Reaction Time Variability in Children Is Specifically Associated With Attention Problems and Regional White Matter Microstructure

Background Increased intraindividual variability (IIV) in reaction times (RTs) has been suggested as a key cognitive and behavioral marker of attention problems, but findings for other dimensions of psychopathology are less consistent. Moreover, while studies have linked IIV to brain white matter microstructure, large studies testing the robustness of these associations are needed. Methods We used data from the Adolescent Brain Cognitive Development (ABCD) Study baseline assessment to test the associations between IIV and psychopathology (n = 8622, age = 8.9–11.1 years) and IIV and white matter microstructure (n = 7958, age = 8.9–11.1 years). IIV was investigated using an ex-Gaussian distribution analysis of RTs in correct response go trials in the stop signal task. Psychopathology was measured by the Child Behavior Checklist and a bifactor structural equation model was performed to extract a general p factor and specific factors reflecting internalizing, externalizing, and attention problems. To investigate white matter microstructure, fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity were examined in 23 atlas-based tracts. Results Increased IIV in both short and long RTs was positively associated with the specific attention problems factor (Cohen’s d = 0.13 and d = 0.15, respectively). Increased IIV in long RTs was also positively associated with radial diffusivity in the left and right corticospinal tract (both tracts, d = 0.12). Conclusions Using a large sample and a data-driven dimensional approach to psychopathology, the results provide novel evidence for a small but specific association between IIV and attention problems in children and support previous findings on the relevance of white matter microstructure for IIV.publishedVersio

Sensory prediction or timing? : clarifying cerebellar function by examining the mismatch negativity in patients with cerebellar degeneration

Abstract Background and aim: Over the last few decades increasing evidence suggests that the functional domain of the cerebellum extends beyond motor control. Two functional hypotheses attempting to account for cerebellar involvement also in a range of perceptual and cognitive tasks are the sensory prediction hypothesis and the timing hypothesis. The sensory prediction hypothesis postulates that the cerebellum is critical in generating expectancies regarding forthcoming sensory information. The timing hypothesis postulates that this structure is critical for the learning and retention of temporal information, a more limited, yet specific form of prediction. Recent functional imaging and patient studies have produced evidence compatible with both of these positions. The aim of the present experiment was to contrast these two hypotheses by examining the mismatch negativity (MMN) response in patients with cerebellar cortical atrophy. While the timing hypothesis would predict a selective impairment in the MMN response to the deviants of a longer duration than the standard, the sensory prediction hypothesis would also predict similar impairments in the MMN response to deviants of higher pitch, lower intensity and a different spatial location. Method: Patients and matched controls were presented with a stream of short sounds while watching a silent movie. A standard auditory stimulus was presented 60% of the time, composed of a fixed duration, intensity, and pitch, and presented at a fixed location. The remaining sounds deviated on one of these four dimensions (10 % each). Key result: Compared to controls, the patients exhibited delayed duration MMN latency, as well as a similar trend for the intensity MMN. The pitch and location MMNs did not differ between patients and controls. Conclusion: The present results fail to support a more general role in sensory prediction as predicted by the sensory prediction hypothesis, while the timing hypothesis receives partial support. Importantly, the present findings add to previous reports of timing deficits in cerebellar patients by demonstrating that this impairment is present at an early stage of auditory processing (100-200 ms), even when the task does not require an overt assessment of temporal regularities or even that the stimuli be attended

Do visual and auditory stimulus-specific response modulation reflect different mechanisms of neocortical plasticity?

