MEG Analysis of Neural Interactions in Attention-Deficit/Hyperactivity Disorder

Producción CientíficaThe aim of the present study was to explore the interchannel relationships of resting-state brain activity in patients with attentiondeficit/hyperactivity disorder (ADHD), one of the most common mental disorders that develop in children. Magnetoencephalographic (MEG) signals were recorded using a 148-channel whole-head magnetometer in 13 patients with ADHD (range: 8–12 years) and 14 control subjects (range: 8–13 years).Three complementary measures (coherence, phase-locking value, and Euclidean distance) were calculated in the conventionalMEG frequency bands: delta, theta, alpha, beta, and gamma. Our results showed that the interactions among MEG channels are higher for ADHD patients than for control subjects in all frequency bands. Statistically significant differences were observed for short-distance values within right-anterior and central regions, especially at delta, beta, and gamma-frequency bands ( < 0.05; Mann-Whitney test with false discovery rate correction). These frequency bands also showed statistically significant differences in long-distance interactions, mainly among anterior and central regions, as well as among anterior, central, and other areas. These differences might reflect alterations during brain development in children with ADHD. Our results support the role of frontal abnormalities in ADHD pathophysiology, which may reflect a delay in cortical maturation in the frontal cortex.Ministerio de Economía, Industria y Competitividad (TEC2014-53196-R)Junta de Castilla y León (programa de apoyo a proyectos de investigación - Ref. VA059U1

Multimodal alterations of directed connectivity profiles in patients with attention-deficit/hyperactivity disorders

Functional and effective connectivity measures for tracking brain region interactions that have been investigated using both electroencephalography (EEG) and magnetoencephalography (MEG) bringing up new insights into clinical research. However, the differences between these connectivity methods, especially at the source level, have not yet been systematically studied. The dynamic characterization of coherent sources and temporal partial directed coherence, as measures of functional and effective connectivity, were applied to multimodal resting EEG and MEG data obtained from 11 young patients (mean age 13.2 ± 1.5 years) with attention-deficit/hyperactivity disorder (ADHD) and age-matched healthy subjects. Additionally, machine-learning algorithms were applied to the extracted connectivity features to identify biomarkers differentiating the two groups. An altered thalamo-cortical connectivity profile was attested in patients with ADHD who showed solely information outflow from cortical regions in comparison to healthy controls who exhibited bidirectional interregional connectivity in alpha, beta, and gamma frequency bands. We achieved an accuracy of 98% by combining features from all five studied frequency bands. Our findings suggest that both types of connectivity as extracted from EEG or MEG are sensitive methods to investigate neuronal network features in neuropsychiatric disorders. The connectivity features investigated here can be further tested as biomarkers of ADHD

MEG analysis of neural dynamics in attention-deficit/hyperactivity disorder with fuzzy entropy

Producción CientíficaThe aim of this study was to analyze the neural dynamics in attention-deficit/hyperactivity disorder (ADHD). For this purpose, magnetoencephalographic (MEG) background activity was analyzed using fuzzy entropy (FuzzyEn), an entropy measure that quantifies signal irregularity, in 13 ADHD patients and 14 control children. Additionally, relative power (RP) was computed in conventional frequency bands (delta, theta, alpha, beta and gamma). FuzzyEn results showed that MEG activity was more regular in ADHD patients than in controls. Moreover, we found an increase of power in delta band and a decrease in the remaining frequency bands. Statistically significant differences (p-values <0.05; nonparametric permutation test for multiple comparisons) were detected for FuzzyEn in the posterior and left temporal regions, and for RP in the posterior, anterior and left temporal regions. Our results support the hypothesis that ADHD involves widespread functional brain abnormalities, affecting more areas than fronto-striatal circuits, such as the left temporal and posterior regions.Ministerio de Economía y Competitividad (project TEC2011-22987)Junta de Castilla y León (project BIO/VA38/14 and project VA059U13

MEG event-related desynchronization and synchronization deficits during basic somatosensory processing in individuals with ADHD

<p>Abstract</p> <p>Background</p> <p>Attention-Deficit/Hyperactivity Disorder (ADHD) is a prevalent, complex disorder which is characterized by symptoms of inattention, hyperactivity, and impulsivity. Convergent evidence from neurobiological studies of ADHD identifies dysfunction in fronto-striatal-cerebellar circuitry as the source of behavioural deficits. Recent studies have shown that regions governing basic sensory processing, such as the somatosensory cortex, show abnormalities in those with ADHD suggesting that these processes may also be compromised.</p> <p>Methods</p> <p>We used event-related magnetoencephalography (MEG) to examine patterns of cortical rhythms in the primary (SI) and secondary (SII) somatosensory cortices in response to median nerve stimulation, in 9 adults with ADHD and 10 healthy controls. Stimuli were brief (0.2 ms) non-painful electrical pulses presented to the median nerve in two counterbalanced conditions: unpredictable and predictable stimulus presentation. We measured changes in strength, synchronicity, and frequency of cortical rhythms.</p> <p>Results</p> <p>Healthy comparison group showed strong event-related desynchrony and synchrony in SI and SII. By contrast, those with ADHD showed significantly weaker event-related desynchrony and event-related synchrony in the alpha (8–12 Hz) and beta (15–30 Hz) bands, respectively. This was most striking during random presentation of median nerve stimulation. Adults with ADHD showed significantly shorter duration of beta rebound in both SI and SII except for when the onset of the stimulus event could be predicted. In this case, the rhythmicity of SI (but not SII) in the ADHD group did not differ from that of controls.</p> <p>Conclusion</p> <p>Our findings suggest that somatosensory processing is altered in individuals with ADHD. MEG constitutes a promising approach to profiling patterns of neural activity during the processing of sensory input (e.g., detection of a tactile stimulus, stimulus predictability) and facilitating our understanding of how basic sensory processing may underlie and/or be influenced by more complex neural networks involved in higher order processing.</p

