Neural bases of social deficits in ADHD: A systematic review. Does the Theory of Mind matter?

INTRODUCTION: The Attention Deficit Hyperactivity Disorder (ADHD) causes serious interpersonal problems from childhood to adulthood, one of them being problematic social functioning. This phenomenon in ADHD should be associated with impairments in the Theory of Mind (ToM). Therefore, understanding the neural correlates of the ToM could be crucial for helping individuals with ADHD with their social functioning. Thus, we aimed to review published literature concerning neuroanatomical and functional correlates of ToM deficits in children and adolescents with ADHD. METHODS: We reviewed studies published between 1970 and 2023. In accordance with PRISMA guidelines, after data from three databases were collected, two authors (LN and PM) independently screened all relevant records (n=638) and consequently, both authors did the data extraction. The quality of the included studies (n=5) was measured by a modified version of The Newcastle-Ottawa Scale and by measures specific for our study. This systematic review was registered on PROSPERO (CRD42020139847). RESULTS: Results indicated that impairments in performing of the ToM tasks were negatively associated with the grey matter volume in the bilateral amygdala and hippocampus in both, ADHD and control group. In EEG studies, a significantly greater electrophysiological activity during ToM tasks was observed in the, frontal, temporal, parietal and occipital lobes in participants with ADHD as compared to healthy subjects. CONCLUSION: More research is needed to explore the ToM deficits in children with ADHD. Future research might focus on the neural circuits associated with attention and inhibition, which deficits seems to contribute to the ToM deficits in children and adolescents with ADHD.

Artificial sharp-wave-ripples to support memory and counter neurodegeneration.

Information processed in our sensory neocortical areas is transported to the hippocampus during memory encoding, and between hippocampus and neocortex during memory consolidation, and retrieval. Short bursts of high-frequency oscillations, so called sharp-wave-ripples, have been proposed as a potential mechanism for this information transfer: They can synchronize neural activity to support the formation of local neural networks to store information, and between distant cortical sites to act as a bridge to transfer information between sensory cortical areas and hippocampus. In neurodegenerative diseases like Alzheimer's Disease, different neuropathological processes impair normal neural functioning and neural synchronization as well as sharp-wave-ripples, which impairs consolidation and retrieval of information, and compromises memory. Here, we formulate a new hypothesis, that artificially inducing sharp-wave-ripples with noninvasive high-frequency visual stimulation could potentially support memory functioning, as well as target the neuropathological processes underlying neurodegenerative diseases. We also outline key challenges for empirical tests of the hypothesis.

Functional EEG connectivity is a neuromarker for adult attention deficit hyperactivity disorder symptoms.

OBJECTIVE: Altered brain functional connectivity has been shown in youth with attention-deficit/hyperactivity disorder (ADHD). However, relatively little is known about functional connectivity in adult ADHD, and how it is linked with the heritability of ADHD. METHODS: We measured eyes-open and eyes-closed resting electroencephalography (EEG) from 38 adults with ADHD, 45 1st degree relatives of people with ADHD and 51 healthy controls. Functional connectivity among all scalp channels was calculated using a weighted phase lag index for delta, theta, alpha, beta and gamma frequency bands. A machine learning analysis using penalized linear regression was used to identify if connectivity features (10,080 connectivity pairs) could predict ADHD symptoms. Furthermore, we examined if EEG connectivity could accurately classify participants into ADHD, 1st degree relatives and/or control groups. RESULTS: Hyperactive symptoms were best predicted by eyes-open EEG connectivity in delta, beta and gamma bands. Inattentive symptoms were predicted by eyes-open EEG connectivity in delta, alpha and gamma bands, and eyes-closed EEG connectivity in delta and gamma bands. EEG connectivity features did not reliably classify participants into groups. CONCLUSIONS: EEG connectivity may represent a neuromarker for ADHD symptoms. SIGNIFICANCE: EEG connectivity may help elucidate the neural basis of adult ADHD symptoms.

EEG spectral power, but not theta/beta ratio, is a neuromarker for adult ADHD.

