Longitudinal fMRI Studies Research Articles

Performance control during longitudinal activation fMRI studies.

The documentation of performance during functional imaging represents a standard procedure employed to control for compliance, sensorimotor, and cognitive demands. In the case of motor tasks, preciseness, force, and frequency have a significant impact on the magnitude of functional activation. Questionnaires are used in psychological investigations to control for cognitive demand, while psychophysiological documentation is employed to record bodily responses. For longitudinal intervention studies, it is of utmost importance to implement meticulous pre- and post-performance controls and balance to accurately assess changes over time. Any changes in compliance may introduce additional uncontrolled variables, which can hinder the interpretation of functional magnetic resonance imaging (fMRI)-related changes. This narrative review presents strategies for controlling and balancing performance in functional imaging approaches to document neuroplasticity in rehabilitative studies. These strategies include not only motor-related aspects, such as precision, velocity, and force, but also timing aspects, such as the start and stop of movement periods. In addition, it discusses strategies for the modulation and control of movement aspects with visual feedback, as well as for the control of physiological changes during experimental modulation. Although these measures require additional care, which is often more demanding than the neuroimaging part of the study, they are crucial for a relevant interpretation and publication of fMRI studies.

Longitudinal amygdala resting state functional connectivity develops differently in adolescents with internalising disorders compared to healthy peers

IntroductionLongitudinal neuroimaging studies focused on adolescents with internalising psychopathology (i.e. with clinical anxiety and/or depression) are scarce, even though anxiety and depression are highly prevalent mental illnesses in adolescence. Often linked to comorbidity with anxiety disorders, a large proportion of depressed adolescents displays more severe symptoms and poorer response to treatment. Previous longitudinal resting-state fMRI (RS-fMRI) studies of intrinsic functional connectivity (iFC) in depressed adolescents point to dysregulation of underlying neural networks such as the corticolimbic network, including among others the amygdala and frontal regions, which are involved in emotion processing and regulation.ObjectivesThis naturalistic study investigates longitudinal changes in resting-state iFC in adolescents with internalising disorders, compared with healthy peers.Methods23 treatment naïve adolescent patients with clinical depression and comorbid anxiety (INT) and 24 healthy controls (HC) participated in RS-fMRI scans at baseline and after three months. Questionnaires measuring anxiety and depression were completed at both timepoints. Imaging analyses were conducted using independent component analysis (ICA) to extract 7 networks, being the default mode, frontoparietal (bilateral), affective, salience, executive control and dorsal attention network. Additional iFC of amygdala subregions, being laterobasal (LB) and centromedial (CM), was investigated using seed-based analyses. To investigate changes over time between groups, voxelwise analyses were conducted using FSL’s PALM.ResultsNo significant results within ICA defined networks were found. iFC between the left LB amygdala and left frontal pole significantly increased over time in patients and decreased in HC. iFC between the right LB amygdala and right pre- and postcentral gyrus also significantly increased over time in patients and decreased in HC, and was significantly associated with reduction in depressive symptoms within patients.ConclusionsThis study provides initial evidence that iFC between the laterobasal amygdala and frontal regions develops differently over time in adolescents with internalising disorders compared to healthy peers and that it is associated with reduction in depressive symptoms.Disclosure of InterestNone Declared

Vacuum formed coils for MRI.

To describe a digital fabrication method used for custom MRI receive coils with vacuum forming and electroless copper plating. Our process produces intricate copper traces on curved surfaces. A three-dimensional scan of a desired anatomy is obtained and used to design coil elements. The layout is predistorted with a self built simulation of the vacuum forming process and the geometric overlaps are tested with electromagnetic simulation software. The desired coil geometry is patterned onto a polycarbonate sheet by sandblasting through a tape mask. The sandblasted areas are then catalyzed with a palladium-tin solution and vacuum formed. The catalyzed, three-dimensional part is placed into a custom built plating tank and copper plated. Electronic components are attached to the copper traces to form resonant receive coils. The methods described here are demonstrated and tested with an 8 channel visual cortex coil array. The prototype coils exhibit quality factor ratios higher than three, indicating body noise dominance. The coil array shows high signal-to-noise ratio (SNR) near the periphery of a head shaped phantom. In vivo images with up to spatial resolution were acquired on a human volunteer. This work presents the first example of vacuum formed coils with direct electroless copper plating. Our fabrication method results in coil arrays that are in close proximity to the body. This methods described here may enable the rapid development of a set of coils of different sizes for applications including longitudinal fMRI studies and MR-guided therapies.

