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Current neurocognitive models of attention-deficit/hyperactivity disorder (ADHD) suggest that neural circuits involving both attentional and affective processing make independent contributions to the phenomenology of the disorder. However, a clear dissociation of attentional and affective circuits and their behavioral correlates has yet to be shown in medication-naïve children with ADHD. Using resting-state functional connectivity MRI (rs-fcMRI) in a cohort of medication naïve children with (N=22) and without (N=20) ADHD, we demonstrate that children with ADHD have reduced connectivity in two neural circuits: one underlying executive attention (EA) and the other emotional regulation (ER). We also demonstrate a double dissociation between these two neural circuits and their behavioral correlates such that reduced connectivity in the EA circuit correlates with executive attention deficits but not with emotional lability, while on the other hand, reduced connectivity in the ER circuit correlates with emotional lability but not with executive attention deficits. These findings suggest potential avenues for future research such as examining treatment effects on these two neural circuits as well as the potential prognostic and developmental significance of disturbances in one circuit vs the other., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Schizophrenia is associated with extensive neurocognitive and behavioral impairments. Studies indicate that N-acetylaspartate (NAA), a marker of neuronal integrity, and choline, a marker of cell membrane turnover and white matter integrity, may be altered in schizophrenia. Davunetide is a neurotrophic peptide that can enhance cognitive function in animal models of neurodegeneration. Davunetide has recently demonstrated modest functional improvement in a study of people with schizophrenia. In a subset of these subjects, proton magnetic resonance spectroscopy ((1)H-MRS) was conducted to explore the effects of davunetide on change in NAA/creatine (NAA/Cr) and choline/creatine (choline/Cr) over 12 weeks of treatment. Of 63 outpatients with schizophrenia who received randomized davunetide (5 and 30 mg/day) or placebo in the parent clinical trial, 18 successfully completed (1)H-MRS in dorsolateral prefrontal cortex (DLPFC) at baseline and at 12 weeks. Cognition was assessed using the MATRICS Consensus Cognitive Battery (MCCB). NAA/Cr was unchanged for combined high- and low-dose davunetide groups (N=11). NAA/Cr in the high-dose davunetide group (N=8) suggested a trend increase of 8.0% (P=0.072) over placebo (N=7). Choline/Cr for combined high- and low-dose davunetide groups suggested a 6.4% increase (P=0.069), while the high-dose group showed a 7.9% increase (P=0.040) over placebo. Baseline NAA/Cr correlated with the composite MCCB score (R=0.52, P=0.033), as did individual cognitive domains of attention/vigilance, verbal learning, and social cognition; however, neither metabolite correlated with functional capacity. In this exploratory study, 12 weeks of adjunctive davunetide appeared to produce modest increases in NAA/Cr and choline/Cr in DLPFC in people with schizophrenia. This is consistent with a potential neuroprotective mechanism for davunetide. The data also support use of MRS as a useful biomarker of baseline cognitive function in schizophrenia. Future clinical and preclinical studies are needed to fully define the mechanism of action and cognitive effects of davunetide in schizophrenia.

Behavioral interference elicited by competing response tendencies adapts to contextual changes. Recent nonhuman primate research suggests a key mnemonic role of distinct prefrontal cells in supporting such context-driven behavioral adjustments by maintaining conflict information across trials, but corresponding prefrontal functions have yet to be probed in humans. Using event-related functional magnetic resonance imaging, we investigated the human neural substrates of contextual adaptations to conflict. We found that a neural system comprising the rostral dorsomedial prefrontal cortex and portions of the dorsolateral prefrontal cortex specifically encodes the history of previously experienced conflict and influences subsequent adaptation to conflict on a trial-by-trial basis. This neural system became active in anticipation of stimulus onsets during preparatory periods and interacted with a second neural system engaged during the processing of conflict. Our findings suggest that a dynamic interaction between a system that represents conflict history and a system that resolves conflict underlies the contextual adaptation to conflict.

