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Uncovering the relationships between neural circuits, behavior, and neural dysfunction may require rodent pose tracking. While open-source toolkits such as DeepLabCut have revolutionized markerless pose estimation using deep neural networks, the training process still requires human intervention for annotating key points of interest in video data. To further reduce human labor for neural network training, we developed a method that automatically generates annotated image datasets of rodent paw placement in a laboratory setting. It uses invisible but fluorescent markers that become temporarily visible under UV light. Through stroboscopic alternating illumination, adjacent video frames taken at 720â Hz are either UV or white light illuminated. After color filtering the UV-exposed video frames, the UV markings are identified and the paw locations are deterministically mapped. This paw information is then transferred to automatically annotate paw positions in the next white light-exposed frame that is later used for training the neural network. We demonstrate the effectiveness of our method using a KineWheel-DeepLabCut setup for the markerless tracking of the four paws of a harness-fixed mouse running on top of the transparent wheel with mirror. Our automated approach, made available open-source, achieves high-quality position annotations and significantly reduces the need for human involvement in the neural network training process, paving the way for more efficient and streamlined rodent pose tracking in neuroscience research.
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Redes Neurais de Computação , Raios Ultravioleta , Animais , Camundongos , Gravação em Vídeo/métodos , Iluminação/métodos , Comportamento Animal/fisiologia , Luz , Processamento de Imagem Assistida por Computador/métodos , Masculino , Aprendizado ProfundoRESUMO
Objectives: Neurofeedback (NF) and self-management training (SMT) may be viable treatment options for patients with attention deficit hyperactivity disorder (ADHD) if they alleviate core symptoms, enhance the patients' self-concept and improve their quality of life (QoL). Aim of the current study is evaluating both interventions accordingly and to test whether specific improvements in core symptoms lead to more general improvements in self-concept and QoL. Methods: In a psychotherapeutic outpatient clinic in Germany, a total of N = 139 children with ADHD were screened for eligibility, of which 111 fulfilled inclusion criteria and participated in the study in accordance with the CONSORT 2010 statement. These were randomly assigned to NF vs. SMT interventions. Changes from pre- to post-intervention in core ADHD symptoms relying on parent and teacher reports (CONNERS 3) and objective tests (Qb-Test) as well as self-concept (interview with the children) and QoL assessments (using the KINDL-R self-report) were compared between patients receiving NF or SMT. Results: Significant improvements in ADHD symptoms were achieved similarly in both treatment groups, whilst QoL and self-concept improved after SMT only. Conclusion: This treatment study provides further evidence that SMT and NF may reduce core symptoms, but SMT may also improve patients' self-concept and QoL and may thus in its current form be the favorable treatment option in naturalistic settings. However, several limitations of the current study implicate that further research is required before definitive conclusions and recommendations for clinical practice can be given. Clinical trial registration: [www.clinicaltrials.gov], identifier [NCT01879644].
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INTRODUCTION: Research has shown non-trivial base rates of noncredible symptom report and performance in the clinical evaluation of attention-deficit/hyperactivity disorder (ADHD) in adulthood. The goal of this study is to estimate and replicate base rates of symptom and performance validity test failure in the clinical evaluation of adult ADHD and derive prediction models based on routine clinical measures. METHODS: This study reuses data of a previous publication of 196 adults seeking ADHD assessment and replicates the findings on an independent sample of 700 adults recruited in the same referral context. Measures of symptom and performance validity (one SVT, two PVTs) were applied to estimate base rates. Prediction models were developed using machine learning. RESULTS: Both samples showed substantial rates of noncredible symptom report (one SVT failure: 35.7% - 36.6%), noncredible test performance (one PVT failure: 32.1% - 49.3%; two PVT failures: 18.9% - 27.3%), or both (each one SVT and PVT failure: 13.3% - 22.4%; one SVT and two PVT failures: 9.7% - 13.7%). Machine learning algorithms resulted in generally moderate to weak prediction models, with advantages of the reused sample compared to the independent replication sample. Associations between measures of symptom and performance validity were negligible to small. CONCLUSIONS: This study highlights the necessity to include measures of symptom and performance validity in the clinical evaluation of adult ADHD. Further, this study demonstrates the difficulty to characterize the group failing symptom or performance validity assessment.