Longitudinal surface‐based spatial Bayesian GLM reveals complex trajectories of motor neurodegeneration in ALS

Longitudinal fMRI studies hold great promise for the study of neurodegenerative diseases, development and aging, but realizing their full potential depends on extracting accurate fMRI-based measures of brain function and organization in individual subjects over time. This is especially true for studies of rare, heterogeneous and/or rapidly progressing neurodegenerative diseases. These often involve small samples with heterogeneous functional features, making traditional group-difference analyses of limited utility. One such disease is amyotrophic lateral sclerosis (ALS), a severe disease resulting in extreme loss of motor function and eventual death. Here, we use an advanced individualized task fMRI analysis approach to analyze a rich longitudinal dataset containing 190 hand clench fMRI scans from 16 ALS patients (78 scans) and 22 age-matched healthy controls (112 scans). Specifically, we adopt our cortical surface-based spatial Bayesian general linear model (GLM), which has high power and precision to detect activations in individual subjects, and propose a novel longitudinal extension to leverage information shared across visits. We perform all analyses in native surface space to preserve individual anatomical and functional features. Using mixed-effects models to subsequently study the relationship between size of activation and ALS disease progression, we observe for the first time an inverted U-shaped trajectory of motor activations: at relatively mild motor disability we observe enlarging activations, while at higher levels of motor disability we observe severely diminished activation, reflecting progression toward complete loss of motor function. We further observe distinct trajectories depending on clinical progression rate, with faster progressors exhibiting more extreme changes at an earlier stage of disability. These differential trajectories suggest that initial hyper-activation is likely attributable to loss of inhibitory neurons, rather than functional compensation as earlier assumed. These findings substantially advance scientific understanding of the ALS disease process. This study also provides the first real-world example of how surface-based spatial Bayesian analysis of task fMRI can further scientific understanding of neurodegenerative disease and other phenomena. The surface-based spatial Bayesian GLM is implemented in the BayesfMRI R package

Verbal and Non-Verbal Color-Emotional Subjective Spaces Are Four-Dimensional, Spherical and Isomorphic

The brain at wakefulness is active even in the absence of goal-directed behavior or salient stimuli. However, patterns of this resting-state (RS) activity can undergo long-term alterations following exposure to preceding meaningful stimuli. This study was aimed to develop an unbiased method to detect such changes in the RS activity after exposure to emotionally meaningful stimuli. For this purpose, we used functional magnetic resonance imaging (fMRI) of RS brain activity before and after acquisition and extinction of experimental conditioned fear. A group of healthy volunteers participated in three fMRI sessions: a RS before fear conditioning, a fear extinction session, and a RS immediately after fear extinction. The fear-conditioning paradigm consisted of three neutral visual stimuli paired with a partial reinforcement by a mild electric current. We used both linear and non-linear dimensionality reduction approaches to distinguish between the initial RS and the RS after stimuli exposure. The principal component analysis (PCA) as a linear dimensionality reduction method showed significantly worse results than non-linear methods (Isomap, LLE, Laplacian eigenmaps). Using the Laplacian eigenmaps manifold learning method, we were able to show significant differences between the two RSs at the level of individual participants. This detection was further improved by smoothing the BOLD signal with the wavelet multiresolution analysis. The developed method can improve the discrimination of functional states collected in longitudinal fMRI studies.

