Michael N. Hallquist

The nuisance of nuisance regression: spectral misspecification in a common approach to resting-state fMRI preprocessing reintroduces noise and obscures functional connectivity.

Recent resting-state functional connectivity fMRI (RS-fcMRI) research has demonstrated that head motion during fMRI acquisition systematically influences connectivity estimates despite bandpass filtering and nuisance regression, which are intended to reduce such nuisance variability. We provide evidence that the effects of head motion and other nuisance signals are poorly controlled when the fMRI time series are bandpass-filtered but the regressors are unfiltered, resulting in the inadvertent reintroduction of nuisance-related variation into frequencies previously suppressed by the bandpass filter, as well as suboptimal correction for noise signals in the frequencies of interest. This is important because many RS-fcMRI studies, including some focusing on motion-related artifacts, have applied this approach. In two cohorts of individuals (n=117 and 22) who completed resting-state fMRI scans, we found that the bandpass-regress approach consistently overestimated functional connectivity across the brain, typically on the order of r=.10-.35, relative to a simultaneous bandpass filtering and nuisance regression approach. Inflated correlations under the bandpass-regress approach were associated with head motion and cardiac artifacts. Furthermore, distance-related differences in the association of head motion and connectivity estimates were much weaker for the simultaneous filtering approach. We recommend that future RS-fcMRI studies ensure that the frequencies of nuisance regressors and fMRI data match prior to nuisance regression, and we advocate a simultaneous bandpass filtering and nuisance regression strategy that better controls nuisance-related variability.

Developmental Stages and Sex Differences of White Matter and Behavioral Development through Adolescence: A Longitudinal Diffusion Tensor Imaging (DTI) Study

White matter (WM) continues to mature through adolescence in parallel with gains in cognitive ability. To date, developmental changes in human WM microstructure have been inferred using analyses of cross-sectional or two time-point follow-up studies, limiting our understanding of individual developmental trajectories. The aims of the present longitudinal study were to characterize the timing of WM growth and investigate how sex and behavior are associated with different developmental trajectories. We utilized diffusion tensor imaging (DTI) in 128 individuals aged 8-28, who received annual scans for up to 5 years and completed motor and cognitive tasks. Flexible nonlinear growth curves indicated a hierarchical pattern of WM development. By late childhood, posterior cortical-subcortical connections were similar to adults. During adolescence, WM microstructure reached adult levels, including frontocortical, frontosubcortical and cerebellar connections. Later to mature in adulthood were major corticolimbic association tracts and connections at terminal gray matter sites in cortical and basal ganglia regions. These patterns may reflect adolescent maturation of frontal connectivity supporting cognitive abilities, particularly the protracted refinement of corticolimbic connectivity underlying cognition-emotion interactions. Sex and behavior also played a large role. Males showed continuous WM growth from childhood through early adulthood, whereas females mainly showed growth during mid-adolescence. Further, earlier WM growth in adolescence was associated with faster and more efficient responding and better inhibitory control whereas later growth in adulthood was associated with poorer performance, suggesting that the timing of WM growth is important for cognitive development.

The Contribution of Network Organization and Integration to the Development of Cognitive Control.

Abstract Cognitive control, which continues to mature throughout adolescence, is supported by the ability for well-defined organized brain networks to flexibly integrate information. However, the development of intrinsic brain network organization and its relationship to observed improvements in cognitive control are not well understood. In the present study, we used resting state functional magnetic resonance imaging (RS-fMRI), graph theory, the antisaccade task, and rigorous head motion control to characterize and relate developmental changes in network organization, connectivity strength, and integration to inhibitory control development. Subjects were 192 10–26-y-olds who were imaged during 5 min of rest. In contrast to initial studies, our results indicate that network organization is stable throughout adolescence. However, cross-network integration, predominantly of the cingulo-opercular/salience network, increased with age. Importantly, this increased integration of the cingulo-opercular/salience network significantly moderated the robust effect of age on the latency to initiate a correct inhibitory control response. These results provide compelling evidence that the transition to adult-level inhibitory control is dependent upon the refinement and strengthening of integration between specialized networks. Our findings support a novel, two-stage model of neural development, in which networks stabilize prior to adolescence and subsequently increase their integration to support the cross-domain incorporation of information processing critical for mature cognitive control.

Preoccupied Attachment and Emotional Dysregulation: Specific Aspects of Borderline Personality Disorder or General Dimensions of Personality Pathology?

Emotional dysregulation and impaired attachment are seen by many clinical researchers as central aspects of borderline personality disorder (BPD). Alternatively, these constructs may represent general impairments in personality that are nonspecific to BPD. Using multitraitmultimethod models, the authors examined the strength of associations among preoccupied attachment, difficulties with emotion regulation, BPD features, and features of two other personality disorders (i.e., antisocial and avoidant) in a combined psychiatric outpatient and community sample of adults. Results suggested that preoccupied attachment and difficulties with emotion regulation shared strong positive associations with each other and with each of the selected personality disorders. However, preoccupied attachment and emotional dysregulation were more strongly related to BPD features than to features of other personality disorders. Findings suggest that although impairments in relational and emotional domains may underlie personality pathology in general, preoccupied attachment and emotional dysregulation also have specificity for understanding core difficulties in those with BPD.

Effects of incentives, age, and behavior on brain activation during inhibitory control: a longitudinal fMRI study.

Highlights • Reward-modulated cognitive control is supported by amygdalar incentive processing.• NAcc activation supports inhibitory control in youths.• NAcc activation hinders inhibitory control in adults.

