Tom A. Hummer

Characteristics and variability of structural networks derived from diffusion tensor imaging

Structural brain networks were constructed based on diffusion tensor imaging (DTI) data of 59 young healthy male adults. The networks had 68 nodes, derived from FreeSurfer parcellation of the cortical surface. By means of streamline tractography, the edge weight was defined as the number of streamlines between two nodes normalized by their mean volume. Specifically, two weighting schemes were adopted by considering various biases from fiber tracking. The weighting schemes were tested for possible bias toward the physical size of the nodes. A novel thresholding method was proposed using the variance of number of streamlines in fiber tracking. The backbone networks were extracted and various network analyses were applied to investigate the features of the binary and weighted backbone networks. For weighted networks, a high correlation was observed between nodal strength and betweenness centrality. Despite similar small-worldness features, binary networks and weighted networks are distinctive in many aspects, such as modularity and nodal betweenness centrality. Inter-subject variability was examined for the weighted networks, along with the test-retest reliability from two repeated scans on 44 of the 59 subjects. The inter-/intra-subject variability of weighted networks was discussed in three levels - edge weights, local metrics, and global metrics. The variance of edge weights can be very large. Although local metrics show less variability than the edge weights, they still have considerable amounts of variability. Weighting scheme one, which scales the number of streamlines by their lengths, demonstrates stable intra-class correlation coefficients against thresholding for global efficiency, clustering coefficient and diversity. The intra-class correlation analysis suggests the current approach of constructing weighted network has a reasonably high reproducibility for most global metrics.

Neural Activation During Facial Emotion Processing in Unmedicated Bipolar Depression, Euthymia, and Mania

BACKGROUND Studies incorporating direct comparisons across all phases of bipolar (BP) disorder are needed to elucidate the pathophysiology of bipolar disorder. However, functional neuroimaging studies that differentiate bipolar mood states from each other and from healthy subjects are few and have yielded inconsistent findings. METHODS One hundred five unmedicated adults were recruited: 30 with current bipolar depression (BPD), 30 with current bipolar hypomania or mania (BPM), 15 bipolar euthymic (BPE), and 30 healthy control subjects (HC). All subjects were diagnosed with DSM-IV BP (type I or II) using a structured clinical interview. Groups were age- and gender-ratio matched. In 3T functional magnetic resonance imaging experiments, subjects completed a negative facial emotion matching task. RESULTS Bipolar euthymic and BPD groups exhibited increased amygdala activation compared with HCs in response to the negative faces; however, in the BPM group, this increase was not seen. Conversely, both BPE and BPM groups had increased activation in the insula relative to HCs, but in the BPD group, this effect was not seen. All three BP groups exhibited increased activation of the putamen compared with HCs. In the cortical areas, the BPM group exhibited decreased left lateral orbitofrontal cortex activation compared with both BPEs and HCs, increased dorsal anterior cingulate cortex activation compared with the BPD group, and increased dorsolateral prefrontal cortical activation compared with all other groups. CONCLUSIONS Both state- and trait-related abnormalities in corticolimbic activation were seen in response to the negative facial emotion processing in a large sample of unmedicated adults across BP mood states.

Abnormal amygdala functional connectivity associated with emotional lability in children with attention-deficit/hyperactivity disorder

OBJECTIVE A substantial proportion of children with attention-deficit/hyperactivity disorder (ADHD) also display emotion regulation deficits manifesting as chronic irritability, severe temper outbursts, and aggression. The amygdala is implicated in emotion regulation, but its connectivity and relation to emotion regulation in ADHD has yet to be explored. The purpose of this study was to examine the relationship between intrinsic functional connectivity (iFC) of amygdala circuits and emotion regulation deficits in youth with ADHD. METHOD Bilateral amygdala iFC was examined using functional magnetic resonance imaging in 63 children with ADHD, aged 6 to 13 years. First, we examined the relationship between amygdala IFC and parent ratings of emotional lability (EL) in children with ADHD. Second, we compared amygdala iFC across subgroups of children with ADHD and high EL (n = 18), ADHD and low EL (n = 20), and typically developing children (TDC), all with low EL (n = 19). RESULTS Higher EL ratings were associated with greater positive iFC between the amygdala and rostral anterior cingulate cortex in youth with ADHD. EL scores were also negatively associated with iFC between bilateral amygdala and posterior insula/superior temporal gyrus. Patterns of amygdala-cortical iFC in ADHD participants with low EL were not different from the comparison group, and the effect sizes for these comparisons were smaller than those for the trend-level differences observed between the high-EL and TDC groups. CONCLUSIONS In children with ADHD and a range of EL, deficits in emotion regulation were associated with altered amygdala-cortical iFC. When comparing groups that differed on ADHD status but not EL, differences in amygdala iFC were small and nonsignificant, highlighting the specificity of this finding to emotional deficits, independent of other ADHD symptoms.

