Amygdala task-evoked activity and task-free connectivity independently contribute to feelings of arousal.

Individual differences in the intensity of feelings of arousal while viewing emotional pictures have been associated with the magnitude of task-evoked blood-oxygen dependent (BOLD) response in the amygdala. Recently, we reported that individual differences in feelings of arousal are associated with task-free (resting state) connectivity within the salience network. There has not yet been an investigation of whether these two types of functional magnetic resonance imaging (MRI) measures are redundant or independent in their relationships to behavior. Here we tested the hypothesis that a combination of task-evoked amygdala activation and task-free amygdala connectivity within the salience network relate to individual differences in feelings of arousal while viewing of negatively potent images. In 25 young adults, results revealed that greater task-evoked amygdala activation and stronger task-free amygdala connectivity within the salience network each contributed independently to feelings of arousal, predicting a total of 45% of its variance. Individuals who had both increased task-evoked amygdala activation and stronger task-free amygdala connectivity within the salience network had the most heightened levels of arousal. Task-evoked amygdala activation and task-free amygdala connectivity within the salience network were not related to each other, suggesting that resting-state and task-evoked dynamic brain imaging measures may provide independent and complementary information about affective experience, and likely other kinds of behaviors as well.

Atrophy in distinct corticolimbic networks in frontotemporal dementia relates to social impairments measured using the Social Impairment Rating Scale.

Patients with frontotemporal dementia (FTD) often exhibit prominent, early and progressive impairments in social behaviour. We developed the Social Impairment Rating Scale (SIRS), rated by a clinician after a structured interview, which grades the types and severity of social behavioural symptoms in seven domains. In 20 FTD patients, we used the SIRS to study the anatomic basis of social impairments. In support of hypotheses generated from a prior study of healthy adults, we found that the relative magnitude of brain atrophy in three partially dissociable corticolimbic networks anchored in the amygdala predicted the severity of distinct social impairments measured using the SIRS. Patients with the greatest atrophy in a mesolimbic, reward-related (affiliation) network exhibited the most severe socioemotional detachment, whereas patients with the greatest atrophy in an interoceptive, pain-related (aversion) network exhibited the most severe lack of social apprehension. Patients with the greatest atrophy in a perceptual network exhibited the most severe lack of awareness or understanding of others' social and emotional behaviour. Our findings underscore observations that FTD is associated with heterogeneous social symptoms that can be understood in a refined manner by measuring impairments in component processes subserved by dissociable neural networks. Furthermore, these findings support the validity of the SIRS as an instrument to measure the social symptoms of patients with FTD. Ultimately, we hope it will be useful as a longitudinal outcome measure in natural history studies and in clinical trials of putative interventions to improve social functioning.

Intrinsic amygdala-cortical functional connectivity predicts social network size in humans.

Using resting-state functional magnetic resonance imaging data from two independent samples of healthy adults, we parsed the amygdala's intrinsic connectivity into three partially distinct large-scale networks that strongly resemble the known anatomical organization of amygdala connectivity in rodents and monkeys. Moreover, in a third independent sample, we discovered that people who fostered and maintained larger and more complex social networks not only had larger amygdala volumes, but also amygdalae with stronger intrinsic connectivity within two of these networks: one putatively subserving perceptual abilities and one subserving affiliative behaviors. Our findings were anatomically specific to amygdalar circuitry in that individual differences in social network size and complexity could not be explained by the strength of intrinsic connectivity between nodes within two networks that do not typically involve the amygdala (i.e., the mentalizing and mirror networks), and were behaviorally specific in that amygdala connectivity did not correlate with other self-report measures of sociality.

A Review of Family Environment and Neurobehavioral Outcomes Following Pediatric Traumatic Brain Injury: Implications of Early Adverse Experiences, Family Stress, and Limbic Development.

Pediatric traumatic brain injury (TBI) is a public health crisis, with neurobehavioral morbidity observed years after an injury associated with changes in related brain structures. A substantial literature base has established family environment as a significant predictor of neurobehavioral outcomes following pediatric TBI. The neural mechanisms linking family environment to neurobehavioral outcomes have, however, received less empiric study in this population. In contrast, limbic structural differences as well as challenges with emotional adjustment and behavioral regulation in non-TBI populations have been linked to a multitude of family environmental factors, including family stress, parenting style, and adverse childhood experiences. In this article, we systematically review the more comprehensive literature on family environment and neurobehavioral outcomes in pediatric TBI and leverage the work in both TBI and non-TBI populations to expand our understanding of the underlying neural mechanisms. Thus, we summarize the extant literature on the family environment's role in neurobehavioral sequelae in children with TBI and explore potential neural correlates by synthesizing the wealth of literature on family environment and limbic development, specifically related to the amygdala. This review underscores the critical role of environmental factors, especially those predating the injury, in modeling recovery outcomes post-TBI in childhood, and discusses clinical and research implications across pediatric populations. Given the public health crisis of pediatric TBI, along with the context of sparse available medical interventions, a broader understanding of factors contributing to outcomes is warranted to expand the range of intervention targets.

Frontoamygdala hyperconnectivity predicts affective dysregulation in adolescent moderate-severe TBI.

