Search

Background Attention-deficit/hyperactivity disorder (ADHD) is characterized by deficits in reward sensitivity and response inhibition. The relative contribution of these frontostriatal mechanisms to ADHD symptoms and their genetic determinants is largely unexplored. Methods Using functional magnetic resonance imaging and genetic analysis of the monoamine oxidase A ( MAOA ) gene, we investigated how striatal and inferior frontal activation patterns contribute to ADHD symptoms depending on MAOA genotype in a sample of adolescent boys ( n = 190). Results We demonstrate an association of ADHD symptoms with distinct blood oxygen level–dependent (BOLD) responses depending on MAOA genotype. In A hemizygotes of the expression single nucleotide polymorphism rs12843268, which express lower levels of MAOA , ADHD symptoms are associated with lower ventral striatal BOLD response during the monetary incentive delay task and lower inferior frontal gyrus BOLD response during the stop signal task. In G hemizygotes, ADHD symptoms are associated with increased inferior frontal gyrus BOLD response during the stop signal task in the presence of increased ventral striatal BOLD response during the monetary incentive delay task. Conclusions Depending on MAOA genotype, ADHD symptoms in adolescent boys are associated with either reward deficiency or insufficient response inhibition. Apart from its mechanistic interest, our finding may aid in developing pharmacogenetic markers for ADHD.

Background The catecholamine agonists methylphenidate and atomoxetine effectively treat attention-deficit/hyperactivity disorder (ADHD). Furthermore, dopamine agonists have shown to improve time estimation in ADHD, a core cognitive deficit. However, few have compared the effects of methylphenidate and atomoxetine on brain function in ADHD, and none during time estimation. Using single dose challenges, we investigated shared and drug-specific effects in ADHD adolescents on the neural substrates of time discrimination (TD). Methods Twenty ADHD adolescent male subjects were compared in a randomized double-blind cross-over design after single doses of methylphenidate, atomoxetine, and placebo in functional magnetic resonance imaging during TD. Normalization effects were assessed by comparing brain activation under each drug condition with that of 20 healthy age-matched control subjects. Results Relative to control subjects, patients under placebo showed TD deficits and reduced activation of ventrolateral prefrontal cortex (VLPFC)/insula, inferior frontal cortex, and supplementary motor area. Performance differences were normalized only by methylphenidate, relative to both atomoxetine and placebo. Both medications, however, significantly upregulated right VLPFC/insula activation within patients and normalized its underactivation in ADHD boys under placebo relative to control subjects. The supplementary motor area and inferior frontal cortex activation differences that were observed under placebo were reduced by methylphenidate and atomoxetine, respectively, but neither survived rigorous testing for normalization. Conclusions While only methylphenidate had a drug-specific effect of improving TD performance deficits, both drugs significantly upregulated and normalized right VLPFC underactivation in ADHD boys under placebo relative to control subjects, suggesting shared effects of stimulants and nonstimulants on a key prefrontal dysfunction during timing.

BackgroundThe catecholamine reuptake inhibitors methylphenidate (MPH) and atomoxetine (ATX) are the most common treatments for attention deficit hyperactivity disorder (ADHD). This study compares the neurofunctional modulation and normalization effects of acute doses of MPH and ATX within medication-naive ADHD boys during working memory (WM).MethodA total of 20 medication-naive ADHD boys underwent functional magnetic resonance imaging during a parametric WM n-back task three times, under a single clinical dose of either MPH, ATX or placebo in a randomized, double-blind, placebo-controlled, cross-over design. To test for normalization effects, brain activations in ADHD under each drug condition were compared with that of 20 age-matched healthy control boys.ResultsRelative to healthy boys, ADHD boys under placebo showed impaired performance only under high WM load together with significant underactivation in the bilateral dorsolateral prefrontal cortex (DLPFC). Both drugs normalized the performance deficits relative to controls. ATX significantly enhanced right DLPFC activation relative to MPH within patients, and significantly normalized its underactivation relative to controls. MPH, by contrast, both relative to placebo and ATX, as well as relative to controls, upregulated the left inferior frontal cortex (IFC), but only during 2-back. Both drugs enhanced fronto-temporo-striatal activation in ADHD relative to control boys and deactivated the default-mode network, which were negatively associated with the reduced DLPFC activation and performance deficits, suggesting compensation effects.ConclusionsThe study shows both shared and drug-specific effects. ATX upregulated and normalized right DLPFC underactivation, while MPH upregulated left IFC activation, suggesting drug-specific laterality effects on prefrontal regions mediating WM.

This study investigated the internal reliability, temporal stability and plasticity of commonly used measures of inhibition-related functions. Stop-signal, go/no-go, antisaccade, Simon, Eriksen flanker, Stroop and Continuous Performance tasks were administered twice to 23 healthy participants over a period of approximately 11 weeks in order to assess test–retest correlations, internal consistency (Cronbach’s alpha), and systematic between as well as within session performance changes. Most of the inhibition-related measures showed good test–retest reliabilities and internal consistencies, with the exception of the stop-signal reaction time measure, which showed poor reliability. Generally no systematic performance changes were observed across the two assessments with the exception of four variables of the Eriksen flanker, Simon and Stroop task which showed reduced variability of reaction time and an improvement in the response time for incongruent trials at second assessment. Predominantly stable performance within one test session was shown for most measures. Overall, these results are informative for studies with designs requiring temporally stable parameters e.g. genetic or longitudinal treatment studies.

Studies have long reported that aging is associated with declines in several functions modulated by the prefrontal cortex, including executive functions like working memory, set shifting, and inhibitory control. The neurochemical basis to this is poorly understood, but may include the serotonergic system. We investigated the modulatory effect of serotonin using acute tryptophan depletion (ATD) during a cognitive switching task involving visual-spatial set shifting modified for a functional MRI environment. Ten healthy women over 55 years were tested on two separate occasions in this within-group double-blind sham-controlled crossover study to compare behavioral and physiological brain functioning following ATD and following a ("placebo") sham depletion condition. ATD did not significantly affect task performance. It did modulate brain functional recruitment. During sham depletion women significantly activated the expected task-relevant brain regions associated with the Switch task including prefrontal and anterior cingulate cortices. In contrast, following ATD participants activated posterior regions of brain more during switch than repeat trials. In addition to the main effects of depletion condition, a comparison of the ATD relative to the sham condition confirmed this anterior-to-posterior shift in activation. The posterior (increased) activation clusters significantly and negatively correlated with the reduced prefrontal activation clusters suggesting a compensation mechanism for reduced prefrontal activation during ATD. Thus, serotonin modulates an anterior-to-posterior shift of activation during cognitive switching in older adults. Neural adaptation to serotonin challenge during cognitive control may prove useful in determining cognitive vulnerability in older adults with a predisposition for serontonergic down-regulation (e.g., in vascular or late life depression).

Objective Accumulating evidence implicates a strong association between abnormal frontostriatal-limbic brain circuits, executive dysfunction, and late-life depression (LLD). The stop signal task (SST) was designed by Rubia et al. for use with functional magnetic resonance imaging (fMRI) to identify the neural correlates of motor response inhibition, a well-characterized executive function. In this study, we compared brain activation between a group of unmedicated participants with LLD and an unmedicated healthy cohort during SST performance. Methods Participants 55–85 years of age were screened, clinically evaluated, and entered into either the LLD (n = 15) or healthy comparison group (n = 13). Both groups underwent neuroimaging while performing the SST under similar conditions. The brain circuitry of successful motor inhibition was evaluated by contrasting the condition of correctly inhibiting responses with the condition of correctly responding to Go signals. Differential areas of brain activation between the LLD and comparison groups were determined with FMRIB Software Library. Results Despite comparable SST performance measures, LLD participants demonstrated greater blood oxygen level dependent activation relative to the comparison group in predominantly left-lateralized frontostriatal-limbic circuitry that included the bilateral superior frontal cortices and left-hemispheric orbitofrontal gyri, insular cortex, cingulate cortex, caudate, and putamen. Conversely, the healthy comparison group did not exhibit any areas of greater activation than the LLD group. Conclusion Unmedicated participants with LLD activate additional areas within frontostriatal-limbic brain circuitry when performing the SST at a level comparable to a healthy cohort.

