Andrew J. Gerber

The Role of Adaptive Behavior in Autism Spectrum Disorders: Implications for Functional Outcome

The relationship between adaptive functioning and autism symptomatology was examined in 1,089 verbal youths with ASD examining results on Vineland-II, IQ, and measures of ASD severity. Strong positive relationships were found between Vineland subscales and IQ. Vineland Composite was negatively associated with age. IQ accounted a significant amount of the variance in overall adaptive skills (55%) beyond age and ASD severity. Individuals with ASD demonstrated significant adaptive deficits and negligible associations were found between the level of autism symptomatology and adaptive behavior. The results indicate that IQ is a strong predictor of adaptive behavior, the gap between IQ and adaptive impairments decreases in lower functioning individuals with ASD, and older individuals have a greater gap between IQ and adaptive skills.

Neuroimaging Studies of Normal Brain Development and Their Relevance for Understanding Childhood Neuropsychiatric Disorders

OBJECTIVE To review the maturational events that occur during prenatal and postnatal brain development and to present neuroimaging findings from studies of healthy individuals that identify the trajectories of normal brain development. METHOD Histological and postmortem findings of early brain development are presented, followed by a discussion of anatomical, diffusion tensor, proton spectroscopy, and functional imaging findings from studies of healthy individuals, with special emphasis on longitudinal data. RESULTS Early brain development occurs through a sequence of major events, beginning with the formation of the neural tube and ending with myelination. Brain development at a macroscopic level typically proceeds first in sensorimotor areas, spreading subsequently and progressively into dorsal and parietal, superior temporal, and dorsolateral prefrontal cortices throughout later childhood and adolescence. These patterns of anatomical development parallel increasing activity in frontal cortices that subserves the development of higher-order cognitive functions during late childhood and adolescence. Disturbances in these developmental patterns seem to be involved centrally in the pathogenesis of various childhood psychiatric disorders including childhood-onset schizophrenia, attention-deficit/hyperactivity disorder, developmental dyslexia, Tourettes syndrome, and bipolar disorder. CONCLUSIONS Advances in imaging techniques have enhanced our understanding of normal developmental trajectories in the brain, which may improve insight into the abnormal patterns of development in various childhood psychiatric disorders.

Neural Systems Subserving Valence and Arousal During the Experience of Induced Emotions

The circumplex model of affect construes all emotions as linear combinations of 2 independent neurophysiological dimensions, valence and arousal. We used functional magnetic resonance imaging to identify the neural networks subserving valence and arousal, and we assessed, in 10 participants, the associations of the BOLD (blood oxygen level-dependent) response, an indirect index of neural activity, with ratings of valence and arousal during the emotional experiences induced by the presentation of evocative sentences. Unpleasant emotional experience was associated with increased BOLD signal intensities in the supplementary motor, anterior midcingulate, right dorsolateral prefrontal, occipito-temporal, inferior parietal, and cerebellar cortices. Highly arousing emotions were associated with increased BOLD signal intensities in the left thalamus, globus pallidus, caudate, parahippocampal gyrus, amygdala, premotor cortex, and cerebellar vermis. Separate analyses using a finite impulse response model confirmed these results and revealed that pleasant emotions engaged an additional network that included the midbrain, ventral striatum, and caudate nucleus, all portions of a reward circuit. These findings suggest the existence of distinct networks subserving the valence and arousal dimensions of emotions, with midline and medial temporal lobe structures mediating arousal and dorsal cortical areas and mesolimbic pathways mediating valence.

The neural circuits that generate tics in Tourette's syndrome.

OBJECTIVE The purpose of this study was to examine neural activity and connectivity within cortico-striato-thalamo-cortical circuits and to reveal circuit-based neural mechanisms that govern tic generation in Tourettes syndrome. METHOD Functional magnetic resonance imaging data were acquired from 13 individuals with Tourettes syndrome and 21 healthy comparison subjects during spontaneous or simulated tics. Independent component analysis with hierarchical partner matching was used to isolate neural activity within functionally distinct regions of cortico-striato-thalamo-cortical circuits. Granger causality was used to investigate causal interactions among these regions. RESULTS The Tourettes syndrome group exhibited stronger neural activity and interregional causality than healthy comparison subjects throughout all portions of the motor pathway, including the sensorimotor cortex, putamen, pallidum, and substantia nigra. Activity in these areas correlated positively with the severity of tic symptoms. Activity within the Tourettes syndrome group was stronger during spontaneous tics than during voluntary tics in the somatosensory and posterior parietal cortices, putamen, and amygdala/hippocampus complex, suggesting that activity in these regions may represent features of the premonitory urges that generate spontaneous tic behaviors. In contrast, activity was weaker in the Tourettes syndrome group than in the healthy comparison group within portions of cortico-striato-thalamo-cortical circuits that exert top-down control over motor pathways (the caudate and anterior cingulate cortex), and progressively less activity in these regions accompanied more severe tic symptoms, suggesting that faulty activity in these circuits may result in their failure to control tic behaviors or the premonitory urges that generate them. CONCLUSIONS Our findings, taken together, suggest that tics are caused by the combined effects of excessive activity in motor pathways and reduced activation in control portions of cortico-striato-thalamo-cortical circuits.

