Analysis of structural brain asymmetries in attention-deficit/hyperactivity disorder in 39 datasets.

OBJECTIVE: Some studies have suggested alterations of structural brain asymmetry in attention-deficit/hyperactivity disorder (ADHD), but findings have been contradictory and based on small samples. Here, we performed the largest ever analysis of brain left-right asymmetry in ADHD, using 39 datasets of the ENIGMA consortium. METHODS: We analyzed asymmetry of subcortical and cerebral cortical structures in up to 1,933 people with ADHD and 1,829 unaffected controls. Asymmetry Indexes (AIs) were calculated per participant for each bilaterally paired measure, and linear mixed effects modeling was applied separately in children, adolescents, adults, and the total sample, to test exhaustively for potential associations of ADHD with structural brain asymmetries. RESULTS: There was no evidence for altered caudate nucleus asymmetry in ADHD, in contrast to prior literature. In children, there was less rightward asymmetry of the total hemispheric surface area compared to controls (t = 2.1, p = .04). Lower rightward asymmetry of medial orbitofrontal cortex surface area in ADHD (t = 2.7, p = .01) was similar to a recent finding for autism spectrum disorder. There were also some differences in cortical thickness asymmetry across age groups. In adults with ADHD, globus pallidus asymmetry was altered compared to those without ADHD. However, all effects were small (Cohen's d from -0.18 to 0.18) and would not survive study-wide correction for multiple testing. CONCLUSION: Prior studies of altered structural brain asymmetry in ADHD were likely underpowered to detect the small effects reported here. Altered structural asymmetry is unlikely to provide a useful biomarker for ADHD, but may provide neurobiological insights into the trait.

The BOLD sensitivity of rapid steady-state sequences.

PURPOSE: Relaxation and dephasing of water protons embedded in a vascular network is driven by local magnetic field inhomogeneities around deoxygenated blood vessels. These effects strongly depend on the relation between mean diffusion length and diameter of blood vessels, as well as on the chosen imaging sequence. In this work, the BOLD sensitivity of steady-state sequences as a function of vessel size, field strength, and sequence parameters are analyzed. METHODS: Steady-state magnetization within a network of artificial cylinders is simulated with Monte Carlo methods for different coherence pathways. In addition, measurements on microspheres were performed to confirm theoretical results. RESULTS: Simulations and phantom results demonstrate a vessel size-dependent signal attenuation effect of all coherence pathways. Both the FID and ECHO pathways show a signal profile similar to spin echo sequences where in the static dephasing regime the effect of larger vessels is suppressed. CONCLUSION: The BOLD effect measured in steady-state sequences is most sensitive to microvessels and might therefore be closer to the underlying neuronal event compared to gradient echo sequences.

Neurobiology of knowledge and misperception of lyrics.

We conducted two functional magnetic resonance imaging (fMRI) experiments to investigate the neural underpinnings of knowledge and misperception of lyrics. In fMRI experiment 1, a linear relationship between familiarity with lyrics and activation was found in left-hemispheric speech-related as well as bilateral striatal areas which is in line with previous research on generation of lyrics. In fMRI experiment 2, we employed so called Mondegreens and Soramimi to induce misperceptions of lyrics revealing a bilateral network including middle temporal and inferior frontal areas as well as anterior cingulate cortex (ACC) and mediodorsal thalamus. ACC activation also correlated with the extent to which misperceptions were judged as amusing corroborating previous neuroimaging results on the role of this area in mediating the pleasant experience of chills during music perception. Finally, we examined the areas engaged during misperception of lyrics using diffusion-weighted imaging (DWI) to determine their structural connectivity. These combined fMRI/DWI results could serve as a neurobiological model for future studies on other types of misunderstanding which are events with potentially strong impact on our social life.

Gait decline while dual-tasking is an early sign of white matter deterioration in middle-aged and older adults.

