This review focuses on the cognitive neuroscience of Attention Deficit Hyperactivity Disorder (ADHD) based on functional magnetic resonance imaging (fMRI) studies and on recent clinically relevant ...applications such as fMRI-based diagnostic classification or neuromodulation therapies targeting fMRI deficits with neurofeedback (NF) or brain stimulation. Meta-analyses of fMRI studies of executive functions (EFs) show that ADHD patients have cognitive-domain dissociated complex multisystem impairments in several right and left hemispheric dorsal, ventral and medial fronto-cingulo-striato-thalamic and fronto-parieto-cerebellar networks that mediate cognitive control, attention, timing and working memory (WM). There is furthermore emerging evidence for abnormalities in orbital and ventromedial prefrontal and limbic areas that mediate motivation and emotion control. In addition, poor deactivation of the default mode network (DMN) suggests an abnormal interrelationship between hypo-engaged task-positive and poorly "switched off" hyper-engaged task-negative networks, both of which are related to impaired cognition. Translational cognitive neuroscience in ADHD is still in its infancy. Pattern recognition analyses have attempted to provide diagnostic classification of ADHD using fMRI data with respectable classification accuracies of over 80%. Necessary replication studies, however, are still outstanding. Brain stimulation has been tested in heterogeneously designed, small numbered proof of concept studies targeting key frontal functional impairments in ADHD. Transcranial direct current stimulation (tDCS) appears to be promising to improve ADHD symptoms and cognitive functions based on some studies, but larger clinical trials of repeated stimulation with and without cognitive training are needed to test clinical efficacy and potential costs on non-targeted functions. Only three studies have piloted NF of fMRI-based frontal dysfunctions in ADHD using fMRI or near-infrared spectroscopy, with the two larger ones finding some improvements in cognition and symptoms, which, however, were not superior to the active control conditions, suggesting potential placebo effects. Neurotherapeutics seems attractive for ADHD due to their safety and potential longer-term neuroplastic effects, which drugs cannot offer. However, they need to be thoroughly tested for short- and longer-term clinical and cognitive efficacy and their potential for individualized treatment.
Attention-deficit/hyperactivity disorder (ADHD) and conduct disorder overlap behaviorally, clinically, and cognitively. An important question of potential future clinical relevance is whether these ...two overlapping disorders are mediated by similar or distinct underlying brain substrates. This article reviews the modern neuroimaging literature on brain structure, function, and connectivity in both disorders, shaping out commonalities and differences. Findings show that ADHD is characterized predominantly by abnormalities in inferior frontal, striatal, parietotemporal, and cerebellar regions and networks that mediate “cool”-cognitive, i.e., inhibitory, attention and timing functions associated with the disorder. Conduct disorder, by contrast, has consistently been associated with abnormalities of the “hot” paralimbic system that regulates motivation and affect, comprising lateral orbital and ventromedial prefrontal cortices, superior temporal lobes, and underlying limbic structures, most prominently the amygdala. Direct comparisons in functional imaging show that these associations of cool inferior fronto-striato-cerebellar dysfunction in ADHD and of hot orbitofrontal-paralimbic dysfunction in conduct disorder are disorder-specific. There is, hence, evidence for dissociated underlying pathophysiologies for these two disorders that may have implications for future anatomy-based differential diagnosis and prevention and intervention.
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.
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.
Childhood maltreatment acts as a severe stressor that produces a cascade of physiological and neurobiological changes that lead to enduring alterations in brain structure. However, structural ...neuroimaging findings have been inconsistent. The authors conducted a meta-analysis of published whole-brain voxel-based morphometry studies in childhood maltreatment to elucidate the most robust volumetric gray matter abnormalities relative to comparison subjects to date.
Twelve data sets were included, comprising 331 individuals (56 children/adolescents and 275 adults) with a history of childhood maltreatment and 362 comparison subjects (56 children/adolescents and 306 adults). Anisotropic effect size-signed differential mapping, a voxel-based meta-analytic method, was used to examine regions of smaller and larger gray matter volumes in maltreated individuals relative to comparison subjects.
Relative to comparison subjects, individuals exposed to childhood maltreatment exhibited significantly smaller gray matter volumes in the right orbitofrontal/superior temporal gyrus extending to the amygdala, insula, and parahippocampal and middle temporal gyri and in the left inferior frontal and postcentral gyri. They had larger gray matter volumes in the right superior frontal and left middle occipital gyri. Deficits in the right orbitofrontal-temporal-limbic and left inferior frontal regions remained in a subgroup analysis of unmedicated participants. Abnormalities in the left postcentral and middle occipital gyri were found only in older maltreated individuals relative to age-matched comparison subjects.
The findings demonstrate that the most consistent gray matter abnormalities in individuals exposed to childhood maltreatment are in relatively late-developing ventrolateral prefrontal-limbic-temporal regions that are known to mediate late-developing functions of affect and cognitive control, which are typically compromised in this population.
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. (Contains 5 figures.)
Structural neuroimaging studies in attention-deficit hyperactivity disorder (ADHD) have been relatively inconsistent and have mainly been conducted with pediatric samples. Furthermore, there is ...evidence that stimulant medication may have an effect on brain structure. The authors conducted a meta-analysis of voxel-based morphometry studies in children and adults with ADHD and examined the potential effects of age and stimulant medication on regional gray matter volumes.
