EEG microstates show different features in focal epilepsy and psychogenic nonepileptic seizures.

OBJECTIVE: Electroencephalography (EEG) microstate analysis seeks to cluster the scalp's electric field into semistable topographical EEG activity maps at different time points. Our study aimed to investigate the features of EEG microstates in subjects with focal epilepsy and psychogenic nonepileptic seizures (PNES). METHODS: We included 62 adult subjects with focal epilepsy or PNES who received video-EEG monitoring at the epilepsy monitoring unit. The subjects (mean age = 42.8 ± 21.2 years) were distributed equally between epilepsy and PNES groups. We extracted microstates from a 4.4 ± 1.0-min, 21-channel resting-state EEG. We excluded subjects with interictal epileptiform discharges during resting-state EEGs. After preprocessing, we derived five main EEG microstates-MS1 to MS5-for the full frequency band (1-30 Hz) and frequency subbands (delta, 1-4 Hz; theta, 4-8 Hz; alpha, 8-12 Hz; beta, 12-30 Hz), using the MATLAB-based EEGLAB toolkit. Statistical features of microstates (duration, occurrence, contribution, global field power [GFP]) were compared between the groups, using logistic regression corrected for age and sex. RESULTS: We detected no differences in microstate parameters in the full frequency band. We found a longer duration (delta: B = -7.680, p = .046; theta: B = -16.200, p = .043) and a higher contribution (delta: B = -7.414, p = .035; theta: B = -7.509, p = .031) of MS4 in lower frequency bands in the epilepsy group. The PNES group showed a higher occurrence of MS5 in the delta subband (B = 3.283, p = .032). In the theta subband, a higher GFP of MS1 was associated with the PNES group (B = 5.674, p = .025), whereas a higher GFP of MS2 was associated with the epilepsy group (B = -6.579, p = .026). SIGNIFICANCE: Microstate features show differences between patients with focal epilepsy and PNES. EEG microstates could be a promising parameter, helping to understand changes in brain dynamics in subjects with epilepsy, and should be explored as a potential biomarker.

How brain networks tic: Predicting tic severity through rs-fMRI dynamics in Tourette syndrome.

Tourette syndrome (TS) is a neuropsychiatric disorder characterized by motor and phonic tics, which several different theories, such as basal ganglia-thalamo-cortical loop dysfunction and amygdala hypersensitivity, have sought to explain. Previous research has shown dynamic changes in the brain prior to tic onset leading to tics, and this study aims to investigate the contribution of network dynamics to them. For this, we have employed three methods of functional connectivity to resting-state fMRI data - namely the static, the sliding window dynamic and the ICA based estimated dynamic; followed by an examination of the static and dynamic network topological properties. A leave-one-out (LOO-) validated regression model with LASSO regularization was used to identify the key predictors. The relevant predictors pointed to dysfunction of the primary motor cortex, the prefrontal-basal ganglia loop and amygdala-mediated visual social processing network. This is in line with a recently proposed social decision-making dysfunction hypothesis, opening new horizons in understanding tic pathophysiology.

The expectant brain-pregnancy leads to changes in brain morphology in the early postpartum period.

There is growing evidence that pregnancy may have a significant impact on the maternal brain, causing changes in its structure. To investigate the patterns of these changes, we compared nulliparous women (n = 40) with a group of primiparous women (n = 40) and multiparous mothers (n = 37) within 1-4 days postpartum, using voxel-based and surface-based morphometry (SBM). Compared with the nulliparous women, the young mothers showed decreases in gray matter volume in the bilateral hippocampus/amygdala, the orbitofrontal/subgenual prefrontal area, the right superior temporal gyrus and insula, and the cerebellum. These pregnancy-related changes in brain structure did not predict the quality of mother-infant attachment at either 3 or 12 weeks postpartum nor were they more pronounced among the multiparous women. SBM analyses showed significant cortical thinning especially in the frontal and parietal cortices, with the parietal cortical thinning likely potentiated by multiple pregnancies. We conclude that, compared with the brain of nulliparous women, the maternal brain shows widespread morphological changes shortly after childbirth. Also, the experience of pregnancy alone may not be the underlying cause of the adaptations for mothering. As regards the exact biological function of the changes in brain morphology, longitudinal research will be needed to draw any definitive conclusions.