In survivors of moderate to severe traumatic brain injury (msTBI), affective disruptions often remain underdetected and undertreated, in part due to poor understanding of the underlying neural mechanisms. We hypothesized that limbic circuits are integral to affective dysregulation in msTBI. To test this, we studied 19 adolescents with msTBI 17 months post-injury (TBI: M age 15.6, 5 females) as well as 44 matched healthy controls (HC: M age 16.4, 21 females). We leveraged two previously identified, large-scale resting-state (rsfMRI) networks of the amygdala to determine whether connectivity strength correlated with affective problems in the adolescents with msTBI. We found that distinct amygdala networks differentially predicted externalizing and internalizing behavioral problems in patients with msTBI. Specifically, patients with the highest medial amygdala connectivity were rated by parents as having greater externalizing behavioral problems measured on the BRIEF and CBCL, but not cognitive problems. The most correlated voxels in that network localize to the rostral anterior cingulate (rACC) and posterior cingulate (PCC) cortices, predicting 48% of the variance in externalizing problems. Alternatively, patients with the highest ventrolateral amygdala connectivity were rated by parents as having greater internalizing behavioral problems measured on the CBCL, but not cognitive problems. The most correlated voxels in that network localize to the ventromedial prefrontal cortex (vmPFC), predicting 57% of the variance in internalizing problems. Both findings were independent of potential confounds including ratings of TBI severity, time since injury, lesion burden based on acute imaging, demographic variables, and other non-amygdalar rsfMRI metrics (e.g., rACC to PCC connectivity), as well as macro- and microstructural measures of limbic circuitry (e.g., amygdala volume and uncinate fasciculus fractional anisotropy). Supporting the clinical significance of these findings, patients with msTBI had significantly greater externalizing problem ratings than healthy control participants and all the brain-behavior findings were specific to the msTBI group in that no similar correlations were found in the healthy control participants. Taken together, frontoamygdala pathways may underlie chronic dysregulation of behavior and mood in patients with msTBI. Future work will focus on neuromodulation techniques to directly affect frontoamygdala pathways with the aim to mitigate such dysregulation problems.

The ENIGMA sports injury working group:- an international collaboration to further our understanding of sport-related brain injury.

Sport-related brain injury is very common, and the potential long-term effects include a wide range of neurological and psychiatric symptoms, and potentially neurodegeneration. Around the globe, researchers are conducting neuroimaging studies on primarily homogenous samples of athletes. However, neuroimaging studies are expensive and time consuming, and thus current findings from studies of sport-related brain injury are often limited by small sample sizes. Further, current studies apply a variety of neuroimaging techniques and analysis tools which limit comparability among studies. The ENIGMA Sports Injury working group aims to provide a platform for data sharing and collaborative data analysis thereby leveraging existing data and expertise. By harmonizing data from a large number of studies from around the globe, we will work towards reproducibility of previously published findings and towards addressing important research questions with regard to diagnosis, prognosis, and efficacy of treatment for sport-related brain injury. Moreover, the ENIGMA Sports Injury working group is committed to providing recommendations for future prospective data acquisition to enhance data quality and scientific rigor.

Corticospinal tract location in internal capsule of human brain: diffusion tensor tractography and functional MRI study.

We attempted to elucidate the corticospinal tract location at the posterior limb of the internal capsule in the human brain. Ten healthy volunteers were recruited. Probabilistic mapping was performed using the functional MRI activation resulting from a hand motor task as region of interest 1 and the corticospinal tract area of the anterior pons as region of interest 2. The average location of the highest density point of the corticospinal tract was mid-posterior portion with the standard from the most medial point to the most posterior point of the lenticular nucleus. In conclusion, we demonstrated that the corticospinal tract for the hand descended through the posterior portion of the posterior limb at the mid-thalamic level.

Involvement of Sensory Regions in Affective Experience: A Meta-Analysis.

A growing body of work suggests that sensory processes may also contribute to affective experience. In this study, we performed a meta-analysis of affective experiences driven through visual, auditory, olfactory, gustatory, and somatosensory stimulus modalities including study contrasts that compared affective stimuli to matched neutral control stimuli. We found, first, that limbic and paralimbic regions, including the amygdala, anterior insula, pre-supplementary motor area, and portions of orbitofrontal cortex were consistently engaged across two or more modalities. Second, early sensory input regions in occipital, temporal, piriform, mid-insular, and primary sensory cortex were frequently engaged during affective experiences driven by visual, auditory, olfactory, gustatory, and somatosensory inputs. A classification analysis demonstrated that the pattern of neural activity across a contrast map diagnosed the stimulus modality driving the affective experience. These findings suggest that affective experiences are constructed from activity that is distributed across limbic and paralimbic brain regions and also activity in sensory cortical regions.

The amygdala as a hub in brain networks that support social life.

A growing body of evidence suggests that the amygdala is central to handling the demands of complex social life in primates. In this paper, we synthesize extant anatomical and functional data from rodents, monkeys, and humans to describe the topography of three partially distinct large-scale brain networks anchored in the amygdala that each support unique functions for effectively managing social interactions and maintaining social relationships. These findings provide a powerful componential framework for parsing social behavior into partially distinct neural underpinnings that differ among healthy people and disintegrate or fail to develop in neuropsychiatric populations marked by social impairment, such as autism, antisocial personality disorder, and frontotemporal dementia.

Amygdala volume and social network size in humans.

We found that amygdala volume correlates with the size and complexity of social networks in adult humans. An exploratory analysis of subcortical structures did not find strong evidence for similar relationships with any other structure, but there were associations between social network variables and cortical thickness in three cortical areas, two of them with amygdala connectivity. These findings indicate that the amygdala is important in social behavior.