Is resting-state functional connectivity altered in regular cannabis users? A systematic review of the literature.

Regular cannabis use has been associated with brain functional alterations within frontal, temporal, and striatal pathways assessed during various cognitive tasks. Whether such alterations are consistently reported in the absence of overt task performance needs to be elucidated to uncover the core neurobiological mechanisms of regular cannabis use. We aim to systematically review findings from studies that examine spontaneous fluctuations of brain function using functional Magnetic Resonance Imaging (fMRI) resting-state functional connectivity (rsFC) in cannabis users versus controls, and the association between rsFC and cannabis use chronicity, mental health symptoms, and cognitive performance. We conducted a PROSPERO registered systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and searched eight databases. Twenty-one studies were included for review. Samples comprised 1396 participants aged 16 to 42years, of which 737 were cannabis users and 659 were controls. Most studies found greater positive rsFC in cannabis users compared to controls between frontal-frontal, fronto-striatal, and fronto-temporal region pairings. The same region pairings were found to be preliminarily associated with varying measures of cannabis exposure. The evidence to date shows that regular cannabis exposure is consistently associated with alteration of spontaneous changes in Blood Oxygenation Level-Dependent signal without any explicit cognitive input or output. These findings have implications for interpreting results from task-based fMRI studies of cannabis users, which may additionally tax overlapping networks. Future longitudinal rsFC fMRI studies are required to determine the clinical relevance of the findings and their link to the chronicity of use, mental health, and cognitive performance.

Functional connectivity in multiple sclerosis modelled as connectome stability: A 5-year follow-up study

Background: Brain functional connectivity (FC) in multiple sclerosis (MS) is abnormal compared to healthy controls (HCs). More longitudinal studies in MS are needed to evaluate whether FC stability is clinically relevant. Objective: To compare functional magnetic resonance imaging (fMRI)-based FC between MS and HC, and to determine the relationship between longitudinal FC changes and structural brain damage, cognitive performance and physical disability. Methods: T1-weighted MPRAGE and resting-state fMRI (1.5T) were acquired from 70 relapsing-remitting MS patients and 94 matched HC at baseline (mean months since diagnosis 14.0 ± 11) and from 60 MS patients after 5 years. Independent component analysis and network modelling were used to measure longitudinal FC stability and cross-sectional comparisons with HC. Linear mixed models, adjusted for age and sex, were used to calculate correlations. Results: At baseline, patients with MS showed FC abnormalities both within networks and in single connections compared to HC. Longitudinal analyses revealed functional stability and no significant relationships with clinical disability, cognitive performance, lesion or brain volume. Conclusion: FC abnormalities occur already at the first decade of MS, yet we found no relevant clinical correlations for these network deviations. Future large-scale longitudinal fMRI studies across a range of MS subtypes and outcomes are required.

The Laplacian eigenmaps dimensionality reduction of fMRI data for discovering stimulus-induced changes in the resting-state brain activity

The brain at wakefulness is active even in the absence of goal-directed behavior or salient stimuli. However, patterns of this resting-state (RS) activity can undergo long-term alterations following exposure to preceding meaningful stimuli. This study was aimed to develop an unbiased method to detect such changes in the RS activity after exposure to emotionally meaningful stimuli. For this purpose, we used functional magnetic resonance imaging (fMRI) of RS brain activity before and after acquisition and extinction of experimental conditioned fear. A group of healthy volunteers participated in three fMRI sessions: a RS before fear conditioning, a fear extinction session, and a RS immediately after fear extinction. The fear-conditioning paradigm consisted of three neutral visual stimuli paired with a partial reinforcement by a mild electric current. We used both linear and non-linear dimensionality reduction approaches to distinguish between the initial RS and the RS after stimuli exposure. The principal component analysis (PCA) as a linear dimensionality reduction method showed significantly worse results than non-linear methods (Isomap, LLE, Laplacian eigenmaps). Using the Laplacian eigenmaps manifold learning method, we were able to show significant differences between the two RSs at the level of individual participants. This detection was further improved by smoothing the BOLD signal with the wavelet multiresolution analysis. The developed method can improve the discrimination of functional states collected in longitudinal fMRI studies.