Functional neuroimaging studies of attention-deficit/hyperactivity disorder (ADHD) have focused on the neural correlates of cognitive control. However, for many youths with ADHD, emotional lability is an important clinical feature of the disorder. We aimed to identify the neural substrates associated with emotional lability that were distinct from impairments in cognitive control and to assess the effects that stimulants have on those substrates. We used functional magnetic resonance imaging (fMRI) to assess neural activity in adolescents with (N=15) and without (N=15) ADHD while they performed cognitive and emotional versions of the Stroop task that engage cognitive control and emotional processing, respectively. The participants with ADHD were scanned both on and off stimulant medication in a counterbalanced fashion. Controlling for differences in cognitive control, we found that during the emotional Stroop task, adolescents with ADHD as compared with controls demonstrated atypical activity in the medial prefrontal cortex (mPFC). Stimulants attenuated activity in the mPFC to levels comparable with controls., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Objective: Emotional reactivity is one of the most disabling symptoms associated with attention-deficit/hyperactivity disorder (ADHD). We aimed to identify neural substrates associated with emotional reactivity and to assess the effects of stimulants on those substrates., Method: We used functional magnetic resonance imaging (fMRI) to assess neural activity in adolescents with (n = 15) and without (n = 15) ADHD while they performed a task involving the subliminal presentation of fearful faces. Using dynamic causal modeling, we also examined the effective connectivity of two regions associated with emotional reactivity, i.e., the amygdala and the lateral prefrontal cortex (LPFC). The participants with ADHD underwent scanning both on and off stimulant medication in a counterbalanced fashion., Results: During the task, we found that activity in the right amygdala was greater in adolescents with ADHD than in control subjects. In addition, in adolescents with ADHD, greater connectivity was detected between the amygdala and LPFC. Stimulants had a normalizing effect on both the activity in the right amygdala and the connectivity between the amygdala and LPFC., Conclusions: Our findings demonstrate that in adolescents with ADHD, a neural substrate of fear processing is atypical, as is the connectivity between the amygdala and LPFC. These findings suggest possible neural substrates for the emotional reactivity that is often present in youths with ADHD, and provide putative neural targets for the development of novel therapeutic interventions for this condition., (Copyright © 2011 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Attempts to correlate measures of intellectual ability with localized anatomical imaging features of the brain have yielded variable findings distributed across frontal, parietal, and temporal lobes. To better define the gray and white matter correlates of intellectual ability and the effects of sex and age, we analyzed the brains of 105 healthy individuals, ages 7-57 years, who had a Full Scale Intelligence Quotient (FSIQ) of 70 or higher. We examined associations of FSIQ with cortical thickness and with white matter volume throughout the cerebrum. Thinning of left ventromedial and right dorsolateral prefrontal cortices correlated significantly with FSIQ. Sex modified correlations of cortical thickness with FSIQ in the left inferior frontal, left cingulate, and right dorsomedial prefrontal cortices. Correlations of local white matter volumes with FSIQ varied by age, with adults showing inverse correlations of white matter volume with FSIQ in a large territory of right frontal white matter likely corresponding to fiber tracts of the superior corona radiata and superior longitudinal fasciculus. These findings corroborate the role of frontal and parietal association cortices and long association white matter fibers in higher intelligence and suggest ways in which the neuroanatomical correlates of higher intelligence may vary by sex and age., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Neuroimaging data suggest that deficits in ventral prefrontal cortex (VPFC) function in bipolar disorder (BD) progress during adolescence and young adulthood. However, the developmental trajectory of VPFC morphological abnormalities in BD is unknown. This study investigated potential age-dependent volume abnormalities in VPFC in BD., Methods: Thirty-seven individuals diagnosed with BD I (14 adolescents, 10 young adults and 13 older adults) and 56 healthy comparison subjects (HC) participated in imaging. Gray and white matter volumes of VPFC were measured using high-resolution structural magnetic resonance imaging (MRI). We used a mixed model, repeated measures analysis to examine VPFC volumes across age groups while co-varying for total brain volume. Potential effects of illness features including rapid-cycling and medication were explored., Results: VPFC volumes declined with age (p < .001). The diagnosis-by-age group interaction was significant (p = .01). Relative to HC subjects, VPFC gray and white matter volumes were significantly smaller in BD patients only in young adulthood (p = .04). In participants with BD, VPFC volumes were significantly smaller in participants with rapid-cycling than participants without rapid-cycling (p = .02). Conversely, current use of medication was associated with larger VPFC gray matter volumes (p = .005), independent of age., Conclusions: These preliminary findings suggest the presence of a more rapid initial decline in VPFC volumes with age in adolescents and young adults with BD than HC. These findings also suggest that the rapid-cycling subtype of BD is associated with larger VPFC volume deficits than the non-rapid-cycling subtype, and that pharmacotherapy may have trophic or protective effects on VPFC volumes in BD patients.

