Functional neuroimaging and behavioral correlates of multisite tDCS as an add-on to language training in a person with post-stroke non-fluent aphasia: a year-long case study.

Mary, who experienced non-fluent aphasia as a result of an ischemic stroke, received 10 years of personalized language training (LT), resulting in transient enhancements in speech and comprehension. To enhance these effects, multisite transcranial Direct Current Stimulation (tDCS) was added to her LT regimen for 15 sessions. Assessment using the Reliable Change Index showed that this combination improved her left inferior frontal connectivity and speech production for two months and significantly improved comprehension after one month. The results indicate that using multisite transcranial direct current stimulation (tDCS) can improve the effectiveness of language therapy (LT) for individuals with non-fluent aphasia.

Larger dlPFC and vmPFC grey matter volumes are associated with high adherence to the Mediterranean diet: A cross-sectional study in older adults.

Dietary self-control is associated with inter-individual differences in neuroanatomy. Yet, whether such inter-individual differences are also associated with healthier dietary patterns is yet to be determined. In this cross-sectional study, a total of 100 northern Portuguese older community-dwellers were assessed with regards to i) the adherence to a healthy dietary eating pattern - the Mediterranean diet (MedDiet), and ii) grey matter density (GMD) of brain regions associated with valuation and dietary self-regulation, the ventromedial (vmPFC) and dorsolateral prefrontal cortex (dlPFC), through voxel-based morphometry. Healthy food choices were ascertained through the Mediterranean Diet Adherence Screener (MEDAS) where higher scores indicated greater adherence to the MedDiet. Voxel-based morphometry showed that greater grey matter density in the dlPFC and vmPFC associated with a higher adherence to the MedDiet. These results replicate previous links between dietary decision-making measured under laboratory conditions and the neuroanatomy of the brain's valuation and self-control system. Importantly, they shed new light on the potential relevance of inter-individual differences in the neuroanatomy of these two brain regions for adhering to healthier dietary patterns in everyday life.

Nodes of the default mode network implicated in the quality of empathic responses: A clinical perspective of the empathic response

The ability to empathize with another person's inner experience is believed to be a central element of our social interactions. Previous research has focused on cognitive (e.g., theory of mind) and emotional (e.g., emotional contagion) empathy, and less on behavioral factors (i.e., the ability to respond empathically). Recent studies suggest that the Default Mode Network (DMN) mediates individual variability in distinct empathy-related behaviors. However, little is known about DMN activity during actual empathic responses, understood in this study as the ability to communicate our understanding of the others’ experience back to them. This study used an empathy response paradigm with 28 participants (22-37 years old) to analyze the relationship between the quality of empathic responses to 14 empathy-eliciting vignettes and patterns of attenuation in the DMN. Overall, the results suggest that high levels of empathic response, are associated with sustained activation of the DMN when compared with lower levels of empathy. Our results demonstrate that the DMN becomes increasingly involved in empathy-related behavior, as our level of commitment to the other's experience increases. This study represents a first attempt to understand the relation between the capacity for responding in a supportive way to others’ needs and the intra-individual variability of the pattern of the DMN attenuation. Here we underline the critical role that the DMN plays in high-level social cognitive processes and corroborate the DMN role in different psychiatric disorders associated with a lack of empathy. (AU)

Nodes of the default mode network implicated in the quality of empathic responses: A clinical perspective of the empathic response.

The ability to empathize with another person's inner experience is believed to be a central element of our social interactions. Previous research has focused on cognitive (e.g., theory of mind) and emotional (e.g., emotional contagion) empathy, and less on behavioral factors (i.e., the ability to respond empathically). Recent studies suggest that the Default Mode Network (DMN) mediates individual variability in distinct empathy-related behaviors. However, little is known about DMN activity during actual empathic responses, understood in this study as the ability to communicate our understanding of the others' experience back to them. This study used an empathy response paradigm with 28 participants (22-37 years old) to analyze the relationship between the quality of empathic responses to 14 empathy-eliciting vignettes and patterns of attenuation in the DMN. Overall, the results suggest that high levels of empathic response, are associated with sustained activation of the DMN when compared with lower levels of empathy. Our results demonstrate that the DMN becomes increasingly involved in empathy-related behavior, as our level of commitment to the other's experience increases. This study represents a first attempt to understand the relation between the capacity for responding in a supportive way to others' needs and the intra-individual variability of the pattern of the DMN attenuation. Here we underline the critical role that the DMN plays in high-level social cognitive processes and corroborate the DMN role in different psychiatric disorders associated with a lack of empathy.