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Transtorno do Deficit de Atenção com Hiperatividade , Adulto , Algoritmos , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Humanos , Aprendizado de Máquina , Simulação de Doença/diagnóstico , Testes Neuropsicológicos , Reprodutibilidade dos TestesRESUMO
Attention Deficit Hyperactivity Disorder (ADHD) is characterized as a behavioral syndrome with core symptoms of inattention and/or hyperactivity/impulsivity that constitute, according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), predominantly Inattentive and Hyperactive-Impulsive and a combined (additive) presentation that fulfills both criteria. The question remains if the pathophysiological background of both factors is also separate at levels of investigation beyond core symptoms. This would allow a clearer understanding and a more focused treatment approach even with tools derived from these levels. Hence, we assumed that an implicit additive diagnostic model also holds at the levels of associated psychopathology, neuropsychological performance and brain oscillations. We investigated this hypothesis using data of 61 boys (7-12 years old) with ADHD and 43 typically developing children. There were no significant differences in age and IQ between groups. Children were examined with Child Behavior Checklist (CBCL), the Integrated Visual and Auditory Test (IVA), and brain oscillations during eyes closed resting state. Inattention characteristics were associated with more pronounced internalizing problems, lower attention, and vigilance during IVA performance and at the Electroencephalography level with elevated Theta and diminished Beta power during eyes closed rest. In contrast, hyperactivity/impulsivity characteristics led to general psychopathology problems and showed at the neuropsychological level faster response speed and deficits in cognitive control and performance consistency, but were on the electroencephalography level without any deficits in EEG power. Considering differences in behavioral, neuropsychology, and electroencephalography levels in each subtype, separate clinical approaches should be recommended for them and an additive model for their combination.
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Transtorno do Deficit de Atenção com Hiperatividade , Encéfalo , Criança , Cognição , Eletroencefalografia , Humanos , Comportamento Impulsivo , MasculinoRESUMO
Neurophysiological measures of preparation and attention are often atypical in ADHD. Still, replicated findings that these measures predict which patients improve after Neurofeedback (NF), reveal neurophysiological specificity, and reflect ADHD-severity are limited. METHODS: We analyzed children's preparatory (CNV) and attentional (Cue-P3) brain activity and behavioral performance during a cued Continuous Performance Task (CPT) before and after slow cortical potential (SCP)-NF or semi-active control treatment (electromyogram biofeedback). Mixed-effects models were performed with 103 participants at baseline and 77 were assessed for pre-post comparisons focusing on clinical outcome prediction, specific neurophysiological effects of NF, and associations with ADHD-severity. RESULTS: Attentional and preparatory brain activity and performance were non-specifically reduced after treatment. Preparatory activity in the SCP-NF group increased with clinical improvement. Several performance and brain activity measures predicted non-specific treatment outcome. CONCLUSION: Specific neurophysiological effects after SCP-NF were limited to increased neural preparation associated with improvement on ADHD-subscales, but several performance and neurophysiological measures of attention predicted treatment outcome and reflected symptom severity in ADHD. The results may help to optimize treatment.
