Challenges and best practices for recruiting families of children with intellectual disabilities for health research.

Research focused on children with intellectual disabilities has been of increasing interest over the last two decades. However, a considerable lag in the amount of research that is representative and generalizable to this population in comparison to neurotypical children remains, largely attributed to issues with participant engagement and recruitment. Challenges and barriers associated with engaging and recruiting this population include lack of research to provide a sound foundation of knowledge, ethical considerations, parental attitudes, family commitments, and organizational gatekeeping. Researchers can engage children and their families using participatory research methods, honouring the child's right to assent, and collaborating with parents. Recruitment strategies include partnering with organizations, working with parent and patient partners, and using remote methods. Employing evidence-informed engagement and recruitment strategies may provide substantial social and scientific value to the research field by ensuring that this underrepresented population benefits equitably from research findings.

A two for one special: EEG hyperscanning using a single-person EEG recording setup.

EEG hyperscanning refers to recording electroencephalographic (EEG) data from multiple participants simultaneously. Many hyperscanning experimental designs seek to mimic naturalistic behavior, relying on unpredictable participant-generated stimuli. The majority of this research has focused on neural oscillatory activity that is quantified over hundreds of milliseconds or more. This contrasts with traditional event-related potential (ERP) research in which analysis focuses on transient responses, often only tens of milliseconds in duration. Deriving ERPs requires precise time-locking between stimuli and EEG recordings, and thus typically relies on pre-set stimuli that are presented to participants by a system that controls stimulus timing and synchronization with an EEG system. EEG hyperscanning methods typically use separate EEG amplifiers for each participant, increasing cost and complexity - including challenges in synchronizing data between systems. Here, we describe a method that allows for simultaneous acquisition of EEG data from a pair of participants engaged in conversation, using a single EEG system with simultaneous audio data collection that is synchronized with the EEG recording. This allows for the post-hoc insertion of trigger codes so that it is possible to analyze ERPs time-locked to specific events. We further demonstrate methods for deriving ERPs elicited by another person's spontaneous speech, using this setup.•EEG hyperscanning method using a single EEG amplifier•EEG hyperscanning method allowing simultaneous recording of audio data directly into the EEG data file for perfect synchronization•EEG method for naturalistic language and human interaction studies that allows the study of event-related potentials time-locked to spontaneous speech.

Aberrant corticospinal tract characteristics in prodromal PD: A diffusion tensor imaging study.

Introduction: Parkinson's disease (PD) is typically diagnosed when motor symptoms first occur. However, PD-related non-motor symptoms may appear several years before diagnosis. REM sleep behaviour disorder (RBD) and olfactory deficits (hyposmia) are risk factors, but they are not specific for predicting progression towards PD. Other PD-related markers, for example brain imaging markers, may help to identify preclinical PD in hyposmic RBD patients. Studies have reported abnormal structural characteristics in the corticospinal tract (CST) of PD patients, but it is unclear whether hyposmic RBD patients have similar abnormalities that may help to predict PD in these individuals. This study examined whether CST abnormalities may be a potential marker of PD risk by using diffusion tensor imaging (DTI) measures. Methods: Twenty hyposmic RBD patients, 31 PD patients, and 29 healthy controls (HCs) were studied. DTI data were collected on a 1.5 T MRI scanner and CST characteristics (FA, MD, AD, and RD) were evaluated using probabilistic tractography (with seed regions in the bilateral primary motor cortex and mediolateral cerebral peduncles). Olfactory function was assessed with the University of Pennsylvania Smell Identification Test (UPSIT). Results: Hyposmic RBD patients showed significantly higher mean diffusivity (MD) values of the right CST compared to HCs but did not differ from PD patients. PD patients showed a trend of higher MD values compared to HCs. Conclusions: Altered diffusivity in the CST seems to be associated with RBD. The combination of RBD, hyposmia, and CST alterations may be related to later development of PD with comorbid RBD.

Do emotions influence safe browsing? Toward an electroencephalography marker of affective responses to cybersecurity notifications.