Adults with attention-deficit/hyperactivity disorder (ADHD) have been described as having altered resting-state electroencephalographic (EEG) spectral power and theta/beta ratio (TBR). However, a recent review (Pulini et al. 2018) identified methodological errors in neuroimaging, including EEG, ADHD classification studies. Therefore, the specific EEG neuromarkers of adult ADHD remain to be identified, as do the EEG characteristics that mediate between genes and behaviour (mediational endophenotypes). Resting-state eyes-open and eyes-closed EEG was measured from 38 adults with ADHD, 45 first-degree relatives of people with ADHD and 51 unrelated controls. A machine learning classification analysis using penalized logistic regression (Elastic Net) examined if EEG spectral power (1-45 Hz) and TBR could classify participants into ADHD, first-degree relatives and/or control groups. Random-label permutation was used to quantify any bias in the analysis. Eyes-open absolute and relative EEG power distinguished ADHD from control participants (area under receiver operating characteristic = 0.71-0.77). The best predictors of ADHD status were increased power in delta, theta and low-alpha over centro-parietal regions, and in frontal low-beta and parietal mid-beta. TBR did not successfully classify ADHD status. Elevated eyes-open power in delta, theta, low-alpha and low-beta distinguished first-degree relatives from controls (area under receiver operating characteristic = 0.68-0.72), suggesting that these features may be a mediational endophenotype for adult ADHD. Resting-state EEG spectral power may be a neuromarker and mediational endophenotype of adult ADHD. These results did not support TBR as a diagnostic neuromarker for ADHD. It is possible that TBR is a characteristic of childhood ADHD.

A Combination of Impulsivity Subdomains Predict Alcohol Intoxication Frequency.

BACKGROUND: Impulsivity, broadly characterized as the tendency to act prematurely without foresight, is linked to alcohol misuse in college students. However, impulsivity is a multidimensional construct and different subdomains likely underlie different patterns of alcohol misuse. Here, we quantified the association between alcohol intoxication frequency and alcohol consumption frequency and choice, action, cognitive, and trait domains of impulsivity. METHODS: University student drinkers (n = 106) completed a battery of demographic and alcohol-related items, as well as self-report and task-based measures indexing different facets of impulsivity. Two orthogonal latent factors, intoxication frequency and alcohol consumption frequency, were generated. Their validity was demonstrated with respect to adverse consequences of alcohol use. Machine learning with penalized regression and feature selection was then utilized to predict intoxication and alcohol consumption frequency using all impulsivity subdomains. Out-of-sample validation was used to quantify model performance. RESULTS: Impulsivity measures alone were significant predictors of intoxication frequency, but not consumption frequency. Propensity for increased intoxication frequency was characterized by increased trait impulsivity, including the Disinhibition subscale of the Sensation Seeking Scale, Attentional and Non-planning subscales of the Barratt Impulsiveness Scale, increased task-based cognitive impulsivity (response time variability), and increased choice impulsivity (steeper delay discounting on a delay discounting questionnaire). A model combining impulsivity domains with other risk factors (gender; nicotine, cannabis, and other drug use; executive functioning; and learning processes) was also significant but did not outperform the model comprising of impulsivity alone. CONCLUSIONS: Intoxication frequency, but not consumption frequency, was characterized by a number of impulsivity subdomains.

Machine Learning EEG to Predict Cognitive Functioning and Processing Speed Over a 2-Year Period in Multiple Sclerosis Patients and Controls.

Event-related potentials (ERPs) show promise to be objective indicators of cognitive functioning. The aim of the study was to examine if ERPs recorded during an oddball task would predict cognitive functioning and information processing speed in Multiple Sclerosis (MS) patients and controls at the individual level. Seventy-eight participants (35 MS patients, 43 healthy age-matched controls) completed visual and auditory 2- and 3-stimulus oddball tasks with 128-channel EEG, and a neuropsychological battery, at baseline (month 0) and at Months 13 and 26. ERPs from 0 to 700 ms and across the whole scalp were transformed into 1728 individual spatio-temporal datapoints per participant. A machine learning method that included penalized linear regression used the entire spatio-temporal ERP to predict composite scores of both cognitive functioning and processing speed at baseline (month 0), and months 13 and 26. The results showed ERPs during the visual oddball tasks could predict cognitive functioning and information processing speed at baseline and a year later in a sample of MS patients and healthy controls. In contrast, ERPs during auditory tasks were not predictive of cognitive performance. These objective neurophysiological indicators of cognitive functioning and processing speed, and machine learning methods that can interrogate high-dimensional data, show promise in outcome prediction.

Differential diagnosis and comorbidity of ADHD and anxiety in adults.