Longitudinal studies of functional magnetic resonance imaging in first-episode psychosis: A systematic review

BackgroundLittle is known about changes in brain functioning after first-episode psychosis (FEP). Such knowledge is important for predicting the course of disease and adapting interventions. Functional magnetic resonance imaging has become a promising tool for exploring brain function at the time of symptom onset and at follow-up. MethodA systematic review of longitudinal fMRI studies with FEP patients according to PRISMA guidelines. Resting-state and task-activated studies were considered together. ResultsEleven studies were included. These reported on a total of 236 FEP patients were evaluated by two fMRI scans and clinical assessments. Five studies found hypoactivation at baseline in prefrontal cortex areas, two studies found hypoactivation in the amygdala and hippocampus, and three others found hypoactivation in the basal ganglia. Other hypoactivated areas were the anterior cingulate cortex, thalamus and posterior cingulate cortex. Ten out of eleven studies reported (partial) normalization by increased activation after antipsychotic treatment. A minority of studies observed hyperactivation at baseline. ConclusionsThis review of longitudinal FEP samples studies reveals a pattern of predominantly hypoactivation in several brain areas at baseline that may normalize to a certain extent after treatment. The results should be interpreted with caution given the small number of studies and their methodological and clinical heterogeneity.

Reliability in adolescent fMRI within two years \u2013 a comparison of three tasks

Longitudinal developmental fMRI studies just recently began to focus on within-subject reliability using the intraclass coefficient (ICC). It remains largely unclear which degree of reliability can be achieved in developmental studies and whether this depends on the type of task used. Therefore, we aimed to systematically investigate the reliability of three well-classified tasks: an emotional attention, a cognitive control, and an intertemporal choice paradigm. We hypothesized to find higher reliability in the cognitive task than in the emotional or reward-related task. 104 healthy mid-adolescents were scanned at age 14 and again at age 16 within M = 1.8 years using the same paradigms, scanner, and scanning protocols. Overall, we found both variability and stability (i.e. poor to excellent ICCs) depending largely on the region of interest (ROI) and task. Contrary to our hypothesis, whole brain reliability was fair for the cognitive control task but good for the emotional attention and intertemporal choice task. Subcortical ROIs (ventral striatum, amygdala) resulted in lower ICCs than visual ROIs. Current results add to the yet sparse overall ICC literature in both developing samples and adults. This study shows that analyses of stability, i.e. reliability, are helpful benchmarks for longitudinal studies and their implications for adolescent development.

350. Cognitive Behavioral Therapy Improves Fronto-Parietal Network Neuroplasticity across Major Depression and PTSD: Evidence from Longitudinal fMRI Studies of Functional Connectivity

350. Cognitive Behavioral Therapy Improves Fronto-Parietal Network Neuroplasticity across Major Depression and PTSD: Evidence from Longitudinal fMRI Studies of Functional Connectivity

Secular Mindfulness-Based Interventions: Efficacy and Neurobiology.

Secular Mindfulness-Based Interventions: Efficacy and Neurobiology.

Quantitative assessment of visual cortex function with fMRI at 7 Tesla-test-retest variability.

fMRI-based retinotopic mapping was used to assess systematic variations in activated cortical surface area, amplitude, and coherence across sessions. Seven healthy subjects were scanned at 7 T in three separate sessions with intervals of 51.4 ± 5.4 days (Sessions 1 and 2) and 167.9 ± 24.4 days (Sessions 2 and 3). We found a reduction between Sessions 1 and 2 for activated cortical surface area, between Sessions 1 and 3 for amplitude, and between Sessions 1 and 2/3 for coherence. The results do not support head motion as a major cause of the observed effect seen in Session 1, suggesting that cognitive effects were the underlying cause of change. The phase correlations for both eccentricity and polar angle mapping were highly correlated between sessions, demonstrating the stability of the maps. Furthermore, the sensitivity in determining inter-session changes of cortical surface area, response amplitude, and coherence were, at a 5% significance level, estimated to be 1.5, 6, and 5%, respectively. Any future longitudinal fMRI study should carefully evaluate activation across sessions to determine the eligibility of inclusion of all time points. This experimental design provides guidance in methodological issues of clinical longitudinal fMRI-studies, specifically regarding effects of subject experience.