Objective: Functional magnetic resonance imaging (fMRI)studies in conduct disorder and in oppositional defiant disorderhave shown inconsistencies. The aim of this metaanalysisof fMRI studies in disruptive behavior disorders wasto establish the most consistent brain dysfunctions and toaddress task- and subtype-related heterogeneity.Method: Web-based publication databases were searchedto conduct a meta-analysis of all whole-brain fMRI studiesof youths with disruptive behavior disorder or conduct problemsup to August 2015. Sub-meta-analyses were conductedin functional subdomains of emotion processing; in cool andhot executive functions, which refer to goal-directed highercognitive functions with and without motivational andaffective significance; and in a subgroup of youths with additionalpsychopathic traits. The authors performed a metaanalysisof voxel-based group differences in functionalactivation using the anisotropic effect-size version of seedbasedd mapping.Results: Across 24 studies, 338 youths with disruptive behaviordisorder or conduct problems relative to 298 typicallydevelopingyouthshadconsistentunderactivationintherostraland dorsal anterior cingulate and in the medial prefrontalcortex andventral caudate. Sub-meta-analysesof fMRI studiesshowed that medial fronto-cingulate dysfunction was drivenby hot executive function. The sub-meta-analysis of emotionprocessing fMRI studies showed the most consistent underactivationin the dorsolateral prefrontal cortex and temporalpole, while cool executive functions were associated withtemporal abnormalities. Youths with disruptive behavior disorderwith psychopathic traits showed reduced ventromedialprefrontal-hypothalamic-limbic activation, but they alsoshowed hyperactivation in cognitive control mediating dorsolateralprefrontal-dorsal and striatal regions.Conclusions: The findings show that the most consistentdysfunction in youths with disruptive behavior disorder isin the rostro-dorsomedial, fronto-cingulate, and ventralstriatalregions that mediate reward-based decision making,which is typically compromised in the disorder. Youthswith psychopathic traits, on the other hand, have dysfunctionsassociated with the ventromedial prefrontal cortex andlimbic system, together with dorsal and fronto-striatal hyperfunctioning,which may reflect poor affect reactivity andempathy in the presence of hyperactive executive control.These findings provide potential targets for neurotherapeuticand pharmacological interventions.

People with autism spectrum disorder (ASD) have poor decision‐making and temporal foresight. This may adversely impact on their everyday life, mental health, and productivity. However, the neural substrates underlying poor choice behavior in people with ASD, or its’ neurofunctional development from childhood to adulthood, are unknown. Despite evidence of atypical structural brain development in ASD, investigation of functional brain maturation in people with ASD is lacking. This cross‐sectional developmental fMRI study investigated the neural substrates underlying performance on a temporal discounting (TD) task in 38 healthy (11–35 years old) male adolescents and adults with ASD and 40 age, sex, and IQ‐matched typically developing healthy controls. Most importantly, we assessed group differences in the neurofunctional maturation of TD across childhood and adulthood. Males with ASD had significantly poorer task performance and significantly lower brain activation in typical regions that mediate TD for delayed choices, in predominantly right hemispheric regions of ventrolateral/dorsolateral prefrontal cortices, ventromedial prefrontal cortex, striatolimbic regions, and cerebellum. Importantly, differential activation in ventromedial frontal cortex and cerebellum was associated with abnormal functional brain maturation; controls, in contrast to people with ASD, showed progressively increasing activation with increasing age in these regions; which furthermore was associated with performance measures and clinical ASD measures (stereotyped/restricted interests). Findings provide first cross‐sectional evidence that reduced activation of TD mediating brain regions in people with ASD during TD is associated with abnormal functional brain development in these regions between childhood and adulthood, and this is related to poor task performance and clinical measures of ASD. Hum Brain Mapp 38:5343–5355, 2017. © 2017 Wiley Periodicals, Inc.

Background: Autism spectrum disorder (ASD) and obsessive-compulsive disorder (OCD) share inhibitory control deficits possibly underlying poor control over stereotyped and repetitive g., v/r/ dACC /MPFC); and (iv) to indicate a pathway (e.g., if this is a pathway: bilateral putamen/caudate/nucleus accumbens / pallidum /amygdala/insula). BPS style does not allow virgules to be used to represent expressions of duality or alternatives. Please express these as and/or, and, or or . BPS style does not allow virgules to be used to represent a compound modifier such as rostral/ dorsomedial , which should be changed to hyphen(s), such as rostral- dorsomedial . BPS does not allow virgules to be used to separate elements of lists (e.g., if this is a list: bilateral putamen/caudate/nucleus accumbens / pallidum /amygdala/insula). Please use commas in lists. BPS does not allow use of virgules to mean of between numbers (e.g., 4/12). Please use of. >and compulsive behaviors, respectively. However, it is unclear whether these symptom profiles are mediated by common or distinct neural profiles. This comparative multimodal meta-analysis assessed shared and disorder-specific neuroanatomy and neurofunction of inhibitory functions. Methods: A comparative meta-analysis of 62 voxel-based morphometry and 26 functional magnetic resonance imaging (fMRI) studies of inhibitory control was conducted comparing gray matter volume and activation abnormalities between patients with ASD (structural MRI: 911; fMRI: 188) and OCD (structural MRI: 928; fMRI: 247) and control subjects. Multimodal meta-analysis compared groups across voxel-based morphometry and fMRI. Results: Both disorders shared reduced function and structure in the rostral and dorsomedial prefrontal cortex including the anterior cingulate. OCD patients had a disorder-specific increase in structure and function of left basal ganglia (BG) and insula relative to control subjects and ASD patients, who had reduced right BG and insula volumes versus OCD patients. In fMRI, ASD patients showed disorder-specific reduced left dorsolateral-prefrontal activation and reduced posterior cingulate deactivation, whereas OCD patients showed temporoparietal underactivation. Conclusions: The multimodal comparative meta-analysis shows shared and disorder-specific abnormalities. Whereas the rostrodorsomedial prefrontal cortex was smaller in structure and function in both disorders, this was concomitant with increased structure and function in BG and insula in OCD patients, but a reduction in ASD patients, presumably reflecting a disorder-specific frontostriatoinsular dysregulation in OCD in the form of poor frontal control over overactive BG, and a frontostriatoinsular maldevelopment in ASD with reduced structure and function in this network. Disorder-differential mechanisms appear to drive overlapping phenotypes of inhibitory control abnormalities in patients with ASD and OCD.

Background:The present study examined pain perception in children and adolescents with ADHD and the interaction between pain perception and the administration of methylphenidate (MPH) in order to generate hypotheses for further research that will help to clarify the association between ADHD diagnosis, MPH treatment and pain perception.Methods:We included 260 children and adolescents of the “German Health Interview and Examination Survey for Children and Adolescents” (KiGGS) and analyzed parent’s assessments of children’s pain distribution and pain perception, as well as the influence of MPH administration on pain perception in affected children and adolescents.Results:Pain perception was associated with ADHD and MPH administration, indicating that children and adolescents suffering from ADHD without MPH treatment were reported to have lower pain perception compared to both, healthy controls (HC) and ADHD patients medicated with MPH.Conclusion:We suggest that reduced pain perception in children and adolescents with ADHD not medicated with MPH may lead to higher risk tolerance by misjudgments of dangerous situations, expanding the importance of MPH administration in affected children and adolescents.