Clarifying Interpersonal Heterogeneity in Borderline Personality Disorder Using Latent Mixture Modeling

Significant interpersonal impairment is a cardinal feature of borderline personality disorder (BPD). However, past research has demonstrated that the interpersonal profile associated with BPD varies across samples, which is evidence for considerable interpersonal heterogeneity. The current study used inventory of interpersonal problems-circumplex (IIP-C; Alden, Wiggins, & Pincus, 1990) scale scores to investigate interpersonal inhibitions and excesses in a large sample (N = 255) selected for significant borderline pathology. Results indicated that BPD symptom counts were unrelated to the primary dimensions of the IIPC, but were related to generalized interpersonal distress. A latent class analysis clarified this finding by revealing six homogeneous interpersonal classes with prototypical profiles associated with Intrusive, Vindictive, Avoidant, Nonassertive, and moderate and severe Exploitable interpersonal problems. These classes differed in clinically relevant features (e.g., antisocial behaviors, self-injury, past suicide attempts). Findings are discussed in terms of the incremental clinical utility of the interpersonal circumplex model and the implications for developmental and nosological models of BPD.

Refining the phenotype of borderline personality disorder: Diagnostic criteria and beyond.

Borderline personality disorder (BPD) is a heterogeneous disorder, and previous analyses have parsed its phenotype in terms of subtypes or underlying traits. We refined the BPD construct by testing a range of latent variable models to ascertain whether BPD is composed of traits, latent classes, or both. We also tested whether subtypes of BPD could be distinguished by anger, aggressiveness, antisocial behavior, and mis-trustfulness, additional putative indicators drawn from Kernbergs (1967, 1975) theory of BPD. In a mixed clinical and nonclinical sample (N = 362), a factor mixture model consisting of two latent classes (symptomatic and asymptomatic) and a single severity dimension fit the BPD criteria, as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), data better than latent class or factor analytic approaches. In the second analytic phase, finite mixture modeling of the symptomatic latent class (n = 100) revealed four BPD subtypes: angry/aggressive, angry/mistrustful, poor identity/low anger, and prototypical. Our results support a hybrid categorical-dimensional model of the BPD DSM-IV criteria. The BPD subtypes emerging from this model have important implications for treatment and etiological research.

Prospective Associations Among Borderline Personality Disorder Symptoms, Interpersonal Problems, and Aggressive Behaviors

This study examined the prospective relationships among borderline personality disorder (BPD) symptoms, interpersonal problems, and types of aggressive behaviors (i.e., experiencing psychological and physical victimization and perpetrating psychological and physical aggression) in a psychiatric sample (N = 139) over the course of 2 years. We controlled for other PD symptoms and demographic variables. BPD symptoms at baseline were associated with interpersonal sensitivity, interpersonal ambivalence, interpersonal aggression, need for social approval, and lack of sociability 6 months later. In turn, interpersonal sensitivity predicted not experiencing physical aggression, interpersonal aggression predicted experiencing physical aggression and perpetrating both psychological and physical aggression, need for social approval predicted experiencing both psychological and physical aggression, and lack of sociability predicted perpetrating physical aggression 2 years later. Results demonstrated that interpersonal problems mediated the relationship between BPD and later violent behaviors. Our findings suggest the importance of distinguishing between these groups of aggressive behaviors in terms of etiological pathways, maintenance processes, and treatment interventions.

Integrating Competing Dimensional Models of Personality: Linking the SNAP, TCI, and NEO Using Item Response Theory

Mounting evidence suggests that several inventories assessing both normal personality and personality disorders measure common dimensional personality traits (i.e., Antagonism, Constraint, Emotional Instability, Extraversion, and Unconventionality), albeit providing unique information along the underlying trait continuum. We used Widiger and Simonsens (2005) pantheoretical integrative model of dimensional personality assessment as a guide to create item pools. We then used Item Response Theory (IRT) to compare the assessment of these five personality traits across three established dimensional measures of personality: the Schedule for Nonadaptive and Adaptive Personality (SNAP), the Temperament and Character Inventory (TCI), and the Revised NEO Personality Inventory (NEO PI-R). We found that items from each inventory map onto these five common personality traits in predictable ways. The IRT analyses, however, documented considerable variability in the item and test information derived from each inventory. Our findings support the notion that the integration of multiple perspectives will provide greater information about personality while minimizing the weaknesses of any single instrument.

EEG Asymmetry in Borderline Personality Disorder and Depression Following Rejection

Borderline personality disorder (BPD) and major depressive disorder (MDD) share numerous features, including dysphoric affect, irritability, suicidality, and a heightened sensitivity to perceived interpersonal rejection. However, these disorders are associated with divergent profiles of reactivity to rejection: Individuals with MDD are more likely to respond with withdrawal and isolation, and those with BPD appear to respond with increased approach behaviors and greater hostility. Potential mechanisms underlying these divergent patterns of response have not been elaborated. The goal of the present study was to assess whether prefrontal cortical asymmetry is associated with these behavioral profiles. EEG alpha activity was recorded at baseline and after individuals with BPD, MDD and healthy controls (HCs) participated in a rejection task. Although no differences were found at baseline, results demonstrated that following rejection, individuals with BPD showed greater left cortical activation, consistent with approach motivation, whereas those with MDD showed greater right cortical activation, consistent with withdrawal motivation. HCs evidenced a more balanced cortical profile, as hypothesized. Although BPD and MDD are highly comorbid, are easily confused, and are phenomenologically similar in a number of ways, individuals with these two disorders respond in very different ways to perceived rejection.