Short-Term Violent Video Game Play by Adolescents Alters Prefrontal Activity During Cognitive Inhibition

Prior research has indicated an association between exposure to violent media and aggressive thoughts, feelings, and behavior, potentially as a result of effects on inhibitory mechanisms. However, the role of violence in video games in modulating subsequent neural activity related to cognitive inhibition has received little attention. To examine short-term effects of playing a violent video game, 45 adolescents were randomly assigned to play either a violent or a nonviolent video game for 30 minutes immediately prior to functional magnetic resonance imaging (fMRI). During the fMRI procedure, participants performed a go/no-go task that required them to press a button for each target stimulus and withhold the response for non-target stimuli. Participants who played the violent game demonstrated a lower BOLD response in right dorsolateral prefrontal cortex (DLPFC) when responses were appropriately inhibited. The DLPFC is involved with executive functioning, including suppression of unwanted thoughts and behaviors. In addition, responses in the DLPFC demonstrated stronger inverse connectivity with precuneus in the nonviolent game players. These results provide evidence that playing a violent video game can modulate prefrontal activity during cognitive inhibition.

Putative human pheromone androstadienone attunes the mind specifically to emotional information

The putative human pheromone Delta4,16-androstadien-3-one (androstadienone), a non-androgenic steroid found in sweat and saliva, modulates psychological, physiological and hormonal responses without detection as an odor. To determine the specific psychological processes altered by androstadienone, four studies were completed by 50 men and women after solutions of 250 microM androstadienone or clove-odor control carrier, on separate days, were applied to their upper lip: (1) face pairs were subliminally presented, with one face neutral and the other happy or angry. Androstadienone accelerated speed to locate a subsequent dot probe appearing on the same side as emotional faces, without affecting overall reaction times, indicating that androstadienone specifically enhanced automatic attention to emotional information. (2) In two Stroop paradigms, emotional or mismatched color words interfered with ink color identification. Androstadienone slowed ink color identification of emotional words, demonstrating greater allocation of attentional resources towards emotional information, with no effect on the cognitive Stroop. (3) To test effects on social cognition, participants performed two working memory tasks with distinct stimuli, neutral faces or shapes. Androstadienone did not alter attention to either the social or nonsocial images. (4) The ameliorative effects of androstadienone on self-reported attentiveness were replicated, consistent with increased attention to emotional visual stimuli. Moreover, androstadienone did not alter positive or negative mood, as participants were alone during testing, which removed emotional stimuli from social interactions with a tester. Taken together, these findings demonstrate that subliminal androstadienone guides psychological resources to specifically engage stimuli with emotional significance and does not alter attention to social or general cognitive information.

Executive functioning characteristics associated with ADHD comorbidity in adolescents with disruptive behavior disorders

The nature of executive dysfunction in youth with disruptive behavior disorders (DBD) remains unclear, despite extensive research in samples of children with attention-deficit hyperactivity disorder (ADHD). To determine the relationship between DBD, ADHD, and executive function deficits in aggressive teens, adolescents with DBD and comorbid ADHD (DBD + ADHD; n = 25), DBD without ADHD (DBD-ADHD; n = 23), and healthy controls (HC; n = 25) were compared on neurocognitive tests and questionnaires measuring executive functioning. Teens with DBD + ADHD performed worse on both neurocognitive and questionnaire measures of executive function than the DBD-ADHD and HC groups. Results suggest that subgroups of DBD may exist depending on the presence or absence of comorbid ADHD, which may have implications for the selection and efficacy of treatment strategies.

Optimization of seed density in DTI tractography for structural networks

Diffusion tensor imaging (DTI) has been used for mapping the structural network of the human brain. The network can be constructed by choosing various brain regions as nodes and fiber tracts connecting those regions as links. The structural network generated from DTI data can be affected by noise in the scans and the choice of tractography algorithm. This study aimed to examine the effect of the number of seeds in tractography on the variance of structural networks. The variance of the network was characterized using an approach similar to the National Electrical Manufacturers Association (NEMA) standards for measurement of image noise. It was shown that the variance of the network is inversely related to the square root of seed density. Consequently, the number of seeds has a large impact on local characteristics and metrics of the network architecture. As the number of seeds increased, increased stability of structural network metrics was observed. However, more seeds can also lead to more spurious fibers and thus affect nodal degrees and edge weights, and proper thresholding may be necessary to create an appropriate weighted network. Because the variance of the network is also influenced by other imaging factors, further increase in the number of seeds has little effect in reducing the network variance. The selection of the seed number should be a balance between the network variance and computational effort.