Test-retest stability of spontaneous brain activity and functional connectivity in the core resting-state networks assessed with ultrahigh field 7-Tesla resting-state functional magnetic resonance imaging.

The growing demand for precise and reliable biomarkers in psychiatry is fueling research interest in the hope that identifying quantifiable indicators will improve diagnoses and treatment planning across a range of mental health conditions. The individual properties of brain networks at rest have been highlighted as a possible source for such biomarkers, with the added advantage that they are relatively straightforward to obtain. However, an important prerequisite for their consideration is their reproducibility. While the reliability of resting-state (RS) measurements has often been studied at standard field strengths, they have rarely been investigated using ultrahigh-field (UHF) magnetic resonance imaging (MRI) systems. We investigated the intersession stability of four functional MRI RS parameters-amplitude of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF; representing the spontaneous brain activity), regional homogeneity (ReHo; measure of local connectivity), and degree centrality (DC; measure of long-range connectivity)-in three RS networks, previously shown to play an important role in several psychiatric diseases-the default mode network (DMN), the central executive network (CEN), and the salience network (SN). Our investigation at individual subject space revealed a strong stability for ALFF, ReHo, and DC in all three networks, and a moderate level of stability in fALFF. Furthermore, the internetwork connectivity between each network pair was strongly stable between CEN/SN and moderately stable between DMN/SN and DMN/SN. The high degree of reliability and reproducibility in capturing the properties of the three major RS networks by means of UHF-MRI points to its applicability as a potentially useful tool in the search for disease-relevant biomarkers.

mGluR5 and GABAA receptor-specific parametric PET atlas construction-PET/MR data processing pipeline, validation, and application.

The glutamate and γ-aminobutyric acid neuroreceptor subtypes mGluR5 and GABAA are hypothesized to be involved in the development of a variety of psychiatric diseases. However, detailed information relating to their in vivo distribution is generally unavailable. Maps of such distributions could potentially aid clinical studies by providing a reference for the normal distribution of neuroreceptors and may also be useful as covariates in advanced functional magnetic resonance imaging (MR) studies. In this study, we propose a comprehensive processing pipeline for the construction of standard space, in vivo distributions of non-displaceable binding potential (BPND ), and total distribution volume (VT ) based on simultaneously acquired bolus-infusion positron emission tomography (PET) and MR data. The pipeline was applied to [11 C]ABP688-PET/MR (13 healthy male non-smokers, 26.6 ± 7.0 years) and [11 C]Flumazenil-PET/MR (10 healthy males, 25.8 ± 3.0 years) data. Activity concentration templates, as well as VT and BPND atlases of mGluR5 and GABAA , were generated from these data. The maps were validated by assessing the percent error δ from warped space to native space in a selection of brain regions. We verified that the average δABP  = 3.0 ± 1.0% and δFMZ  = 3.8 ± 1.4% were lower than the expected variabilities σ of the tracers (σABP  = 4.0%-16.0%, σFMZ  = 3.9%-9.5%). An evaluation of PET-to-PET registrations based on the new maps showed higher registration accuracy compared to registrations based on the commonly used [15 O]H2 O-template distributed with SPM12. Thus, we conclude that the resulting maps can be used for further research and the proposed pipeline is a viable tool for the construction of standardized PET data distributions.

A meta-analysis on shared and distinct neural correlates of the decision-making underlying altruistic and retaliatory punishment.