Cybersecurity notifications play an important role in encouraging users to use computers safely. Emotional reactions to such notifications are known to positively influence users' adherence to these notifications, though it is challenging for researchers to identify and quantify users' emotional reactions. In this study, we explored electroencephalography (EEG) signals that were elicited by the presentation of various emotionally charged image stimuli provided by the International Affective Picture System (IAPS) and compared signals to those elicited by images of cybersecurity notifications and other computer-related stimuli. Participants provided behavioral assessments of valence and arousal elicited by the images which were used to cross-reference the results. We found that EEG amplitudes corresponding to the late positive potential (LPP) were elevated in reaction to images of cybersecurity notifications as well as IAPS images known to elicit strong positive and negative valence, when compared to neutral valence or other computer-related stimuli. These findings suggest that the LPP may account for emotional deliberation about cybersecurity notifications, which could be a useful measure when conducting future studies into the role such emotional reactions play in encouraging safe computer behavior.

Native Word Order Processing Is Not Uniform: An ERP Study of Verb-Second Word Order.

Studies of native syntactic processing often target phrase structure violations that do not occur in natural production. In contrast, this study examines how variation in basic word order is processed, looking specifically at structures traditionally labelled as violations but that do occur naturally. We examined Swedish verb-second (V2) and verb-third (V3) word order processing in adult native Swedish speakers, manipulating sentence-initial adverbials (temporal idag 'today', spatial hemma 'at home' and sentential kanske 'maybe') in acceptability judgements, in simultaneously recorded event-related potentials (ERP) to visually presented sentences and in a written sentence completion task. An initial corpus study showed that the adverbials differ in frequency in fronted position (idag > kanske > hemma), and although all occur mainly with V2 word order, kanske occurs more frequently with V3 in natural production than both idag and hemma. The experimental results reflected these patterns such that V2 sentences were overall more frequently produced and were deemed more acceptable than V3 sentences. The ERP results consisted of a biphasic N400/P600 response to V3 word order that indicated effects of word retrieval and sentence reanalysis. We also found consistent effects of adverbials. As predicted, V3 was produced more frequently and judged as more acceptable in Kanske sentences than in sentences with the other two adverbials. The ERP analyses showed stronger effects for idag and hemma with V3, especially regarding the P600. The results suggest that the naturally occurring word order 'violation', V3 with kanske, is processed differently than V3 with other adverbials where the V2 norm is stronger. Moreover, these patterns are related to individuals' own production patterns. Overall, the results suggest a more varied native word order processing than previously reported.

Neural correlates of the production effect: An fMRI study.

Recognition memory is improved for items produced at study (e.g., by reading them aloud) relative to a non-produced control condition (e.g., silent reading). This production effect is typically attributed to the extra elements in the production task (e.g., motor activation, auditory perception) enhancing item distinctiveness. To evaluate this claim, the present study examined the neural mechanisms underlying the production effect. Prior to a recognition memory test, different words within a study list were read either aloud, silently, or while saying "check" (as a sensorimotor control condition). Production improved recognition, and aloud words yielded higher rates of both recollection and familiarity judgments than either silent or control words. During encoding, fMRI revealed stronger activation in regions associated with motor, somatosensory, and auditory processing for aloud items than for either silent or control items. These activations were predictive of recollective success for aloud items at test. Together, our findings are compatible with a distinctiveness-based account of the production effect, while also pointing to the possible role of other processing differences during the aloud trials as compared to silent and control.

Enhancement of visual biological motion recognition in early-deaf adults: Functional and behavioral correlates.

Deafness leads to brain modifications that are generally associated with a cross-modal activity of the auditory cortex, particularly for visual stimulations. In the present study, we explore the cortical processing of biological motion that conveyed either non-communicative (pantomimes) or communicative (emblems) information, in early-deaf and hearing individuals, using fMRI analyses. Behaviorally, deaf individuals showed an advantage in detecting communicative gestures relative to hearing individuals. Deaf individuals also showed significantly greater activation in the superior temporal cortex (including the planum temporale and primary auditory cortex) than hearing individuals. The activation levels in this region were correlated with deaf individuals' response times. This study provides neural and behavioral evidence that cross-modal plasticity leads to functional advantages in the processing of biological motion following lifelong auditory deprivation.

