Complexity Analysis of Spontaneous Brain Activity in Attention-Deficit/Hyperactivity Disorder: Diagnostic Implications

Background: Attention-deficit/hyperactivity disorder (ADHD) is defined as the most common neurobehavioral disorder of childhood, but an objective diagnostic test is not available yet to date. Neurophychological, neuroimaging, and neurophysiological research offer ample evidence of brain and behavioral dysfunctions in ADHD, but these findings have not been useful as a diagnostic test. Methods: Whole-head magnetoencephalographic recordings were obtained from 14 diagnosed ADHD patients and 14 healthy children during resting conditions. Lempel-Ziv complexity (LZC) values were obtained for each channel and child and averaged in five sensor groups: anterior, central, left lateral, right lateral, and posterior. Results: Lempel-Ziv complexity scores were significantly higher in control subjects, with the maximum value in anterior region. Combining age and anterior complexity values allowed the correct classification of ADHD patients and control subjects with a 93% sensitivity and 79% specificity. Control subjects showed an age-related monotonic increase of LZC scores in all sensor groups, while children with ADHD exhibited a nonsignificant tendency toward decreased LZC scores. The age-related divergence resulted in a 100% specificity in children older than 9 years. Conclusions: Results support the role of a frontal hypoactivity in the diagnosis of ADHD. Moreover, the age-related divergence of complexity scores between ADHD patients and control subjects might reflect distinctive developmental trajectories. This interpretation of our results is in agreement with recent investigations reporting a delay of cortical maturation in the prefrontal corte

What do ADHD neuroimaging studies reveal for teachers, teacher educators and inclusive education?

Background: Ongoing debate about Attention Deficit Hyperactivity Disorder (ADHD) has not resolved ambivalent teacher beliefs about ADHD. This is an important matter since teachers’ beliefs influence their pedagogy, classroom management, and their referral procedures for formal diagnoses of ADHD. They therefore must be provided with up-to-date professional learning about ADHD. Objective: To synthesise neuroimaging studies, which examined differences in brain organisation and function in those with ADHD compared to matched unaffected controls. The overarching goal was to enhance teachers’ understanding of ADHD by providing synthesised research findings around the neurological basis of ADHD. Method: The PRISMA method was used to search the Medline, PsycINFO, Web of Science and Scopus databases to complete a systematic review of peer-reviewed research that compared individuals with ADHD with matched controls published between 2010 and December 2015. Results: The identification and analyses of 174 MRI and fMRI relevant studies across a sample of over 24,000 showed that there are significant differences in neural anatomy and processing in ADHD compared to unaffected matched controls. Conclusions: Compelling evidence shows ADHD is a neurodevelopmental disability, not a socially determined set of behaviours. Results point to an urgent need for teacher professional learning and systematic up-to-date preservice teacher education along with inclusive education policy reform

Brain network alterations in Attention-Deficit and Hyperactivity Disorder: towards an integrative perspective based on systems neuroscience