Individuals who violate social norms will most likely face social punishment sanctions. Those sanctions are based on different motivation aspects, depending on the context. Altruistic punishment occurs if punishment aims to re-establish the social norms even at cost for the punisher. Retaliatory punishment is driven by anger or spite and aims to harm the other. While neuroimaging research highlighted the neural networks supporting decision-making in both types of punishment in isolation, it remains unclear whether they rely on the same or distinct neural systems. We ran an activation likelihood estimation meta-analysis on functional magnetic resonance imaging data on 24 altruistic and 19 retaliatory punishment studies to investigate the neural correlates of decision-making underlying social punishment and whether altruistic and retaliatory punishments share similar brain networks. Social punishment reliably activated the bilateral insula, inferior frontal gyrus, midcingulate cortex (MCC), and superior and medial frontal gyri. This network largely overlapped with activation clusters found for altruistic punishment. However, retaliatory punishment revealed only one cluster in a posterior part of the MCC, which was not recruited in altruistic punishment. Our results support previous models on social punishment and highlight differential involvement of the MCC in altruistic and retaliatory punishments, reflecting the underlying different motivations.

Comparison of EEG microstates with resting state fMRI and FDG-PET measures in the default mode network via simultaneously recorded trimodal (PET/MR/EEG) data.

Simultaneous trimodal positron emission tomography/magnetic resonance imaging/electroencephalography (PET/MRI/EEG) resting state (rs) brain data were acquired from 10 healthy male volunteers. The rs-functional MRI (fMRI) metrics, such as regional homogeneity (ReHo), degree centrality (DC) and fractional amplitude of low-frequency fluctuations (fALFFs), as well as 2-[18F]fluoro-2-desoxy-d-glucose (FDG)-PET standardised uptake value (SUV), were calculated and the measures were extracted from the default mode network (DMN) regions of the brain. Similarly, four microstates for each subject, showing the diverse functional states of the whole brain via topographical variations due to global field power (GFP), were estimated from artefact-corrected EEG signals. In this exploratory analysis, the GFP of microstates was nonparametrically compared to rs-fMRI metrics and FDG-PET SUV measured in the DMN of the brain. The rs-fMRI metrics (ReHO, fALFF) and FDG-PET SUV did not show any significant correlations with any of the microstates. The DC metric showed a significant positive correlation with microstate C (rs  = 0.73, p = .01). FDG-PET SUVs indicate a trend for a negative correlation with microstates A, B and C. The positive correlation of microstate C with DC metrics suggests a functional relationship between cortical hubs in the frontal and occipital lobes. The results of this study suggest further exploration of this method in a larger sample and in patients with neuropsychiatric disorders. The aim of this exploratory pilot study is to lay the foundation for the development of such multimodal measures to be applied as biomarkers for diagnosis, disease staging, treatment response and monitoring of neuropsychiatric disorders.

Bolus infusion scheme for the adjustment of steady state [11C]Flumazenil levels in the grey matter and in the blood plasma for neuroreceptor imaging.

The use of hybrid PET/MR imaging facilitates the simultaneous investigation of challenge-related changes in ligand binding to neuroreceptors using PET, while concurrently measuring neuroactivation or blood flow with MRI. Having attained a steady state of the PET radiotracer using a bolus-infusion protocol, it is possible to observe alterations in ligand neuroreceptor binding through changes in distribution volumes. Here, we present an iterative procedure for establishing an administration scheme to obtain steady state [11C]flumazenil concentrations in grey matter in the human brain. In order to achieve a steady state in the shortest possible time, the bolus infusion ratio from a previous examination was adapted to fit the subsequent examination. 17 male volunteers were included in the study. Boli and infusions with different weightings were given to the subjects and were characterised by kbol values from 74 â€‹min down to 42 â€‹min. Metabolite analysis was used to ascertain the value of unmetabolised flumazenil in the plasma, and PET imaging was used to assess its binding in the grey matter. The flumazenil time-activity curves (TACs) in the brain were decomposed into activity contributions from pure grey and white matter and analysed for 12 â€‹vol of interest (VOIs). The curves highlighted a large variability in metabolic rates between the subjects, with kbol â€‹= â€‹54.3 â€‹min being a reliable value to provide flumazenil equilibrium conditions in the majority of the VOIs and cases. The distribution volume of flumazenil in all 12 VOIs was determined.

mGluR5 receptor availability is associated with lower levels of negative symptoms and better cognition in male patients with chronic schizophrenia.

