Longitudinal fMRI Research Articles

Effects of compassion training on brain responses to suffering others.

Compassion meditation (CM) is a promising intervention for enhancing compassion, although its active ingredients and neurobiological mechanisms are not well-understood. To investigate these, we conducted a three-armed placebo-controlled randomized trial (N = 57) with longitudinal functional magnetic resonance imaging (fMRI). We compared a 4-week CM program delivered by smartphone application with (i) a placebo condition, presented to participants as the compassion-enhancing hormone oxytocin, and (ii) a condition designed to control for increased familiarity with suffering others, an element of CM which may promote compassion. At pre- and post-intervention, participants listened to compassion-eliciting narratives describing suffering others during fMRI. CM increased brain responses to suffering others in the medial orbitofrontal cortex (mOFC) relative to the familiarity condition, p < 0.05 family-wise error rate corrected. Among CM participants, individual differences in increased mOFC responses positively correlated with increased compassion-related feelings and attributions, r = 0.50, p = 0.04. Relative to placebo, the CM group exhibited a similar increase in mOFC activity at an uncorrected threshold of P < 0.001 and 10 contiguous voxels. We conclude that the mOFC, a region closely related to affiliative affect and motivation, is an important brain mechanism of CM. Effects of CM on mOFC function are not explained by familiarity effects and are partly explained by placebo effects.

Decreased emotional reactivity after 3-month socio-affective but not attention- or meta-cognitive-based mental training: A randomized, controlled, longitudinal fMRI study

Meditation-based mental training interventions show physical and mental health benefits. However, it remains unclear how different types of mental practice affect emotion processing at both the neuronal and the behavioural level. In the context of the ReSource project, 332 participants underwent an fMRI scan while performing an emotion anticipation task before and after three 3-month training modules cultivating 1) attention and interoceptive awareness (Presence); 2) socio-affective skills, such as compassion (Affect); 3) socio-cognitive skills, such as theory of mind (Perspective). Only the Affect module led to a significant reduction of experienced negative affect when processing images depicting human suffering. In addition, after the Affect module, participants showed significant increased activation in the right supramarginal gyrus when confronted with negative stimuli. We conclude that socio-affective, but not attention- or meta-cognitive based mental training is specifically effective to improve emotion regulation capabilities when facing adversity.

Brain and Behavioral Correlates of the Patient-Clinician Relationship: A longitudinal fMRI hyper-scanning study of chronic pain patients

Research suggests that a good patient-clinician therapeutic alliance can improve clinical outcomes. In this ongoing, longitudinal study, we applied fMRI hyper-scanning to determine whether behavioral, neural, and clinical variables associated with the therapeutic relationship between chronic pain patients and their clinicians influences clinical outcomes. Ten women with fibromyalgia (mean age=40, SD=10.71, each group N=5) were randomly assigned to either an Augmented (warm/attentive) or Limited (neutral/business-like) interaction style, and were treated with electro-acupuncture for 6 biweekly sessions. Before and after acupuncture therapy, each patient-clinician dyad underwent a simultaneously recorded fMRI hyper-scanning procedure with video connection between two scanners and an evoked cuff pressure pain/treatment paradigm. Clinical outcomes and the quality of the patient-clinician relationship were assessed by questionnaires targeting treatment-related changes in clinical pain levels, therapeutic alliance, trust, and the clinician's warmth and competence. Pooled therapeutic alliance (assessed after treatment sessions 1, 3, and 6; scale 0-50) in the Augmented group (mean=43.17, SD=2.97) was significantly higher than in the Limited group (mean=27.27, SD=10.44; t(8)=3.28, p=0.011). Similarly, clinicians’ warmth, as rated by patients, was significantly higher in the Augmented (mean=4.00, SD=0.0) than in the Limited group (3.02, SD=0.73; t(8)=3.00; p=0.017). Preliminary results show that over all 6 acupuncture treatment sessions, irrespective of group assignments, most patients experienced post-treatment clinical pain relief (p

Longitudinal fMRI measures of cortical reactivation and hand use with and without training after sensory loss in primates