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Transtorno do Deficit de Atenção com Hiperatividade , Neurorretroalimentação , Atenção , Criança , Sinais (Psicologia) , Eletroencefalografia , HumanosRESUMO
AIM: Discriminant validity of the Attention Deficits/Hyperactive Disorders (ADHD) subtypes/presentations is not yet clear. The purpose of this study was to investigate joint contribution of the strongest factors of the three dimensions, namely psychopathology, neuropsychology and electrophysiology for subtyping of presentations. METHOD: A sample of 104 boys aged 7-12 years was subdivided into three groups with ADHD combined (n = 22), inattentive (n = 25) and hyperactive/impulsive subtype (n = 14), and 43 typically developing controls (TDC). Children were investigated regarding the Child Behavior Checklist (CBCL), the Integrated Visual and Auditory Test (IVA), and EEG spectral power during eyes closed resting state. Subsequently, statistical analysis included discriminant functional analysis and principle component analysis. RESULTS: Neuropsychological parameters had the highest contribution in classifying of the groups. EEG parameters had no effect on differentiation of the groups, and among the psychopathological parameters, only the oppositional behavioral disorder score contributed to correctly classify 74.3% of the groups. Furthermore, we found four factors with eigenvalues higher than 1 in the ADHD and typical groups, with one factor characterized by four CBCL scales, another one by auditory and visual vigilance, speed and beta band power, the third by auditory and visual prudence, and forth by theta band power. CONCLUSIONS: Our results demonstrated that ADHD subtypes/presentations can be differentiated from each other at different levels of investigation despite some clinical symptoms overlap. The results suggested that not only psychopathology but also the impairment of sensory processing should be assessed in children with ADHD in order to use this additional information for a jointly multilevel clinical intervention, which may improve treatment success.
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Transtorno do Deficit de Atenção com Hiperatividade , Transtornos do Comportamento Infantil , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Criança , Cognição , Humanos , Comportamento Impulsivo , MasculinoRESUMO
Background: Despite a large body of evidence demonstrating the effectiveness of psychotherapy for posttraumatic stress for children and adolescents, the adoption of empirically supported treatments (ESTs) in routine care is low. Objective: This implementation study aims to evaluate the dissemination of Trauma-Focused Cognitive Behavioural Therapy (TF-CBT) for children and adolescents with posttraumatic stress symptoms (PTSS) after child abuse and neglect (CAN) with a focus on supervision. Method: In a cluster-randomized controlled trial, the study will evaluate the implementation of TF-CBT focussing on the training of therapists including the provision of supervision. The effectiveness of specialized trauma-focused supervision will be compared to supervision as usual with respect to the successful implementation of TF-CBT for youths with PTSS administered by psychotherapists with different levels of professional experience. The primary outcome is whether the patient receives a treatment with sufficient adherence to the TF-CBT manual. The unit of randomization will be the therapists. The main outcome will be analysed using multilevel logistic regressions. Secondary outcomes will concern further patient-related (reduction of PTSS and depressive symptoms) and therapist-related (professional quality of life) variables. Additional exploratory analyses are planned. Discussion: Since the trial is designed as an implementation study, it permits naturalistic referrals to the participating therapists by patients, caregivers, child and youth welfare agencies and paediatricians. The strict primary outcome will help evaluating the role of model-based supervision in the implementation process. The explorative outcomes will evaluate whether implementation success translates into better patient outcomes. We expect that the dissemination measures will lead to a successful implementation of TF-CBT and promote sustainable structures in routine care that will remain in place after study completion and offer access to ESTs for future children and youths with a history of CAN.
Antecedentes: A pesar de que existe un robusto cuerpo de evidencia que demuestra la efectividad de la psicoterapia para el trastorno de estrés postraumático en niños y adolescentes, la adherencia a tratamientos basados en evidencia (TBEs) es baja en la atención de rutina.Objetivo: El objetivo de este estudio de implementación es el de evaluar la difusión de la terapia cognitiva conductual enfocada en trauma (TCC-ET) para niños y adolescentes con síntomas de estrés postraumático (SEPT) secundarios al abuso y la negligencia infantiles con un enfoque en la supervisión.Método: Dentro de un estudio por racimos controlado y aleatorizado, el estudio evaluará la implementación de la TCC-ET enfocándose en el entrenamiento de terapeutas e incluyendo el brindar supervisión a este entrenamiento. La efectividad de la supervisión especializada enfocada en trauma se comparará con la supervisión habitual ya realizada en la implementación exitosa de la TCC-ET para jóvenes con SEPT brindada por psicoterapeutas con diferentes niveles de experiencia profesional. El objetivo primario es evaluar si el paciente recibe un tratamiento con adecuada adherencia al manual de la TCC-ET. La unidad de aleatorización serán los terapeutas. El objetivo principal será analizado empleando regresiones logísticas multinivel. Los objetivos secundarios serán variables relacionadas con preocupaciones asociadas a los pacientes (reducción de SEPT y de síntomas depresivos) y asociadas a los terapeutas (calidad de vida profesional). Se planea realizar análisis exploratorios adicionales.Discusión: Debido a que el ensayo clínico está diseñado como un estudio de implementación, este permite generar derivaciones naturalísticas a los terapeutas participantes por parte de los pacientes, cuidadores, organismos de bienestar de niños y adolescentes y por pediatras. El riguroso objetivo primario ayudará a evaluar el papel de la supervisión basada en modelos durante el proceso de implementación. Los resultados exploratorios evaluarán si el éxito de la implementación se traduce en mejores resultados para los pacientes. Se espera que las medidas adoptadas para la difusión de la TCC-ET conlleven a su implementación exitosa y promuevan estructuras sostenibles en el cuidado rutinario que continúen luego de terminado el estudio. Además, se espera que estas medidas permitan que en un futuro los niños y jóvenes con antecedentes de abuso y negligencia infantiles cuenten con acceso a TBEs.