Consistent findings postulate disturbed glutamatergic function (more specifically a hypofunction of the ionotropic NMDA receptors) as an important pathophysiologic mechanism in schizophrenia. However, the role of the metabotropic glutamatergic receptors type 5 (mGluR5) in this disease remains unclear. In this study, we investigated their significance (using [11 C]ABP688) for psychopathology and cognition in male patients with chronic schizophrenia and healthy controls. In the patient group, lower mGluR5 binding potential (BPND ) values in the left temporal cortex and caudate were associated with higher general symptom levels (negative and depressive symptoms), lower levels of global functioning and worse cognitive performance. At the same time, in both groups, mGluR5 BPND were significantly lower in smokers (F[27,1] = 15.500; p = .001), but without significant differences between the groups. Our findings provide support for the concept that the impaired function of mGluR5 underlies the symptoms of schizophrenia. They further supply a new perspective on the complex relationship between tobacco addiction and schizophrenia by identifying glutamatergic neurotransmission-in particularly mGluR5-as a possible connection to a shared vulnerability.

Self-enucleation of the right eye by a 38-year-old woman diagnosed with schizoaffective disorder: a case report.

BACKGROUND: Autoenucleation is a rare form of self-mutilation typically associated with psychiatric disorders such as schizophrenia, substance-induced psychosis and bipolar disorder. The act is usually unilateral, although bilateral attempts are also well documented in the literature. CASE PRESENTATION: It is a case study involving a female patient (NN) diagnosed with schizoaffective disorder who self-enucleated her right eye following sexual intercourse with a fellow patient, and was forcefully prevented by staff from enucleating the second eye. We report recurrent episodes of her illness culminating in this severe act of self-mutilation. The motivational reasons behind this form of self-harm along with differential diagnosis and potential treatment options are discussed in the context of the available literature. CONCLUSION: Autoenucleation is commonly associated with religious and sexual delusions, and patients are thought to be at a greater risk of further self-harm. Timely antipsychotic treatment is likely to reduce the risk of such extreme forms of self-harm, although they can occur despite robust therapeutic intervention and treatment attempts. While self-inflicted eye injuries are rare, their prevention in what is typically a difficult patient group is fraught with challenges.

Functional connectivity of supplementary motor area during finger-tapping in major depression.

Psychomotor disturbance has been consistently regarded as an essential feature of depressive disorders. Studying objectively measurable motor behaviors like finger-tapping may help advance the diagnostic methods. Twenty-five patients with major depressive disorder (MDD) and 15 healthy participants underwent functional magnetic resonance imaging (fMRI) measurements while tapping their index fingers. The finger-tapping (FT) task was performed by the right hand (the tapping frequency varied between 1, 2 and 4 Hz) or both hands either in synchrony or alternation (the tapping frequency varied between 1 and 2 Hz). A mixed-model ANOVA was used for between- and within-group comparisons of the task accuracy and fMRI percent signal change in the supplementary motor area (SMA) during 26-second sequences of finger-tapping. Furthermore, using seed-based correlation analyses we compared the connectivity of the SMA between the two samples. At the behavioral level, no significant group differences in FT performance between the patient and control groups was observed. The mean fMRI percent signal change of the SMA was significantly elevated at higher levels of speed in both groups. In the MDD group, an increased connectivity of the left SMA with the bilateral cortical and cerebellar motor- and vision-related regions was found. Most importantly, a decreased connectivity between the SMA and the basal ganglia was found at frequencies of 4 Hz. Our findings support the contention that, in depression, brain connectivity measures during motor performance may reveal deviant neural processes that are potentially relevant to measurable (bio)markers for individual diagnosis and treatment.

Association between Cortical GABA and Loudness Dependence of Auditory Evoked Potentials (LDAEP) in Humans.