The Neurophysiological Bases of Emotion: An fMRI Study of the Affective Circumplex Using Emotion-Denoting Words

Objective: We aimed to study the neural processing of emotion‐denoting words based on a circumplex model of affect, which posits that all emotions can be described as a linear combination of two neurophysiological dimensions, valence and arousal. Based on the circumplex model, we predicted a linear relationship between neural activity and incremental changes in these two affective dimensions. Methods: Using functional magnetic resonance imaging, we assessed in 10 subjects the correlations of BOLD (blood oxygen level dependent) signal with ratings of valence and arousal during the presentation of emotion‐denoting words. Results: Valence ratings correlated positively with neural activity in the left insular cortex and inversely with neural activity in the right dorsolateral prefrontal and precuneus cortices. The absolute value of valence ratings (reflecting the positive and negative extremes of valence) correlated positively with neural activity in the left dorsolateral and medial prefrontal cortex (PFC), dorsal anterior cingulate cortex, posterior cingulate cortex, and right dorsal PFC, and inversely with neural activity in the left medial temporal cortex and right amygdala. Arousal ratings and neural activity correlated positively in the left parahippocampus and dorsal anterior cingulate cortex, and inversely in the left dorsolateral PFC and dorsal cerebellum. Conclusion: We found evidence for two neural networks subserving the affective dimensions of valence and arousal. These findings clarify inconsistencies from prior imaging studies of affect by suggesting that two underlying neurophysiological systems, valence and arousal, may subserve the processing of affective stimuli, consistent with the circumplex model of affect. Hum Brain Mapp, 2009.

Deficient Activity in the Neural Systems That Mediate Self-regulatory Control in Bulimia Nervosa

CONTEXT Disturbances in neural systems that mediate voluntary self-regulatory processes may contribute to bulimia nervosa (BN) by releasing feeding behaviors from regulatory control. OBJECTIVE To study the functional activity in neural circuits that subserve self-regulatory control in women with BN. DESIGN We compared functional magnetic resonance imaging blood oxygenation level-dependent responses in patients with BN with healthy controls during performance of the Simon Spatial Incompatibility task. SETTING University research institute. PARTICIPANTS Forty women: 20 patients with BN and 20 healthy control participants. Main Outcome Measure We used general linear modeling of Simon Spatial Incompatibility task-related activations to compare groups on their patterns of brain activation associated with the successful or unsuccessful engagement of self-regulatory control. RESULTS Patients with BN responded more impulsively and made more errors on the task than did healthy controls; patients with the most severe symptoms made the most errors. During correct responding on incongruent trials, patients failed to activate frontostriatal circuits to the same degree as healthy controls in the left inferolateral prefrontal cortex (Brodmann area [BA] 45), bilateral inferior frontal gyrus (BA 44), lenticular and caudate nuclei, and anterior cingulate cortex (BA 24/32). Patients activated the dorsal anterior cingulate cortex (BA 32) more when making errors than when responding correctly. In contrast, healthy participants activated the anterior cingulate cortex more during correct than incorrect responses, and they activated the striatum more when responding incorrectly, likely reflecting an automatic response tendency that, in the absence of concomitant anterior cingulate cortex activity, produced incorrect responses. CONCLUSIONS Self-regulatory processes are impaired in women with BN, likely because of their failure to engage frontostriatal circuits appropriately. These findings enhance our understanding of the pathogenesis of BN by pointing to functional abnormalities within a neural system that subserves self-regulatory control, which may contribute to binge eating and other impulsive behaviors in women with BN.

An affective circumplex model of neural systems subserving valence, arousal, and cognitive overlay during the appraisal of emotional faces

Increasing evidence supports the existence of distinct neural systems that subserve two dimensions of affect--arousal and valence. Ten adult participants underwent functional magnetic resonance imaging during which they were presented a range of standardized faces and then asked, during the scan, to rate the emotional expressions of the faces along the dimensions of arousal and valence. Lower ratings of arousal accompanied greater activity in the amygdala complex, cerebellum, dorsal pons, and right medial prefrontal cortex (mPFC). More negative ratings of valence accompanied greater activity in the dorsal anterior cingulate (dACC) and parietal cortices. Extreme ratings of valence (highly positive and highly negative ratings) accompanied greater activity in the temporal cortex and fusiform gyrus. Building on an empirical literature which suggests that the amygdala serves as a salience and ambiguity detector, we interpret our findings as showing that a face rated as having low arousal is more ambiguous and a face rated as having extreme valence is more personally salient. This explains how both low arousal and extreme valence lead to greater activation of an ambiguity/salience system subserved by the amygdala, cerebellum, and dorsal pons. In addition, the right medial prefrontal cortex appears to down-regulate individual ratings of arousal, whereas the fusiform and related temporal cortices seem to up-regulate individual assessments of extreme valence when individual ratings are studied relative to group reference ratings for each stimulus. The simultaneous assessment of the effects of arousal and valence proved essential for the identification of neural systems contributing to the processing of emotional faces.

