A longitudinal functional magnetic resonance imaging study of task control circuits and bulimic symptoms over adolescence.

BACKGROUND: Previous cross-sectional findings from adolescents and adults with Bulimia Nervosa (BN) suggest disturbances in fronto-striatal and cingulo-opercular task control circuits that support self-regulatory processes, including the resolution of cognitive conflict. Herein, we used longitudinal data to examine the developmental trajectories of such disturbances and how the functioning of these circuits relates to changes in BN symptoms over adolescence. METHODS: Thirty-two adolescent females with BN symptoms and 28 healthy control (HC) adolescents participated in the study. Functional magnetic resonance images (fMRI) during performance of a Simon task were acquired at three time points within 2-year intervals over adolescence. From the initial sample, 70% and 30% of the participants completed the second and third time points, respectively. Participants who completed all study time points did not differ from those lost to attrition on baseline demographic characteristics or any outcome measures. Using a region-of-interest approach, growth curve models tested group differences in the trajectory of conflict-related activation in task control circuits over time. Cross-lagged panel models examined transactional relationships between conflict-related activation in the same regions and BN symptoms over time. RESULTS: Growth curve models revealed different trajectories of conflict-related activation in right task control regions across BN and HC adolescents, such that HC but not BN adolescents showed activation decreases over time. These group differences were greatest when including only the BN adolescents whose symptoms remitted over time. Cross-lagged panel models revealed that less frequent bulimic episodes at first follow-up predicted later increases in conflict-related activation in bilateral task control regions. CONCLUSIONS: These longitudinal findings suggest overengagement of task control circuits in BN adolescents, especially those most resilient to persistent illness. Such overengagement may compensate for regulatory disturbances, allowing them to regulate eating behaviors over development. Thus, task control circuits may constitute targets for early interventions that enhance self-regulatory control.

Altered cortical thickness and attentional deficits in adolescent girls and women with bulimia nervosa.

BACKGROUND: Frontostriatal and frontoparietal abnormalities likely contribute to deficits in control and attentional processes in individuals with bulimia nervosa and to the persistence of dysregulated eating across development. This study assessed these processes and cortical thickness in a large sample of adolescent girls and women with bulimia nervosa compared with healthy controls. METHODS: We collected anatomical MRI data from adolescent girls and women (ages 12-38 yr) with full or subthreshold bulimia nervosa and age-matched healthy controls who also completed the Conners Continuous Performance Test-II (CPT-II). Groups were compared on task performance and cortical thickness. Mediation analyses explored associations among cortical thickness, CPT-II variables, bulimia nervosa symptoms and age. RESULTS: We included 60 girls and women with bulimia nervosa and 54 controls in the analyses. Compared with healthy participants, those with bulimia nervosa showed increased impulsivity and inattention on the CPT-II, along with reduced thickness of the right pars triangularis, right superior parietal and left dorsal posterior cingulate cortices. In the bulimia nervosa group, exploratory analyses revealed that binge eating frequency correlated inversely with cortical thickness of frontoparietal and insular regions and that reduced frontoparietal thickness mediated the association between age and increased symptom severity and inattention. Binge eating frequency also mediated the association between age and lower prefrontal cortical thickness. LIMITATIONS: These findings are applicable to only girls and women with bulimia nervosa, and our cross-sectional design precludes understanding of whether cortical thickness alterations precede or result from bulimia nervosa symptoms. CONCLUSION: Structural abnormalities in the frontoparietal and posterior cingulate regions comprising circuits that support control and attentional processes should be investigated as potential contributors to the maintenance of bulimia nervosa and useful targets for novel interventions.

Altered cortical thickness and attentional deficits in adolescent girls and women with bulimia nervosa.

BACKGROUND: Frontostriatal and frontoparietal abnormalities likely contribute to deficits in control and attentional processes in individuals with bulimia nervosa and to the persistence of dysregulated eating across development. This study assessed these processes and cortical thickness in a large sample of adolescent girls and women with bulimia nervosa compared with healthy controls. METHODS: We collected anatomical MRI data from adolescent girls and women (ages 12-38 yr) with full or subthreshold bulimia nervosa and age-matched healthy controls who also completed the Conners Continuous Performance Test-II (CPT-II). Groups were compared on task performance and cortical thickness. Mediation analyses explored associations among cortical thickness, CPT-II variables, bulimia nervosa symptoms and age. RESULTS: We included 60 girls and women with bulimia nervosa and 54 controls in the analyses. Compared with healthy participants, those with bulimia nervosa showed increased impulsivity and inattention on the CPT-II, along with reduced thickness of the right pars triangularis, right superior parietal and left dorsal posterior cingulate cortices. In the bulimia nervosa group, exploratory analyses revealed that binge eating frequency correlated inversely with cortical thickness of frontoparietal and insular regions and that reduced frontoparietal thickness mediated the association between age and increased symptom severity and inattention. Binge eating frequency also mediated the association between age and lower prefrontal cortical thickness. LIMITATIONS: These findings are applicable to only girls and women with bulimia nervosa, and our cross-sectional design precludes understanding of whether cortical thickness alterations precede or result from bulimia nervosa symptoms. CONCLUSION: Structural abnormalities in the frontoparietal and posterior cingulate regions comprising circuits that support control and attentional processes should be investigated as potential contributors to the maintenance of bulimia nervosa and useful targets for novel interventions.

Reduced Inferior and Orbital Frontal Thickness in Adolescent Bulimia Nervosa Persists Over Two-Year Follow-Up.