Loudness dependence of auditory evoked potentials (LDAEP) is a widely used EEG-based biomarker for central serotonergic activity. Serotonin has been shown to be associated with different psychiatric disorders such as depression and schizophrenia. Despite its clinical significance, the underlying neurochemical mechanism of this promising marker is not fully understood, and further research is needed to improve its validity. Other neurotransmitters might have a significant impact on this measure. Thus, we assessed the inhibitory action through individual GABA/H20 concentrations and GABA/glutamate ratios by means of magnetic resonance spectroscopy at 3T in healthy subjects. The measurements were assessed in the primary auditory cortex to investigate the association with the LDAEP, whose generators are mainly in the primary auditory cortex. For the first time, this study examines the link between GABAergic neurotransmission and LDAEP, and the data preliminary show that GABA may not contribute to the generation of EEG-based LDAEP.

Diffusion kurtosis metrics as biomarkers of microstructural development: A comparative study of a group of children and a group of adults.

The most common modality of diffusion MRI used in the ageing and development studies is diffusion tensor imaging (DTI) providing two key measures, fractional anisotropy and mean diffusivity. Here, we investigated diffusional changes occurring between childhood (average age 10.3 years) and mitddle adult age (average age 54.3 years) with the help of diffusion kurtosis imaging (DKI), a recent novel extension of DTI that provides additional metrics quantifying non-Gaussianity of water diffusion in brain tissue. We performed voxelwise statistical between-group comparison of diffusion tensor and kurtosis tensor metrics using two methods, namely, the tract-based spatial statistics (TBSS) and the atlas-based regional data analysis. For the latter, fractional anisotropy, mean diffusivity, mean diffusion kurtosis, and other scalar diffusion tensor and kurtosis tensor parameters were evaluated for white matter fibres provided by the Johns-Hopkins-University Atlas in the FSL toolkit (http://fsl.fmrib.ox.ac.uk/fsl/fslwiki/Atlases). Within the same age group, all evaluated parameters varied depending on the anatomical region. TBSS analysis showed that changes in kurtosis tensor parameters beyond adolescence are more widespread along the skeleton in comparison to the changes of the diffusion tensor metrics. The regional data analysis demonstrated considerably larger between-group changes of the diffusion kurtosis metrics than of diffusion tensor metrics in all investigated regions. The effect size of the parametric changes between childhood and middle adulthood was quantified using Cohen's d. We used Cohen's d related to mean diffusion kurtosis to examine heterogeneous maturation of various fibres. The largest changes of this parameter (interpreted as reflecting the lowest level of maturation by the age of children group) were observed in the association fibres, cingulum (gyrus) and cingulum (hippocampus) followed by superior longitudinal fasciculus and inferior longitudinal fasciculus. The smallest changes were observed in the commissural fibres, forceps major and forceps minor. In conclusion, our data suggest that DKI is sensitive to developmental changes in local microstructure and environment, and is particularly powerful to unravel developmental differences in major association fibres, such as the cingulum and superior longitudinal fasciculus.

GABA metabolism and its role in gamma-band oscillatory activity during auditory processing: An MRS and EEG study.

Gamma-aminobutyric acid (GABA) and glutamate are believed to have inhibitory and exhibitory neuromodulatory effects that regulate the brain's response to sensory perception. Furthermore, frequency-specific synchronization of neuronal excitability within the gamma band (30-80 Hz) is attributable to a homeostatic balance between excitation and inhibition. However, our understanding of the physiological mechanism underlying gamma rhythms is based on animal models. Investigations of the relationship between GABA concentrations, glutamate concentrations, and gamma band activity in humans were mostly restricted to the visual cortex and are conflicting. Here, we performed a multimodal imaging study combining magnetic resonance spectroscopy (MRS) with electroencephalography (EEG) in the auditory cortex. In 14 healthy subjects, we investigated the impact of individual differences in GABA and glutamate concentration on gamma band response (GBR) following auditory stimulus presentation. We explored the effects of bulk GABA on the GBR across frequency (30-200 Hz) and time (-200 to 600 ms) and found no significant relationship. Furthermore, no correlations were found between gamma peak frequency or power measures and metabolite concentrations (GABA, glutamate, and GABA/glutamate ratio). These findings suggest that, according to MRS measurements, and given the auditory stimuli used in this study, GABA and glutamate concentrations are unlikely to play a significant role in the inhibitory and excitatory drive in the generation of gamma band activity in the auditory cortex. Hum Brain Mapp 38:3975-3987, 2017. © 2017 Wiley Periodicals, Inc.