A sinister subject: Quantifying handedness-based recruitment biases in current neuroimaging research.

Approximately ten per cent of humans are left-handed or ambidextrous (adextral). It has been suggested that, despite their sizable representation at the whole-population level, this demographic is largely avoided by researchers within the neuroimaging community. To date, however, no formal effort has been made to quantify the extent to which adextrals are excluded from neuroimaging-based research. Here, we aimed to address this question in a review of over 1,000 recent articles published in high-impact, peer-reviewed, neuroimaging-focused journals. Specifically, we sought to ascertain whether, and the extent to which adextrals are underrepresented in neuroimaging study samples, and to delineate potential trends in this bias. Handedness data were available for over 30,000 research subjects; only around 3%-4% of these individuals were adextral-considerably less than the 10% benchmark one would expect if neuroimaging samples were truly representative of the general population. This observation was generally consistent across different areas of research, but was modulated by the demographic characteristics of neuroimaging participants. The epistemological and ethical implications of these findings are discussed.

The impacts of actual and perceived nicotine administration on insula functional connectivity with the anterior cingulate cortex and nucleus accumbens.

BACKGROUND: Changes in resting state functional connectivity between the insula and dorsal anterior cingulate cortex as well as between the insula and nucleus accumbens have been linked to nicotine withdrawal and/or administration. However, because many of nicotine's effects in humans appear to depend, at least in part, on the belief that nicotine has been administered, the relative contribution of nicotine's pharmacological actions to such effects requires clarification. AIMS: The purpose of this study was to examine the impacts of perceived and actual nicotine administration on neural responses. METHODS: Twenty-six smokers were randomly assigned to receive either a nicotine inhaler (4 mg deliverable) or a nicotine-free inhaler across two sessions. Inhaler content instructions (told nicotine vs told nicotine-free) differed across sessions. Resting state functional connectivity between sub-regions of the insula and the dorsal anterior cingulate cortex and nucleus accumbens was measured using magnetic resonance imaging before and after inhaler administration. RESULTS: Both actual and perceived nicotine administration independently altered resting state functional connectivity between the anterior insula and the dorsal anterior cingulate cortex, with actual administration being associated with decreased resting state functional connectivity, and perceived administration with increased resting state functional connectivity. Actual nicotine administration also contralaterally reduced resting state functional connectivity between the anterior insula and nucleus accumbens, while reductions in resting state functional connectivity between the mid-insula and right nucleus accumbens were observed when nicotine was administered unexpectedly. Changes in resting state functional connectivity associated with actual or perceived nicotine administration were unrelated to changes in subjective withdrawal and craving. Changes in withdrawal and craving were however independently associated with resting state functional connectivity between the nucleus accumbens and insula. CONCLUSIONS: Our findings highlight the importance of considering non-pharmacological factors when examining drug mechanisms of action.

Microstructural Findings in White Matter Associated with Cannabis and Alcohol Use in Early-Phase Psychosis: A Diffusion Tensor Imaging and Relaxometry Study.