3. Functional MRI in the diagnosis and prognosis of multiple sclerosis

Whereas morphological MR imaging provides clear evidence of white and gray matter lesions reflecting multiple sclerosis (MS) pathology, functional MRI (fMRI) studies of the motor, visual and cognitive networks in MS patients have provided evidence of more diffuse cortical changes. Compared with healthy subjects, fMRI changes are characterized by expansion within physiological task-related networks, such as more prominent participation of higher-level areas or recruitment of additional areas, as well as differences in resting state networks and disrupted within-network connectivity. Longitudinal fMRI studies have demonstrated that the observed abnormalities vary over the course of the disease, even in patients in disease remission (i.e., outside of relapses). Treatment interventions, such as treatment of leg spasticity with intramuscular botulinum toxin, may cause notable, even if transient, normalization of task-related networks. Functional MRI changes in MS reflect morphological MRI abnormalities, especially when more sensitive techniques are applied to detect normal-appearing white and gray matter of the brain and spinal cord. This phenomenon fits in the more widely described mechanism of increased recruitment within functional networks to at least partially compensate for structural damage in brain diseases as diverse as stroke and amyotrophic lateral sclerosis ( Weiller et al., 2006 ). While notable progress has been made to improve prognosis of the clinical course of MS using sophisticated morphological markers, e.g., ( Kalincik et al., 2012 , Zivadinov et al., 2013 ), functional MRI might also contribute to improve disease monitoring prognosis. Finally, functional MRI may be used to study the effects of different therapies on central nervous system engagement ( Filippi and Rocca, 2013 ).

Monitoring the stress-level of rats with different types of anesthesia: A tail-artery cannulation protocol

IntroductionFunctional MRI in rats under anesthesia can largely minimize motion artifacts and attenuate the stress of the animal. However, two issues remain to be clarified and improved. First, fMRI results obtained with different types of anesthesia during surgical preparation and imaging show a large variability, which could be caused by the variable stress level of the rodents. Second, the most common surgical procedure used for anesthesia, blood gas analysis and mean arterial blood-pressure (MABP) monitoring is the femoral vein and artery catheterization that makes longitudinal studies difficult. Methods:In order to examine the variability of the stress level with three different anesthesia protocols using isoflurane (Iso), medetomidine–ketamine (MK) or propofol–remifentanil (PR), we measured the plasma corticosterone (CORT) concentration with 125I-radioimmunoassay in blood samples collected prior to, immediately after and 60min after surgery. Tail-artery and vein catheterization was adapted for long-term monitoring of MABP with periodic blood sampling and is proposed as a less invasive and technically simple alternative to femoral vessel catheterization in fMRI preparation protocols. Results:We show that the CORT concentration depends on the anesthesia protocol with both alternatives providing more efficient stress reduction than the protocol using Iso. However, only the protocol using PR achieved a significant hormone reduction during surgery. Stress was not reliably manifested in changes in heart-rate and breathing-rate. Anesthesia and strain related changes in these two physiological parameters may be assigned to the pharmacological effects of the premedication and anesthetic agents. The results indicate also that MABP can be monitored over a long period of time (e.g. functional imaging session) through an arterial access point in the rat tail after cannulation with the proposed procedure. Discussion and conclusion:Animals can experience stress during fMRI preparation protocols without obvious signs in commonly monitored physiological parameters. Our results challenge the efficiency of surgical protocols using Iso as mono-anesthetic agent, even when extended with topical analgesia. It was demonstrated that the CORT-based stress-level measurement through tail-artery cannulation can be used for developing anesthesia protocols (i.e. the presented PR protocol) when setting up future fMRI studies. The proposed surgical method for the tail is expected to facilitate longitudinal fMRI studies with permanent arterial access.