Microstructural and functional correlates of glutamate concentration in the posterior cingulate cortex.

Glutamate is the major excitatory neurotransmitter in the human brain and has a central role in both intrinsic and stimulus-induced activity. We conducted a study in a cohort of healthy, male volunteers in which glutamate levels were measured in the posterior cingulate cortex (PCC) using 1H magnetic resonance spectroscopy at 3T. The advantages of simultaneous electroencephalography and magnetic resonance imaging (EEG-MRI) were exploited and the subjects were measured in the same session and under the same physiological conditions. Diffusion tensor imaging (DTI), functional MRI (fMRI) and EEG were measured in order to investigate the functional and microstructural correlates of glutamate. The concentration of glutamate (institute units) was calculated and those values were tested for correlation with the metrics of resting state fMRI, DTI, and EEG electrical sources. Our results showed that the concentration of glutamate in the PCC had a significant negative correlation with the tissue mean diffusivity in the same area. The analysis of resting state networks did not show any relationship between the concentration of glutamate and the intrinsic activity of the resting state networks. The concentration of glutamate showed a positive correlation with the electrical generators of α-1 frequency and a negative correlation with the generators of α-2 and ß-1 electrical generators. © 2017 Wiley Periodicals, Inc.

Attention to detail: why considering task demands is essential for single-trial analysis of BOLD correlates of the visual P1 and N1.

Single-trial fluctuations in the EEG signal have been shown to temporally correlate with the fMRI BOLD response and are valuable for modeling trial-to-trial fluctuations in responses. The P1 and N1 components of the visual ERP are sensitive to different attentional modulations, suggesting that different aspects of stimulus processing can be modeled with these ERP parameters. As such, different patterns of BOLD covariation for P1 and N1 informed regressors would be expected; however, current findings are equivocal. We investigate the effects of variations in attention on P1 and N1 informed BOLD activation in a visual oddball task. Simultaneous EEG-fMRI data were recorded from 13 healthy participants during three conditions of a visual oddball task: Passive, Count, and Respond. We show that the P1 and N1 components of the visual ERP can be used in the integration-by-prediction method of EEG-fMRI data integration to highlight brain regions related to target detection and response production. Our data suggest that the P1 component of the ERP reflects changes in sensory encoding of stimulus features and is more informative for the Passive and Count conditions. The N1, on the other hand, was more informative for the Respond condition, suggesting that it can be used to model the processing of stimulus, meaning specifically discriminating one type of stimulus from another, and processes involved in integrating sensory information with response selection. Our results show that an understanding of the underlying electrophysiology is necessary for a thorough interpretation of EEG-informed fMRI analysis.

Simultaneous EEG-fMRI acquisition at low, high and ultra-high magnetic fields up to 9.4 T: perspectives and challenges.

In this perspectives article we highlight the advantages of simultaneous acquisition of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). As MRI moves towards using ultra-high magnetic fields in the quest for increased signal-to-noise, the question arises whether combined EEG-fMRI measurements are feasible at magnetic fields of 7 T and higher. We describe the challenges of MRI-EEG at 1.5, 3, 7 and 9.4 T and review the proposed solutions. In an outlook, we discuss further developments such as simultaneous trimodal imaging using MR, positron emission tomography (PET) and EEG under the same physiological conditions in the same subject.

[Tourette syndrome and other tic disorders in DSM-5 ­ a comment]. / DSM-5 Kommentar: Tourette Syndrom und andere Tic-Störungen im DSM-5.