Childhood maltreatment is associated with adverse affective and cognitive consequences including impaired emotion processing, inhibition and attention. However, the majority of functional magnetic resonance imaging (fMRI) studies in childhood maltreatment have examined emotion processing, while very few studies have tested the neurofunctional substrates of cognitive functions and none of attention. This study investigated the association between severe childhood abuse and fMRI brain activation during a parametric sustained attention task with a progressively increasing load of sustained attention in 21 medication-naive, drug-free young people with a history of childhood abuse controlling for psychiatric comorbidities by including 19 psychiatric controls matched for psychiatric diagnoses, and 27 healthy controls. Behaviorally, the participants exposed to childhood abuse showed increased omission errors in the task which correlated positively trend-wise with the duration of their abuse. Neurofunctionally, the participants with a history of childhood abuse, but not the psychiatric controls, displayed significantly reduced activation relative to the healthy controls during the most challenging attention condition only in typical attention regions including left inferior and dorsolateral prefrontal cortex, insula and temporal areas. We therefore show for the first time that severe childhood abuse is associated with neurofunctional abnormalities in key ventral frontal-temporal sustained attention regions. The findings represent a first step towards the delineation of abuse-related neurofunctional abnormalities in sustained attention, which may help in the development of effective treatments for victims of childhood abuse.

Attention-deficit hyperactivity disorder (ADHD) is associated with deficits in timing functions with, however, inconclusive findings on the underlying neurofunctional deficits. We therefore conducted a meta-analysis of 11 functional magnetic resonance imaging (fMRI) studies of timing in ADHD, comprising 150 patients and 145 healthy controls. Peak coordinates were extracted from significant case–control activation differences as well as demographic, clinical, and methodological variables. In addition, meta-regression analyses were used to explore medication effects.The most consistent deficits in ADHD patients relative to controls were reduced activation in typical areas of timing such as left inferior prefrontal cortex (IFC)/insula, cerebellum, and left inferior parietal lobe. The findings of left fronto-parieto-cerebellar deficits during timing functions contrast with well documented right fronto-striatal dysfunctions for inhibitory and attention functions, suggesting cognitive domain-specific neurofunctional deficits in ADHD. The meta-regression analysis showed that right dorsolateral prefrontal cortex (DLPFC) activation was reduced in medication-naïve patients but normal in long-term stimulant medicated patients relative to controls, suggesting potential normalization effects on the function of this prefrontal region with long-term psychostimulant treatment.

Callous/unemotional (CU) temperament traits may denote a more severe form of conduct disorder (CD) and have been associated with abnormal cortical thinning. The present study investigated the maturational decline in N200 amplitude, and the association between N200 amplitude and callous/unemotional traits, in adolescents with CD. Twenty adolescent males (aged 10–18 years old) with CD were age-matched to 27 clinical controls with Attention Deficit Hyperactivity Disorder (ADHD) and 30 non-clinical, typically developing controls. Participants completed a visual continuous performance task. As expected, N200 amplitude in response to background stimuli was inversely associated with age in controls (at frontal and temporal brain regions). Similar associations were seen in clinical controls. In contrast, the CD group showed a significant positive correlation between age and the right temporal N200 amplitude. Further, CU traits were positively correlated with N200 amplitude at midline frontal and temporal electrodes, even after covarying for age. These results highlight links between CU traits and abnormal neurodevelopment as indexed by N200 amplitude. This is in line with an impairment or delay in regressive maturational changes such as cortical thinning, as suggested by neuroimaging studies, which may underlie the persistence of certain psychopathic tendencies.

The stimulant methylphenidate (MPX) and the nonstimulant atomoxetine (ATX) are the most commonly prescribed medications for attention deficit hyperactivity disorder (ADHD). However, no functional magnetic resonance imaging (fMRI) study has as yet investigated the effects of ATX on inhibitory or any other brain function in ADHD patients or compared its effects with those of MPX. A randomized, double-blind, placebo-controlled, crossover pharmacological design was used to compare the neurofunctional effects of single doses of MPX, ATX, and placebo during a stop task, combined with fMRI within 19 medication-naive ADHD boys, and their potential normalization effects relative to 29 age-matched healthy boys. Compared with controls, ADHD boys under placebo showed bilateral ventrolateral prefrontal, middle temporal, and cerebellar underactivation. Within patients, MPX relative to ATX and placebo significantly upregulated right ventrolateral prefrontal activation, which correlated with enhanced inhibitory capacity. Relative to controls, both drugs significantly normalized the left ventrolateral prefrontal underactivation observed under placebo, while MPX had a drug-specific effect of normalizing right ventrolateral prefrontal and cerebellar underactivation observed under both placebo and ATX. The findings show shared and drug-specific effects of MPX and ATX on performance and brain activation during inhibitory control in ADHD patients with superior upregulation and normalization effects of MPX.

The developmental cognitive neuroscience literature has grown exponentially over the last decade. This paper reviews the functional magnetic resonance imaging (fMRI) literature on brain function development of typically late developing functions of cognitive and motivation control, timing and attention as well as of resting state neural networks. Evidence shows that between childhood and adulthood, concomitant with cognitive maturation, there is progressively increased functional activation in task-relevant lateral and medial frontal, striatal and parieto-temporal brain regions that mediate these higher level control functions. This is accompanied by progressively stronger functional inter-regional connectivity within task-relevant fronto-striatal and fronto-parieto-temporal networks. Negative age associations are observed in earlier developing posterior and limbic regions, suggesting a shift with age from the recruitment of “bottom-up” processing regions towards “top-down” fronto-cortical and fronto-subcortical connections, leading to a more mature, supervised cognition. The resting state fMRI literature further complements this evidence by showing progressively stronger deactivation with age in anti-correlated task-negative resting state networks, which is associated with better task performance. Furthermore, connectivity analyses during the resting state show that with development increasingly stronger long-range connections are being formed, for example, between fronto-parietal and fronto-cerebellar connections, in both task-positive networks and in task-negative default mode networks, together with progressively lesser short-range connections, suggesting progressive functional integration and segregation with age. Overall, evidence suggests that throughout development between childhood and adulthood, there is progressive refinement and integration of both task-positive fronto-cortical and fronto-subcortical activation and task-negative deactivation, leading to a more mature and controlled cognition.

Objective This article aims to review basic and clinical studies outlining the roles of prefrontal cortical (PFC) networks in the behavior and cognitive functions that are compromised in childhood neurodevelopmental disorders and how these map into the neuroimaging evidence of circuit abnormalities in these disorders. Method Studies of animals, normally developing children, and patients with neurodevelopmental disorders were reviewed, with focus on neuroimaging studies. Results The PFC provides "top–down" regulation of attention, inhibition/cognitive control, motivation, and emotion through connections with posterior cortical and subcortical structures. Dorsolateral and inferior PFC regulate attention and cognitive/inhibitory control, whereas orbital and ventromedial structures regulate motivation and affect. PFC circuitries are very sensitive to their neurochemical environment, and small changes in the underlying neurotransmitter systems, e.g. by medications, can produce large effects on mediated function. Neuroimaging studies of children with neurodevelopmental disorders show altered brain structure and function in distinctive circuits respecting this organization. Children with attention-deficit/hyperactivity disorder show prominent abnormalities in the inferior PFC and its connections to striatal, cerebellar, and parietal regions, whereas children with conduct disorder show alterations in the paralimbic system, comprising ventromedial, lateral orbitofrontal, and superior temporal cortices together with specific underlying limbic regions, regulating motivation and emotion control. Children with major depressive disorder show alterations in ventral orbital and limbic activity, particularly in the left hemisphere, mediating emotions. Finally, children with obsessive-compulsive disorder appear to have a dysregulation in orbito-fronto-striatal inhibitory control pathways, but also deficits in dorsolateral fronto-parietal systems of attention. Conclusions Altogether, there is a good correspondence between anatomical circuitry mediating compromised functions and patterns of brain structure and function changes in children with neuropsychiatric disorders. Medications may optimize the neurochemical environment in PFC and associated circuitries, and improve structure and function.