Mención Internacional en el título de doctorAttention-Deficit and Hyperactivity Disorder (ADHD) is one of the most common neurodevelopmental disorders, affecting mainly the school-age population but also having a moderate prevalence rate into adulthood. It is characterized by symptoms of inattention, impulsivity, and hyperactivity improper for the patient’s age. However, this agedependent characterization of ADHD makes the diagnosis such a problematic issue: the maturation rate is different for each child, making the evaluation of what is age-proper a subjective and difficult question. All of this leads to the ubiquitous question of ADHD, namely, whether there is overdiagnosis of the disease or if it even exists. That is why studying the brain is crucial in ADHD, because finding effective biomarkers able to characterize the disease will allow us to diagnose it more accurately. Magnetic Resonance Imaging (MRI) is one of the most powerful and versatile tools for studying the brain, providing information about both its structure and activity. Traditional MRI studies have focused on analyzing properties of specific brain regions in terms of their shape (e.g., the volume of a structure) or their relation with a cognitive function (e.g., if a structure activates during object recognition), finding multiple alterations in ADHD [8]. However, these widespread regions that present abnormalities are connected between them and with other areas forming the brain network, and their alterations may indeed represent different parts of a more global phenomenon [8, 9]. There are four main neurobiological models that explain ADHD: the maturational lag hypothesis, the dual-pathway model, the Default Mode Network (DMN) interference hypothesis, and multinetwork models. The maturational lag hypothesis is based on ADHD diagnostic criteria and posits that the brain of people with this condition will resemble a younger one [10]. The dual-pathway model proposes two different processing streams for the main symptoms of ADHD: inattention is related to alterations in the corticostriatal executive circuits, while impulsivity/hyperactivity is associated with abnormalities in emotional processing [11, 12]. The DMN interference hypothesis posits that this functional network is not properly suppressed during goal-directed tasks, which is translated into intrusion of inner mental activity [13]. Finally, multinetwork models approach the neurobiology of people with ADHD as an alteration of multiple functional networks [14, 15]. All of these models have received substantial support from neuroimaging studies, which suggests that all of them are correct but incomplete descriptions of the brain profile of people with ADHD. The present dissertation aims to determine whether there is an alteration of the global brain organization in people with ADHD that may underlie the features that characterize the different neurobiological models of the disorder. For that, we will apply two different graph-theory methods based on systems science to the restingstate functional Magnetic Resonance Imaging data of adults and children with ADHD. The two proposed metrics are Stepwise Functional Connectivity (SFC) and Local and Distant Functional Connectivity (LFC and DFC). The first one measures the integration of information from sensory cortices to areas related to high-order cognitive functions, and in Study 1 [16], it will be applied to a sample of medication-naïve adults with ADHD. LFC and DFC study topological properties with physical distance restrictions, that is, the level of connectivity of each voxel with those around it or those far away. This method will be applied to a sample of children with ADHD in Study 2 [17] and the same sample of adults used in Study 1 in Study 3 [18]. Our results consist of alterations in widespread regions that overlap with most functional networks [19]. Specifically, in adults with ADHD, we observed a decrease in integration in the DMN that locally affects the Posterior Cingulate Cortex and its functional connectivity with the medial Prefrontal Cortex. Additionally, the integration of sensory information in these areas was also found to be reduced in the same sample. The integration of the DMN and its development into cortical hubs is a crucial process in the maturation of the brain [20], which relates this finding with a maturational lag. In both children and adults with ADHD, we also observed a lack of segregation between the DMN, the Ventral Attentional Network, and the Frontoparietal Network in a frontal area of the brain. The developmental trajectory of this area consists of the differentiation of three regions, each of them pertaining to one of these networks [21], and thus, it is a sign of brain immaturity. Also, overconnectivity (lack of segregation) between these networks underlies the DMN interference hypothesis and is indeed a multinetwork alteration [14, 22]. We also found abnormalities in the Visual Network in the form of increased integration of information in these areas while decreased local functional integration of the region, which reflects a behavior more typical of associative than sensory cortices [23, 24]. Finally, local connectivity of sensorimotor cortices presents different maturation trends between ADHD and controls while predicting ADHD symptomatology in all of them. In conclusion, our results suggest that for understanding ADHD, we cannot focus just on a few areas related to high-order cognitive functions, but the whole brain functional network is compromised. This goes in line with a recent meta-analysis [8] that was unable to find convergence in specific regions abnormalities and proposed an analysis based on network interactions. Altogether, this dissertation reflects the need to approach ADHD from a systems neuroscience perspective that encompasses all the currently available models instead of proposing alternative reductionist ones.Programa de Doctorado en Ciencia y Tecnología Biomédica por la Universidad Carlos III de MadridPresidente: Juan Domingo Gispert López.- Secretario: Carles Soriano Mas.- Vocal: Óscar Esteban Sanz-Drangue