Perceived stress modulates the activity between the amygdala and the cortex.

The significant link between stress and psychiatric disorders has prompted research on stress's impact on the brain. Interestingly, previous studies on healthy subjects have demonstrated an association between perceived stress and amygdala volume, although the mechanisms by which perceived stress can affect brain function remain unknown. To better understand what this association entails at a functional level, herein, we explore the association of perceived stress, measured by the PSS10 questionnaire, with disseminated functional connectivity between brain areas. Using resting-state fMRI from 252 healthy subjects spanning a broad age range, we performed both a seed-based amygdala connectivity analysis (static connectivity, with spatial resolution but no temporal definition) and a whole-brain data-driven approach to detect altered patterns of phase interactions between brain areas (dynamic connectivity with spatiotemporal information). Results show that increased perceived stress is directly associated with increased amygdala connectivity with frontal cortical regions, which is driven by a reduced occurrence of an activity pattern where the signals in the amygdala and the hippocampus evolve in opposite directions with respect to the rest of the brain. Overall, these results not only reinforce the pathological effect of in-phase synchronicity between subcortical and cortical brain areas but also demonstrate the protective effect of counterbalanced (i.e., phase-shifted) activity between brain subsystems, which are otherwise missed with correlation-based functional connectivity analysis.

Association of amygdala size with stress perception: Findings of a transversal study across the lifespan.

Daily routines are getting increasingly stressful. Interestingly, associations between stress perception and amygdala volume, a brain region implicated in emotional behaviour, have been observed in both younger and older adults. Life stress, on the other hand, has become pervasive and is no longer restricted to a specific age group or life stage. As a result, it is vital to consider stress as a continuum across the lifespan. In this study, we investigated the relationship between perceived stress and amygdala size in 272 healthy participants with a broad age range. Participants were submitted to a structural magnetic resonance imaging (MRI) to extract amygdala volume, and the Perceived Stress Scale (PSS) scores were used as the independent variable in volumetric regressions. We found that perceived stress is positively associated with the right amygdala volume throughout life.

The Association of Metabolic Dysfunction and Mood Across Lifespan Interacts With the Default Mode Network Functional Connectivity.

Background: Numerous studies suggest a relationship between depression and metabolic syndrome, which is likely influenced by age. Interestingly, functional imaging analysis has shown an association between functional connectivity in the default mode network (DMN-FC) and components of metabolic syndrome, which is explored in this study. Methods: From a larger longitudinal cohort study on healthy aging, 943 individuals were extensively characterized for mood and cognition. Among these, 120 individuals who were selected for displaying extreme cognitive performance within the normal range (good and poor performers) were further studied. Here, in a cross-sectional design, using confirmatory factor analysis (CFA), the association between metabolic dysfunction and depressive mood as a function of age and its relationship with DMN-FC was studied. Results: Metabolic dysfunction was modeled as a second-order latent variable using CFA. First-order latent variables were obesity, glucose dysmetabolism, lipids imbalance, and blood pressure. Using multiple linear regression models, this study observed that metabolic dysfunction, glucose dysmetabolism, and lipids imbalance were linearly associated with depressive mood, and the association with obesity was U-shaped. The association of metabolic dysfunction, obesity, and glucose dysmetabolism with depressive mood is positive for the younger individuals in our sample and vanishes with aging. The FC of the right superior temporal gyrus with the DMN correlated with both obesity and depressive mood. In participants with higher obesity scores, FC increased with higher GDS scores, while in those with lower GDS scores, FC decreased. Age and blood pressure were associated with a more complex pattern of association between FC of the right supramarginal gyrus and GDS score. Conclusion: The association of metabolic dysfunction with depressive mood is influenced by age and relates with differential patterns of DMN-FC. The combination of the effects of age, mood, and metabolic dysfunction is likely to explain the heterogeneity of DMN-FC, which deserves further investigation with larger and longitudinal studies.