The PubMed, ScienceDirect, Web of Knowledge, and Scopus databases were searched for articles published between 2001 and 2011. Manual searches were also conducted, and authors of studies were contacted for additional data. Coordinates were extracted from clusters of significant gray matter difference between ADHD patients and healthy comparison subjects. Metaregression methods were used to explore potential age and stimulant medication effects.
Fourteen data sets comprising 378 patients with ADHD and 344 healthy subjects met inclusion criteria. The ADHD group had global reductions in gray matter volumes, which were robustly localized in the right lentiform nucleus and extended to the caudate nucleus. Both increasing age and percentage of patients taking stimulant medication were found to be independently associated with more normal values in this region. Patients also had slightly greater gray matter volumes in the left posterior cingulate cortex.
These findings confirm that the most prominent and replicable structural abnormalities in ADHD are in the basal ganglia. They furthermore suggest that ADHD patients may progressively catch up with their developmental delay with advancing age and that use of stimulant medication may be associated with normalization of structural abnormalities in ADHD, although longitudinal studies are needed to confirm both observations.
Abstract Objective Autism spectrum disorder (ASD) and obsessive-compulsive disorder (OCD) share inhibitory control deficits possibly underlying poor control over stereotyped/repetitive and compulsive ...behaviours, 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 (VBM) and 26 functional magnetic resonance imaging (fMRI) studies of inhibitory control was conducted comparing grey matter volume (GMV) and activation abnormalities between ASD (sMRI:911;fMRI:188) and OCD (sMRI:928;fMRI:247) patients versus controls. Multimodal meta-analysis compared groups across VBM and fMRI. Results Both disorders shared reduced function and structure in rostral/dorsomedial prefrontal cortex including anterior cingulate. OCD had disorder-specific increase in structure and function of left basal ganglia (BG)/insula relative to controls and ASD, who had reduced right BG/insula volumes versus OCD. In fMRI, ASD patients showed disorder-specific reduced left dorsolateral-prefrontal activation and reduced posterior cingulate deactivation, while OCD patients showed temporo-parietal underactivation. Conclusions The multimodal comparative meta-analysis shows shared and disorder-specific abnormalities. While rostro-dorsomedial prefrontal cortex was smaller in structure and function in both disorders, this was concomitant with increased structure and function in BG/insula in OCD, but a reduction in ASD, presumably reflecting a disorder-specific fronto-striato-insular dysregulation in OCD in the form of poor frontal control over overactive BG, and a fronto-striato-insular maldevelopment in ASD with reduced structure and function in this network. Disorder-differential mechanisms appear to drive overlapping phenotypes of inhibitory control abnormalities in ASD and OCD.
Relatively recently, neurocognitive and neuroimaging studies have indicated that individuals with attention-deficit/hyperactivity disorder (ADHD) may have deficits in a range of timing functions and ...their underlying neural networks. Despite this evidence, timing deficits in ADHD are still somewhat neglected in the literature and mostly omitted from reviews on ADHD. There is therefore a lack of integrative reviews on the up-to-date evidence on neurocognitive and neurofunctional deficits of timing in ADHD and their significance with respect to other behavioural and cognitive deficits. The present review provides a synthetic overview of the evidence for neurocognitive and neurofunctional deficits in ADHD in timing functions, and integrates this evidence with the cognitive neuroscience literature of the neural substrates of timing. The review demonstrates that ADHD patients are consistently impaired in three major timing domains, in motor timing, perceptual timing and temporal foresight, comprising several timeframes spanning milliseconds, seconds, minutes and longer intervals up to years. The most consistent impairments in ADHD are found in sensorimotor synchronisation, duration discrimination, reproduction and delay discounting. These neurocognitive findings of timing deficits in ADHD are furthermore supported by functional neuroimaging studies that show dysfunctions in the key inferior fronto-striato-cerebellar and fronto-parietal networks that mediate the timing functions. Although there is evidence that these timing functions are inter-correlated with other executive functions that are well established to be impaired in the disorder, in particular working memory, attention, and to a lesser degree inhibitory control, the key timing deficits appear to survive when these functions are controlled for, suggesting independent cognitive deficits in the temporal domain. There is furthermore strong evidence for an association between timing deficits and behavioural measures of impulsiveness and inattention, suggesting that timing problems are key to the clinical behavioural profile of ADHD. Emerging evidence shows that the most common treatment of ADHD with the dopamine agonist and psychostimulant Methylphenidate attenuates most timing deficits in ADHD and normalises the abnormally blunted recruitment of the underlying fronto-striato-cerebellar networks. Timing function deficits in ADHD, therefore, next to executive function deficits, form an independent impairment domain, and should receive more attention in neuropsychological, neuroimaging, and pharmacological basic research as well as in translational research aimed to develop pharmacological or non-pharmacological treatment of abnormal timing behaviour and cognition in ADHD.
► ADHD patients show deficits in motor timing, perceptual timing and temporal foresight. ► ADHD patients show impairments in fronto-striato-parieto-cerebellar timing networks. ► Temporal abnormalities in ADHD interact with inattention and behavioural impulsivity.
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