In a series of previous studies, we demonstrated that damage to the dorsal column in the cervical spinal cord deactivates the contralateral somatosensory hand cortex and impairs hand use in a reach-to-grasp task in squirrel monkeys. Nevertheless, considerable cortical reactivation and behavioral recovery occurs over the following weeks to months after lesion. This timeframe may also be a window for targeted therapies to promote cortical reactivation and functional reorganization, aiding in the recovery process. Here we asked if and how task specific training of an impaired hand would improve behavioral recovery and cortical reorganization in predictable ways, and if recovery related cortical changes would be detectable using noninvasive functional magnetic resonance imaging (fMRI). We further asked if invasive neurophysiological mapping reflected fMRI results. A reach-to-grasp task was used to test impairment and recovery of hand use before and after dorsal column lesions (DC-lesion). The activation and organization of the affected primary somatosensory cortex (area 3b) was evaluated with two types of fMRI – either blood oxygenation level dependent (BOLD) or cerebral blood volume (CBV) with a contrast agent of monocrystalline iron oxide nanocolloid (MION) – before and after DC-lesion. At the end of the behavioral and fMRI studies, microelectrode recordings in the somatosensory areas 3a, 3b and 1 were used to characterize neuronal responses and verify the somatotopy of cortical reactivations. Our results indicate that even after nearly complete DC lesions, monkeys had both considerable post-lesion behavioral recovery, as well as cortical reactivation assessed with fMRI followed by extracellular recordings. Generalized linear regression analyses indicate that lesion extent is correlated with the behavioral outcome, as well as with the difference in the percent signal change from pre-lesion peak activation in fMRI. Monkeys showed behavioral recovery and nearly complete cortical reactivation by 9–12 weeks post-lesion (particularly when the DC-lesion was incomplete). Importantly, the specific training group revealed trends for earlier behavioral recovery and had higher magnitude of fMRI responses to digit stimulation by 5–8 weeks post-lesion. Specific kinematic measures of hand movements in the selected retrieval task predicted recovery time and related to lesion characteristics better than overall task performance success. For measures of cortical reactivation, we found that CBV scans provided stronger signals to vibrotactile digit stimulation as compared to BOLD scans, and thereby may be the preferred non-invasive way to study the cortical reactivation process after sensory deprivations from digits. When the reactivation of cortex for each of the digits was considered, the reactivation by digit 2 stimulation as measured with microelectrode maps and fMRI maps was best correlated with overall behavioral recovery.

Reciprocal relations between reading skill and the neural basis of phonological awareness in 7- to 9-year-old children

By using a longitudinal design and functional magnetic resonance imaging (fMRI), our previous study (Wang et al., 2020) found a scaffolding effect of early phonological processing in the superior temporal gyrus (STG) in 6-year-old children on later behavioral reading skill in 7.5-year-old children. Other than this previous study, nothing is known about longitudinal change in the bidirectional relation between reading skill and phonological processing in the brain. To fill this gap, in the current study, we used the same experimental paradigm as in Wang et al. (2020) to measure children's reading skill and brain activity during an auditory phonological awareness task, but with children who were 7.5 years old at Time 1 (T1) and about 1.5 years later when they were 9 years old at Time 2 (T2). The phonological awareness task included both small grain (i.e., onset) and large grain (i.e., rhyme) conditions. In a univariate analysis, we found that better reading skill at T1 predicted lower brain activation in IFG at T2 for onset processing after controlling for brain activation and non-verbal IQ at T1. This suggests that early reading ability reduces the effort of phonemic access, thus supporting the refinement hypothesis. When using general psychophysiological interaction (gPPI), we found that higher functional connectivity from IFG to STG for rhyme processing at T1 predicted better reading skill at T2 after controlling for reading skill and non-verbal IQ at T1. This suggests that the early effectiveness of accessing rhyme representations scaffolds reading acquisition. As both results did not survive multiple comparison corrections, replication of these findings is needed. However, both findings are consistent with prior studies demonstrating that phonological access in the frontal lobe becomes important in older elementary school readers. Moreover, the refinement effect for onsets is consistent with the hypothesis that learning to read allows for better access of small grain phonology, and the scaffolding effect for rhymes supports the idea that reading progresses to larger grain orthography-to-phonology mapping in older skilled readers. The current study, along with our previous study on younger children, indicates that the development of reading skill is associated with (1) the early importance of the quality of the phonological representations to later access of these representations, and (2) early importance of small grain sizes to later development of large grain ones.