Amygdala size varies with stress perception.

Stress is inevitably linked to life. It has many and complex facets. Notably, perception of stressful stimuli is an important factor when mounting stress responses and measuring its impact. Indeed, moved by the increasing number of stress-triggered pathologies, several groups drew on advanced neuroimaging techniques to explore stress effects on the brain. From that, several regions and circuits have been linked to stress, and a comprehensive integration of the distinct findings applied to common individuals is being pursued, but with conflicting results. Herein, we performed a volumetric regression analysis using participants' perceived stress as a variable of interest. Data shows that increased levels of perceived stress positively associate with the right amygdala and anterior hippocampal volumes.

Alterations in functional connectivity are associated with white matter lesions and information processing efficiency in multiple sclerosis.

Functional connectivity (FC) is typically altered in individuals with Multiple Sclerosis (MS). However, in relapsing-remitting multiple sclerosis (RRMS) patients, the relationship between brain FC, tissue integrity and cognitive impairment is still unclear as contradictory findings have been documented. In this exploratory study we compared both the whole brain connectome and resting state networks (RSNs) FC of twenty-one RRMS and seventeen healthy controls (HCs), using combined network based statistics and independent component analyses. The total white matter (WM) lesion volume and information processing efficiency were also correlated with FC in the RRMS group. Both whole brain connectome and individual RSNs FC were diminished in patients with RRMS compared to HC. Additionally, the reduction in FC was found to be a function of the total WM lesion volume, with greatest impact in those harboring the largest lesion volume. Finally, a positive correlation between FC and information processing efficiency was observed in RRMS. This complimentary whole brain and RSNs FC approach can contribute to clarify literature inconsistencies regarding FC alterations and provide new insights on the white matter structural damage in explaining functional abnormalities in RRMS.

Higher Adherence to the Mediterranean Diet Is Associated With Preserved White Matter Integrity and Altered Structural Connectivity.

The Mediterranean diet (MedDiet) has been associated with cognitive performance. Yet, controlled trials have yielded contradictory results. To tackle this controversy, a comprehensive multimodal analysis of the association of the MedDiet with cognitive performance and brain structure in normative aging is still necessary. Here, community dwellers ≥50 years from a cohort study on normative aging (n = 76) underwent a (i) magnetic resonance imaging session with two acquisitions: structural and diffusion-weighted imaging (DWI); (ii) neuropsychological battery of tests focusing on memory and executive functioning; and (iii) dietary assessment through the Mediterranean Diet Assessment Screener (MEDAS, score range: 0-14, scores ≥10 indicate high adherence to the Mediterranean diet) 18 months prior to the brain imaging and neuropsychological assessment. We found that high adherence to the MedDiet (MEDAS ≥10) was associated with higher values of fractional anisotropy and lower diffusivity values in the brain white matter. Similarly, high adherence to the MedDiet was associated with higher structural connectivity between left hemisphere brain regions. Specifically, the amygdala, lingual, olfactory, middle occipital gyrus, and calcarine areas. No association was found between high adherence to the MedDiet and total brain volumes or hypointensities. Higher adherence to the MedDiet was positively associated with executive functioning scores. These results suggest that high adherence to the MedDiet positively associates with brain health, specifically with executive function scores and white matter integrity of bundles related to the processing and integration of taste, reward, and decision making. These findings seem to support the view that the MedDiet should be part of recommendations to promote a healthy brain.

Changes in the Effective Connectivity of the Social Brain When Making Inferences About Close Others vs. the Self.