The classification of tic disorders has been revised in the new fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). The previously expressed suggestion to categorize tic disorders within the "Anxiety and Obsessive Compulsive Disorders" was not implemented. The section "Disorders Usually First Diagnosed in Infancy, Childhood, or Adolescence" was revised and renamed as "Neurodevelopmental Disorders." Tic disorders are classified there as movement disorders. Most of the changes are distinct improvements from both a clinical and a scientific perspective. For example, by removing the adjective "stereotype," the definition of tics is more precise and unified. Also, the new time-oriented criteria are more practical in the clinical setting, e.g., the exclusion criterion of a tic-free interval more than 3 months given for chronic tic disorders has been deleted. The renamings from "Transient" to "Provisional Tic Disorder" as well as from "Chronic" to "Persistent Tic Disorder" are welcome changes from a clinical perspective. Overall, the revision of the criteria is an important step towards providing more clarity and feasibility. However, the revised classification of tic disorders is still based only on clinical experience and not on evidence. Future studies should show whether the revised and improved criteria truly provide the optimal classification.

Aberrant Functional Connectivity of the Salience Network in Adult Patients with Tic Disorders: A Resting-State fMRI Study.

Tic disorders (TD) are characterized by the presence of motor and/or vocal tics. Common neurophysiological frameworks suggest dysregulations of the cortico-striatal-thalamo-cortical (CSTC) brain circuit that controls movement execution. Besides common tics, there are other "non-tic" symptoms that are primarily related to sensory perception, sensorimotor integration, attention, and social cognition. The existence of these symptoms, the sensory tic triggers, and the modifying effect of attention and cognitive control mechanisms on tics may indicate the salience network's (SN) involvement in the neurophysiology of TD. Resting-state functional MRI measurements were performed in 26 participants with TD and 25 healthy controls (HC). The group differences in resting-state functional connectivity patterns were measured based on seed-to-voxel connectivity analyses. Compared to HC, patients with TD exhibited altered connectivity between the core regions of the SN (insula, anterior cingulate cortex, and temporoparietal junction) and sensory, associative, and motor-related cortices. Furthermore, connectivity changes were observed in relation to the severity of tics in the TD group. The SN, particularly the insula, is likely to be an important site of dysregulation in TD. Our results provide evidence for large-scale neural deviations in TD beyond the CSTC pathologies. These findings may be relevant for developing treatment targets.

Spatiotemporal Patterns of White Matter Maturation after Pre-Adolescence: A Diffusion Kurtosis Imaging Study.

Diffusion tensor imaging (DTI) enables the assessment of changes in brain tissue microstructure during maturation and ageing. In general, patterns of cerebral maturation and decline render non-monotonic lifespan trajectories of DTI metrics with age, and, importantly, the rate of microstructural changes is heterochronous for various white matter fibres. Recent studies have demonstrated that diffusion kurtosis imaging (DKI) metrics are more sensitive to microstructural changes during ageing compared to those of DTI. In a previous work, we demonstrated that the Cohen's d of mean diffusional kurtosis (dMK) represents a useful biomarker for quantifying maturation heterochronicity. However, some inferences on the maturation grades of different fibre types, such as association, projection, and commissural, were of a preliminary nature due to the insufficient number of fibres considered. Hence, the purpose of this follow-up work was to further explore the heterochronicity of microstructural maturation between pre-adolescence and middle adulthood based on DTI and DKI metrics. Using the effect size of the between-group parametric changes and Cohen's d, we observed that all commissural fibres achieved the highest level of maturity, followed by the majority of projection fibres, while the majority of association fibres were the least matured. We also demonstrated that dMK strongly correlates with the maxima or minima of the lifespan curves of DTI metrics. Furthermore, our results provide substantial evidence for the existence of spatial gradients in the timing of white matter maturation. In conclusion, our data suggest that DKI provides useful biomarkers for the investigation of maturation spatial heterogeneity and heterochronicity.