Attention Deficit Hyperactivity Disorder (ADHD) has long been associated with abnormalities in frontal brain regions. In this paper we review the current structural and functional imaging evidence for abnormalities in children and adults with ADHD in fronto-striatal, fronto-parieto-temporal, fronto-cerebellar and fronto-limbic regions and networks. While the imaging studies in children with ADHD are more numerous and consistent, an increasing number of studies suggests that these structural and functional abnormalities in fronto-cortical and fronto-subcortical networks persist into adulthood, despite a relative symptomatic improvement in the adult form of the disorder. We furthermore present new data that support the notion of a persistence of neurofunctional deficits in adults with ADHD during attention and motivation functions. We show that a group of medication-naive young adults with ADHD behaviours who were followed up 20 years from a childhood ADHD diagnosis show dysfunctions in lateral fronto-striato-parietal regions relative to controls during sustained attention, as well as in ventromedial orbitofrontal regions during reward, suggesting dysfunctions in cognitive-attentional as well as motivational neural networks. The lateral fronto-striatal deficit findings, furthermore, were strikingly similar to those we have previously observed in children with ADHD during the same task, reinforcing the notion of persistence of fronto-striatal dysfunctions in adult ADHD. The ventromedial orbitofrontal deficits, however, were associated with comorbid conduct disorder (CD), highlighting the potential confound of comorbid antisocial conditions on paralimbic brain deficits in ADHD. Our review supported by the new data therefore suggest that both adult and childhood ADHD are associated with brain abnormalities in fronto-cortical and fronto-subcortical systems that mediate the control of cognition and motivation. The brain deficits in ADHD therefore appear to be multi-systemic and to persist throughout the lifespan.

Background Methylphenidate improves motor response inhibition, typically assessed with the stop-signal task. The exact underlying mechanism for this, however, remains unknown. In addition, recent studies highlight that stop signals can have a confounding attentional-capture effect because of their low frequency in the task. In the current study, we assessed the effects of methylphenidate on neural networks of inhibitory control and attentional-capture within the context of two inhibitory control tasks. Methods The effects of methylphenidate (40 mg) were assessed using functional magnetic resonance imaging in 16 healthy volunteers in a within-subject, double-blind, placebo-controlled design. Results Methylphenidate significantly reduced activation of different regions within the right inferior frontal gyrus/insula to infrequent stimuli associated with successful inhibition, failed inhibition, and attentional capture. These inferior frontal gyrus regions showed different interregional connections with inhibitory and attention networks. For failed inhibitions, methylphenidate increased activation within performance-monitoring regions, including the superior frontal, anterior cingulate, and parietal-occipital cortices, but only after controlling for attentional capture. Conclusions Our findings suggest that the improvement of response inhibition seen following methylphenidate administration is due to its influence on underlying attentional mechanisms linked to response control requirements.

Background Pediatric major depressive disorder (MDD) is associated with deficits in sustained attention, thought to be related to underlying motivation deficits. This hypothesis, however, has never directly been tested using functional magnetic resonance imaging. In this study, we investigated the neurofunctional correlates of the interplay between attention and motivation in medication-naive pediatric MDD using a rewarded sustained attention task. Methods Functional magnetic resonance imaging was used to compare brain activation between 20 medication-naive, noncomorbid, first-episode adolescents with MDD aged 13 to 18 years and 21 gender-, age-, and IQ-matched healthy adolescents. Participants performed a sustained attention task with and without a monetary reward to assess the impact of reward on sustained attention networks. Results During nonrewarded sustained attention, adolescents with MDD showed reduced activation compared with healthy control subjects in occipital cortex. When sustained attention was rewarded, however, the underactivation in adolescents with MDD was in an extensive right hemispheric network of inferior fronto-striato-thalamic attention and limbic hippocampus-anterior cingulate reward processing areas. Major depressive disorder patients showed increased activation in cerebellum, which correlated with reduced frontal activation and depressive symptoms, suggesting compensatory response. Further analysis showed that reward upregulated fronto-striatal and hippocampal/temporal activation in control subjects but deactivated these regions in MDD, with opposite effects in the cerebellum. Conclusions Medication-naive MDD adolescents show abnormalities in the regulation in fronto-striato-cerebellar brain regions involved in attention and reward during motivated but not unmotivated attention. This suggests a dysfunctional interplay between motivation and cognition in pediatric MDD, where motivation appears less capable of upregulating attention networks relative to healthy youths.

Background Anorexia nervosa (AN) is a serious mental disorder with multiple comorbidities and complications. In those with a severe and enduring form of the illness (SEED-AN), treatment responsivity is poor and the evidence base limited. Thus, there is a need for novel treatment strategies. This paper describes the theoretical background and protocol of a feasibility randomised controlled trial (RCT) of real versus sham (placebo) therapeutic repetitive transcranial magnetic stimulation (rTMS) in SEED-AN. The aim of this trial is to obtain information that will guide decision making and protocol development in relation to a future large-scale RCT of rTMS in this group of patients, and also to assess the preliminary efficacy and neural correlates of rTMS treatment. Design Forty-four adults from the community with a DSM-5 diagnosis of AN, an illness duration >3 years and a previous course of unsuccessful treatment will be randomly allocated to receive 20 sessions of either real or sham rTMS, in a parallel group design. As this is a feasibility study, no primary outcome has been defined and a broad range of outcome variables will be examined. These include weight/body mass index (BMI), eating disorder psychopathology, other psychopathology (for example, depression, anxiety), quality of life, neuropsychological processes (such as self-regulation, attentional bias and food choice behaviour), neuroimaging measures (that is, changes in brain structure or function), tolerability and acceptability of rTMS, and additional service utilisation. The feasibility of conducting a large-scale RCT of rTMS and the appropriateness of rTMS as a treatment for SEED-AN will be evaluated through: assessment of recruitment and retention rates, acceptability of random allocation, blinding success (allocation concealment), completion of treatment sessions and research assessments (baseline, post-treatment and follow-up assessments). The acceptability and tolerability of the treatment will be assessed via semi-structured interviews. Discussion The effect sizes generated and other findings from this trial will inform a future large-scale RCT with respect to decisions on primary outcome measures and other aspects of protocol development. Additionally, results from this study will provide a preliminary indication of the efficacy of rTMS treatment for AN, the neural correlates of the illness, and potential biomarkers of clinical response. Trial registration ISRCTN14329415. Date of registration: 23 July 2015. Electronic supplementary material The online version of this article (doi:10.1186/s13063-015-1069-3) contains supplementary material, which is available to authorized users.

Background: Children with oppositional defiant disorder/conduct disorder (ODD/CD) have shown deficits in ‘cool’ abstract-cognitive, and ‘hot’ reward-related executive function (EF) tasks. However, it is currently unclear to what extent ODD/CD is associated with neuropsychological deficits, independently of attention deficit hyperactivity disorder (ADHD). Methods: Fifty-nine adolescents with a history of early-onset oppositional problems, 28 with pure ODD/CD symptoms and 31 with ADHD with or without ODD/CD, and 34 healthy controls were administered a task battery measuring motor response inhibition, sustained attention, cognitive flexibility and reward-related decision-making. Findings were analysed using dimensional and group analyses. Results: In group analyses both groups with and without ADHD were impaired in EF measures. Dimensional analyses, however, showed that ODD/CD but not ADHD was related to hot EF based on increased risky decision-making in the Iowa Gambling Task. ODD/CD was also independently related to aspects of cool EF independently of ADHD, namely slower speeds of inhibitory responding and increased intra-subject variability. Conclusions: These findings show EF deficits associated with ODD/CD independently of ADHD, and implicate reward-related abnormalities in theories of antisocial behaviour development.

Background Children with attention-deficit/hyperactivity disorder (ADHD) have deficits in performance monitoring often improved with the indirect catecholamine agonist methylphenidate (MPH). We used functional magnetic resonance imaging to investigate the effects of single-dose MPH on activation of error processing brain areas in medication-naive boys with ADHD during a stop task that elicits 50% error rates. Methods Twelve medication-naive boys with ADHD were scanned twice, under either a single clinical dose of MPH or placebo, in a randomized, double-blind design while they performed an individually adjusted tracking stop task, designed to elicit 50% failures. Brain activation was compared within patients under either drug condition. To test for potential normalization effects of MPH, brain activation in ADHD patients under either drug condition was compared with that of 13 healthy age-matched boys. Results During failed inhibition, boys with ADHD under placebo relative to control subjects showed reduced brain activation in performance monitoring areas of dorsomedial and left ventrolateral prefrontal cortices, thalamus, cingulate, and parietal regions. MPH, relative to placebo, upregulated activation in these brain regions within patients and normalized all activation differences between patients and control subjects. During successful inhibition, MPH normalized reduced activation observed in patients under placebo compared with control subjects in parietotemporal and cerebellar regions. Conclusions MPH normalized brain dysfunction in medication-naive ADHD boys relative to control subjects in typical brain areas of performance monitoring, comprising left ventrolateral and dorsomedial frontal and parietal cortices. This could underlie the amelioration of MPH of attention and academic performance in ADHD.