Stimulus response modulation (SRM) of sensory evoked potentials represents a promising method as a non‐invasive index of long‐term potentiation (LTP)‐like synaptic plasticity in the human sensory cortices. As of today, however, no consensus exists regarding which experimental parameters elicit the most robust SRM response. The aim of the current study was twofold; firstly, we aimed to replicate former studies demonstrating visual SRM in healthy adults. Second, we integrated visual and auditory stimuli within the same SRM recording session to assay potential cross‐modal associations. Such an association between modalities would strengthen the assumption that the SRM effect reflects common mechanisms underlying synaptic plasticity rather than reflecting modality‐specific phenomena. A replication of previous findings showing robust potentiation of the visual evoked potential was evident, supporting the majority of previous work using similar paradigms, lending further support to the notion that high‐frequent visual stimulation is a viable probe into LTP‐like synaptic plasticity in the human visual cortex. The auditory evoked potentials (AEPs) did not, however, fully replicate previous work, though a significant increase of temporally later AEP components was found. In contrast to our hypothesis, there were no significant within‐subject cross‐modality correlations between the visual and auditory SRM. This lack of significant association might suggest that auditory and visual SRM depend on different mechanisms, and that further SRM studies on non‐invasive LTP‐like synaptic plasticity should focus on optimizing paradigms within the visual modality

Detecting violations of sensory expectancies following cerebellar degeneration:

Two hypotheses concerning cerebellar function and predictive behavior are the sensory prediction hypothesis and the timing hypothesis. The former postulates that the cerebellum is critical in generating expectancies regarding forthcoming sensory information. The latter postulates that this structure is critical in generating expectancies that are precisely timed; for example, the expected duration of an event or the time between events. As such, the timing hypothesis constitutes a more specific form of prediction. The present experiment contrasted these two hypotheses by examining the mismatch negativity (MMN) response in patients with cerebellar cortical atrophy and matched controls. While watching a silent movie, a stream of task-irrelevant sounds was presented. A standard sound was presented 60% of the time, whereas the remaining sounds deviated from the standard on one of four dimensions: duration, intensity, pitch, or location. The timing between stimuli was either periodic or aperiodic. Based on the sensory prediction hypothesis, the MMN for the patients should be abnormal across all four dimensions. In contrast, the timing hypothesis would predict a selective impairment of the duration MMN. Moreover, the timing hypothesis would also predict that the enhancement of the MMN observed in controls when the stimuli are presented periodically should be attenuated in the patients. Compared to controls, the patients exhibited a delayed latency in the MMN to duration deviants and a similar trend for the intensity deviants, while pitch and location MMNs did not differ between groups. Periodicity had limited and somewhat inconsistent effects. The present results are at odds with a general role for the cerebellum in sensory prediction and provide partial support for the timing hypothesis

Exploring neurophysiological markers of visual perspective taking: Methodological considerations

Rationale: For visual perspective taking (VPT) using the avatar task, examinations of neural processes using event related potentials (ERP) indicate a distinction between an early posterior perspective calculation process (P3) and a later frontal process (LFSW) managing perspective conflict. While it is unknown if these neural processes are affected in clinical populations, it is unclear if the avatar task can be applied to this group, due to the long duration and sensitivity to data loss. Thus, we performed a methodological study of the avatar task, testing the feasibility of a shortened experimental paradigm. Objective: To investigate whether previously reported behavioural and ERP effects in the avatar task can also be seen if analysing all trials (matching/non-matching) jointly, and whether they remain robust if only a subset of the data is analysed. Method: Healthy individuals (n = 20) completed the avatar task with ERP measurement. ERP components (P3, LFSW) and behavioural data were investigated by A) comparing use of only matching trials (n = 384) versus all trials (n = 768), and B) examining if reduced duration of assessment, by analysing only a subset of the data, impacts ERP findings. Results: We observed minimal differences when analysing data from only matching trial types compared to all trial types. Further, ERP amplitudes and latency findings were replicated when analysing only a subset of the data. Conclusions: The duration of the avatar task can be reduced to avoid long testing times, thus making it better suited for use in clinical populations

Neurophysiological Indicators of Residual Cognitive Capacity in the Minimally Conscious State