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PURPOSE OF REVIEW: Emotional symptoms are common and persistent in youth and adults with attention-deficit/hyperactivity disorder (ADHD) and cause clinically significant impairments. We review recent neuropsychological, neurophysiological, and peripheral psychophysiological evidence for emotion and emotion regulation deficits in ADHD across youth and adults. RECENT FINDINGS: Central and autonomous nervous system correlates argue in favor of more general self-regulation deficits and also specific emotional deficits in ADHD. These include general performance deficits in executive functions, and structural as well as functional impairments in neuronal networks associated with top-down self-regulation. Specific deficits with bottom-up emotional activation in the amygdala and emotion evaluation associated with the orbitofrontal cortex have also been described. Furthermore, vagally mediated, high-frequency heart rate variability is associated with emotional self-regulation deficits throughout the life span. The current evidence is based on multilevel studies that assess associations of emotion regulation. However, further studies that adequately consider the processual recursive character of emotion generation and regulation may give important new insights into emotional regulation of ADHD. Emotion regulation deficits in ADHD are associated with specific as well as general self-regulation deficits traceable on the level of neuropsychological, neurophysiological, and psychophysiological assessments. The temporal dynamics of the interplay of those different systems need further study in order to optimize and personalize treatment of emotion regulation difficulties, including emotional reactivity, in patients with ADHD.
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Envelhecimento/psicologia , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Regulação Emocional , Tonsila do Cerebelo/fisiopatologia , Emoções/fisiologia , Função Executiva/fisiologia , Humanos , Córtex Pré-Frontal/fisiopatologia , PsicofisiologiaRESUMO
Performance deficits and diminished brain activity during cognitive control and error processing are frequently reported in attention deficit/hyperactivity disorder (ADHD), indicating a "top-down" deficit in executive attention. So far, these findings are almost exclusively based on the processing of static visual forms, neglecting the importance of visual motion processing in everyday life as well as important attentional and neuroanatomical differences between processing static forms and visual motion. For the current study, we contrasted performance and electrophysiological parameters associated with cognitive control from two Flanker-Tasks using static stimuli and moving random dot patterns. Behavioral data and event-related potentials were recorded from 16 boys with ADHD (combined type) and 26 controls (aged 8-15 years). The ADHD group showed less accuracy especially for moving stimuli, and prolonged response times for both stimulus types. Analyses of electrophysiological parameters of cognitive control revealed trends for diminished N2-enhancements and smaller error-negativities (indicating medium effect sizes), and we detected significantly lower error positivities (large effect sizes) compared to controls, similarly for both static and moving stimuli. Taken together, the study supports evidence that motion processing is not fully developed in childhood and that the cognitive control deficit in ADHD is of higher order and independent of stimulus type.