Predictors of weight loss in participants with obesity following bariatric surgery – A prospective longitudinal fMRI study

Prevalence rates of overweight and obesity are increasing worldwide and are amongst the leading causes of death. Participants with obesity also suffer from poorer mental health with a concomitant reduced quality of life. Bariatric surgery outperforms other existing weight optimization approaches. However, hitherto, it was not possible to identify factors predicting weight loss following surgery. Therefore, we aimed at investigating neural and behavioral predictors of weight loss, as well as the neurological underpinnings of food cue-induced craving before and after bariatric surgery. The total sample consisted of 26 participants with obesity (17 females and 9 males, mean age 41 ± 12 years, mean BMI 46 ± 6 kg/m2, 21 received Roux-en-Y gastric bypass and 5 sleeve gastrectomy). Participants with obesity were prospectively assessed using functional magnetic resonance imaging two weeks before, as well as eight and 24 weeks after surgery. Imaging data were available for 11 individuals; 10 received Roux-en-Y gastric bypass and one sleeve gastrectomy. Subjective cue-induced food craving correlated positively with brain activation in the amygdala, the parahippocampal gyrus, and hippocampus, and negatively with brain activation in frontal brain regions. In the total sample (N = 26), perceived feeling of hunger and YFAS sum score explained 50.6% of the variance (R2 = 0.506, F(1,23) = 10.759, p < 0.001) and in the imaging sample, cue-induced food craving at baseline before surgery explained 49.6% of the variance (R2 = 0.496, F(1,23) = 7.862, p = 0.023) of % total weight loss (%TWL). In other words, with respect to %TWL, bariatric surgery was most efficient in candidates characterized by high cue-induced food craving, high-perceived feeling of hunger and a low YFAS sum score.

Maternal parenting behavior and functional connectivity development in children: A longitudinal fMRI study

Parenting behavior is associated with internalizing symptoms in children, and cross-sectional research suggests that this association may be mediated by the influence of parenting on the development of frontoamygdala circuitry. However, longitudinal studies are lacking. Moreover, there is a paucity of studies that have investigated parenting and large-scale networks implicated in affective functioning. In this longitudinal study, data from 95 (52 female) children and their mothers were included. Children underwent magnetic resonance imaging that included a 6 min resting state sequence at wave 1 (mean age = 8.4 years) and wave 2 (mean age = 9.9 years). At wave 1, observational measures of positive and negative maternal behavior were collected during mother-child interactions. Region-of-interest analysis of the amygdala, and independent component and dual-regression analyses of the Default Mode Network (DMN), Executive Control Network (ECN) and the Salience Network (SN) were carried out. We identified developmental effects as a function of parenting: positive parenting was associated with decreased coactivation of the superior parietal lobule with the ECN at wave 2 compared to wave 1. Thus our findings provide preliminary longitudinal evidence that positive maternal behavior is associated with maturation of the connectivity between higher-order control networks.

Tracking second language immersion across time: Evidence from a bi-directional longitudinal cross-linguistic fMRI study

Parallel cohorts of Hebrew speakers learning English in the U.S., and American-English speakers learning Hebrew in Israel were tracked over the course of two years of immersion in their L2. We utilised a functional MRI semantic judgement task with print and speech tokens, as well as a battery of linguistic and cognitive behavioural measures prior to and after immersion, to track changes in both L1 and L2 processing. fMRI activation for print tokens produced a similar network of activation in both English and Hebrew, irrespective of L1 or L2 status. Significant convergence of print and speech processing was also observed in both languages across a network of left-hemisphere regions joint for both L1 and L2. Despite significant increases in behavioural measures of L2 proficiency, only a few signs of longitudinal change in L2 brain activation were found. In contrast, L1 showed widespread differences in processing across time, suggesting that the neurobiological footprint of reading is dynamic and plastic even in adults, with L2 immersion impacting L1 processing. Print/speech convergence showed little longitudinal change, suggesting that it is a stable marker of the differences in L1 and L2 processing across L2 proficiency.