Accumulating evidence suggests that brain white matter (WM) abnormalities may be central to the pathophysiology of psychotic disorders. In addition, there is evidence that cannabis use and alcohol use each is associated with WM abnormalities. However, there are very limited data on the effects of these substances on WM microstructure in patients with psychosis, especially for those at the early phase of illness. This project aimed to examine the impact of cannabis use and alcohol use on WM tissue in early-phase psychosis (EPP). WM was investigated in 21 patients with EPP using diffusion tensor imaging (DTI) and transverse relaxation time of tissue water (T2), with the primary outcomes being mean fractional anisotropy (FA) and T2. DTI analyses were performed at the full-brain level using tract-based spatial statistics with both DTI and T2 analysis done within a WM volume of interest (VOI) implicated in psychosis (containing the left superior longitudinal fasciculus). Our findings revealed that younger age of onset of regular alcohol use (more than one drink per week) was associated with lower FA values in the left thalamic radiation and left parahippocampal and left amygdalar WM. More frequent lifetime cannabis use was correlated with increased mean full-brain FA. There was no significant relationship found between FA and alcohol or cannabis use within the VOI. Relaxometry analysis revealed trend-level evidence of shortened T2 with later onset of regular alcohol use and with more frequent cannabis use. This study provides novel data demonstrating cortical and subcortical WM findings related to alcohol use in EPP and is the first to combine DTI and relaxometry, relating to this patient population.

Do emotion-induced blindness and the attentional blink share underlying mechanisms? An event-related potential study of emotionally-arousing words.

When two targets are presented within approximately 500 ms of each other in the context of rapid serial visual presentation (RSVP), participants' ability to report the second target is reduced compared to when the targets are presented further apart in time. This phenomenon is known as the attentional blink (AB). The AB is increased in magnitude when the first target is emotionally arousing. Emotionally arousing stimuli can also capture attention and create an AB-like effect even when these stimuli are presented as to-be-ignored distractor items in a single-target RSVP task. This phenomenon is known as emotion-induced blindness (EIB). The phenomenological similarity in the behavioral results associated with the AB with an emotional T1 and EIB suggest that these effects may result from similar underlying mechanisms - a hypothesis that we tested using event-related electrical brain potentials (ERPs). Behavioral results replicated those reported previously, demonstrating an enhanced AB following an emotionally arousing target and a clear EIB effect. In both paradigms highly arousing taboo/sexual words resulted in an increased early posterior negativity (EPN) component that has been suggested to represent early semantic activation and selection for further processing in working memory. In both paradigms taboo/sexual words also produced an increased late positive potential (LPP) component that has been suggested to represent consolidation of a stimulus in working memory. Therefore, ERP results provide evidence that the EIB and emotion-enhanced AB effects share a common underlying mechanism.

Preliminary Investigation of the Passively Evoked N400 as a Tool for Estimating Speech-in-Noise Thresholds.

PURPOSE: Speech-in-noise testing relies on a number of factors beyond the auditory system, such as cognitive function, compliance, and motor function. It may be possible to avoid these limitations by using electroencephalography. The present study explored this possibility using the N400. METHOD: Eleven adults with typical hearing heard high-constraint sentences with congruent and incongruent terminal words in the presence of speech-shaped noise. Participants ignored all auditory stimulation and watched a video. The signal-to-noise ratio (SNR) was varied around each participant's behavioral threshold during electroencephalography recording. Speech was also heard in quiet. RESULTS: The amplitude of the N400 effect exhibited a nonlinear relationship with SNR. In the presence of background noise, amplitude decreased from high (+4 dB) to low (+1 dB) SNR but increased dramatically at threshold before decreasing again at subthreshold SNR (-2 dB). CONCLUSIONS: The SNR of speech in noise modulates the amplitude of the N400 effect to semantic anomalies in a nonlinear fashion. These results are the first to demonstrate modulation of the passively evoked N400 by SNR in speech-shaped noise and represent a first step toward the end goal of developing an N400-based physiological metric for speech-in-noise testing.

Using CForest to Analyze Diffusion Tensor Imaging Data: A Study of White Matter Integrity in Healthy Aging.