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In order to better understand the underpinnings of attention-deficit/hyperactivity disorder (ADHD), we targeted the relationship of attentional, cognitive control and motivational processes with DNA methylation patterns of 60 candidate genes in boys at early school age. Participants (6 to 8 years; N = 82) were selected from a German longitudinal cohort (FRANCES). ADHD-related behaviour was assessed via maternal ratings. Performance and event-related potential measures (inter alia Cue-P3 and Nogo-P3), which were recorded in a motivational go/nogo task, indicated diminished attentional orienting, reduced inhibitory response control and a larger motivational effect on performance in ADHD already at this relatively young age. Methylation patterns were analysed in buccal cell DNA with the Illumina HumanMethylation 450K array. For CpG sites at genes of the dopaminergic (COMT, ANKK1) and the neurotrophic (BDNF, NGFR) system, associations with the Nogo-P3 as well as ADHD symptom severity were found suggesting that these systems are involved in response control deficits in ADHD. Methylation effects related to both functional aspects and ADHD behaviour were also observed for DPP10 and TPH2. Epigenetic mechanisms may play a role in ADHD-associated deficits but findings need to be replicated in larger samples and are limited by the fact that only peripheral methylation could be considered.
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Transtorno do Deficit de Atenção com Hiperatividade , Atenção , Cognição , Ilhas de CpG , Metilação de DNA , Epigênese Genética , Potenciais Evocados , Transtorno do Deficit de Atenção com Hiperatividade/genética , Transtorno do Deficit de Atenção com Hiperatividade/metabolismo , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Criança , Seguimentos , Humanos , Masculino , Estudos ProspectivosRESUMO
OBJECTIVE: Attention Deficit / Hyperactivity Disorder (ADHD) and Chronic Tic Disorder (CTD) are two common and frequently co-existing disorders, probably following an additive model. But this is not yet clear for the basic sensory function of colour processing sensitive to dopaminergic functioning in the retina and higher cognitive functions like attention and interference control. The latter two reflect important aspects for psychoeducation and behavioural treatment approaches. METHODS: Colour discrimination using the Farnsworth-Munsell 100-hue Test, sustained attention during the Frankfurt Attention Inventory (FAIR), and interference liability during Colour- and Counting-Stroop-Tests were assessed to further clarify the cognitive profile of the co-existence of ADHD and CTD. Altogether 69 children were classified into four groups: ADHD (N = 14), CTD (N = 20), ADHD+CTD (N = 20) and healthy Controls (N = 15) and compared in cognitive functioning in a 2×2-factorial statistical model. RESULTS: Difficulties with colour discrimination were associated with both ADHD and CTD factors following an additive model, but in ADHD these difficulties tended to be more pronounced on the blue-yellow axis. Attention problems were characteristic for ADHD but not CTD. Interference load was significant in both Colour- and Counting-Stroop-Tests and unrelated to colour discrimination. Compared to Controls, interference load in the Colour-Stroop was higher in pure ADHD and in pure CTD, but not in ADHD+CTD, following a sub-additive model. In contrast, interference load in the Counting-Stroop did not reveal ADHD or CTD effects. CONCLUSION: The co-existence of ADHD and CTD is characterized by additive as well as sub-additive performance impairments, suggesting that their co-existence may show simple additive characteristics of both disorders or a more complex interaction, depending on demand. The equivocal findings on interference control may indicate limited validity of the Stroop-Paradigm for clinical assessments.