Reduced cognitive control is considered a core feature of bipolar disorder (BD). Abnormalities in ventrolateral prefrontal cortex (VLPFC) and other functionally linked regions that underpin cognitive control during the Stroop Colour Word Task (SCWT) have been reported in patients with BD and their relatives. In this functional magnetic resonance study we used psychophysiological interaction analysis to examine functional connectivity during the SCWT in 39 euthymic BD patients, 39 of their first-degree relatives (25 with no Axis I disorders and 14 with major depressive disorder) and 48 healthy controls. The aim of this study was to identify potential diagnosis-specific functional connectivity changes differentiating patients with BD from their relatives with MDD, as well as functional connectivity correlates of resilience in relatives of BD patients who remain well. Psychophysiological interactions in healthy controls revealed a negative functional connectivity between the VLPFC and the ventral anterior cingulate cortex and insula and a positive connectivity between the VLPFC and the caudate and parietal cortices. Abnormalities in fronto-insular connectivity emerged as a key correlate of predisposition and disease expression for BD. Reduced fronto-cingulate connectivity was also observed in association with predisposition to BD irrespective of clinical outcome. BD patients and their MDD relatives showed additional abnormalities in frontal–basal ganglia connectivity while increased coupling between the ventral and dorsal lateral PFC was observed in relatives without any Axis I disorder. These findings suggest that during the SCWT the VLPFC and subcortical regions are involved in a dynamic interplay. Breakdown in these interactions is associated with risk and disease expression for mood disorders while increased functional coupling between dorsal and ventral prefrontal regions may reflect adaptive functional changes associated with resilience.

Adolescence is typified by significant maturation in higher-level attention functions coupled with less developed control over motivation, and enhanced sensitivity to novelty and reward. This study used event-related functional magnetic resonance imaging (fMRI) in seventy male and female participants aged between 10 and 43 years to identify age-related linear changes in cognitive sustained attention systems and the impact of reward on these systems, using a sustained attention task with and without a rewarded condition. For the non-rewarded sustained attention contrast, increasing age was associated with activation increases in typical regions of sustained attention including right inferior frontal, superior temporo-parietal and cerebellar cortices. Age-related activation decreases were observed within more posterior regions including posterior cingulate, insula and posterior cerebellar cortices, presumably mediating visual–spatial saliency detection. The effect of reward on sustained attention networks was associated with increased activation with age in regions associated with both executive attention control and reward processing, including dorsolateral, inferior and ventromedial prefrontal cortices (PFC), striatum, and temporo-parietal regions, suggestive of greater integration and executive control of motivation and cognition with maturity. Activation in paralimbic posterior cingulate and inferior temporal brain regions of visual–spatial saliency processing was progressively reduced in activation with increasing development. Thus, with increasing development between adolescence and adulthood, reward appears to enhance maturing cognitive sustained attention and executive reward-processing networks, whilst reducing paralimbic regions of saliency detection. These findings may be the neural underpinnings for the progressive maturation of motivational control over risk taking behaviours between adolescence and adulthood.

Youth with attention deficit hyperactivity disorder (ADHD) have deficits in interference inhibition, which can be improved with the indirect catecholamine agonist methylphenidate (MPH). Functional magnetic resonance imaging was used to investigate the effects of a single dose of MPH on brain activation during interference inhibition in medication-naive ADHD boys. Medication-naive boys with ADHD were scanned twice, in a randomized, double-blind design, under either a single clinical dose of MPH or placebo, while performing a Simon task that measures interference inhibition and controls for the oddball effect of low-frequency appearance of incongruent trials. Brain activation was compared within patients under either drug condition. To test for potential normalization effects of MPH, brain activation in ADHD patients under either drug condition was compared with that of healthy age-matched comparison boys. During incongruent trials compared with congruent–oddball trials, boys with ADHD under placebo relative to controls showed reduced brain activation in typical areas of interference inhibition, including right inferior prefrontal cortex, left striatum and thalamus, mid-cingulate/supplementary motor area, and left superior temporal lobe. MPH relative to placebo upregulated brain activation in right inferior prefrontal and premotor cortices. Under the MPH condition, patients relative to controls no longer showed the reduced activation in right inferior prefrontal and striato-thalamic regions. Effect size comparison, furthermore, showed that these normalization effects were significant. MPH significantly normalized the fronto-striatal underfunctioning in ADHD patients relative to controls during interference inhibition, but did not affect medial frontal or temporal dysfunction. MPH therefore appears to have a region-specific upregulation effect on fronto-striatal activation.

Background: Disinhibited traits, assessed both at the self-report and at the cognitive/behavioral levels, have been frequently implicated in externalizing behaviors, such as conduct disorder (CD), binge drinking, and drug use. However, self-report measures of disinhibition, such as impulsivity (IMP) and sensation seeking (SS), and cognitive measures of disinhibition are not often studied together in the same participants. Thus, it is still unclear how cognitive measures such as response inhibition and reward response bias relate to self-report measures of IMP and SS, and whether they can explain some of the association found between these self-report measures and specific facets of externalizing problems. Methods: The aim of this study was to assess whether cognitive measures of disinhibition relate to self-report measures of disinhibition and can mediate the specific relationships between self-report measures of disinhibition and CD symptoms, binge drinking and drug use in adolescence. Seventy-six adolescents were assessed on personality, substance use, and conduct problems every 6 months from 14 to 16 years of age and completed a test battery that included a Stop task, rewarded go/no–go task, digit span, and intelligence quotient tests at 16 years of age. Results: Multiple regression analyses showed that self-report IMP at 14 and deficits in response inhibition were associated with a 2-year average CD symptoms score and that deficits in response inhibition partially mediated the association between self-report IMP and CD symptoms (ab = 0.018 CI: 0.00002 to 0.04827). In contrast, SS and reward response bias were significantly associated with the unique variance in binge drinking, and that part of the overlap between SS and binge drinking was mediated by reward response bias (ab = 0.019, CI: 0.00131 to 0.04662). Conclusions: Findings show a dissociation between inhibitory measures associated with CD symptoms and those associated with binge drinking, with “cool” inhibitory and executive functions being associated with CD but “hot,” reward-related disinhibition measures being specific mediators between SS and binge drinking. The findings support the theoretical conceptualization for dual cognitive/motivational pathways of disinhibition, in this case IMP and SS, and their unique association with externalizing behavior in adolescence.

Background: Abnormalities in inhibitory control and underlying fronto‐striatal networks is common to both attention deficit hyperactivity disorder (ADHD) and obsessive‐compulsive‐disorder (OCD). The aim of this study was to investigate disorder‐specific abnormalities in neural networks mediating interference inhibition and selective attention. Method: Event‐related functional magnetic resonance imaging (fMRI) was used to compare brain activation of boys with ADHD (18), with OCD (10), and healthy boys during (20) during a Simon task that measures interference inhibition and controls for and therefore comeasures attention allocation. Results: During interference inhibition, both patient groups shared mesial frontal dysfunction compared to controls. Disorder‐specific dysfunctions were observed in OCD patients in dorsolateral prefrontal cortex during the oddball condition and in ADHD patients in inferior parietal lobe during interference inhibition and in caudate and posterior cingulate during the simpler oddball condition. The decreased activation in caudate and cingulate in ADHD was furthermore negatively correlated with ADHD symptoms and positively with OCD behavioral traits. Conclusions: The study shows that ADHD and OCD patients have shared but also disorder‐specific brain dysfunctions during interference inhibition and attention allocation. Both disorders shared dysfunction in mesial frontal cortex. Disorder‐specific dysfunctions, however, were observed in dorsolateral prefrontal cortex in OCD patients and in caudate, cingulate, and parietal brain regions in ADHD patients. The disorder‐specific dissociation of striato‐cingulate activation that was increased in OCD compared to ADHD patients, was furthermore inversely related to the symptomatology of the two disorders, and may potentially reflect differential dopamine modulation of striatal brain regions. Hum Brain Mapp, 2011. © 2010 Wiley‐Liss, Inc.