Changes in working memory-related cortical responses following pediatric mild traumatic brain injury: A longitudinal fMRI study

Persistent post-concussion symptoms (PPCS) lasting longer than 4 weeks affect 25% of children with mild traumatic brain injury (mTBI) or concussion. Working memory (WM) problems are a common complaint in children with PPCS. Despite normal function on traditional neuropsychological tests, these children exhibit aberrant cortical responses within the dorsolateral prefrontal cortex (dlPFC) and default mode network (DMN) regions – both of which are implicated in WM. Using a prospective, longitudinal cohort study design, we investigated changes in cortical fMRI responses within the dlPFC and DMN during an nback WM task at two timepoints: one and two months post-injury. Across these timepoints, the primary outcome was change in cortical activations (increase in BOLD) and deactivations (decrease in BOLD) of both dlPFC and DMN. Twenty-nine children (mean age 15.49 ± 2.15; 48.3% male) with fMRI scans at both timepoints were included, following data quality control. Student’s t-tests were used to examine cortical activations across time and task difficulty. ANCOVA F-tests examined cortical responses after removal of baseline across time, task difficulty and recovery. Volumes of interest (5 mm sphere) were placed in peak voxel regions of the DMN and dlPFC to compare cortical responses between recovered and unrecovered participants over time (one-way ANOVA). Between one and two months post-injury, we found significant increases in dlPFC activations and significant activations and deactivations in the DMN with increasing task difficulty, alongside improved task performance. Cortical responses of the DMN and bilateral dlPFC displayed increased intensity in recovered participants, together with improved attention and behavioural symptoms. Overall, our findings suggest evidence of neural compensation and ongoing cognitive recovery from pediatric TBI over time between one and two months post injury in children with PPCS. These results highlight the wider and persisting implications of mTBI in children, whose maturing brains are particularly vulnerable to TBI.

Reliability of neural food cue-reactivity in participants with obesity undergoing bariatric surgery: a 26-week longitudinal fMRI study

Obesity is highly prevalent worldwide and results in a high disease burden. The efforts to monitor and predict treatment outcome in participants with obesity using functional magnetic resonance imaging (fMRI) depends on the reliability of the investigated task-fMRI brain activation. To date, no study has investigated whole-brain reliability of neural food cue-reactivity. To close this gap, we analyzed the longitudinal reliability of an established food cue-reactivity task. Longitudinal reliability of neural food-cue-induced brain activation and subjective food craving ratings over three fMRI sessions (T0: 2 weeks before surgery, T1: 8 weeks and T2: 24 weeks after surgery) were investigated in N = 11 participants with obesity. We computed an array of established reliability estimates, including the intraclass correlation (ICC), the Dice and Jaccard coefficients and similarity of brain activation maps. The data indicated good reliability (ICC > 0.6) of subjective food craving ratings over 26 weeks and excellent reliability (ICC > 0.75) of brain activation signals for the contrast of interest (food > neutral) in the caudate, putamen, thalamus, middle cingulum, inferior, middle and superior occipital gyri, and middle and superior temporal gyri and cunei. Using similarity estimates, it was possible to re-identify individuals based on their neural activation maps (73%) with a fading degree of accuracy, when comparing fMRI sessions further apart. The results show excellent reliability of task-fMRI neural brain activation in several brain regions. Current data suggest that fMRI-based measures might indeed be suitable to monitor and predict treatment outcome in participants with obesity undergoing bariatric surgery.

Improvement in prefrontal thalamic connectivity during the early course of the illness in recent-onset psychosis: a 12-month longitudinal follow-up resting-state fMRI study.

