Faculty Bibliography

Auditory hallucinations (AH) are the most frequent positive symptoms in patients with schizophrenia. Hallucinations have been related to emotional processing disturbances, altered functional connectivity and effective connectivity deficits. Previously, we observed that, compared to healthy controls, the limbic network responses of patients with auditory hallucinations differed when the subjects were listening to emotionally charged words. We aimed to compare the synchrony patterns and effective connectivity of task-related networks between schizophrenia patients with and without AH and healthy controls. Schizophrenia patients with AH (n = 27) and without AH (n = 14) were compared with healthy participants (n = 31). We examined functional connectivity by analyzing correlations and cross-correlations among previously detected independent component analysis time courses. Granger causality was used to infer the information flow direction in the brain regions. The results demonstrate that the patterns of cortico-cortical functional synchrony differentiated the patients with AH from the patients without AH and from the healthy participants. Additionally, Granger-causal relationships between the networks clearly differentiated the groups. In the patients with AH, the principal causal source was an occipital-cerebellar component, versus a temporal component in the patients without AH and the healthy controls. These data indicate that an anomalous process of neural connectivity exists when patients with AH process emotional auditory stimuli. Additionally, a central role is suggested for the cerebellum in processing emotional stimuli in patients with persistent AH.

The vast majority of mental illnesses can be conceptualized as developmental disorders of neural interactions within the connectome, or developmental miswiring. The recent maturation of pediatric in vivo brain imaging is bringing the identification of clinically meaningful brain-based biomarkers of developmental disorders within reach. Even more auspicious is the ability to study the evolving connectome throughout life, beginning in utero, which promises to move the field from topological phenomenology to etiological nosology. Here, we scope advances in pediatric imaging of the brain connectome as the field faces the challenge of unraveling developmental miswiring. We highlight promises while also providing a pragmatic review of the many obstacles ahead that must be overcome to significantly impact public health.

Purpose To comprehensively assess brain iron levels in typically developing control subjects and patients with attention deficit hyperactivity disorder (ADHD) when psychostimulant medication history is accounted for. Materials and Methods This prospective study was approved by the institutional review board, and informed consent was obtained. Brain iron was indexed noninvasively by using magnetic resonance (MR) imaging relaxation rates (R2, R2*, R2') and magnetic field correlation (MFC) in the globus pallidus, putamen, caudate nucleus, and thalamus for 22 patients with ADHD (12 medication-naive patients and 10 with a history of psychostimulant treatment) and 27 control subjects (age range, 8-18 years). Serum iron measures were also collected. Subgroup differences were analyzed with data-appropriate omnibus tests followed by post hoc pairwise comparisons; false discovery rate correction was conducted to control for multiple comparisons. Results Medication-naive ADHD patients had significantly lower striatal and thalamic MFC indexes of brain iron than did control subjects (putamen, P = .012; caudate nucleus, P = .008; thalamus, P = .012) and psychostimulant-medicated ADHD patients (putamen, P = .006; caudate nucleus, P = .010; thalamus, P = .021). Conversely, the MFC indexes in medicated patients were comparable to those in control subjects. No significant differences were detected with R2, R2*, R2', or serum measures. Conclusion Lower MFC indexes of striatal and thalamic brain iron in medication-naive ADHD patients and lack of differences in psychostimulant-medicated patients suggest that MFC indexes of brain iron may represent a noninvasive diagnostic biomarker that responds to psychostimulant treatment. (c) RSNA, 2014 Online supplemental material is available for this article.

Increasing attention is being paid to the relationship between attention deficit/hyperactivity disorder (ADHD) and obesity. While most available research focused on determining the extent of the association between ADHD and obesity, a few studies have examined the clinical implications of diagnosing/treating ADHD in individuals with obesity. Here, we provide a narrative review of studies addressing the impact of ADHD, or its treatment, in individuals with obesity. Reviewed studies suggest that ADHD impedes the successful treatment of obesity in individuals with comorbid ADHD and obesity. Preliminary evidence also suggests that ADHD treatment might significantly increase the effectiveness of weight management strategies. We discuss the limitations of the reviewed studies and provide suggestions for future research in the field.