OBJECTIVE: Cross-sectional data suggest functional and anatomical disturbances in inferior and orbital frontal regions in bulimia nervosa (BN). Using longitudinal data, we investigated whether reduced cortical thickness (CT) in these regions arises early and persists over adolescence in BN, independent of symptom remission, and whether CT reductions are markers of BN symptoms. METHOD: A total of 33 adolescent females with BN symptoms (BN or other specified feeding or eating disorder) and 28 healthy adolescents participated in this study. Anatomical magnetic resonance imaging and clinical data were acquired at 3 time points within 2-year intervals over adolescence, with 31% average attrition between assessments. Using a region-of-interest approach, we assessed group differences in CT at baseline and over time, and tested whether between- and within-subject variations in CT were associated with the frequency of BN symptoms. RESULTS: Reduced CT in the right inferior frontal gyrus persisted over adolescence in BN compared to healthy adolescents, even in those who achieved full or partial remission. Within the BN group, between-subject variations in CT in the inferior and orbital frontal regions were inversely associated with specific BN symptoms, suggesting, on average over time, greater CT reductions in individuals with more frequent BN symptoms. CONCLUSION: Reduced CT in inferior frontal regions may contribute to illness persistence into adulthood. Reductions in the thickness of the inferior and orbital frontal regions may be markers of specific BN symptoms. Because our sample size precluded correcting for multiple comparisons, these findings should be replicated in a larger sample. Future study of functional changes in associated fronto-striatal circuits could identify potential circuit-based intervention targets.

Implicit learning on a probabilistic classification task in adults and adolescents with Bulimia Nervosa.

BACKGROUND: Dysfunction in frontostriatal circuits likely contributes to impaired regulatory control in Bulimia Nervosa (BN), resulting in binge-eating and purging behaviors that resemble maladaptive habits. Less is known about the implicit learning processes of these circuits, which may contribute to habit formation. METHODS: We compared 52 adolescent and adult females with BN to 55 healthy matched-controls during performance of a probabilistic classification learning task, one form of implicit learning. Groups were compared in accuracy and response times, using mixed-models with block, age, and diagnosis as predictors, corrected for multiple comparisons with confounds covaried. RESULTS: BN participants showed differences in performance on a probabilistic classification learning task that varied by age. Adolescents with BN initially performed as accurately as healthy adolescents, but showed poorer perseverance over time. Adults with BN initially performed less accurately than healthy adults, but improved to perform equivalently. Symptom severity was associated with poorer accuracy in both adults and adolescents with BN. CONCLUSIONS: Frontostriatal dysfunction may underlie abnormalities in regulatory control and probabilistic classification learning in BN, likely contributing to the dysregulation of implicitly learned, maladaptive binge-eating and purging behaviors. Such dysfunction in BN may progress with increasing age, first manifesting in poor regulatory control over behaviors and then expanding to implicit learning processes that may underlie habitual behaviors.

Altered White Matter Microstructure in Adolescents and Adults with Bulimia Nervosa.

Previous data suggest structural and functional deficits in frontal control circuits in adolescents and adults with bulimia nervosa (BN), but less is known about the microstructure of white matter in these circuits early in the course of the disorder. Diffusion tensor imaging (DTI) data were acquired from 28 female adolescents and adults with BN and 28 age- and BMI-matched healthy female participants. Tract-based spatial statistics (TBSS) was used to detect group differences in white matter microstructure and explore the differential effects of age on white matter microstructure across groups. Significant reductions in fractional anisotropy (FA) were detected in the BN compared with healthy control group in multiple tracts including forceps minor and major, superior longitudinal, inferior fronto-occipital, and uncinate fasciculi, anterior thalamic radiation, cingulum, and corticospinal tract. FA reductions in forceps and frontotemporal tracts correlated inversely with symptom severity and Stroop interference in the BN group. These findings suggest that white matter microstructure is abnormal in BN in tracts extending through frontal and temporoparietal cortices, especially in those with the most severe symptoms. Age-related differences in both FA and RD in these tracts in BN compared with healthy individuals may represent an abnormal trajectory of white matter development that contributes to the persistence of functional impairments in self-regulation in BN.

Reward-Based Spatial Learning in Teens With Bulimia Nervosa.

OBJECTIVE: To assess the functioning of mesolimbic and fronto-striatal areas involved in reward-based spatial learning in teenaged girls with bulimia nervosa (BN) that might be involved in the development and maintenance of maladaptive behaviors characteristic of the disorder. METHOD: We compared functional magnetic resonance imaging blood oxygen level-dependent response in 27 adolescent girls with BN to that of 27 healthy, age-matched control participants during a reward-based learning task that required learning to use extra-maze cues to navigate a virtual 8-arm radial maze to find hidden rewards. We compared groups in their patterns of brain activation associated with reward-based spatial learning versus a control condition in which rewards were unexpected because they were allotted pseudo-randomly to experimentally prevent learning. RESULTS: Both groups learned to navigate the maze to find hidden rewards, but group differences in brain activity associated with maze navigation and reward processing were detected in the fronto-striatal regions and right anterior hippocampus. Unlike healthy adolescents, those with BN did not engage the right inferior frontal gyrus during maze navigation, activated the right anterior hippocampus during the receipt of unexpected rewards (control condition), and deactivated the left superior frontal gyrus and right anterior hippocampus during expected reward receipt (learning condition). These patterns of hippocampal activation in the control condition were significantly associated with the frequency of binge-eating episodes. CONCLUSION: Adolescents with BN displayed abnormal functioning of the anterior hippocampus and fronto-striatal regions during reward-based spatial learning. These findings suggest that an imbalance in control and reward circuits may arise early in the course of BN. Clinical trial registration information-An fMRI Study of Self-Regulation in Adolescents With Bulimia Nervosa; https://clinicaltrials.gov/; NCT00345943.