Previous research showed that the ability to make inferences about our own and other's mental states rely on common brain pathways; particularly in the case of close relationships (e.g., romantic relationships). Despite the evidence for shared neural representations of self and others, less is known about the distributed processing within these common neural networks, particularly whether there are specific patterns of internode communication when focusing on other vs. self. This study aimed to characterize context-sensitive coupling among social brain regions involved in self and other understanding. Participants underwent an fMRI while watching emotional video vignettes of their romantic partner and elaborated on their partner's (other-condition) or on their own experience (self-condition). We used dynamic causal modeling (DCM) to quantify the associated changes in effective connectivity (EC) in a network of brain regions involved in social cognition including the temporoparietal junction (TPJ), the posterior cingulate (PCC)/precuneus and middle temporal gyrus (MTG). DCM revealed that: the PCC plays a central coordination role within this network, the bilateral MTG receives driving inputs from other nodes suggesting that social information is first processed in language comprehension regions; the right TPJ evidenced a selective increase in its sensitivity when focusing on the other's experience, relative to focusing on oneself.

Altered response to risky decisions and reward in patients with obsessive­compulsive disorder

Background: Patients with obsessive­compulsive disorder (OCD) employ ritualistic behaviours to reduce or even neutralize the anxiety provoked by their obsessions. The presence of excessive rumination and indecision has motivated the view of OCD as a disorder of decision-making. Most studies have focused on the "cold," cognitive aspects of decision-making. This study expands current understanding of OCD by characterizing the abnormalities associated with affective, or "hot" decision-making. Methods: We performed a functional MRI study in a sample of 34 patients with OCD and 33 sex- and age-matched healthy controls, during which participants made 2-choice gambles taking varying levels of risk. Results: During risky decisions, patients showed significantly reduced task-related activation in the posterior cingulum, lingual gyrus and anterior cingulate cortex. We identified significant group × risk interactions in the calcarine cortex, precuneus, amygdala and anterior cingulate cortex. During the outcome phase, patients with OCD showed stronger activation of the orbitofrontal cortex, anterior cingulate cortex and putamen in response to unexpected losses. Limitations: The group of patients not receiving medication was very small (n = 5), which precluded us from assessing the effect of medication on risk-taking behaviour in these patients. Conclusion: Obsessive­compulsive disorder is associated with abnormal brain activity patterns during risky decision-making in a set of brain regions that have been consistently implicated in the processing of reward prediction errors. Alterations in affective "hot" processes implicated in decision-making may contribute to increased indecisiveness and intolerance to uncertainty in patients with OCD.

The resting-brain of obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is one of the most debilitating psychiatric conditions, having a dramatic impact on patients' daily living. In this work, we aimed to explore resting-state functional connectivity in OCD patients, using an independent component analysis. Eighty individuals (40 patients and 40 healthy controls) performed a resting state fMRI protocol. OCD patients displayed reduced functional connectivity (FC) in visual and sensorimotor networks. In addition, patients displayed decreased FC between sensory networks and increased FC between default-mode and cerebellar networks.

Brain circuits involved in understanding our own and other's internal states in the context of romantic relationships.

Social interactions require the capacity to understand both our and other's internal states. These semi-independent skills, the ability to understand oneself and others, seem to rely on the same type of representations and recruit similar brain areas. In this study, we looked at the neural basis of self and other processing in the context of an interaction with a significant other. Fourty-two participants in a monogamous relationship completed an fMRI task in which they watched a set of video-vignettes of his/her romantic partner expressing emotional contents. Participants were asked to elaborate on his/her spouse´s experience (other condition) and on his/her own experience when watching the video-vignettes (self-condition). The results showed a significant overlap in the brain activation for both conditions (e.g. anterior insula, posterior cingulate/precuneus, inferior frontal gyrus, inferior parietal lobule). In addition, the self-condition recruited brain areas associated with interoceptive processing and affect sharing (e.g., posterior insula), whereas the other-condition engaged brain areas involved in the cognitive representation of another's internal states and self-other distinction (e.g., fusiform, supramarginal gyrus, angular gyrus and temporoparietal junction).