The prefrontal cortex (PFC) is relatively smaller, and the corpus callosum (CC) larger, in adults with Tourette syndrome (TS). The authors explored the possible roles of the PFC and the CC in mediating interhemispheric interference and coordination in TS adults. They measured performance on M. Kinsbourne and J. Cook's (1971) verbal-manual interference task and on the bimanual Purdue Pegboard in 38 adults with TS and 34 healthy adults. Compared with controls, TS subjects were impaired on the bimanual Purdue Pegboard. On the dual task, right-hand performance did not differ between groups, but the normally expected left-hand advantage (opposite hemisphere condition) was absent in TS subjects. In the control group only, better left-hand performance accompanied larger PFC volumes but not CC cross-sectional area. PFC dysfunction might have precluded executive control of interference in the TS group.

The deficits of executive control of emotions and impulses of adult BD implicate involvement of a ventral prefrontal cortex (VPFC) neural system that subserves these functions that include the VPFC, as well as its subcortical connection sites of amygdala, striatum, and thalamus. Differences in the timing of major developmental changes in the structures within this neural system suggest that abnormalities in particular components of this neural system may emerge during critical developmental epochs during the course of the illness. Our recent neuroimaging data suggest that abnormalities in the subcortical components of VPFC neural systems may be evident by early adolescence in BD, whereas VPFC deficits progress over the course of adolescence and may be difficult to detect prior to late adolescence or early adulthood. This potential neurodevelopmental model for BD could have important implications for the recognition of early signs of the disorder and for age-specific treatment strategies.

Objective: Function of the ventromedial prefrontal cortex has been implicated in impulse control. The authors used the Stroop paradigm to test attention and response inhibition during the presentation of congruent and incongruent stimuli in male pathological gamblers and a group of comparison subjects., Method: Event-related functional magnetic resonance imaging was used to examine ventromedial prefrontal cortex function during Stroop performance., Results: In response to infrequent incongruent stimuli, pathological gamblers demonstrated decreased activity in the left ventromedial prefrontal cortex relative to the comparison subjects. Both groups demonstrated similar activity changes in multiple brain regions, including activation of the dorsal anterior cingulate and dorsolateral frontal cortex., Conclusions: Pathological gamblers share many neural correlates of Stroop task performance with healthy subjects but differ in a brain region previously implicated in disorders characterized by poor impulse control.

Objective: This study investigated whether the functional abnormalities in prefrontal systems observed in adult bipolar disorder are manifested in adolescents with this illness., Method: Ten adolescents with bipolar disorder and 10 healthy comparison subjects participated in a color-naming Stroop task during event-related functional magnetic resonance imaging., Results: Signal increases in the left putamen and thalamus were significantly greater in the bipolar disorder group than in the healthy group. Age correlated positively with signal increases in the bilateral rostroventral prefrontal cortex and the striatum in the healthy group but not in the bipolar disorder group. In the bipolar disorder subjects, depressive symptoms correlated positively with signal increases in the ventral striatum., Conclusions: These findings suggest the presence of dysfunction in the subcortical portions of the frontostriatal circuits in adolescents with bipolar disorder. The absence of the prefrontal abnormalities that were observed previously in adults and the absence of the age-related increases in prefrontal activity observed in normal comparison subjects suggest that a developmental disturbance in prefrontal function may emerge in bipolar disorder over the course of adolescence.