Local neuronal dynamics in planning during Wisconsin card sorting test in ADHD

Jotta tehokkaiden ja tuotteliaiden päätösten tekeminen on mahdollista, ihmisen tulee suunnitella toimintaansa läpi elämän oleellisen tiedon ylläpitämisen ja päivittämisen avulla. Tällaiset tavoitteelliset tilanteet vaativat joustavaa käyttäytymisen hienosäätöä ja epäoleellisen tiedon vaimentamista. Toiminnanohjauksessa vaadittava kognitiivinen joustavuus, työmuisti ja inhibitio, on liitetty poikkeavaa etuaivokuoren toimintaan. Etuaivokuoren on aiemmin havaittu toimivan taaemmilta alueilta tulevan aistitiedon prosessoijana. Rakenteellisia ja toiminnallisia poikkeavuuksia on löydetty aktiivisuuden ja tarkkaavuuden häiriössä (ADHD) liittyen toiminnanohjauksen aivoalueisiin. Perustana oleva syy toiminnanohjauksen häiriöön ja vaikeuksiin suunnittelussa sekä päätöksenteossa saattaa löytyä yllä mainituista poikkeavuuksista. On silti epäselvää, miten aivojen oskillaatiot muokkaavat erilasia kognitiivisia toimintoja suunnitteluun ja päätöksentekoon liittyen. Tämän tutkimiseksi aivotoimintaa mitattiin MEG-laitteella koehenkilöiden (21 ADHD, 28 kontrolliosallistujaa) suorittaessa Wisconsin korttienlajittelutehtävää (WCST). WCST on nopeatempoinen tehtävä, jossa lajitellaan kortteja muuttuvien sääntöjen mukaan palautetta apuna käyttäen. Tämän tutkimuksen tarkoituksena oli tutkia ADHD-aikuisia ja kontrolliryhmää WCST-suunnitteluvaiheen aikana verraten kokeen suorittamista aiemmin saadun oikean tai väärän palautteen mukaan. ADHD ja kontrolliryhmän välillä odotettiin eroa paikallisessa hermosolutoiminnassa etuaivokuorella ja taaemmilla alueilla. Data-analyysi sekä lähdemallinnus ja - rekonstruktio tehtiin neuronaalisten (MEG) mittausten ja aivojen rakenteellisten (MRI) mittausten perusteella. Tilastolliset analyysit tehtiin selvittäen paikallisten hermosolujen amplitudidynamiikkaa ja visualisoitiin ryhmien sisällä ja välillä. Reaktioajat ja osumatarkkuus eivät osoittaneet merkittäviä eroja ryhmien välillä. Kuitenkin kontrasti suunnittelun aikana verraten oikeita-vääriä vastauksia, ilmensi tehostunutta ja vaimentunutta aivotoimintaa delta-, theta-, alfa- ja beta-oskillaatioissa. Kontrolliryhmä osoitti aktiivisuutta etuaivokuoressa-, parietaalisessa, temporaalisessa ja näköaivoalueilla. Nämä alueet on aiemmin liitetty ns. oletustilan verkostoon sekä somaattis liikkeelliseen verkostoon. Tehostunutta aktiivisuutta havaittiin beta- ja alfa -oskillaatioissa. ADHD -ryhmässä suurin positiivinen aktiivisuus havaittiin etuaivolohkossa ja parietaali- sekä kuuloaivoalueella, jotka on liitetty kahteen huomioverkostoon ja somaattis-liikkeelliseen, mutta myös oletustilan ja näköaivoalueiden verkkoon. Ryhmien välisessä vertailussa havaittiin vaimentunutta delta-, theta- ja alfa -oskillaatioiden aktiivisuutta aivojen lateraalisilla alueilla temporaalilohkolla. Nämä alueet liittyivät ventraalisen huomion ja somaattis-liikkeelliseen verkkoihin. Heikentynyttä aivotoimintaa havaittiin ADHD -ryhmässä vaimentuneissa positiivisesti aktivoituneissa betaoskillaatioissa verrattuna kontrolliryhmään ja kokonaan puuttuvista positiivisesti aktivoituneissa alfa -oskillaatioissa. Tulevien tutkimusten tehtäväksi jää näiden värähtelyiden toiminnan roolien tulkitseminen. Suuntaa-antavia tuloksia ADHD potilaiden aivotoiminnan poikkeavuudesta voitiin löytää aivoalueista ja toiminnasta jotka liittyvät joustavuuden ja työmuistin rooleihin suunnittelussa ja päätöksenteossa. Tulokset viittaavat myös siihen, että WCST:n suunnittelu edellyttää monien kognitiivisten toimintojen ja prosessien joustavaa organisaatiota, joita moduloivat tehostuneet alfa- ja beta -oskillaatiot sekä vaimentuneet delta- ja theta -värähtelyt.To make fast and efficient decisions in changing environments, humans must plan their actions throughout their lives by maintaining and updating relevant information. Such goal-directed situations demand flexible adjustment of behavior and the suppression of task-irrelevant details. Executive dysfunctions in cognitive flexibility, working memory and inhibition have been related to aberrant prefrontal cortex functioning. The prefrontal cortex has previously been found to have an important role in these executive functions as a supervisory modulator and processor of information from posterior sensory brain areas. Structural and functional abnormalities in these brain areas have been found in attention deficit/hyperactivity disorder (ADHD). These impairments may be the underlying reason for problems in decision making and planning for people with ADHD. However how the brain’s oscillatory activity modulates different cognitive functions in areas relating to planning and decision making is still unclear. To investigate thisthe brain’s activity was measured with MEG while participants (21 ADHD patients, 28 controls) performed in Wisconsin card sorting test (WCST). WCST is a fast-paced task, where cards are sorted according to changing rule categories with the direction of feedback. The aim of this study was to investigate planning in adults with ADHD and a control group during WCST planning period and compare trials with previous feedback being correct or incorrect. Difference in the local neuronal activity in prefrontal and posterior areas were expected between the ADHD and control groups. Data-analysis and source modelling and reconstruction were conducted on the neuronal (MEG) data and structural (MRI) data. Statistical analyses were run for local neuronal amplitude dynamics and visualized within and between groups. The behavioral results of reaction times and hit rates did not show significant differences between groups. Clinical questionnaire scores did not correlate with reaction times. However, contrast of planning in correct-incorrect feedback trials within groups showed increased and decreased brain activity in delta, theta, alpha and beta oscillations. The control group showed activity in frontal, parietal, temporal, and occipital regions related to default mode, somatomotor with increased activity in the beta and alpha bands. For the ADHD group greatest positive activity was seen in beta band in frontal and parietal areas, but also in occipital regions. These activation sites were mostly related to dorsal and ventral attention and somatomotor networks but also to default mode and visual networks. Mostly temporal activity of suppressed delta, theta and alpha oscillations in the lateral areas was seen in the between groups comparison. These areas related to ventral attention and somatomotor networks. Impaired neuronal activity in the ADHD group was seen in weaker increased beta than the control group and the missing increased alpha oscillations. It remains for the future studies to interpret the roles of this oscillatory activity but direction towards impairments in cognitive functions like flexibility, working memory and inhibition in planning in ADHD. These data also suggest that planning in the WCST needs the flexible modulation of many cognitive functions and processes that are modulated by increased alpha and beta oscillations and the suppressed delta and theta oscillations