Background Neurocognitive models and previous neuroimaging work posit that auditory verbal hallucinations (AVH) arise due to increased auditory cortex (AC) activity and altered connectivity between the AC and other speech and language regions [e.g. 1]. In the present study we examined if patients with schizophrenia (SCZ) and AVH could be trained to down-regulate AC activity using real time functional Magnetic Resonance Imaging neurofeedback (rtfMRI-NF) [2]. We also examined the effects of rtfMRI-NF training on functional connectivity between the AC and other speech and language regions. Methods Eleven patients with SCZ (Table 1) and treatment refractory AVH were recruited to participate in the study and were trained to down-regulate auditory cortex (AC) activity over an average of fourteen rtfMRI-NF runs conducted during a two-week training period (Fig 1). We used a functional localiser to identify the speech sensitive superior temporal cortex (STG) (Figure 2A). At the end of the training period, AC activity, functional connectivity and AVH symptom levels were compared pre and post training. Results Patients successfully learnt to down-regulate activity in their AC over the rtfMRI-NF training period. Post training, patients showed increased connectivity between the AC, the inferior prefrontal gyrus and the inferior parietal lobe Figure. There was also a modest reduction in AVH symptom levels post compared to pre training (Table 2). Discussion The AC is as suitable target region for rtfMRI-NF in patients with SCZ and treatment refractory AVH. Successful down-regulation of AC activity can increase functional connectivity between speech motor and perception regions. These findings raise the possibility that rtfMRI-NF training could be used as a novel therapeutic intervention in this clinical population.

Attention-deficit/hyperactivity disorder (ADHD) is a childhood disorder that persists into adulthood. Nevertheless, there are far fewer imaging studies in adult compared with childhood ADHD. Here we review the imaging literature on brain structure, function and structural and functional connectivity in adult ADHD, as well as the effects of psychostimulants on brain dysfunctions. Importantly, we discuss similarities and differences between these deficit findings and those in childhood ADHD to address the key question of continuity of brain abnormalities into adulthood. Findings show strikingly similar but more inconsistent abnormalities in adult ADHD in key childhood ADHD deficit areas of frontostriatal, temporoparietal and cerebellar regions, presumably due to highly prevalent confounding factors in adult ADHD of elevated rates of comorbidity and medication history.

Background Children with Attention Deficit Hyperactivity Disorder (ADHD) have deficits in motivation and attention that can be ameliorated with the indirect dopamine agonist Methylphenidate (MPH). We used functional magnetic resonance imaging (fMRI) to investigate the effects of MPH in medication-naive children with ADHD on the activation and functional connectivity of “cool” attentional as well as “hot” motivation networks. Methods 13 medication-naive children with ADHD were scanned twice, under either an acute clinical dose of MPH or Placebo, in a randomised, double-blind design, while they performed a rewarded continuous performance task that measured vigilant selective attention and the effects of reward. Brain activation and functional connectivity was compared to that of 13 healthy age-matched controls to test for normalisation effects of MPH. Results MPH normalised performance deficits that were observed in children with ADHD compared to controls. Under placebo, children with ADHD showed reduced activation and functional inter-connectivity in bilateral fronto-striato-parieto-cerebellar networks during the attention condition, but enhanced activation in the orbitofrontal and superior temporal cortices for reward. MPH within children with ADHD enhanced the activation of fronto-striato-cerebellar and parieto-temporal regions. Compared to controls, MPH normalised differences during vigilant attention in parieto-temporal activation and fronto-striatal and fronto-cerebellar connectivity; MPH also normalised the enhanced orbitofrontal activation in children with ADHD in response to reward. Conclusions MPH normalised attention differences between children with ADHD and controls by both up-regulation of dysfunctional fronto-striato-thalamo-cerebellar and parieto-temporal attention networks and down-regulation of hyper-sensitive orbitofrontal activation for reward processing. MPH thus shows context-dependent dissociative modulation of both motivational and attentional neuro-functional networks in children with ADHD.

Developmental functional imaging studies of cognitive control show progressive age-related increase in task-relevant fronto-striatal activation in male development from childhood to adulthood. Little is known, however, about how gender affects this functional development. In this study, we used event related functional magnetic resonance imaging to examine effects of sex, age, and their interaction on brain activation during attentional switching and interference inhibition, in 63 male and female adolescents and adults, aged 13 to 38. Linear age correlations were observed across all subjects in task-specific frontal, striatal and temporo-parietal activation. Gender analysis revealed increased activation in females relative to males in fronto-striatal areas during the Switch task, and laterality effects in the Simon task, with females showing increased left inferior prefrontal and temporal activation, and males showing increased right inferior prefrontal and parietal activation. Increased prefrontal activation clusters in females and increased parietal activation clusters in males furthermore overlapped with clusters that were age-correlated across the whole group, potentially reflecting more mature prefrontal brain activation patterns for females, and more mature parietal activation patterns for males. Gender by age interactions further supported this dissociation, revealing exclusive female-specific age correlations in inferior and medial prefrontal brain regions during both tasks, and exclusive male-specific age correlations in superior parietal (Switch task) and temporal regions (Simon task). These findings show increased recruitment of age-correlated prefrontal activation in females, and of age-correlated parietal activation in males, during tasks of cognitive control. Gender differences in frontal and parietal recruitment may thus be related to gender differences in the neurofunctional maturation of these brain regions.

This paper reviews the evidence for changes of Meditation on body and brain physiology and for clinical effectiveness in disorders of psychiatry. The aim of Meditation is to reduce or eliminate irrelevant thought processes through training of internalised attention, thought to lead to physical and mental relaxation, stress reduction, psycho-emotional stability and enhanced concentration. Physiological evidence shows a reduction with Meditation of stress-related autonomic and endocrine measures, while neuroimaging studies demonstrate the functional up-regulation of brain regions of affect regulation and attention control. Clinical studies show some evidence for the effectiveness of Meditation in disorders of affect, anxiety and attention. The combined evidence from neurobiological and clinical studies seems promising. However, a more thorough understanding of the neurobiological mechanisms of action and clinical effectiveness of the different Meditative practices is needed before Meditative practices can be leveraged in the prevention and intervention of mental illness.

Age-related declines in prefrontal functions and age-related declines in prefrontal serotonin (5-HT) are documented. The effect of 5-HT on prefrontal cortex (PFC) is also documented; however, no one has examined the effect of experimental 5-HT modulation on PFC in healthy older adults. We investigated the effect of 5-HT on brain functioning in 10 women over 55 (mean = 63.0 ± 5.3 years) during cognitive interference inhibition (Simon task) using fMRI and acute tryptophan depletion (ATD). ATD did not affect task performance; it did affect brain function. During sham/no depletion, participants activated brain regions associated with the Simon (e.g., left inferior PFC). During ATD, there was no prefrontal but alternative posterior brain activation. ATD relative to sham reduced activity in left inferior PFC, anterior cingulate and basal ganglia but increased activity within neocerebellum and parietal lobe. In older adults, ATD modulates task-relevant brain activation for cognitive interference inhibition and is associated with an anterior-to-posterior activation shift. Maintaining successful Simon performance during ATD is achieved by increasing cerebellar and parietal contributions to compensate for decreased fronto-cingulo-striatal involvement.