OBJECTIVES: The aim of this study was to examine symptom profiles of people diagnosed with attention-deficit/hyperactivity disorder (ADHD) and/or anxiety (ANX) in order to determine the validity of widely used ADHD and ANX rating scales for differential diagnostic use and to develop modified measures that take symptom overlap into account. DESIGN: A cross-sectional design was used to assess differences in rating scale scores between clinical (n = 52) and control (n = 74) samples as well as differences among subgroups of the clinical sample (22 ADHD; 16 ADHD + ANX; 14 ANX). METHOD: Participants completed an online questionnaire where they responded to the Conners Adult ADHD Rating Scale (CAARS; Conners, Erhardt, & Sparrow, ) and State Trait Anxiety Inventory scales (STAI; Spielberger, Gorsuch, Lushene, Vagg, & Jacobs, ). RESULTS: Results showed that the CAARS and STAI had limited sensitivity and specificity and may lack in ability to differentially diagnose ADHD and/or ANX. Cluster analysis was used to guide the proposal of modifications for the two scales, which were to use inattentive items only for the CAARS and to exclude state ANX-present items on the STAI for use in differential diagnosis. Further parametric analysis supported these proposed modifications. CONCLUSIONS: Clinicians should be made aware of the limitations of the CAARS and STAI scales in terms of specificity, when used to inform differential diagnosis of ADHD and ANX. Further analysis on the psychometric properties of these modified scales is needed in order to confirm that they are valid and reliable scales. PRACTITIONER POINTS: Clinical implications It is possible that widely used self-report rating scales are not valid for use in the context of assessing adult ADHD when ANX is present. Clinicians should take alternative approaches to measuring ADHD symptoms in the context of ANX. Findings of the present study suggest the use of inattentive items only for the CAARS and to exclude state ANX-present items on the STAI for differential diagnostic use. Limitations of the study The sample sizes of the clinical subgroups were relatively small. Diagnoses were not confirmed using a semi-structured clinical interview. Alternative cluster approaches (e.g., two-step clustering using larger samples) would provide further insight.

Perceptual and Social Attributes Underlining Age-Related Preferences for Faces.

Although aesthetic preferences are known to be important in person perception and can play a significant role in everyday social decisions, the effect of the age of the observer on aesthetic preferences for faces of different ages has not yet been fully investigated. In the present study we investigated whether aesthetic preferences change with aging, with an age-related bias in favoring faces from one's own age group. In addition, we examined the role of age on both the perceptual qualities and the social attributes of faces that may influence these aesthetic judgements. Both younger and older adult observers provided ratings to images of younger, middle-aged and older unfamiliar faces. As well as attractiveness, the rating dimensions included other perceptual (distinctiveness, familiarity) and social (competence, trustworthiness and dominance) factors. The results suggested a consistent aesthetic preference for youthful faces across all ages of the observers but, surprisingly, no evidence for an age-related bias in attractiveness ratings. Older adults tended to provide higher ratings of attractiveness, competence and trustworthiness to the unfamiliar faces, consistent with the positivity effect previously reported. We also tested whether perceptual factors such as face familiarity or distinctiveness affected aesthetic ratings. Only ratings of familiarity, but not distinctiveness, were positively associated with the attractiveness of the faces. Moreover, ratings of familiarity decreased with increasing age of the face. With regard to the social characteristics of the faces, we found that the age of the face negatively correlated with ratings of trustworthiness provided by all observers, but with the competence ratings of older observers only. Interestingly, older adults provided higher ratings of perceived competence and trustworthiness to younger than older faces. However, our results also suggest that higher attractiveness ratings, together with older aged faces, led to more positive evaluations of competence. The results are discussed within the context of an age-related decline in the differentiation of faces in memory. Our findings have important implications for a better understanding of age-related perceptual factors and cognitive determinants of social interactions with unfamiliar others across the adult lifespan.

Delayed P100-Like Latencies in Multiple Sclerosis: A Preliminary Investigation Using Visual Evoked Spread Spectrum Analysis.