White matter abnormalities associated with disruptive behavior disorder in adolescents with and without attention-deficit/hyperactivity disorder.

Disruptive behavior disorders (DBD) are among the most commonly diagnosed mental disorders in children and adolescents. Some important characteristics of DBD vary based on the presence or absence of comorbid attention-deficit/hyperactivity disorder (ADHD), which may affect the understanding of and treatment decision-making related to the disorders. Thus, identifying neurobiological characteristics of DBD with comorbid ADHD (DBD+ADHD) can provide a basis to establish a better understanding of the condition. This study aimed to assess abnormal white matter microstructural alterations in DBD+ADHD as compared to DBD alone and healthy controls using diffusion tensor imaging (DTI). Thirty-three DBD (19 with comorbid ADHD) and 46 age-matched healthy adolescents were studied using DTI. Fractional anisotropy (FA), and mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD) were analyzed using tract-based spatial statistics (TBSS). Significantly lower FA and higher MD, RD and AD in many white matter fibers were found in adolescents with DBD+ADHD compared to controls. Moreover, lower FA and higher RD were also found in the DBD+ADHD versus the DBD alone group. Alterations of white matter integrity found in DBD patients were primarily associated with ADHD, suggesting that ADHD comorbidity in DBD is reflected in greater abnormality of microstructural connections.

Emotional Response Inhibition in Bipolar Disorder: A Functional Magnetic Resonance Imaging Study of Trait- and State-Related Abnormalities

BACKGROUND Impaired response inhibition and poor impulse control are hallmarks of the manic phase of bipolar disorder but are also present during depressive and, to a lesser degree, euthymic periods. The neural mechanisms underlying these impairments are poorly understood, including how mechanisms are related to bipolar trait or state effects. METHODS One-hundred four unmedicated participants with bipolar mania (BM) (n = 30), bipolar depression (BD) (n = 30), bipolar euthymia (BE) (n = 14), and healthy control subjects (n = 30) underwent functional magnetic resonance imaging during emotional and nonemotional go/no-go tasks. The go/no-go task requires participants to press a button for go stimuli, while inhibiting the response to no-go trials. In separate blocks, participants inhibited the response to happy faces, sad faces, or letters. RESULTS The BE group had higher insula activity during happy face inhibition and greater activity in left inferior frontal gyrus during sad face inhibition, demonstrating bipolar trait effects. Relative to the BE group, BD and BM groups demonstrated lower insula activity during inhibition of happy faces, though the depressed sample had lower activity than manic patients. The BD and BM groups had a greater response to inhibiting sad faces in emotion processing and regulation regions, including putamen, insula, and lateral prefrontal cortex. The manic group also had higher activity in insula and putamen during neutral letter inhibition. CONCLUSIONS These results suggest distinct trait- and state-related neural abnormalities during response inhibition in bipolar disorder, with implications for future research and treatment.

The interacting role of media violence exposure and aggressive-disruptive behavior in adolescent brain activation during an emotional Stroop task

Only recently have investigations of the relationship between media violence exposure (MVE) and aggressive behavior focused on brain functioning. In this study, we examined the relationship between brain activation and history of media violence exposure in adolescents, using functional magnetic resonance imaging (fMRI). Samples of adolescents with no psychiatric diagnosis or with disruptive behavior disorder (DBD) with aggression were compared to investigate whether the association of MVE history and brain activation is moderated by aggressive behavior/personality. Twenty-two adolescents with a history of aggressive behavior and diagnosis of either conduct disorder or oppositional-defiant disorder (DBD sample) and 22 controls completed an emotional Stroop task during fMRI. Primary imaging results indicated that controls with a history of low MVE demonstrated greater activity in the right inferior frontal gyrus and rostral anterior cingulate during the violent word condition. In contrast, in adolescents with DBD, those with high MVE exhibited decreased activation in the right amygdala, compared with those with low MVE. These findings are consistent with research demonstrating the importance of fronto-limbic structures for processing emotional stimuli, and with research suggesting that media violence may affect individuals in different ways depending on the presence of aggressive traits.