Background: There is increasing recognition of major depressive disorder (MDD) in adolescence. In adult MDD, abnormalities of fronto-striatal and fronto-cingulate circuitries mediating cognitive control functions have been implicated in the pathogenesis and been related to problems with controlling negative thoughts. No neuroimaging studies of cognitive control functions, however, exist in paediatric depression. This study investigated whether medication-naive adolescents with MDD show abnormal brain activation of fronto-striatal and fronto-cingulate networks when performing tasks of attentional and cognitive control. Methods: Event-related functional magnetic resonance imaging was used to compare brain activation between 21 medication-naive adolescents with a first-episode of MDD aged 14–17 years and 21 healthy adolescents, matched for handedness, age, sex, demographics and IQ. Activation paradigms were tasks of selective attention (Simon task), attentional switching (Switch task), and motor response inhibition and error detection (Stop task). Results: In all three tasks, adolescents with depression compared to healthy controls demonstrated reduced activation in task-relevant right dorsolateral (DLPFC), inferior prefrontal cortex (IFC) and anterior cingulate gyrus (ACG). Additional areas of relatively reduced activation were in the parietal lobes during the Stop and Switch tasks, putamen, insula and temporal lobes during the Switch task and precuneus during the Simon task. Conclusions: This study shows first evidence that medication-naive adolescents with MDD are characterised by abnormal function in ACG and right lateral prefrontal cortex during tasks of attention and performance monitoring, suggesting an early pathogenesis of these functional abnormalities attributed to MDD.

Children and adolescents born before 33 weeks of gestation, that is very preterm, may experience problems with the inhibitory control of behaviour and the allocation of attention. Previous functional magnetic resonance imaging (fMRI) studies have found preterm‐born adolescents to display altered brain activation in tasks measuring inhibitory control. However, adolescence is a period during which dynamic changes are occurring in the brain, and it is not yet known whether these functional alterations will persist into adulthood, or instead reflect developmental delay. This study used an event‐related fMRI Go/No‐Go motor response inhibition paradigm, which included an oddball task measuring attention allocation to infrequent stimuli, to compare blood‐oxygen‐level‐dependent (BOLD) signal between 26 preterm‐born adults and 21 controls. Group differences in brain activation were observed in inhibition and attention networks during both conditions. During motor response inhibition, preterm‐born participants compared to controls showed increased BOLD signal in medial and right lateral posterior brain regions, including middle temporal/occipital gyrus, posterior cingulate gyrus and precuneus. During oddball trials, preterm‐born young adults displayed attenuated brain activation in a fronto‐parietal‐cerebellar network which is involved in mediating attention allocation. This pattern of reduced brain activation in task‐relevant regions of attention allocation, and increased activation in posterior brain regions during inhibitory control, suggests adult alteration of inhibition and attention processing following very preterm birth, which may reflect a developmental delay. Hum Brain Mapp, 2009. © 2008 Wiley‐Liss, Inc.

Affective impairment is observed in children and adolescents with attention-deficit hyperactivity disorder (ADHD). Low levels of long-chain polyunsaturated fatty acids (LC-PUFA), specifically omega-3 (omega-3) fatty acids in blood measures have been linked to a range of behavioural and mood disorders including ADHD. However, nothing is known about the relationship between omega-3 and brain function in children with ADHD. In the current study, 20 adolescent boys with ADHD were assessed for total lipid fractions in red blood cells and their event-related potential (ERP) response to the presentation of facial expressions of happiness, sadness and fearfulness. The results supported the hypothesis of a positive association between eicosapentaenoic acid (EPA) and a cognitive bias in orientation to overt expressions of happiness over both sad and fearful faces as indexed by midline frontal P300 amplitude. Additional exploratory analyses revealed a positive association between levels of docosahexaenoic acid (DHA) and the right temporal N170 amplitude in response to covert expressions of fear. The arachidonic (AA)/DHA ratio was negatively associated with the right temporal N170 amplitude also to covert expressions of fear. These findings indicate that EPA and DHA may be involved in distinct aspects of affect processing in ADHD and have implications for understanding currently inconsistent findings in the literature on EFA supplementation in ADHD and depression.

Background This study examined the effect of Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) on brain activation during a motor inhibition task. Methods Functional magnetic resonance imaging and behavioural measures were recorded while 15 healthy volunteers performed a Go/No-Go task following administration of either THC or CBD or placebo in a double-blind, pseudo-randomized, placebo-controlled repeated measures within-subject design. Results Relative to placebo, THC attenuated activation in the right inferior frontal and the anterior cingulate gyrus. In contrast, CBD deactivated the left temporal cortex and insula. These effects were not related to changes in anxiety, intoxication, sedation, and psychotic symptoms. Conclusions These data suggest that THC attenuates the engagement of brain regions that mediate response inhibition. CBD modulated function in regions not usually implicated in response inhibition.

Neuroimaging studies have identified frontal lobe brain abnormalities in migraineurs. Neuropsychological investigations highlighted frontal lobe related cognitive impairments in migraineurs, including working memory and executive function deficits. The relationship between brain anatomy and cognitive function in migraine, however, is unclear. The aim of this study was to simultaneously investigated cortex structure and executive function (EF) in patients with migraine and control subjects. Thus, we assessed grey matter (GM) density in 25 adult patients with migraine, compared to age and sex-matched control subjects, using magnetic resonance imaging (MRI) and voxel-based-morphometry (VBM), and we measured EF in the same population, employing three EF tasks of the Maudsley attention and response suppression (MARS) battery. Migraineurs, compared to control subjects, showed decreased frontal and parietal lobe GM density and slower response time to task set-shifting and, the delayed response time correlated significantly with reduced GM density of the frontal lobes in migraineurs. Frontal and parietal lobe abnormalities in migraineurs could be an underlying cause of significantly slower response time during cognitive set-shifting.

ResumenObjetivoEste estudio investiga tres funciones de control inhibidoras diferentes en pacientes con trastorno obsesivo compulsivo (TOC). La inhibición selectiva de la respuesta motora se investigó con un paradigma GO/NO-GO, la inhibición de una respuesta motora desencadenada con el paradigma STOP y la capacidad de inhibir la interferencia cognitiva con el paradigma motor STROOP.MétodosSe aplicaron los tests GO/NO-GO (ejecución-no ejecución), STOP y STROOP a 27 pacientes que cumplieron los criterios del DSM-IV para TOC y 25 sujetos de control sanos apareados por edad, lateralidad y CI.ResultadosLos pacientes con TOC tuvieron un rendimiento significativamente peor que los controles en la inhibición selectiva de las respuestas (GO/NO-GO) y en la inhibición de la interferencia cognitiva (STROOP) y también tuvieron peor rendimiento en la inhibición de respuestas motoras previamente desencadenadas (STOP).ConclusionesLos pacientes con TOC tienen deficiencias en los mecanismos inhibidores motores y cognitivos. Los resultados coinciden con los modelos psicobiológicos y neuropsicológicos de TOC que sugieren que existe un deterioro en los circuitos frontoestriatales que regulan las funciones de control inhibidor.

Inhibitory and performance‐monitoring functions have been shown to develop throughout adolescence. The developmental functional magnetic resonance imaging (fMRI) literature on inhibitory control, however, has been relatively inconsistent with respect to functional development of prefrontal cortex in the progression from childhood to adulthood. Age‐related performance differences between adults and children have been shown to be a confound and may explain inconsistencies in findings. The development of error‐related processes has not been studied so far using fMRI. The aim of this study was to investigate the neural substrates of the development of inhibitory control and error‐related functions by use of an individually adjusted task design that forced subjects to fail on 50% of trials, and therefore controlled for differences in task difficulty and performance between different age groups. Event‐related fMRI was used to compare brain activation between 21 adults and 26 children/adolescents during successful motor inhibition and inhibition failure. Adults compared with children/adolescents showed increased brain activation in right inferior prefrontal cortex during successful inhibition and in anterior cingulate during inhibition failure. A whole‐brain age‐regression analysis between 10 and 42 years showed progressive age‐related changes in activation in these two brain regions, with additional changes in thalamus, striatum, and cerebellum. Age‐correlated brain regions correlated with each other and with inhibitory performance, suggesting they form developing fronto‐striato‐thalamic and fronto‐cerebellar neural pathways for inhibitory control. This study shows developmental specialization of the integrated function of right inferior prefrontal cortex, basal ganglia, thalamus, and cerebellum for inhibitory control and of anterior cingulate gyrus for error‐related processes. Hum Brain Mapp 2007. © 2007 Wiley‐Liss, Inc.