Conduction along the optic nerve is often slowed in multiple sclerosis (MS). This is typically assessed by measuring the latency of the P100 component of the Visual Evoked Potential (VEP) using electroencephalography. The Visual Evoked Spread Spectrum Analysis (VESPA) method, which involves modulating the contrast of a continuous visual stimulus over time, can produce a visually evoked response analogous to the P100 but with a higher signal-to-noise ratio and potentially higher sensitivity to individual differences in comparison to the VEP. The main objective of the study was to conduct a preliminary investigation into the utility of the VESPA method for probing and monitoring visual dysfunction in multiple sclerosis. The latencies and amplitudes of the P100-like VESPA component were compared between healthy controls and multiple sclerosis patients, and multiple sclerosis subgroups. The P100-like VESPA component activations were examined at baseline and over a 3-year period. The study included 43 multiple sclerosis patients (23 relapsing-remitting MS, 20 secondary-progressive MS) and 42 healthy controls who completed the VESPA at baseline. The follow-up sessions were conducted 12 months after baseline with 24 MS patients (15 relapsing-remitting MS, 9 secondary-progressive MS) and 23 controls, and again at 24 months post-baseline with 19 MS patients (13 relapsing-remitting MS, 6 secondary-progressive MS) and 14 controls. The results showed P100-like VESPA latencies to be delayed in multiple sclerosis compared to healthy controls over the 24-month period. Secondary-progressive MS patients had most pronounced delay in P100-like VESPA latency relative to relapsing-remitting MS and controls. There were no longitudinal P100-like VESPA response differences. These findings suggest that the VESPA method is a reproducible electrophysiological method that may have potential utility in the assessment of visual dysfunction in multiple sclerosis.

Symptom overlap in anxiety and multiple sclerosis.

BACKGROUND: The validity of self-rated anxiety inventories in people with multiple sclerosis (pwMS) is unclear. However, the appropriateness of self-reported depression scales has been widely examined. Given somatic symptom overlap between depression and MS, research emphasises caution when using such scales. OBJECTIVE: This study evaluates symptom overlap between anxiety and MS in a group of 33 individuals with MS, using the Beck Anxiety Inventory (BAI). METHODS: Participants underwent a neurological examination and completed the BAI. RESULTS: A novel procedure using hierarchical cluster analysis revealed three distinct symptom clusters. Cluster one ('wobbliness' and 'unsteady') grouped separately from all other BAI items. These symptoms are well-recognised MS-related symptoms and we question whether their endorsement in pwMS can be considered to reflect anxiety. A modified 19-item BAI (mBAI) was created which excludes cluster one items. This removal reduced the number of MS participants considered 'anxious' by 21.21% (low threshold) and altered the level of anxiety severity for a further 27.27%. CONCLUSION: Based on these data, it is suggested that, as with depression measures, researchers and clinicians should exercise caution when using brief screening measures for anxiety in pwMS.

Only low frequency event-related EEG activity is compromised in multiple sclerosis: insights from an independent component clustering analysis.

Cognitive impairment (CI), often examined with neuropsychological tests such as the Paced Auditory Serial Addition Test (PASAT), affects approximately 65% of multiple sclerosis (MS) patients. The P3b event-related potential (ERP), evoked when an infrequent target stimulus is presented, indexes cognitive function and is typically compared across subjects' scalp electroencephalography (EEG) data. However, the clustering of independent components (ICs) is superior to scalp-based EEG methods because it can accommodate the spatiotemporal overlap inherent in scalp EEG data. Event-related spectral perturbations (ERSPs; event-related mean power spectral changes) and inter-trial coherence (ITCs; event-related consistency of spectral phase) reveal a more comprehensive overview of EEG activity. Ninety-five subjects (56 MS patients, 39 controls) completed visual and auditory two-stimulus P3b event-related potential tasks and the PASAT. MS patients were also divided into CI and non-CI groups (n = 18 in each) based on PASAT scores. Data were recorded from 128-scalp EEG channels and 4 IC clusters in the visual, and 5 IC clusters in the auditory, modality were identified. In general, MS patients had significantly reduced ERSP theta power versus controls, and a similar pattern was observed for CI vs. non-CI MS patients. The ITC measures were also significantly different in the theta band for some clusters. The finding that MS patients had reduced P3b task-related theta power in both modalities is a reflection of compromised connectivity, likely due to demyelination, that may have disrupted early processes essential to P3b generation, such as orientating and signal detection. However, for posterior sources, MS patients had a greater decrease in alpha power, normally associated with enhanced cognitive function, which may reflect a compensatory mechanism in response to the compromised early cognitive processing.