Previous research in resting-state functional magnetic resonance imaging (rs-fMRI) has shown a mixed pattern of disrupted thalamocortical connectivity in psychosis. The clinical meaning of these findings and their stability over time remains unclear. We aimed to study thalamocortical connectivity longitudinally over a 1-year period in participants with recent-onset psychosis. To this purpose, 129 individuals with recent-onset psychosis and 87 controls were clinically evaluated and scanned using rs-fMRI. Among them, 43 patients and 40 controls were re-scanned and re-evaluated 12 months later. Functional connectivity between the thalamus and the rest of the brain was calculated using a seed to voxel approach, and then compared between groups and correlated with clinical features cross-sectionally and longitudinally. At baseline, participants with recent-onset psychosis showed increased connectivity (compared to controls) between the thalamus and somatosensory and temporal regions (k = 653, T = 5.712), as well as decreased connectivity between the thalamus and left cerebellum and right prefrontal cortex (PFC; k = 201, T = -4.700). Longitudinal analyses revealed increased connectivity over time in recent-onset psychosis (relative to controls) in the right middle frontal gyrus. Our results support the concept of abnormal thalamic connectivity as a core feature in psychosis. In agreement with a non-degenerative model of illness in which functional changes occur early in development and do not deteriorate over time, no evidence of progressive deterioration of connectivity during early psychosis was observed. Indeed, regionally increased connectivity between thalamus and PFC was observed.

Second language learning tunes the language control network: a longitudinal fMRI study

ABSTRACT The current longitudinal study investigated how classroom second language (L2) learning modulates the neural correlates of bilingual language control during language production. Chinese college freshmen majoring in English undertook two test sessions (i.e. pre-learning and post-learning) over the course of one year. Specifically, while in the scanner, participants were instructed to name pictures in either their first or second language in response to cues. Behavioral results showed that language switch costs in the post-learning session were reduced as compared to the pre-learning session. fMRI results showed that, compared to the pre-learning session, the connectivity strength between the dorsal anterior cingulate gyrus and the left caudate was increased in the post-learning session. Critically, this increased connectivity strength was correlated with the reduction in language switch costs. These findings suggest that the language control network used during bilingual language production could be modulated by long-term L2 learning in a naturalistic classroom setting.

Development of the default-mode network during childhood and adolescence: A longitudinal resting-state fMRI study

The default-mode network (DMN) is a set of functionally connected regions that play crucial roles in internal cognitive processing. Previous resting-state fMRI studies have demonstrated that the intrinsic functional organization of the DMN undergoes remarkable reconfigurations during childhood and adolescence. However, these studies have mainly focused on cross-sectional designs with small sample sizes, limiting the consistency and interpretations of the findings. Here, we used a large sample of longitudinal resting-state fMRI data comprising 305 typically developing children (6–12 years of age at baseline, 491 scans in total) and graph theoretical approaches to delineate the developmental trajectories of the functional architecture of the DMN. For each child, the DMN was constructed according to a prior parcellation with 32 brain nodes. We showed that the overall connectivity increased in strength from childhood to adolescence and became spatially similar to that in the young adult group (N = 61, 18–28 years of age). These increases were primarily located in the midline structures. Global and local network efficiency in the DMN also increased with age, indicating an enhanced capability in parallel information communication within the brain system. Based on the divergent developmental rates of nodal centrality, we identified three subclusters within the DMN, with the fastest rates in the cluster mainly comprising the anterior medial prefrontal cortex and posterior cingulate cortex. Together, our findings highlight the developmental patterns of the functional architecture in the DMN from childhood to adolescence, which has implications for the understanding of network mechanisms underlying the cognitive development of individuals.

Functional reorganization of the reading network in the course of foreign language acquisition

During foreign language acquisition neural representations of native language and foreign language assimilate. In the reading network, this assimilation leads to a shift from effortful processing to automated reading. Longitudinal studies can track this transition and reveal dynamics that might not become apparent in behavior. Here, we report results from a longitudinal functional magnetic resonance imaging (fMRI) study, which tracked functional changes in the reading network of beginning learners of Greek over one year. We deliberately chose Greek as foreign language that would have similar orthographic transparency but a different alphabet than the native language (Polish). fMRI scans with lexical and semantic decision tasks were performed at five different time points (every ~3 months). Classical language areas (the left inferior frontal gyrus, the left precentral gyrus, and the bilateral supplementary motor cortex), and cognitive control areas (left inferior parietal lobe and bilateral anterior cingulate cortex) showed stronger activation after the first months of instruction as compared to the activation before instruction. This pattern occured in both tasks. Task-related activity in the reading network remained constant throughout the remaining 6 months of learning and was also present in a follow-up scan 3 months after the end of the course. A similar pattern was demonstrated by the analysis of convergence between foreign and native languages occurring within the first months of learning. Additionally, in the lexical task, the extent of spatial overlap, between foreign and native language in Broca's area increased constantly from the beginning till the end of training. Our findings support the notion that reorganization of language networks is achieved after a relatively short time of foreign language instruction. We also demonstrate that cognitive control areas are recruited in foreign language reading at low proficiency levels. No apparent changes in the foreign or native reading network occur after the initial 3 months of learning. This suggests that task demand might be more important than proficiency in regulating the resources needed for efficient foreign language reading.