Healthy aging has been associated with a global reduction in white matter integrity, which is thought to reflect cognitive decline. The present study aimed to investigate this reduction over a broad range of the life span, using diffusion tensor imaging analyzed with conditional inference random forest modeling (CForest). This approach is sensitive to subtle and potentially nonlinear effects over the age continuum and was used to characterize the progression of decline in greater detail than has been possible in the past. Data were collected from 45 healthy individuals ranging in age from 19 to 67 years. Fractional anisotropy (FA) was estimated using probabilistic tractography for a number of major tracts across the brain. Age coincided with a nonlinear decrease in FA, with onset beginning at ∼30 years of age and the steepest declines occurring later in life. However, several tracts showed a transient increase before this decline. The progression of decline varied by tract, with steeper but later decline occurring in more anterior tracts. Finally, strongly right-handed individuals demonstrated relatively preserved FA until more than a decade following the onset of decline of others. These results demonstrate that using a novel, nonparametric analysis approach, previously reported reductions in FA with healthy aging were confirmed, while at the same time, new insight was provided into the onset and progression of decline, with evidence suggesting increases in integrity continuing into adulthood.

Asymmetric Weighting to Optimize Regional Sensitivity in Combined fMRI-MEG Maps.

Functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) are neuroimaging techniques that measure inherently different physiological processes, resulting in complementary estimates of brain activity in different regions. Combining the maps generated by each technique could thus provide a richer understanding of brain activation. However, present approaches to integration rely on a priori assumptions, such as expected patterns of brain activation in a task, or use fMRI to bias localization of MEG sources, diminishing fMRI-invisible sources. We aimed to optimize sensitivity to neural activity by developing a novel method of integrating data from the two imaging techniques. We present a data-driven method of integration that weights fMRI and MEG imaging data by estimates of data quality for each technique and region. This method was applied to a verbal object recognition task. As predicted, the two imaging techniques demonstrated sensitivity to activation in different regions. Activity was seen using fMRI, but not MEG, throughout the medial temporal lobes. Conversely, activation was seen using MEG, but not fMRI, in more lateral and anterior temporal lobe regions. Both imaging techniques were sensitive to activation in the inferior frontal gyrus. Importantly, integration maps retained activation from individual activation maps, and showed an increase in the extent of activation, owing to greater sensitivity of the integration map than either fMRI or MEG alone.

Neural systems supporting linguistic structure, linguistic experience, and symbolic communication in sign language and gesture.

Sign languages used by deaf communities around the world possess the same structural and organizational properties as spoken languages: In particular, they are richly expressive and also tightly grammatically constrained. They therefore offer the opportunity to investigate the extent to which the neural organization for language is modality independent, as well as to identify ways in which modality influences this organization. The fact that sign languages share the visual-manual modality with a nonlinguistic symbolic communicative system-gesture-further allows us to investigate where the boundaries lie between language and symbolic communication more generally. In the present study, we had three goals: to investigate the neural processing of linguistic structure in American Sign Language (using verbs of motion classifier constructions, which may lie at the boundary between language and gesture); to determine whether we could dissociate the brain systems involved in deriving meaning from symbolic communication (including both language and gesture) from those specifically engaged by linguistically structured content (sign language); and to assess whether sign language experience influences the neural systems used for understanding nonlinguistic gesture. The results demonstrated that even sign language constructions that appear on the surface to be similar to gesture are processed within the left-lateralized frontal-temporal network used for spoken languages-supporting claims that these constructions are linguistically structured. Moreover, although nonsigners engage regions involved in human action perception to process communicative, symbolic gestures, signers instead engage parts of the language-processing network-demonstrating an influence of experience on the perception of nonlinguistic stimuli.

Modeling nonlinear relationships in ERP data using mixed-effects regression with R examples.

In the analysis of psychological and psychophysiological data, the relationship between two variables is often assumed to be a straight line. This may be due to the prevalence of the general linear model in data analysis in these fields, which makes this assumption implicitly. However, there are many problems for which this assumption does not hold. In this paper, we show that, in the analysis of event-related potential (ERP) data, the assumption of linearity comes at a cost and may significantly affect the inferences drawn from the data. We demonstrate why the assumption of linearity should be relaxed and how to model nonlinear relationships between ERP amplitudes and predictor variables within the familiar framework of generalized linear models, using regression splines and mixed-effects modeling.

Handles of manipulable objects attract covert visual attention: ERP evidence.