A Quality-Based Review of Randomized Controlled Trials of Cognitive-Behavioral Therapy for Depression: An Assessment and Metaregression

OBJECTIVE The authors assessed the methodological quality of randomized controlled trials of cognitive-behavioral therapy (CBT) for depression using the Randomized Controlled Trial Psychotherapy Quality Rating Scale (RCT-PQRS). They then compared the quality of CBT trials with that of psychodynamic therapy trials, predicting that CBT trials would have higher quality. The authors also sought to examine the relationship between quality and outcome in the CBT trials. METHOD An independent-samples t test was used to compare CBT and psychodynamic therapy trials for average total quality score. Metaregression was used to examine the relationship between quality score and effect size in the CBT trials. RESULTS A total of 120 trials of CBT for depression met inclusion criteria. Their mean total quality score on the RCT-PQRS was 25.7 (SD=8.90), which falls into the lower range of adequate quality. In contrast to our prediction, no significant difference was observed in overall quality between CBT and psychodynamic therapy trials. Lower quality was related to both larger effect sizes and greater variability of effect sizes when analyzed across all available comparisons to CBT. CONCLUSIONS On average, randomized controlled trials of CBT and of psychodynamic therapy did not differ significantly in quality. In CBT trials, low quality appeared to reduce the reliability and validity of trial results. These findings highlight the importance of discerning quality in individual psychotherapy trials and also point toward specific methodological standards for the future.

Discriminating Risk and Resilience Endophenotypes From Lifetime Illness Effects in Familial Major Depressive Disorder

IMPORTANCE The neural systems that confer risk or vulnerability for developing familial depression, and those that protect against or confer resilience to becoming ill, can be disentangled from the effects of prior illness by comparing brain imaging measures in previously ill and never ill persons who have either a high or low familial risk for depression. OBJECTIVE To distinguish risk and resilience endophenotypes for major depression from the effects of prior lifetime illness. DESIGN, SETTING, AND PARTICIPANTS We used functional magnetic resonance imaging to measure and compare brain function during performance of an attentional, self-regulatory task across a large sample of multigenerational families ascertained specifically to be at either high or low risk for developing major depression. Study procedures were performed in a university setting. A total of 143 community participants were followed up prospectively for more than 20 years in a university setting. The sample was enriched with persons who were at higher or lower familial risk for developing depression based on being biological offspring of either a clinical sample of persons with major depression or a community control sample of persons with no discernible lifetime illness. MAIN OUTCOMES AND MEASURES Task-related change in blood oxygen level-dependent functional magnetic resonance imaging signal. RESULTS A risk endophenotype included greater activation of cortical attention circuits. A resilience endophenotype included greater activation of the dorsal anterior cingulate cortex. The effects of prior lifetime illness were common to both risk groups and included greater deactivation of default-mode circuits. CONCLUSIONS AND RELEVANCE These findings identify neural systems that increase risk for depression, those that protect from illness, and those that endure following illness onset, and they suggest circuits to target for developing novel preventive and therapeutic interventions.

Multimodal Magnetic Resonance Imaging: The Coordinated Use of Multiple, Mutually Informative Probes to Understand Brain Structure and Function

Differing imaging modalities provide unique channels of information to probe differing aspects of the brains structural or functional organization. In combination, differing modalities provide complementary and mutually informative data about tissue organization that is more than their sum. We acquired and spatially coregistered data in four MRI modalities—anatomical MRI, functional MRI, diffusion tensor imaging (DTI), and magnetic resonance spectroscopy (MRS)—from 20 healthy adults to understand how interindividual variability in measures from one modality account for variability in measures from other modalities at each voxel of the brain. We detected significant correlations of local volumes with the magnitude of functional activation, suggesting that underlying variation in local volumes contributes to individual variability in functional activation. We also detected significant inverse correlations of NAA (a putative measure of neuronal density and viability) with volumes of white matter in the frontal cortex, with DTI‐based measures of tissue organization within the superior longitudinal fasciculus, and with the magnitude of functional activation and default‐mode activity during simple visual and motor tasks, indicating that substantial variance in local volumes, white matter organization, and functional activation derives from an underlying variability in the number or density of neurons in those regions. Many of these imaging measures correlated with measures of intellectual ability within differing brain tissues and differing neural systems, demonstrating that the neural determinants of intellectual capacity involve numerous and disparate features of brain tissue organization, a conclusion that could be made with confidence only when imaging the same individuals with multiple MRI modalities. Hum Brain Mapp, 2013.