting the reduction of interference arising in ToM tasks when one’s own perspective differs from that of another person and needs to be inhibited (
71). Changes observed in Perspective partially overlapped with functional activation when the participants performed a ToM task at baseline (
8). However, no thickness increases were found in the dorsomedial PFC and precuneus, regions a priori associated with ToM. Notably, thickness increases in the posterior parietal cortex and TPJ correlated with individual differences in ToM performance improvements after training and may reflect the implication of both regions in cognitive perspective-taking processes (
8–
10,
17,
72). Although we observed cortical thickness increases following Perspective relative to the other modules, we acknowledge that unlike the direct comparison of the 3-month Affect and Presence Modules, we could not test directly for specific effects of the 3-month Perspective training. For practical reasons, we could not include another active training cohort that focused only on perspective-taking in the first 3 months.
In addition to the reliability of effects across cohorts and analyses, the findings were largely consistent across both subcohorts from Berlin and Leipzig. Notably, however, training-related change (
Fig. 1) did not show close spatial correspondence to thickness correlations with behavioral improvements (
Fig. 2). Each module aimed at cultivating broader categories of mindful attention, socio-affective, and socio-cognitive processes but not a specific function per se. This might have possibly resulted in a different pattern of average change as compared to investigating the brain areas underlying specific core functions, such as ToM or compassion. Although STS or ventrolateral PFC may have a more general role in socio-cognitive processing, TPJ may be specifically sensitive to mentalizing abilities, as measured in the present ToM task (
8). This view would be in line with the hypothesis of a specific role of TPJ for false-belief attribution (
15,
16). Similarly, although Affect-related thickness increases in parietal and frontal networks might reflect general enhancement in emotion regulation, insular morphology may be particularly sensitive in capturing individual differences in social emotions, such as empathy and compassion (
8,
21,
73).
Training-related changes may not always follow a linear trajectory (
28,
74–
76), and morphological changes have been reported to consolidate following an initial increase. This argument may be supported by our results, as we found overall training-induced increases in PFC regions, mainly driven by change in the first 3 months. In humans, PFC is central to high-level cognition (
77) and social cognition, in particular (
8–
10,
17,
72,
78), and is likely targeted by all three modules. This might also explain why we did not find a priori predicted increases in medial PFC (for Perspective) and ACC and orbitofrontal regions (for Affect) relative to Presence (ending at T
1), as these regions support functions already targeted in Presence. Post hoc analyses referring to potential sequence effects of Presence on the following modules (see the Supplementary Materials) suggest that initial changes in PFC after Presence modulated changes in subsequent Perspective Modules. Possibly, participants learned functions associated with increases in frontal regions during Presence training that are also needed for perspective-taking. Consolidation processes secondary to the continued practice and increased task skill (
74) could also be the cause of observed decreases in cortical thickness in the training groups compared to RCC. Although we had no a priori hypothesis for learning-dependent decreases of gray matter, cortical thinning may also play a role in learning (
64,
79,
80), possibly through usage-dependent selective elimination of synapses (
81,
82).
Because plasticity research based on this high-level mental training can only be conducted in living humans with noninvasive neuroimaging, we can merely speculate about the neurobiological mechanisms driving the observed structural changes. Learning-induced plasticity might involve synaptic remodeling and changes in neuronal morphology (
27,
83), as well as non-neuronal processes such as angiogenesis and divisions of astrocytes and oligodendrocyte progenitor cells (
84). Because the focus of the current study was on the thickness of the cortical mantle, further research should assess subcortical regions using methods developed to probe whole-brain gray matter (
85) and white matter (
86) changes.
In conclusion, our findings of structural plasticity in healthy adults in faculties relevant to social intelligence and social interactions suggest that the type of mental training matters. Depending on whether participants’ daily practice focused on cultivating socio-emotional capacities (compassion and prosocial motivation) or socio-cognitive skills (putting oneself into the shoes of another person) gray matter increased selectively in areas supporting these functions. Our findings suggest a potential biological basis for how mindfulness and different aspects of social intelligence could be nurtured. Research will be needed to evaluate the utility of training in individuals suffering from deficits in social cognition, such as autism or psychopathy. In addition, it should be investigated whether social cognitive training can contribute to an increase in cooperation and well-being in corporate settings. In the context of education, it may be interesting to evaluate the potential of these techniques to promote children’s soft skills and social intelligence.