Loss of white matter integrity (WMI) is associated with gait deficits in middle-aged and older adults. However, these deficits are often only apparent under cognitively demanding situations, such as walking and simultaneously performing a secondary cognitive task. Moreover, evidence suggests that declining executive functions (EF) are linked to gait decline, and their co-occurrence may point to a common underlying pathology, i.e., degeneration of shared brain regions. In this study, we applied diffusion tensor imaging (DTI) and a standardized gait assessment under single- and dual-tasking (DT) conditions (walking and subtracting) in 74 middle-aged and older adults without any significant gait or cognitive impairments to detect subtle WM alterations associated with gait decline under DT conditions. Additionally, the Trail Making Test (TMT) was used to assess EF, classify participants into three groups based on their performance, and examine a possible interaction between gait, EF, and WMI. Gait speed and subtracting speed while dual-tasking correlated significantly with the fractional anisotropy (FA) in the bilateral anterior corona radiata (highest r = 0.51/p < 0.0125 FWE-corrected). Dual-task costs (DTC) of gait speed correlated significantly with FA in widespread pathways, including the corpus callosum, bilateral anterior and superior corona radiata, as well as the left superior longitudinal fasciculus (highest r = -0.47/p < 0.0125 FWE-corrected). EF performance was associated with FA in the left anterior corona radiata (p < 0.05); however, EF did not significantly mediate the effects of WMI on DTC of gait speed. There were no significant correlations between TMT and DTC of gait and subtracting speed, respectively. Our findings indicate that gait decline under DT conditions is associated with widespread WM deterioration even in middle-aged and older adults without any significant gait or cognitive impairments. However, this relationship was not mediated by EF.

Distinct Relationship Between Cognitive Flexibility and White Matter Integrity in Individuals at Risk of Parkinson's Disease.

BACKGROUND AND OBJECTIVE: Executive dysfunction is the most common cognitive impairment in Parkinson's disease (PD), occurring even in its early stages. In our study, we applied diffusion tensor imaging (DTI) to investigate white matter integrity and its association with a specific executive function such as cognitive flexibility in individuals with risk factors for PD. METHODS: We examined 50 individuals with risk factors for developing PD and 24 healthy controls from the TREND (Tübinger Evaluation of Risk Factors for Early Detection of Neurodegeneration) study including neuropsychological evaluation and DTI. Cognitive flexibility was assessed using the trail making test (TMT). Tract based spatial statistics (TBSS) were employed to assess white matter abnormalities and their correlation with cognitive flexibility. RESULTS: TMT performance correlated with mean and axial diffusivity in several white matter regions, predominantly in the frontoparietal white matter. These effects were stronger in PD risk persons (PD-RP) than in controls as evidenced by a significant group interaction. White matter integrity and TMT performance did not significantly differ across groups. CONCLUSION: Based on our results, PD-RP do no exhibit white matter changes or impaired cognitive flexibility. However, specific executive functions in PD-RP are more related to white matter alterations than in healthy older adults.

Mondegreens and Soramimi as a method to induce misperceptions of speech content--influence of familiarity, wittiness, and language competence.

Expectations and prior knowledge can strongly influence our perception. In vision research, such top-down modulation of perceptual processing has been extensively studied using ambiguous stimuli, such as reversible figures. Here, we propose a novel method to address this issue in the auditory modality during speech perception by means of Mondgreens and Soramimi which represent song lyrics with the potential for misperception within one or across two languages, respectively. We demonstrate that such phenomena can be induced by visual presentation of the alternative percept and occur with a sufficient probability to exploit them in neuroscientific experiments. Song familiarity did not influence the occurrence of such altered perception indicating that this tool can be employed irrespective of the participants' knowledge of music. On the other hand, previous knowledge of the alternative percept had a strong impact on the strength of altered perception which is in line with frequent reports that these phenomena can have long-lasting effects. Finally, we demonstrate that the strength of changes in perception correlated with the extent to which they were experienced as amusing as well as the vocabulary of the participants as source of potential interpretations. These findings suggest that such perceptional phenomena might be linked to the pleasant experience of resolving ambiguity which is in line with the long-existing theory of Hermann von Helmholtz that perception and problem-solving recruit similar processes.