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Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Percepção de Cores/fisiologia , Transtornos de Tique/fisiopatologia , Adolescente , Criança , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Teste de StroopRESUMO
Background: Neurofeedback (NF) in children with attention-deficit/hyperactivity disorder (ADHD) has been investigated in a series of studies over the last years. Previous studies did not unanimously support NF as a treatment in ADHD. Most studies did not control for unspecific treatment effects and did not demonstrate that self-regulation took place. The present study examined the efficacy of NF in comparison to electromyographic (EMG) feedback to control for unspecific effects of the treatment, and assessed self-regulation of slow cortical potentials (SCPs). Methods: A total of 150 children aged 7-9 years diagnosed with ADHD (82% male; 43% medicated) were randomized to 25 sessions of feedback of SCPs (NF) or feedback of coordination of the supraspinatus muscles (EMG). The primary endpoint was the change in parents' ratings of ADHD core symptoms 4 weeks after the end of treatment compared to pre-tests. Results: Children in both groups showed reduced ADHD-core symptoms (NF 0.3, 95% CI -0.42 to -0.18; EMG 0.13, 95% CI -0.26 to -0.01). NF showed a significant superiority over EMG (treatment difference 0.17, 95% CI 0.02-0.3, p = 0.02). This yielded an effect size (ES) of d = 0.57 without and 0.40 with baseline observation carried forward (BOCF). The sensitivity analysis confirmed the primary result. Successful self-regulation of brain activity was observed only in NF. As a secondary result teachers reported no superior improvement from NF compared to EMG, but within-group analysis revealed effects of NF on the global ADHD score, inattention, and impulsivity. In contrast, EMG feedback did not result in changes despite more pronounced self-regulation learning. Conclusions: Based on the primary parent-rated outcome NF proved to be superior to a semi-active EMG feedback treatment. The study supports the feasibility and efficacy of NF in a large sample of children with ADHD, based on both specific and unspecific effects. Trial Register: Current controlled trials ISRCTN76187185, registered 5 February 2009.
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Attention deficit hyperactivity disorder (ADHD) is characterized by severe and age-inappropriate levels of hyperactivity, impulsivity and inattention. ADHD is a heterogeneous disorder, and the majority of patients show comorbid or associated problems from other psychiatric disorders. Also, ADHD is associated with cognitive and motivational problems as well as resting-state abnormalities, associated with impaired brain activity in distinct neuronal networks. This needs to be considered in a multimodal treatment, of which neurofeedback (NF) may be a promising component. During NF, specific brain activity is fed-back using visual or auditory signals, allowing the participants to gain control over these otherwise unaware neuronal processes. NF may be used to directly improve underlying neuronal deficits, and/or to establish more general self-regulatory skills that may be used to compensate behavioral difficulties. The current manuscript describes pathophysiological characteristics of ADHD, heterogeneity of ADHD subtypes and gender differences, as well as frequently associated behavioral problems such as oppositional defiant/conduct or tic disorder. It is discussed how NF may be helpful as a treatment approach within these contexts.
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OBJECTIVES: The side effects, nonresponse, and prejudices against conventional pharmacological treatments call for complementary or alternative medical treatments (CAM) for ADHD. One possible treatment, at least for cognitive problems, might be the administration of Ginkgo biloba, though evidence is currently rare. This study tests the clinical efficacy of a Ginkgo biloba special extract (EGb 761®) and its correlation with brain electrical activity in children with ADHD combined type according to DSM-IV. METHOD: In this open clinical pilot study, EGb 761® was administered to 20 children with ADHD over 3 to 5 weeks. Dosage was increased to a maximum of 240 mg daily if attention problems persisted. Possible drug side effects were assessed using the Side Effect Rating Scale. Efficacy was assessed in a multilevel approach including clinical assessment, quality of life (QoL), as well as performance and preparatory brain-electrical activity evoked during a Continuous Performance Test (Cue-CNV in the CPT). RESULTS: A very low rate of mild adverse effects occurred during the observation period. Following EGb 761® administration, possible improvements in QoL, ADHD core symptoms as well as CPT performance were detected. Improved core symptoms were positively related to elevated CNV amplitude. CONCLUSION: This preliminary evidence suggests that EGb 761® at a maximal dosage of 240 mg daily might be a clinically useful alternative treatment for children with ADHD, but further evidence is required before firm conclusions can be made.