The etiology of ADHD

Attention Deficit/Hyperactivity Disorder (“ADHD”) is a complex multi-factorial disorder that was first described in the late 1800s as a defect in moral control. By the early 1900s, ADHD shifted away from being a behavioral-based to a neurobiological-based disorder. During this period, individuals with ADHD were classified as having minimal brain damage. Early studies focused on the clinical presentation of ADHD. As advances in neuroimaging and molecular marker techniques started to develop, researchers were able to focus more on the neurobiological aspects of ADHD. This shift was instrumental to both the diagnosis and treatment of ADHD. This paper surveys the existing literature on ADHD in an attempt to elucidate its etiology. While several areas of research seem promising, so far, no single major contributor to ADHD has been identified. This paper first looks at the history behind ADHD. The historical background was instrumental in directing the course of ADHD research. Next, the Diagnostic and Statistical Manual of Mental Disorders (“DSM”) is examined with a focus on the changes made to DSM-IV and reflected in DSM-V. While DSM is a valuable diagnostic tool, its purpose in elucidating the etiology behind ADHD is questionable. Despite that, discussion of the DSM is necessary as it is impossible to study a disorder without delineating the normal from the abnormal. What follows this discussion is a brief overview of comorbidities that are often associated, and possibly share, a common etiology with ADHD. The paper then examines the theories promulgated by researchers as to the neurobiological basis of ADHD. This examination is followed by a discussion of recent findings into the pathology behind ADHD, which mainly centers around differences in brain structure and connectivity. Further analysis of these studies reveals that sex plays an instrumental role in the type of brain abnormalities found in ADHD children. In addition, delays in brain development are analyzed, and age is discussed as a factor in the presentation of ADHD. This paper goes on to examine genetics as a contributor to the etiology of ADHD. This examination proves fruitful as several genes of interest seem to indicate a hereditary component of ADHD. Finally, treatment options such as psychosocial therapy and medications that help ADHD patients maintain a quality of life, are discussed. By studying the mechanism of action underlying these medications, additional clues as to the etiology of ADHD may be discovered. There is still a long way to go before a complete picture of ADHD emerges. Already, studies are showing that race and environmental factors play a role in how ADHD presents. These two areas have rarely been studied and doing so will only serve to enhance the current understanding of ADHD. Despite an incomplete picture, the scientific community has come a long way from the 1800s where ADHD was thought to result from a defect in moral control. With early diagnosis and proper treatment, the ADHD individuals of today can live a life as close to that of their neurotypical peers as possible

Gray matter networks associated with attention and working memory deficit in ADHD across adolescence and adulthood

Contains fulltext : 231759.pdf (publisher's version ) (Open Access)Attention-deficit/hyperactivity disorder (ADHD) is a childhood-onset neuropsychiatric disorder and may persist into adulthood. Working memory and attention deficits have been reported to persist from childhood to adulthood. How neuronal underpinnings of deficits differ across adolescence and adulthood is not clear. In this study, we investigated gray matter of two cohorts, 486 adults and 508 adolescents, each including participants from ADHD and healthy controls families. Two cohorts both presented significant attention and working memory deficits in individuals with ADHD. Independent component analysis was applied to the gray matter of each cohort, separately, to extract cohort-inherent networks. Then, we identified gray matter networks associated with inattention or working memory in each cohort, and projected them onto the other cohort for comparison. Two components in the inferior, middle/superior frontal regions identified in adults and one component in the insula and inferior frontal region identified in adolescents were significantly associated with working memory in both cohorts. One component in bilateral cerebellar tonsil and culmen identified in adults and one component in left cerebellar region identified in adolescents were significantly associated with inattention in both cohorts. All these components presented a significant or nominal level of gray matter reduction for ADHD participants in adolescents, but only one showed nominal reduction in adults. Our findings suggest although the gray matter reduction of these regions may not be indicative of persistency of ADHD, their persistent associations with inattention or working memory indicate an important role of these regions in the mechanism of persistence or remission of the disorder