Language control network adapts to second language learning: A longitudinal rs-fMRI study

The current longitudinal resting-state functional magnetic resonance imaging study examined changes in language control network after one year of L2 English classroom learning. A group of Chinese college freshmen majoring in English underwent two scans, one before (i.e., Session 1) and one after (i.e., Session 2) the one-year L2 courses. Learners' language control abilities were assessed via a behavioral language switching task. Our graph theory and functional connectivity analyses revealed that with increased exposure to the L2, nodal betweenness in language control areas, such as the dorsal anterior cingulate cortex (dACC), decreased and connectivity between dACC and pre-supplementary motor area (pre-SMA) increased. Critically, these neural changes were correlated with participants' behavioral performance on the language switching task. Taken together, these findings suggest that the language control network in resting brain could be modulated by long-term L2 learning in a naturalistic classroom setting, and that the dACC/pre-SMA complex appears to play a critical role in language control.

Caudate Functional Connectivity Associated With Weight Change in Adolescents.

BackgroundChildhood obesity has become a global epidemic and the etiology of maladaptive ingestive behavior in children warrants further research. Mounting evidence suggests that the caudate is associated with body weight gain and obesity in adults. In adolescents, however, how caudate-related neural networks are associated with body weight gain is unclear because their central nervous systems are still developing.ObjectivesThe current longitudinal resting-state functional magnetic resonance imaging (rs-fMRI) study was conducted to investigate the hypothesis that caudate-related neural networks have a role in weight gain in adolescents.MethodsThe study included 20 healthy adolescents with a mean age of 17.5 ± 2.0 years and a mean body mass index of 20.6 ± 2.1 who underwent baseline rs-fMRI then follow-up rs-fMRI approximately 1 year later. Body mass index (BMI) was measured at both timepoints. Seed-based functional connectivity analysis was utilized to analyze caudate-related functional connectivity (FC) using the caudate as a seed. Associations between caudate-related FC and BMI at baseline were assessed, as were associations between change in BMI and caudate-related FC between baseline and follow-up.ResultsAt baseline, greater caudate-lateral prefrontal cortex FC was correlated with lower BMI (family wise error-corrected p < 0.05). Compared to the baseline, increased FC in the caudate-lateral prefrontal cortex at follow up were negatively associated with increased BMI (p < 0.05).ConclusionGiven that the lateral prefrontal cortex and caudate are associated with inhibitory control, the caudate-lateral prefrontal cortex FC may have a preventive effect on weight gain in adolescents. The results of the current study suggest that developing inhibitory control would lead to the prevention of childhood obesity.

A robust and reproducible connectome fingerprint of ketamine is highly associated with the connectomic signature of antidepressants.

Over the past decade, various N-methyl-D-aspartate modulators have failed in clinical trials, underscoring the challenges of developing novel rapid-acting antidepressants based solely on the receptor or regional targets of ketamine. Thus, identifying the effect of ketamine on the brain circuitry and networks is becoming increasingly critical. In this longitudinal functional magnetic resonance imaging study of data from 265 participants, we used a validated predictive model approach that allows the full assessment of brain functional connectivity, without the need for seed selection or connectivity summaries. First, we identified a connectome fingerprint (CFP) in healthy participants (Cohort A, n = 25) during intravenous infusion of a subanesthetic dose of ketamine, compared to normal saline. We then demonstrated the robustness and reproducibility of the discovered ketamine CFP in two separate healthy samples (Cohort B, n = 22; Cohort C, n = 18). Finally, we investigated the ketamine CFP connectivity at 1-week post treatment in major depressive disorder patients randomized to 8 weeks of sertraline or placebo (Cohort D, n = 200). We found a significant, robust, and reproducible ketamine CFP, consistent with reduced connectivity within the primary cortices and within the executive network, but increased connectivity between the executive network and the rest of the brain. Compared to placebo, the ketamine CFP connectivity changes at 1 week predicted response to sertraline at 8 weeks. In each of Cohorts A-C, ketamine significantly increased connectivity in a previously identified antidepressant CFP. Investigating the brain connectivity networks, we successfully identified a robust and reproducible ketamine biomarker that is related to the mechanisms of antidepressants.