Previous research has demonstrated that people are faster at making a manual response with the hand that is aligned with the handle of a manipulable object compared to its functional end. According to theories of embodied cognition (ETC), the presentation of a manipulable object automatically elicits sensorimotor simulations of the respective hand and these simulations facilitate the response. However, an alternative interpretation of these data is that handles preferentially attract visual attention, since attended stimuli and locations typically elicit faster responses. We investigated attentional biases elicited by manipulable and non-manipulable objects using event-related-potentials (ERPs). On each trial, a picture of a manipulable object was followed by a target dot that participants had to make a button-press to. The dot was located at either the handle or functional end of the object. Consistent with previous attentional cuing paradigms, we showed that the P1 ERP component was greater in response to targets cued by handles than by functional ends. These results suggest that object handles automatically bias covert attentional processes. These attentional biases may account for earlier behavioural findings, without any recourse to ETC.

Electrophysiological markers of biological motion and human form recognition.

Current models suggest that human form and motion information are initially processed through separate pathways, then integrated in action perception. Testing such a sequential model requires techniques with high temporal resolution. Prior work demonstrated sensitivity of a posterior temporal event-related potential (ERP) effect - the N2 - to biological motion, but did not test whether the N2 indexes biological motion perception specifically, or human form/action perception more generally. We recorded ERPs while participants viewed stimuli across 3 blocks: (1) static (non-moving) point-light displays of humans performing actions; (2) static stick figures with clear forms; and (3) point-light biological motion. A similar sequence of ERP components was elicited by human forms in all blocks (stationary and moving), and reliably discriminated between human and scrambled forms. The N2 showed similar scalp distribution and sensitivity to stimulus manipulations for both stick figures and biological motion, suggesting that it indexes integration of form and motion information, rather than biological motion perception exclusively - and that form and motion information are therefore integrated by approximately 200ms. We identified a component subsequent to the N2, which we label the medial parietal positivity/ventral-anterior negativity (MPP/VAN), that was also sensitive to both human form and motion information. We propose that the MPP/VAN reflects higher-order human action recognition that occurs subsequent to the integration of form and motion information reflected by the N2.

Multimodal neuroimaging of frontal white matter microstructure in early phase schizophrenia: the impact of early adolescent cannabis use.

BACKGROUND: A disturbance in connectivity between different brain regions, rather than abnormalities within the separate regions themselves, could be responsible for the clinical symptoms and cognitive dysfunctions observed in schizophrenia. White matter, which comprises axons and their myelin sheaths, provides the physical foundation for functional connectivity in the brain. Myelin sheaths are located around the axons and provide insulation through the lipid membranes of oligodendrocytes. Empirical data suggests oligodendroglial dysfunction in schizophrenia, based on findings of abnormal myelin maintenance and repair in regions of deep white matter. The aim of this in vivo neuroimaging project is to assess the impact of early adolescent onset of regular cannabis use on brain white matter tissue integrity, and to differentiate this impact from the white matter abnormalities associated with schizophrenia. The ultimate goal is to determine the liability of early adolescent use of cannabis on brain white matter, in a vulnerable brain. METHODS/DESIGN: Young adults with schizophrenia at the early stage of the illness (less than 5 years since diagnosis) will be the focus of this project. Four magnetic resonance imaging measurements will be used to assess different cellular aspects of white matter: a) diffusion tensor imaging, b) localized proton magnetic resonance spectroscopy with a focus on the neurochemical N-acetylaspartate, c) the transverse relaxation time constants of regional tissue water, d) and of N-acetylaspartate. These four neuroimaging indices will be assessed within the same brain region of interest, that is, a large white matter fibre bundle located in the frontal region, the left superior longitudinal fasciculus. DISCUSSION: We will expand our knowledge regarding current theoretical models of schizophrenia with a more comprehensive multimodal neuroimaging approach to studying the underlying cellular abnormalities of white matter, while taking into consideration the important confounding variable of early adolescent onset of regular cannabis use.