Developing multidimensional metrics for evaluating paediatric neurodevelopmental disorders

Healthy brain functioning depends on efficient communication of information between brain regions, forming complex networks. By quantifying synchronisation between brain regions, a functionally connected brain network can be articulated. In neurodevelopmental disorders, where diagnosis is based on measures of behaviour and tasks, a measure of the underlying biological mechanisms holds promise as a potential clinical tool. Graph theory provides a tool for investigating the neural correlates of neuropsychiatric disorders, where there is disruption of efficient communication within and between brain networks. This research aimed to use recent conceptualisation of graph theory, along with measures of behaviour and cognitive functioning, to increase understanding of the neurobiological risk factors of atypical development. Using magnetoencephalography to investigate frequency-specific temporal dynamics at rest, the research aimed to identify potential biological markers derived from sensor-level whole-brain functional connectivity. Whilst graph theory has proved valuable for insight into network efficiency, its application is hampered by two limitations. First, its measures have hardly been validated in MEG studies, and second, graph measures have been shown to depend on methodological assumptions that restrict direct network comparisons. The first experimental study (Chapter 3) addressed the first limitation by examining the reproducibility of graph-based functional connectivity and network parameters in healthy adult volunteers. Subsequent chapters addressed the second limitation through adapted minimum spanning tree (a network analysis approach that allows for unbiased group comparisons) along with graph network tools that had been shown in Chapter 3 to be highly reproducible. Network topologies were modelled in healthy development (Chapter 4), and atypical neurodevelopment (Chapters 5 and 6). The results provided support to the proposition that measures of network organisation, derived from sensor-space MEG data, offer insights helping to unravel the biological basis of typical brain maturation and neurodevelopmental conditions, with the possibility of future clinical utility

Assessment of ADHD Through Electroencephalographic Measures of Functional Connectivity

The main objective of the chapter is to review the types of electroencephalographic measures of functional connectivity that have been used so far in the study/diagnosis of ADHD. The review will include the methods and results so far reported in the literature as well as those conducted by our research group