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Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Adolescente , Atenção/efeitos dos fármacos , Atenção/fisiologia , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Encéfalo/efeitos dos fármacos , Encéfalo/fisiopatologia , Mapeamento Encefálico , Criança , Relação Dose-Resposta a Droga , Esquema de Medicação , Eletroencefalografia/efeitos dos fármacos , Potenciais Evocados/efeitos dos fármacos , Potenciais Evocados/fisiologia , Feminino , Alemanha , Ginkgo biloba , Humanos , Masculino , Testes Neuropsicológicos , Projetos Piloto , Extratos Vegetais/administração & dosagem , Processamento de Sinais Assistido por ComputadorRESUMO
BACKGROUND: Difficulties with performance and brain activity related to attentional orienting (Cue-P3), cognitive or response preparation (Cue-CNV) and inhibitory response control (Nogo-P3) during tasks tapping executive functions are familial in ADHD and may represent endophenotypes. The aim of this study was to clarify the impact of dopamine receptor D4 (DRD4) and dopamine transporter (DAT1) gene polymorphisms on these processes in ADHD and control children. METHODS: Behavioural and electrophysiological parameters from cued continuous performance tests with low and high attentional load were assessed in boys with ADHD combined type (N = 94) and controls without family history of ADHD (N = 31). Both groups were split for the presence of at least one DRD4 7-repeat allele and the DAT1 10-6 haplotype. RESULTS: Children with ADHD showed diminished performance and lower Cue-P3, CNV and Nogo-P3 amplitudes. Children with DRD4 7R showed similar performance problems and lower Cue-P3 and CNV, but Nogo-P3 was not reduced. Children with the DAT1 10-6 haplotype had no difficulties with performance or Cue-P3 and CNV, but contrary to expectations increased Nogo-P3. There were no Genotype by ADHD interactions. CONCLUSIONS: This study detected specific effects of DRD4 7R on performance and brain activity related to attentional orienting and response preparation, while DAT1 10-6 was associated with elevated brain activity related to inhibitory response control, which potentially compensates increased impulsivity. As these genotype effects were additive to the impact of ADHD, the current results indicate that DRD4 and DAT1 polymorphisms are functionally relevant risk factors for ADHD and presumably other disorders sharing these endophenotypes.
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Transtorno do Deficit de Atenção com Hiperatividade/genética , Proteínas da Membrana Plasmática de Transporte de Dopamina/genética , Receptores de Dopamina D4/genética , Adolescente , Alelos , Atenção , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Encéfalo/fisiologia , Estudos de Casos e Controles , Criança , Comportamento Infantil , Variação Contingente Negativa/genética , Potenciais Evocados/genética , Haplótipos/genética , Humanos , Inibição Psicológica , Masculino , Polimorfismo Genético/genética , Tempo de Reação/genéticaRESUMO
To elucidate basic mechanisms underlying neurofeedback we investigated neural mechanisms of training of slow cortical potentials (SCPs) by considering EEG- and fMRI. Additionally, we analyzed the feasibility of a double-blind, placebo-controlled design in NF research based on regulation performance during treatment sessions and self-assessment of the participants. Twenty healthy adults participated in 16 sessions of SCPs training: 9 participants received regular SCP training, 11 participants received sham feedback. At three time points (pre, intermediate, post) fMRI and EEG/ERP-measurements were conducted during a continuous performance test (CPT). Performance-data during the sessions (regulation performance) in the treatment group and the placebo group were analyzed. Analysis of EEG-activity revealed in the SCP group a strong enhancement of the CNV (electrode Cz) at the intermediate assessment, followed by a decrease back to baseline at the post-treatment assessment. In contrast, in the placebo group a continuous but smaller increase of the CNV could be obtained from pre to post assessment. The increase of the CNV in the SCP group at intermediate testing was superior to the enhancement in the placebo group. The changes of the CNV were accompanied by a continuous improvement in the test performance of the CPT from pre to intermediate to post assessment comparable in both groups. The change of the CNV in the SCP group is interpreted as an indicator of neural plasticity and efficiency while an increase of the CNV in the placebo group might reflect learning and improved timing due to the frequent task repetition. In the fMRI analysis evidence was obtained for neuronal plasticity. After regular SCP neurofeedback activation in the posterior parietal cortex decreased from the pre- to the intermediate measurement and increased again in the post measurement, inversely following the U-shaped increase and decrease of the tCNV EEG amplitude in the SCP-trained group. Furthermore, we found a localized increase of activity in the anterior cingulate cortex (ACC). Analyses of the estimation of treatment assignment by the participants indicate feasibility of blinding. Participants could not assess treatment assignment confidently. Participants of the SCP-group improved regulation capability during treatment sessions (in contrast to the participants of the placebo-group), although regulation capability appeared to be instable, presumably due to diminished confidence in the training (SCP- or sham-training). Our results indicate that SCP training in healthy adults might lead to functional changes in neuronal circuits serving cognitive preparation even after a limited number of sessions.