Empathy by default: correlates in the brin at rest / Empatía por defecto: correlatos en el cerebro en reposo

Background: Empathy, defined as the ability to access and respond to the inner world of another person, is a multidimensional construct involving cognitive, emotional and self-regulatory mechanisms. Neuroimaging studies report that empathy recruits brain regions which are part of the social cognition network. Among the different resting state networks, the Default Mode Network (DMN) may be of particular interest for the study of empathy since it has been implicated in social cognition tasks. Method: The current study compared the cognitive and emotional empathy scores, as measured by the Interpersonal Reactivity Index, with the patterns of activation within the DMN, through the neuroimaging methodology of resting-state functional magnetic resonance. Results: Results suggest a significant positive correlation between cognitive empathy and activation of the bilateral superior medial frontal cortex nodes of the DMN. Contrastingly, a negative correlation was found between emotional empathy and the same brain region. Conclusions: Overall, this data highlights a critical role of the medial cortical regions of the DMN, specifically its anterior node, for both cognitive and emotional domains of the empathic process (AU)

Antecedentes: la empatía, definida como la capacidad de acceder y responder al mundo interior de otra persona, es un constructo multidimensional que implica mecanismos cognitivos, emocionales y autorreguladores. Los estudios de neuroimagen informan que la empatía recluta regiones cerebrales que forman parte de la red de cognición social. Entre las diferentes redes de estado de reposo, la Red Neuronal por Defecto (Default Mode Network; DMN) puede ser de particular interés para el estudio de la empatía, ya que ha sido implicada en tareas de cognición social. Método: el presente estudio comparó los valores de empatía cognitiva y emocional, medidos por medio del Índice de Reactividad Interpersonal, con los patrones de activación dentro de la DMN, a través de la metodología de neuroimagen por resonancia magnética funcional en estado de reposo. Resultados: los resultados sugieren una correlación positiva significativa entre la empatía cognitiva y la activación bilateral de los nodos de la región frontomedial superior de la DMN. En contraste, se encontró una correlación negativa entre la empatía emocional y la misma región del cerebro. Conclusiones: en general, estos datos destacan un papel crítico de las regiones corticales mediales de la DMN, específicamente su nodo anterior, para los dominios cognitivo y emocional del proceso empático (AU)

Patterns of Default Mode Network Deactivation in Obsessive Compulsive Disorder.

The objective of the present study was to research the patterns of Default Mode Network (DMN) deactivation in Obsessive Compulsive Disorder (OCD) in the transition between a resting and a non-rest emotional condition. Twenty-seven participants, 15 diagnosed with OCD and 12 healthy controls (HC), underwent a functional neuroimaging paradigm in which DMN brain activation in a resting condition was contrasted with activity during a non-rest condition consisting in the presentation of emotionally pleasant and unpleasant images. Results showed that HC, when compared with OCD, had a significant deactivation in two anterior nodes of the DMN (medial frontal and superior frontal) in the non-rest pleasant stimuli condition. Additional analysis for the whole brain, contrasting the resting condition with all the non-rest conditions grouped together, showed that, compared with OCD, HC had a significantly deactivation of a widespread brain network (superior frontal, insula, middle and superior temporal, putamen, lingual, cuneus, and cerebellum). Concluding, the present study found that OCD patients had difficulties with the deactivation of DMN even when the non-rest condition includes the presentation of emotional provoking stimuli, particularly evident for images with pleasant content.

The association between stress and mood across the adult lifespan on default mode network.

Aging of brain structure and function is a complex process characterized by high inter- and intra-individual variability. Such variability may arise from the interaction of multiple factors, including exposure to stressful experience and mood variation, across the lifespan. Using a multimodal neuroimaging and neurocognitive approach, we investigated the association of stress, mood and their interaction, in the structure and function of the default mode network (DMN), both during rest and task-induced deactivation, throughout the adult lifespan. Data confirmed a decreased functional connectivity (FC) and task-induced deactivation of the DMN during the aging process and in subjects with lower mood; on the contrary, an increased FC was observed in subjects with higher perceived stress. Surprisingly, the association of aging with DMN was altered by stress and mood in specific regions. An increased difficulty to deactivate the DMN was noted in older participants with lower mood, contrasting with an increased deactivation in individuals presenting high stress, independently of their mood levels, with aging. Interestingly, this constant interaction across aging was globally most significant in the combination of high stress levels with a more depressed mood state, both during resting state and task-induced deactivations. The present results contribute to characterize the spectrum of FC and deactivation patterns of the DMN, highlighting the crucial association of stress and mood levels, during the adult aging process. These combinatorial approaches may help to understand the heterogeneity of the aging process in brain structure and function and several states that may lead to neuropsychiatric disorders.