In the accompanying Annual Research Review, Horga and colleagues provide a comprehensive overview of the current limitations of magnetic resonance imaging (MRI) of developmental psychopathologies focusing particularly on experimental design. Horga et al. are unsparing in their assessment of the problems that plague current clinical neuroimaging studies. We will not reiterate the long list of deficiencies in the imaging literature, which persist despite its impressive volume (PubMed lists more than 135,000 papers with the terms 'magnetic resonance imaging' and 'brain'). Rather, in this Commentary, while we agree with Horga et al. that neuroimaging approaches merely represent one more types of tool, we look at where this leave us and the prospects (by attending to the lessons thoughtfully laid out by Horga and colleagues on how to place research design at the forefront in clinical neuroimaging) of better times ahead for our understanding of the pathophysiology of child- and adult-onset developmental psychiatric conditions.

Background: Epidemiological data indicate that rates of pediatric bipolar disorder (BD) and attention deficit/hyperactivity disorder (ADHD) have increased dramatically over the past two decades. Overlapping diagnostic criteria contribute to concerns about over- or mis-diagnosis of both disorders. Movement towards a nosology informed by neurobiology and symptoms, rather than symptoms alone, has the potential to improve the speed and clarity of diagnoses and treatments. To this end, the present study evaluated resting-state functional connectivity (RSFC) in children with primary BD (n=25), primary ADHD (n=24), and typically developing controls (TDCs; n=30) with no history of psychiatric illness. Methods: We enrolled children ages 7-17. Group status was determined via the Child Schedule for Affective Disorders (KSADs-PL). Participants completed an 8-minute RSFC EPI BOLD sequence and a T1 MPRAGE scan. We evaluated RSFC between seeds from the left dorsolateral prefrontal cortex (DLPFC), amygdala, and accumbens areas based on prior research implicating these areas in pediatric BD. Images were analyzed using the CPAC pipeline. Results: Analyses revealed significantly greater RSFC between the (1) left DLPFC and left occipital gyrus proximal to fusiform gyrus and (2) left accumbens area and right superior parietal lobule in TDC vs. BD participants (pairwise comparison ps = .026 and .013, respectively). Conclusions: Data indicate that altered task-independent functional connectivity in the DLPFC and accumbens areas may be specific to pediatric BD. Further study is warranted to determine if this specificity extends to other psychiatric disorders involving irritability, such as anxiety, as a potential biological diagnostic or treatment marker

Brain operation is profoundly rhythmic. Oscillations of neural excitability shape sensory, motor, and cognitive processes. Intrinsic oscillations also entrain to external rhythms, allowing the brain to optimize the processing of predictable events such as speech. Moreover, selective attention to a particular rhythm in a complex environment entails entrainment of neural oscillations to its temporal structure. Entrainment appears to form one of the core mechanisms of selective attention, which is likely to be relevant to certain psychiatric disorders. Deficient entrainment has been found in schizophrenia and dyslexia and mounting evidence also suggests that it may be abnormal in attention-deficit/hyperactivity disorder (ADHD). Accordingly, we suggest that studying entrainment in selective-attention paradigms is likely to reveal mechanisms underlying deficits across multiple disorders.

The ascendancy of functional neuroimaging has facilitated the addition of network-based approaches to the neuropsychologist's toolbox for evaluating the sequelae of brain insult. In particular, intrinsic functional connectivity (iFC) mapping of resting state fMRI (R-fMRI) data constitutes an ideal approach to measuring macro-scale networks in the human brain. Beyond the value of iFC mapping for charting how the functional topography of the brain is altered by insult and injury, iFC analyses can provide insights into experience-dependent plasticity at the macro level of large-scale functional networks. Such insights are foundational to the design of training and remediation interventions that will best facilitate recovery of function. In this review, we consider what is currently known about the origin and function of iFC in the brain, and how this knowledge is informative in neuropsychological settings. We then summarize studies that have examined experience-driven plasticity of iFC in healthy control participants, and frame these findings in terms of a schema that may aid in the interpretation of results and the generation of hypotheses for rehabilitative studies. Finally, we outline some caveats to the R-fMRI approach, as well as some current developments that are likely to bolster the utility of the iFC paradigm for neuropsychology.