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BACKGROUND: Emotional lability (EL) is commonly seen in patients with attention-deficit/hyperactivity disorder (ADHD). The reasons for this association remain currently unknown. To address this question, we examined the relationship between ADHD and EL symptoms, and performance on a range of neuropsychological tasks to clarify whether EL symptoms are predicted by particular cognitive and/or motivational dysfunctions and whether these associations are mediated by the presence of ADHD symptoms. METHODS: A large multi-site sample of 424 carefully diagnosed ADHD cases and 564 unaffected siblings and controls aged 6-18 years performed a broad neuropsychological test battery, including a Go/No-Go Task, a warned four-choice Reaction Time task, the Maudsley Index of Childhood Delay Aversion and Digit span backwards. Neuropsychological variables were aggregated as indices of processing speed, response variability, executive functions, choice impulsivity and the influence of energetic and/or motivational factors. EL and ADHD symptoms were regressed on each neuropsychological variable in separate analyses controlling for age, gender and IQ, and, in subsequent regression analyses, for ADHD and EL symptoms respectively. RESULTS: Neuropsychological variables significantly predicted ADHD and EL symptoms with moderate-to-low regression coefficients. However, the association between neuropsychological parameters on EL disappeared entirely when the effect of ADHD symptoms was taken into account, revealing that the association between the neuropsychological performance measures and EL is completely mediated statistically by variations in ADHD symptoms. Conversely, neuropsychological effects on ADHD symptoms remained after EL symptom severity was taken into account. CONCLUSIONS: The neuropsychological parameters examined, herein, predict ADHD more strongly than EL. They cannot explain EL symptoms beyond what is already accounted for by ADHD symptom severity. The association between EL and ADHD cannot be explained by these cognitive or motivational deficits. Alternative mechanisms, including overlapping genetic influences (pleiotropic effects) and/or alternative neuropsychological processes need to be considered.
Assuntos
Transtornos de Deficit da Atenção e do Comportamento Disruptivo/fisiopatologia , Emoções/fisiologia , Desempenho Psicomotor/fisiologia , Adolescente , Criança , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Índice de Gravidade de Doença , IrmãosRESUMO
BACKGROUND: Although the performance of children with attention-deficit/hyperactivity disorder (ADHD) is impaired in a variety of cognitive tasks, the specific capacity of strategic readaptation after errors as a source of behavioral deficits is not sufficiently understood. This study used an extended and refined behavioral parameterization to assess performance monitoring and posterror adaptation in children with ADHD. METHODS: Twenty-eight healthy control subjects and 47 ADHD patients (7-16 years of age, all males, matched for age and IQ) performed a visual flanker task in which targets were congruent or incongruent with preceding flankers. Posterror adaptation was measured for response speed (posterror slowing), accuracy, and variability by using normalized individual rates of change. Markers of error detection and general performance were also analyzed. RESULTS: Postcorrect response speed and accuracy did not differ between the groups, in contrast to posterror behaviors. Whereas posterror slowing was not evident in any of the groups, the error rate and performance instability (reaction time variance) substantially increased after errors only in ADHD patients, not in control subjects. No reliable between-group differences were found for error detection and global performance. CONCLUSIONS: In healthy children, posterror adaptation preserves performance at its ongoing level. No such adaptation was evident in ADHD, leading to consecutive errors and increased behavioral instability. Performance deficits in ADHD were only present after error but not after correct behaviors, which shapes the general profile of performance impairment in ADHD. The findings have practical implications for strategic designs of behavioral therapy in ADHD.