Intersession reliability of fMRI activation for heat pain and motor tasks.

As the practice of conducting longitudinal fMRI studies to assess mechanisms of pain-reducing interventions becomes more common, there is a great need to assess the test–retest reliability of the pain-related BOLD fMRI signal across repeated sessions. This study quantitatively evaluated the reliability of heat pain-related BOLD fMRI brain responses in healthy volunteers across 3 sessions conducted on separate days using two measures: (1) intraclass correlation coefficients (ICC) calculated based on signal amplitude and (2) spatial overlap. The ICC analysis of pain-related BOLD fMRI responses showed fair-to-moderate intersession reliability in brain areas regarded as part of the cortical pain network. Areas with the highest intersession reliability based on the ICC analysis included the anterior midcingulate cortex, anterior insula, and second somatosensory cortex. Areas with the lowest intersession reliability based on the ICC analysis also showed low spatial reliability; these regions included pregenual anterior cingulate cortex, primary somatosensory cortex, and posterior insula. Thus, this study found regional differences in pain-related BOLD fMRI response reliability, which may provide useful information to guide longitudinal pain studies. A simple motor task (finger-thumb opposition) was performed by the same subjects in the same sessions as the painful heat stimuli were delivered. Intersession reliability of fMRI activation in cortical motor areas was comparable to previously published findings for both spatial overlap and ICC measures, providing support for the validity of the analytical approach used to assess intersession reliability of pain-related fMRI activation. A secondary finding of this study is that the use of standard ICC alone as a measure of reliability may not be sufficient, as the underlying variance structure of an fMRI dataset can result in inappropriately high ICC values; a method to eliminate these false positive results was used in this study and is recommended for future studies of test–retest reliability.

The effect of scan length on the reliability of resting-state fMRI connectivity estimates

There has been an increasing use of functional magnetic resonance imaging (fMRI) by the neuroscience community to examine differences in functional connectivity between normal control groups and populations of interest. Understanding the reliability of these functional connections is essential to the study of neurological development and degenerate neuropathological conditions. To date, most research assessing the reliability with which resting-state functional connectivity characterizes the brain's functional networks has been on scans between 3 and 11min in length. In our present study, we examine the test–retest reliability and similarity of resting-state functional connectivity for scans ranging in length from 3 to 27min as well as for time series acquired during the same length of time but excluding half the time points via sampling every second image. Our results show that reliability and similarity can be greatly improved by increasing the scan lengths from 5min up to 13min, and that both the increase in the number of volumes as well as the increase in the length of time over which these volumes was acquired drove this increase in reliability. This improvement in reliability due to scan length is much greater for scans acquired during the same session. Gains in intersession reliability began to diminish after 9–12min, while improvements in intrasession reliability plateaued around 12–16min. Consequently, new techniques that improve reliability across sessions will be important for the interpretation of longitudinal fMRI studies.

Multilingualism and fMRI: Longitudinal Study of Second Language Acquisition.

BOLD fMRI is often used for the study of human language. However, there are still very few attempts to conduct longitudinal fMRI studies in the study of language acquisition by measuring auditory comprehension and reading. The following paper is the first in a series concerning a unique longitudinal study devoted to the analysis of bi- and multilingual subjects who are: (1) already proficient in at least two languages; or (2) are acquiring Russian as a second/third language. The focus of the current analysis is to present data from the auditory sections of a set of three scans acquired from April, 2011 through April, 2012 on a five-person subject pool who are learning Russian during the study. All subjects were scanned using the same protocol for auditory comprehension on the same General Electric LX 3T Signa scanner in Duke University Hospital. Using a multivariate analysis of covariance (MANCOVA) for statistical analysis, proficiency measurements are shown to correlate significantly with scan results in the Russian conditions over time. The importance of both the left and right hemispheres in language processing is discussed. Special attention is devoted to the importance of contextualizing imaging data with corresponding behavioral and empirical testing data using a multivariate analysis of variance. This is the only study to date that includes: (1) longitudinal fMRI data with subject-based proficiency and behavioral data acquired in the same time frame; and (2) statistical modeling that demonstrates the importance of covariate language proficiency data for understanding imaging results of language acquisition.