Background. The diagnostic usefulness of electrophysiological methods in assessing disorders of consciousness (DoC) remains to be established on an individual patient level, and there is need to determine what constitutes robust experimental paradigm to elicit electrophysiological indices of covert cognitive capacity. Objectives. Two tasks encompassing active and passive conditions were explored in an event-related potentials (ERP) study. The task robustness was studied in healthy controls, and their utility to detect covert signs of command-following on an individual patient level was investigated in patients in a minimally conscious state (MCS). Methods. Twenty healthy controls and 20 MCS patients participated. The active tasks included (1) listening for a change of pitch in the subject’s own name (SON) and (2) counting SON, both contrasted to passive conditions. Midline ERPs are reported. Results. A larger P3 response was detected in the counting task compared to active listening to pitch change in the healthy controls. On an individual level, the counting task revealed a higher rate of responders among both healthy subjects and MCS patients. Conclusion. ERP paradigms involving actively counting SON represent a robust paradigm in probing for volitional cognition in minimally conscious patients and add important diagnostic information in some patients

A history of previous childbirths is linked to women's white matter brain age in midlife and older age

Maternal brain adaptations occur in response to pregnancy, but little is known about how parity impacts white matter and white matter ageing trajectories later in life. Utilising global and regional brain age prediction based on multi-shell diffusion-weighted imaging data, we investigated the association between previous childbirths and white matter brain age in 8,895 women in the UK Biobank cohort (age range = 54–81 years). The results showed that number of previous childbirths was negatively associated with white matter brain age, potentially indicating a protective effect of parity on white matter later in life. Both global white matter and grey matter brain age estimates showed unique contributions to the association with previous childbirths, suggesting partly independent processes. Corpus callosum contributed uniquely to the global white matter association with previous childbirths, and showed a stronger relationship relative to several other tracts. While our findings demonstrate a link between reproductive history and brain white matter characteristics later in life, longitudinal studies are required to establish causality and determine how parity may influence women's white matter trajectories across the lifespan

Mapping the Heterogeneous Phenotype of Schizophrenia and Bipolar Disorder Using Normative Models

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A history of previous childbirths is linked to women's white matter brain age in midlife and older age

Maternal brain adaptations occur in response to pregnancy, but little is known about how parity impacts white matter and white matter ageing trajectories later in life. Utilising global and regional brain age prediction based on multi-shell diffusion-weighted imaging data, we investigated the association between previous childbirths and white matter brain age in 8,895 women in the UK Biobank cohort (age range = 54–81 years). The results showed that number of previous childbirths was negatively associated with white matter brain age, potentially indicating a protective effect of parity on white matter later in life. Both global white matter and grey matter brain age estimates showed unique contributions to the association with previous childbirths, suggesting partly independent processes. Corpus callosum contributed uniquely to the global white matter association with previous childbirths, and showed a stronger relationship relative to several other tracts. While our findings demonstrate a link between reproductive history and brain white matter characteristics later in life, longitudinal studies are required to establish causality and determine how parity may influence women's white matter trajectories across the lifespan

Probing brain developmental patterns of myelination and associations with psychopathology in youths using gray/white matter contrast

Background: Cerebral myeloarchitecture shows substantial development across childhood and adolescence, and aberrations in these trajectories are relevant for a range of mental disorders. Differential myelination between intracortical and subjacent white matter can be approximated using signal intensities in T1-weighted magnetic resonance imaging. Methods: To test the sensitivity of gray/white matter contrast (GWC) to age and individual differences in psychopathology and general cognitive ability in youths (8–23 years), we formed data-driven psychopathology and cognitive components using a large population-based sample, the Philadelphia Neurodevelopmental Cohort (N = 6487, 52% female). We then tested for associations with regional GWC defined by an independent component analysis in a subsample with available magnetic resonance imaging data (n = 1467, 53% female). Results: The analyses revealed a global GWC component, which showed an age-related decrease from late childhood and across adolescence. In addition, we found regional anatomically meaningful components with differential age associations explaining variance beyond the global component. When accounting for age and sex, both higher symptom levels of anxiety or prodromal psychosis and lower cognitive ability were associated with higher GWC in insula and cingulate cortices and with lower GWC in pre- and postcentral cortices. We also found several additional regional associations with anxiety, prodromal psychosis, and cognitive ability. Conclusions: Independent modes of GWC variation are sensitive to global and regional brain developmental processes, possibly related to differences between intracortical and subjacent white matter myelination, and individual differences in regional GWC are associated with both mental health and general cognitive functioning