Objectives To investigate regional differences in grey matter volume associated with the practice of Sahaja Yoga Meditation. Design Twenty three experienced practitioners of Sahaja Yoga Meditation and twenty three non- meditators matched on age, gender and education level, were scanned using structural Magnetic Resonance Imaging and their grey matter volume were compared using Voxel- Based Morphometry. Results Grey matter volume was larger in meditators relative to non-meditators across the whole brain. In addition, grey matter volume was larger in several predominantly right hemispheric regions: in insula, ventromedial orbitofrontal cortex, inferior temporal and parietal cortices as well as in left ventrolateral prefrontal cortex and left insula. No areas with larger grey mat- ter volume were found in non-meditators relative to meditators. Conclusions The study shows that long-term practice of Sahaja Yoga Meditation is associated with larger grey matter volume overall, and with regional enlargement in several right hemispheric corti- cal and subcortical brain regions that are associated with sustained attention, self-control, compassion and interoceptive perception. The increased grey matter volume in these atten- tion and self-control mediating regions suggests use-dependent enlargement with regular practice of this meditation. This work was supported by Ministerio de Ciencia e Innovación (ES), Award Number: IPT-2012-0961-300000 (Grant Recipient: JLGM).

Childhood maltreatment is associated with various cognitive deficits, including inhibitory deficits and hypersensitivity to negative feedback. The authors used a stop-signal task to investigate the association between severe childhood abuse and inhibitory and error processing brain activation in medication-naive, drug-free young people with and without severe childhood abuse, controlling for psychiatric comorbidities by including a psychiatric control group.Using functional MRI, the authors compared brain activation in 22 age- and gender-matched young people exposed to severe childhood abuse, 17 psychiatric comparison subjects matched for psychiatric diagnoses with the abused group, and 27 healthy comparison subjects during an individually adjusted tracking stop-signal task designed to elicit 50% inhibition failures.During failed inhibition, the childhood abuse group showed increased brain activation relative to the healthy comparison group in typical error processing regions of the dorsomedial frontal cortex, including the left and right presupplementary and supplementary motor area and anterior cingulate cortex. The increased activation in a smaller cluster in the supplementary motor area survived comparison with the psychiatric comparison group. No group differences in activation were observed for successful inhibition.The findings suggest that severe childhood abuse is associated with abnormally increased activation in classical dorsomedial frontal error-processing regions; furthermore, the increased activation in the supplementary motor area was abuse specific. However, childhood abuse was not associated with inhibitory dysfunction. Increased sensitivity of error-detection networks in participants in the childhood abuse group may be due to the constant need to monitor their own actions in order to avoid painful mistakes, which are often associated with harsh punishment in abusive settings.

ObjectiveThe present study investigates different three inhibitory control functions in patients with obsessive-compulsive disorder (OCD). Selective motor response inhibition was tested in a GO/NO-GO paradigm, the inhibition of a triggered motor response in a STOP paradigm and the ability to inhibit cognitive interference in a motor STROOP paradigm.Methods27 patients who met DSM-IV criteria for OCD and 25 age, handedness and IQ-matched healthy control subjects were tested in the GO/NO-GO, STOP and motor STROOP tasks.ResultsOCD patients performed significantly worse than controls in the selective inhibition of their motor responses (GO/NO-GO) and in the inhibition of cognitive interference (STROOP), and also showed worse performance in suppressing previously triggered motor responses (STOP).ConclusionPatients with OCD are impaired in motor and cognitive inhibitory mechanisms. The findings are consistent with psychobiological and neuropsychological models of OCD suggesting impairment of frontostriatal circuitries that mediate functions of inhibitory control.

Objective: A relatively small number of functional imaging studies of attention deficit hyperactivity disorder (ADHD) have shown abnormal prefrontal and striatal brain activation during tasks of motor response inhibition. However, the potential confound of previous medication exposure has not yet been addressed, and no functional imaging study exists to date on medication-naive children and adolescents with ADHD. The aim of this study was to investigate the neural substrates of a range of motor and cognitive inhibitory functions in a relatively large group of children and adolescents with ADHD who had never previously been exposed to medication. Method: Nineteen boys with ADHD and 27 healthy age- and IQ-matched boys underwent functional MRI to compare brain activation during performance of tasks that assessed motor response inhibition (go/no go task), cognitive interference inhibition (motor Stroop task), and cognitive flexibility (switch task). Results: Boys with ADHD showed decreased activation in the l...

Timing is an important constituent of speech and language. Different brain regions have been associated with time management functions such as time estimation and motor timing. This study aims to identify the less well known neural networks associated with timing of internally paced covert articulation. Functional MRI was performed on subjects who either spontaneously, or in response to a visual cue, covertly generated words every 2 s. Results show the involvement of anterior cingulate gyrus, right dorsolateral and inferior frontal and right inferior parietal cortices in a putatively modality independent circuit associated with timing of covert speech. Modality specific activation in the right temporal cortex may have reflected the involvement of this region in auditory-verbal processing.

Background Some clinical characteristics of high-functioning individuals with autistic spectrum disorder (ASD) such as repetitive stereotyped behaviors, perseveration, and obsessionality have been related to executive function (EF) deficits, more specifically to deficits in inhibitory control and set shifting and mediating frontostriatal neural pathways. However, to date, no functional imaging study on ASD has investigated inhibition and cognitive flexibility and no one has related EF brain activation to brain structure. Methods We compared brain activation (using functional magnetic resonance imaging) in 10 normal intelligence adults with ASD and 12 healthy control subjects during three different EF tasks: 1) motor-inhibition (GO/NO-GO); 2) cognitive interference-inhibition (spatial STROOP); and 3) set shifting (SWITCH). Using voxel-based morphometry, we investigated if cortical areas which were functionally different in people with ASD were also anatomically abnormal. Results Compared with control subjects, ASD individuals showed significantly increased brain activation in 1) left inferior and orbital frontal gyrus (motor-inhibition); 2) left insula (interference-inhibition); and 3) parietal lobes (set shifting). Moreover, in individuals with ASD, increased frontal gray matter density and increased functional activation shared the same anatomical location. Conclusions Our findings suggest an association between successful completion of EF tasks and increased brain activation in people with ASD, which partially may be explained by differences in brain anatomy.

This paper reviews the current evidence from imaging studies for biological abnormalities in the neurodevelopmental disorders of attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), early-onset schizophrenia (EOS) and major depression. Although these disorders differ in their behavioural manifestations, they have all been associated with abnormalities in fronto-striatal and fronto-cerebellar networks. The frontal lobes and their connections develop relatively late and are more susceptible to abnormal development. Although there is an overlap between these disorders in impairment of frontal and striatal brain regions, there is also evidence for disorder-specific differences regarding the exact anatomical location, laterality, and developmental trajectories of these abnormalities.

The use of complementary and alternative medicine (CAM) as a treatment for children diagnosed with attention deficit-hyperactivity disorder (ADHD) is widespread, but little is known on the effectiveness of many such therapies. This study investigated meditation as a family treatment method for children with ADHD, using the techniques of Sahaja Yoga Meditation (SYM). Parents and children participated in a 6-week programme of twice-weekly clinic sessions and regular meditation at home. Pre- and post-treatment assessments included parent ratings of children’s ADHD symptoms, self-esteem and child–parent relationship quality. Perceptions of the programme were collected via parent questionnaires and child interviews. Results showed improvements in children’s ADHD behaviour, self-esteem and relationship quality. Children described benefits at home (better sleep patterns, less anxiety) and at school (more able to concentrate, less conflict). Parents reported feeling happier, less stressed and more able to manage their child’s behaviour. Indications from this preliminary investigation are that SYM may offer families an effective management tool for family-oriented treatment of childhood ADHD.