A Developmental Study of the Neural Circuitry Mediating Motor Inhibition in Bipolar Disorder

Despite increased interest in the developmental trajectory of the pathophysiology mediating bipolar disorder, few studies have compared adults and youths with bipolar disorder. Deficits in motor inhibition are thought to play an important role in the pathophysiology of the illness across the age spectrum. The authors compared the neural circuitry mediating this process in bipolar youths relative to bipolar adults and in healthy volunteers. Participants were pediatric (N=16) and adult (N=23) patients with bipolar disorder and healthy child (N=21) and adult (N=29) volunteers. Functional MRI (fMRI) data were acquired while participants performed the stop-signal task. During failed inhibition, an age group-by-diagnosis interaction manifested in the anterior cingulate cortex, with bipolar youths exhibiting hypoactivation relative to both healthy youths and bipolar adults, and bipolar adults exhibiting hyperactivation relative to healthy adults. During successful inhibition, a main effect of diagnosis emerged in the right nucleus accumbens and the left ventral prefrontal cortex, with bipolar patients in both age groups showing less activation than healthy subjects. Anterior cingulate cortex dysfunction during failed motor inhibition was observed in both bipolar youths and adults, although the nature of this dysfunction differed between the two groups. Adults and youths with bipolar disorder exhibited similar deficits in activation of the nucleus accumbens and the ventral prefrontal cortex during successful inhibition. Therefore, while subcortical and ventral prefrontal cortex hypoactivation was present in bipolar patients across the lifespan, anterior cingulate cortex dysfunction varied developmentally, with reduced activation in youths and increased activation in adults during failed inhibition. Longitudinal fMRI studies of the developmental trajectory of the neural circuitry mediating motor inhibition in bipolar disorder are warranted.

The Pathology of Social Phobia Is Independent of Developmental Changes in Face Processing

While social phobia in adolescence predicts the illness in adulthood, no study has directly compared the neural responses in social phobia in adults and adolescents. The authors examined neural responses to facial expressions in adults and adolescents with social phobia to determine whether the neural correlates of adult social phobia during face processing also manifest in adolescent social phobia. Blood-oxygen-level-dependent (BOLD) responses were compared in 39 medication-free participants with social phobia (25 adults and 14 adolescents) and 39 healthy comparison subjects (23 adults and 16 adolescents) matched on age, IQ, and gender. During fMRI scans, participants saw angry, fearful, and neutral expression stimuli while making a gender judgment. Significant diagnosis-by-emotion interactions were observed within the amygdala and the rostral anterior cingulate cortex, as has previously been hypothesized. In these regions, both the adolescent and adult social phobia patients showed significantly increased BOLD responses relative to their respective age-matched comparison subjects, and there was no evidence of age-related modulation of between-group differences. These enhanced responses occurred specifically when viewing angry (rostral anterior cingulate cortex) and fearful (amygdala and rostral anterior cingulate cortex) expressions but not when viewing neutral expressions. In addition, the severity of social phobia was significantly correlated with the enhanced rostral anterior cingulate cortex response in the adults. The neural correlates of adult social phobia during face processing also manifest in adolescents. Neural correlates that are observed in adult social phobia may represent the persistence of profiles established earlier in life rather than adaptive responses to such earlier perturbations or maturational changes. These cross-sectional observations might encourage longitudinal fMRI studies of adolescent social phobia.