Cortical Function in Acute Severe Traumatic Brain Injury and at Recovery: A Longitudinal fMRI Case Study.

Differences in the functional integrity of the brain from acute severe brain injury to subsequent recovery of consciousness have not been well documented. Functional magnetic resonance imaging (fMRI) may elucidate this issue as it allows for the objective measurement of brain function both at rest and in response to stimuli. Here, we report the cortical function of a patient with a severe traumatic brain injury (TBI) in a critically ill state and at subsequent functional recovery 9-months post injury. A series of fMRI paradigms were employed to assess sound and speech perception, command following, and resting state connectivity. The patient retained sound perception and speech perception acutely, as indexed by his fMRI responses. Command following was absent acutely, but was present at recovery. Increases in functional connectivity across multiple resting state networks were observed at recovery. We demonstrate the clinical utility of fMRI in assessing cortical function in a patient with severe TBI. We suggest that hallmarks of the recovery of consciousness are associated with neural activity to higher-order cognitive tasks and increased resting state connectivity.

Spectral dynamic causal modelling of resting-state fMRI: an exploratory study relating effective brain connectivity in the default mode network to genetics.

We conduct an imaging genetics study to explore how effective brain connectivity in the default mode network (DMN) may be related to genetics within the context of Alzheimer's disease and mild cognitive impairment. We develop an analysis of longitudinal resting-state functional magnetic resonance imaging (rs-fMRI) and genetic data obtained from a sample of 111 subjects with a total of 319 rs-fMRI scans from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. A Dynamic Causal Model (DCM) is fit to the rs-fMRI scans to estimate effective brain connectivity within the DMN and related to a set of single nucleotide polymorphisms (SNPs) contained in an empirical disease-constrained set which is obtained out-of-sample from 663 ADNI subjects having only genome-wide data. We relate longitudinal effective brain connectivity estimated using spectral DCM to SNPs using both linear mixed effect (LME) models as well as function-on-scalar regression (FSR). In both cases we implement a parametric bootstrap for testing SNP coefficients and make comparisons with p-values obtained from asymptotic null distributions. In both networks at an initial q-value threshold of 0.1 no effects are found. We report on exploratory patterns of associations with relatively high ranks that exhibit stability to the differing assumptions made by both FSR and LME.

Negative Parenting Affects Adolescent Internalizing Symptoms Through Alterations in Amygdala-Prefrontal Circuitry: A Longitudinal Twin Study

BackgroundThe synergic interaction of risk genes and environmental factors has been thought to play a critical role in mediating emotion-related brain circuitry function and dysfunction in depression and anxiety disorders. Little, however, is known regarding neurodevelopmental bases underlying how maternal negative parenting affects emotion-related brain circuitry linking to adolescent internalizing symptoms and whether this neurobehavioral association is heritable during adolescence. MethodsThe effects of maternal parenting on amygdala-based emotional circuitry and internalizing symptoms were examined by using longitudinal functional magnetic resonance imaging among 100 monozygotic twins and 78 dizygotic twins from early adolescence (age 13 years) to mid-adolescence (age 16 years). The mediation effects among variables of interest and their heritability were assessed by structural equation modeling and quantitative genetic analysis, respectively. ResultsExposure to maternal negative parenting was positively predictive of stronger functional connectivity of the amygdala with the ventrolateral prefrontal cortex. This neural pathway mediated the association between negative parenting and adolescent depressive symptoms and exhibited moderate heritability (21%). ConclusionsThese findings highlight that maternal negative parenting in early adolescence is associated with the development of atypical amygdala-prefrontal connectivity in relation to internalizing depressive symptoms in mid-adolescence. Such abnormality of emotion-related brain circuitry is heritable to a moderate degree.