Functional and Structural MRI Studies on Impulsiveness: Attention-Deficit/Hyperactive Disorder and Borderline Personality Disorders

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Deviations in neural activity and network integration underpinning the co-occurrence of emotion dysregulation and attention-deficit/hyperactivity disorder: Analyses of fMRI task activations and functional brain network topology

The aim of this thesis was to improve our understanding of the relationship between Attention-deficit/hyperactivity disorder (ADHD) and emotion dysregulation and the underlying neural activity. Three research articles examine specific aspects of the relationship between ADHD and emotion dysregulation, namely the perception of emotional stimuli, the association between functional brain topology and emotion dysregulation in different ADHD presentations, and emotion dysregulation-related neurobiological and phenotypical predictors of the course of ADHD. All three articles are based on functional magnetic resonance imaging (fMRI) data. Individuals with ADHD exhibited aberrant amygdala reactivity and ventromedial prefrontal cortex coupling in the perception and processing of emotional face stimuli. Moreover, functional network topology of the right insula was shown to affect emotion dysregulation in ADHD and emotion dysregulation and integration of emotion-related brain networks were shown to affect intraindividual change in ADHD severity throughout late adolescence. In Summary, the thesis provides evidence that neural activity and functional connectivity between brain structures affecting emotion may be related to the co-occurrence of emotion dysregulation and ADHD. ADHD and the common co-occurring emotional problems should not be attributed to single, isolated systems, e.g., for executive functions and cognitive control. The neurobiological roots appear to be complex and heterogeneous, involving the interplay of different brain networks that are at least partly emotion-related

Consortium neuroscience of attention deficit/hyperactivity disorder and autism spectrum disorder : the ENIGMA adventure

Neuroimaging has been extensively used to study brain structure and function in individuals with attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) over the past decades. Two of the main shortcomings of the neuroimaging literature of these disorders are the small sample sizes employed and the heterogeneity of methods used. In 2013 and 2014, the ENIGMA-ADHD and ENIGMA-ASD working groups were respectively, founded with a common goal to address these limitations. Here, we provide a narrative review of the thus far completed and still ongoing projects of these working groups. Due to an implicitly hierarchical psychiatric diagnostic classification system, the fields of ADHD and ASD have developed largely in isolation, despite the considerable overlap in the occurrence of the disorders. The collaboration between the ENIGMA-ADHD and -ASD working groups seeks to bring the neuroimaging efforts of the two disorders closer together. The outcomes of case–control studies of subcortical and cortical structures showed that subcortical volumes are similarly affected in ASD and ADHD, albeit with small effect sizes. Cortical analyses identified unique differences in each disorder, but also considerable overlap between the two, specifically in cortical thickness. Ongoing work is examining alternative research questions, such as brain laterality, prediction of case–control status, and anatomical heterogeneity. In brief, great strides have been made toward fulfilling the aims of the ENIGMA collaborations, while new ideas and follow-up analyses continue that include more imaging modalities (diffusion MRI and resting-state functional MRI), collaborations with other large databases, and samples with dual diagnoses