Background: Abnormalities in prefrontal and anterior cingulate cortices are implicated in disturbances of attention, cognition, and impulse regulation in bipolar disorder. Acute episodes have been associated with dysfunction in these brain regions, and more enduring trait-related dysfunction has been implicated by volumetric and cellular abnormalities in these regions. The relative contributions of prefrontal regions to state and trait disturbances in bipolar disorder, however, have not been defined. We sought to characterize state- and trait-related functional impairment in frontal systems in bipolar disorder., Methods: Thirty-six individuals with bipolar disorder I (11 with elevated, 10 with depressed, and 15 with euthymic mood states) and 20 healthy control subjects matched for handedness and sex participated in an event-related functional magnetic resonance imaging study of the color-word Stroop to determine mean percentage of regional task-related signal change., Results: Signal increased during the Stroop task similarly across diagnostic groups in a distribution that included dorsal anterior cingulate and prefrontal cortices, consistent with previously reported activations in this task. Signal changes associated with specific mood states in bipolar disorder were detected in ventral prefrontal cortex, with a blunted increase in signal on the right side in the elevated mood group (P =.005) and an exaggerated increase in signal on the left side in the depressed group (P =.02) compared with the euthymic group. Patients (vs healthy controls) demonstrated blunted activation in a spatially distinct, rostral region of left ventral prefrontal cortex that was independent of mood state (P<.005)., Conclusions: Bipolar disorder is associated with a trait abnormality in left ventral prefrontal cortex. Additional ventral prefrontal abnormalities may be associated with specific acute mood states. The hemispheric laterality of the abnormality and the directions of signal change may relate to the valence of the mood episode.

Objective: The authors examined the effect of psychostimulants on brain activity in children and adolescents with ADHD performing the Stroop Color and Word Test. Method: The authors acquired 52 functional MRI scans in 16 youths with ADHD who were known responders to stimulant medication and 20 healthy comparison youths. Participants with ADHD were scanned on and off medication in a counterbalanced design, and comparison subjects were scanned once without medication. Results: Stimulant medication significantly improved suppression of default-mode activity in the ventral anterior cingulate cortex in the ADHD group. When off medication, youths with ADHD were unable to suppress default-mode activity to the same degree as comparison subjects, whereas when on medication, they suppressed this activity to comparison group levels. Greater activation of the lateral prefrontal cortex when off medication predicted a greater reduction in ADHD symptoms when on medication. Granger causality analyses demonstrated that activity in the lateral prefrontal and ventral anterior cingulate cortices mutually influenced one another but that the influence of the ventral anterior cingulate cortex on the lateral prefrontal cortex was significantly reduced in youths with ADHD off medication relative to comparison subjects and increased significantly to normal levels when ADHD youths were on medication. Conclusions: Psychostimulants in youths with ADHD improved suppression of default-mode activity in the ventral anterior cingulate and posterior cingulate cortices, components of a circuit in which activity has been shown to correlate with the degree of mind-wandering during attentional tasks. Stimulants seem to improve symptoms in youths with ADHD by normalizing activity within this circuit and improving its functional interactions with the lateral prefrontal cortex. [ABSTRACT FROM AUTHOR]

Objective: The corpus callosum is the major commissure connecting the cerebral hemispheres. Prior evidence suggests involvement of the corpus callosum in the pathophysiology of Tourette's disorder. The authors assessed corpus callosum size and anatomical connectivity across the cerebral hemispheres in persons with Tourette's disorder. Method: The size of the corpus callosum was determined on the true midsagittal slices of reformatted, high-resolution magnetic resonance imaging scans and compared across groups in a cross-sectional case-control study of 158 subjects with Tourette's disorder and 121 healthy comparison subjects, ages 5-65 years. Results: In the context of increasing midsagittal corpus callosum area from childhood to age 30 years, children with Tourette's disorder had smaller overall corpus callosum size, whereas adults with Tourette's disorder on average had larger corpus callosum size, yielding a prominent interaction of diagnosis with age. Corpus callosum size correlated positively with tic severity. Corpus callosum size also correlated inversely with dorsolateral prefrontal and orbitofrontal cortical volumes in both the subjects with Tourette's disorder and the comparison subjects, but the magnitudes of the correlations were significantly greater in the group with Tourette's disorder. The effects of medication and comorbid illnesses had no appreciable influence on the findings. Conclusions: Given prior evidence for the role of prefrontal hypertrophy in the regulation of tic symptoms, the current findings suggest that neural plasticity may contribute to smaller corpus callosum size in persons with Tourette's disorder, which thereby limits neuronal trafficking across the cerebral hemispheres and reduces in- put to cortical inhibitory interneurons within the prefrontal cortices. Reduced inhibitory input may in turn enhance prefrontal excitation, thus helping to control tics and possibly contributing to the cortical hyperexcitatibility reported previously in patients with Tourette's disorder. [ABSTRACT FROM AUTHOR]