Alterations of the default mode network connectivity in obsessive-compulsive personality disorder: A pilot study.

Obsessive-compulsive personality (OCPD) disorder is characterized by a pattern of excessive self-control, perfectionism and behavioral and cognitive rigidity. Despite the fact that OCPD is the most common personality disorder in the general population, published studies looking at the brain correlates of this disorder are practically nonexistent. The main goal of this study was to analyze the presence of brain alterations in OCPD when compared to healthy controls, specifically at the level of the Default Mode Network (DMN). The DMN is a well-established resting state network which was found to be associated with psychological processes that may play a key role in OCPD (e.g., self-awareness, episodic future thinking and mental simulation). Ten individuals diagnosed with OCPD and ten healthy controls underwent a clinical assessment interview and a resting-state functional magnetic resonance imaging (fMRI) acquisition. The results show that OCPD patients presented an increased functional connectivity in the precuneus (i.e., a posterior node of the DMN), known to be involved in the retrieval manipulation of past events in order to solve current problems and develop plans for the future. These results suggest that this key node of the DMN may play an important role in the pathophysiology of OCPD.

Altered functional connectivity of the default mode network in Williams syndrome: a multimodal approach.

Resting state brain networks are implicated in a variety of relevant brain functions. Importantly, abnormal patterns of functional connectivity (FC) have been reported in several neurodevelopmental disorders. In particular, the Default Mode Network (DMN) has been found to be associated with social cognition. We hypothesize that the DMN may be altered in Williams syndrome (WS), a neurodevelopmental genetic disorder characterized by an unique cognitive and behavioral phenotype. In this study, we assessed the architecture of the DMN using fMRI in WS patients and typically developing matched controls (sex and age) in terms of FC and volumetry of the DMN. Moreover, we complemented the analysis with a functional connectome approach. After excluding participants due to movement artifacts (n = 3), seven participants with WS and their respective matched controls were included in the analyses. A decreased FC between the DMN regions was observed in the WS group when compared with the typically developing group. Specifically, we found a decreased FC in a posterior hub of the DMN including the precuneus, calcarine and the posterior cingulate of the left hemisphere. The functional connectome approach showed a focalized and global increased FC connectome in the WS group. The reduced FC of the posterior hub of the DMN in the WS group is consistent with immaturity of the brain FC patterns and may be associated with the singularity of their visual spatial phenotype.

Macro- and micro-structural white matter differences correlate with cognitive performance in healthy aging.

Studies have shown that white matter (WM) volumetric reductions and overall degradation occur with aging. Nonetheless little is known about the WM alterations that may underlie different cognitive status in older individuals. The main goal of the present work was to identify and characterize possible macro and microstructural WM alterations that could distinguish between older healthy individuals with contrasting cognitive profiles (i.e., "poor" vs "good" cognitive performers). Structural and diffusion magnetic resonance imaging was performed in order to quantify local WM volumes, white matter signal abnormalities (WMSA) volume (a measure of lesion burden) and diffusion tensor imaging scalar maps known to probe WM microstructure. A battery of neurocognitive/psychological tests was administered to assess the cognitive performance. Poor performers showed a higher slope for the positive association between WMSA volume and age compared to good performers. Even when controlling for WMSA volume, poor performers also evidenced lower fractional anisotropy, as well as positive associations with age with higher slopes of regression parameters in radial and axial diffusivity. Altogether results suggest that cognitive performance is related to differences in WM, with poor cognitive performers displaying signs of faster aging in WM.