Brain functional correlates of theory of mind in neurodevelopmental disorders

[eng] Impairment in social functioning is a common diagnostic criteria for most psychiatric disorders (1,2). Multiples causes may be involved in the loss, or the lack of acquisition, of social skills in psychopathological conditions (3). Social cognition is progressively acquired during childhood and adolescence (4), coinciding with the age of onset of most psychiatric disorders (5) and especially neurodevelopmental disorders, which frequently exhibit impairment in theory of mind performance (6). Along the Introduction, the concept of theory of mind (ToM) (section 4.1) is presented, in addition to the role of functional neuroimaging (section 4.2) for studying the neural correlates underlying ToM (section 4.3). This is contextualized in neurodevelopment (subsections 4.1.1, 4.2.1 and 4.3.1). Secondly, the current knowledge about the impairments in ToM and its associated functional brain correlates is reviewed within three neurodevelopmental disorders (section 4.4): autism spectrum disorders (4.4.1), attention-deficit and hyperactivity disorder (4.4.2) and early-onset psychosis (4.4.3).[spa] La teoría de la mente o mentalización es un dominio cognitivo de la cognición social que se utiliza para designar la capacidad de atribuir emociones, pensamientos e intenciones a otras personas, y que son diferentes a los propios. La teoría de la mente es una habilidad que se adquiere progresivamente durante el neurodesarrollo hasta la edad adulta. Durante tareas que implican la teoría de la mente aumenta la actividad cerebral del córtex prefrontal medial, las uniones temporo-parietales bilaterales y córtex cingulado posterior/precuneus. La conectividad funcional entre estas áreas también incrementa durante las tareas de teoría de la mente. Esta red funcional de mentalización se superpone anatómicamente con la red de activación por defecto, que se activa durante los estados de reposo, en los que no se realiza ninguna actividad concreta. Con frecuencia, durante la divagación mental que caracteriza el estado de reposo, tienen lugar cogniciones de tipo social. Por ello, se han utilizado estudios de neuroimagen con tarea y de reposo para estudiar las bases neuronales de la teoría de la mente. Los déficits en teoría de la mente, tradicionalmente asociados con el trastorno del espectro autista, se han identificado también en otros trastornos del neurodesarrollo, como el trastorno por déficit de atención e hiperactividad y en la esquizofrenia. El trastorno por déficit de atención e hiperactividad es un diagnóstico frecuentemente comórbido a los trastornos del espectro del autismo, aunque las dificultades en teoría de la mente parecen ser menos marcadas en el primero. La esquizofrenia ha sido conceptualizada en las últimas décadas como un trastorno del neurodesarrollo, y algunos estudios apoyan que las dificultades en teoría de la mente son más marcadas cuando el primer episodio de psicosis se produce a edades más tempranas. Además, estos déficits en teoría de la mente podrían iniciarse antes de desarrollarse el primer episodio psicótico. Pese a esto, la literatura que evalúa el rendimiento en teoría de la mente en la presentación comórbida de trastorno del espectro autista con un trastorno por déficit de atención e hiperactividad, en la psicosis de inicio temprano (cuando el primer episodio psicótico tiene lugar durante la infancia o la adolescencia) o en los síndromes de alto riesgo de psicosis es más escasa. En este sentido, el efecto de la edad sobre la adquisición de habilidades de teoría de la mente en adolescentes dentro del espectro de la psicosis ha sido escasamente reportado y con resultados inconcluyentes. Aunque existe evidencia sobre los déficits neuronales que subyacen a los déficits en teoría de la mente de los sujetos con trastorno del espectro autista y los adultos con esquizofrenia, no hay estudios de resonancia magnética funcional que los evalúen en sujetos con trastorno por déficit de atención e hiperactividad, con o sin comorbilidad con el trastorno del espectro autista, en adolescentes con psicosis de inicio temprano o en adolescentes con alto riesgo clínico de psicosis. Dentro del espectro de la psicosis, tampoco se ha estudiado el efecto de la edad sobre los correlatos neuronales de teoría de la mente. Por lo tanto, se desconoce el impacto que ejercen sobre la conectividad cerebral algunos de los principales trastornos del neurodesarrollo, y si los déficits en teoría de la mente subyacen a vías neuronales similares o diferenciales entre diferentes trastornos del neurodesarrollo. El objetivo de esta tesis es evaluar los correlatos neuronales subyacentes a la teoría de la mente en adultos jóvenes con trastorno por déficit de atención e hiperactividad, con o sin comorbilidad con trastorno del espectro de autismo, y adolescentes con psicosis de inicio temprano y con alto riesgo clínico de psicosis