The Stroop and Simon tasks typify a class of interference effects in which the introduction of task-irrelevant stimulus characteristics robustly slows reaction times. Behavioral studies have not succeeded in determining whether the neural basis for the resolution of these interference effects during successful task performance is similar or different across tasks. Event-related functional magnetic resonance imaging (fMRI) studies were obtained in 10 healthy young adults during performance of the Stroop and Simon tasks. Activation during the Stroop task replicated findings from two earlier fMRI studies. These activations were remarkably similar to those observed during the Simon task, and included anterior cingulate, supplementary motor, visual association, inferior temporal, inferior parietal, inferior frontal, and dorsolateral prefrontal cortices, as well as the caudate nuclei. The time courses of activation were also similar across tasks. Resolution of interference effects in the Simon and Stroop tasks engage similar brain regions, and with a similar time course. Therefore, despite the widely differing stimulus characteristics employed by these tasks, the neural systems that subserve successful task performance are likely to be similar as well. [Copyright &y& Elsevier]

Objective: The authors sought to study activity in neural circuits that subserve the inhibition of a semi-involuntary motor behavior, eye blinking, in children and adults with Tourette syndrome and in healthy comparison subjects. Method: Functional magnetic resonance imaging was used to scan 120 participants (51 with Tourette syndrome and 69 comparison subjects) as they either blinked normally or successfully inhibited eye blinking. The authors compared the blood-oxygen-level dependent signal during these two conditions across the Tourette and comparison groups. Results: Results: Relative to comparison subjects, patients with Tourette syndrome activated more strongly the frontal cortex and striatum during eye blink inhibition. Activation increased more with age in the dorsolateral and inferolateral prefrontal cortex and caudate nucleus in the Tourette group relative to comparison subjects. In addition, the Tourette group more strongly activated the middle frontal gyrus, dorsal anterior cingulate, and temporal cortices. The severity of tic symptoms in the Tourette group correlated inversely with activation in the putamen and inferolateral prefrontal cortex. Conclusions: Conclusions: Frontostriatal activity is increased in persons with Tourette syndrome during the inhibition of eye blinks. Activation of frontostriatal circuits in this population may help to maintain regulatory control over semi-involuntary behaviors, whether these are tics or eye blinks. [ABSTRACT FROM AUTHOR]

Abstract: 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. [Copyright &y& Elsevier]

La función de la corteza prefrontal ventromedial se ha relacionado con el control de los impulses. Los autores utilizaron el paradigma Stroop para examinar la atención y la inhibición de la respuesta durante la presentación de estímulos coherentes e incoherentes en individuos de sexo masculino afectos de juego patológico y en un grupo de individuos de control. Método: Se utiliza la resonancia magnética funcional contingente para examinar la corteza prefrontal ventromedial durante la realización de la prueba Stroop. Resultados: En respuesta a estímulos incoherentes poco frecuentes, los individuos afectos de juego patológico demostraran una menor actividad en la corteza prefrontal ventromedial izquierda en comparación con los individuos de control. Ambos grupos mostraron unos cambios de actividad parecidos en múltiples regiones cerebrales, entre ellos la activación del cíngulo dorsal anterior y de la corteza frontal dorsolateral. Conclusiones: Los individuos afectos de juego patológico comparten con los individuos sanos muchos correlatos neuronales de la prueba Stroop, pero se diferencian en una región cerebral involucrada, anteriormente, en los trastornos del control de los impulsos. [ABSTRACT FROM PUBLISHER]