Depressed patients with childhood maltreatment display altered intra- and inter-network resting state functional connectivity.

BACKGROUND: Childhood maltreatment (CM) is a major risk factor for the development of major depressive disorder (MDD). To gain more knowledge on how adverse childhood experiences influence the development of brain architecture, we studied functional connectivity (FC) alterations of neural networks of depressed patients with, or without the history of CM. METHODS: Depressed patients with severe childhood maltreatment (n = 18), MDD patients without maltreatment (n = 19), and matched healthy controls (n = 20) were examined with resting state functional MRI. History of maltreatment was assessed with the 28-item Childhood Trauma Questionnaire. Intra- and inter-network FC alterations were evaluated using FMRIB Software Library and CONN toolbox. RESULTS: We found numerous intra- and inter-network FC alterations between the maltreated and the non-maltreated patients. Intra-network FC differences were found in the default mode, visual and auditory networks, and cerebellum. Network modelling revealed several inter-network FC alterations connecting the default mode network with the executive control, salience and cerebellar networks. Increased inter-network FC was found in maltreated patients between the sensory-motor and visual, cerebellar, default mode and salience networks. LIMITATIONS: Relatively small sample size, cross-sectional design, and retrospective self-report questionnaire to assess adverse childhood experiences. CONCLUSIONS: Our findings confirm that severely maltreated depressed patients display numerous alterations of intra- and inter-network FC strengths, not only in their fronto-limbic circuits, but also in sensory-motor, visual, auditory, and cerebellar networks. These functional alterations may explain that maltreated individuals typically display altered perception and are prone to develop functional neurological symptom disorder (conversion disorder) in adulthood.

Differentiation of hemispheric white matter lesions in migraine and multiple sclerosis with similar radiological features using advanced MRI.

Background and aim: White matter hyperintensities (WMHs), presented on T2-weighted or fluid-attenuated inversion recovery magnetic resonance imaging (MRI) sequences, are lesions in the human brain that can be observed in both migraine and multiple sclerosis (MS). Methods: Seventeen migraine patients and 15 patients with relapsing-remitting multiple sclerosis with WMHs, and 17 healthy subjects age-and sex-matched to the migraine group were prospectively enrolled and underwent conventional and advanced MRI studies with diffusion-and perfusion-weighted imaging and single voxel proton magnetic resonance spectroscopy. Results: In both disease groups, elevated T2 relaxation time, apparent diffusion coefficient (ADC) values, and decreased N-acetyl-aspartate levels were found in the intralesional white matter compared to the contralateral normal-appearing white matter (NAWM), while there was no difference between the hemispheres of the control subjects. Migraine patients had the lowest intralesional creatine + phosphocreatine and myo-inositol (mI) values among the three groups, while patients with MS showed the highest intralesional T1 and T2 relaxation times, ADC, and mI values. In the contralateral NAWM, the same trend with mI changes was observed in migraineurs and MS patients. No differences in perfusion variables were observed in any groups. Conclusion: Our multimodal study showed that tissue damage is detectable in both diseases. Despite the differences in various advanced MRI measures, with more severe injury detected in MS lesions, we could not clearly differentiate the two white matter lesion types.

Volumetric alteration of brainstem in female migraineurs with and without aura.

BACKGROUND AND AIM: Brainstem descending modulatory circuits have been postulated to be involved in migraine. Differences in brainstem volume between migraineurs and healthy controls have been demonstrated in previous research, nevertheless, the effect of migraine aura on brainstem volume is still uncertain. The aim of this study was to investigate the brainstem volume in migraineurs and examine the effect of migraine aura on brainstem volume. METHODS: Our study included 90 female migraine patients without white matter lesions. (29 migraine patients with aura (MwA) and 61 migraine patients without aura (MwoA) and 32 age-matched female healthy controls (HC). Using the FreeSurfer image analysis suite, the volumes of the entire brainstem and its subfields (medulla, pons, and midbrain) were measured and compared between migraine subgroups (MwA vs. MwoA) and the healthy control group. The possible effects of migraine characteristics (i.e., disease duration and migraine attack frequency) on brainstem volume were also investigated. RESULTS: Migraineurs had greater medulla volume (MwoA 3552 ± 459 mm3, MwA 3424 ± 448 mm3) than healthy controls (3236 ± 411 mm3). Statistically, MwA vs. HC p = 0.040, MwoA vs. HC p = 0.002, MwA vs. MwoA p = 0.555. A significant positive correlation was found between disease duration and the volume of medulla in the whole migraine group (r = 0.334, p = 0.001). Neither the whole brainstem nor its subfields were significantly different in volume between migraine subgroups. CONCLUSION: Brainstem volume changes in migraine are mainly localized to the medulla and not specific to the presence of aura.

Altered functional brain networks in problematic smartphone and social media use: resting-state fMRI study.

Nowadays, the limitless availability to the World Wide Web can lead to general Internet misuse and dependence. Currently, smartphone and social media use belong to the most prevalent Internet-related behavioral addiction forms. However, the neurobiological background of these Internet-related behavioral addictions is not sufficiently explored. In this study, these addiction forms were assessed with self-reported questionnaires. Resting-state functional magnetic resonance imaging was acquired for all participants (n = 59, 29 males) to examine functional brain networks. The resting-state networks that were discovered using independent component analysis were analyzed to estimate within network differences. Significant negative associations with social media addiction and smartphone addiction were found in the language network, the lateral visual networks, the auditory network, the sensorimotor network, the executive network and the frontoparietal network. These results suggest that problematic smartphone and social media use are associated with sensory processing and higher cognitive functioning.

The volume of the thalamus and hippocampus in a right-handed female episodic migraine group.

Background/aim: Migraine is a disabling headache with clinical and radiological complications. The aim of this study was to investigate the volume of the thalamus and hippocampus in migraineurs, the role of white matter lesions (WMLs), and the migraine characteristics in volume changes. Methods: Brain MRIs of 161 right-handed female episodic migraine patients and 40 right-handed, age-related, healthy women were performed. Left and right thalamus segmentation was performed on the 3D MPRAGE images using the Freesurfer 5.3 image analysis suite. Hippocampal subfield segmentation was based on a novel statistical atlas built primarily upon ultra-high-resolution ex vivo MRI data. Results: The left hippocampus had a smaller and the left thalamus had a larger total volume than the right one in both the control (p < 0.001) and migraine groups (p <0.001). Patients with white matter lesions (L+) showed smaller right thalamus and right hippocampal tail volumes than patients without lesions (L-) (p = 0.002 and p = 0.015, respectively) and controls (p = 0.039 and p = 0.025, respectively). For the right hippocampal body, we found significantly smaller volume in L+ patients when compared to L- patients (p = 0.018) and a similar trend when compared to the control group (p = 0.064). Patients without aura (A-) showed a larger right hippocampus (p = 0.029), right hippocampal body (p = 0.012), and tail volumes (p = 0.011) than patients with aura (A+). Inverse correlations were found between attack frequency and the volumes of the left and right hippocampal tails (p = 0.018 and p = 0.008, respectively). Conclusion: These findings indicate that WMLs may influence the volume of the right thalamus and hippocampus, while migraine aura and attack frequency may lead to volume changes in different parts of the hippocampi in migraine patients. These data support the necessity of effective migraine management to limit subcortical volume loss in migraineurs.

Circulating microRNAs correlate with structural and functional MRI parameters in patients with multiple sclerosis.

Introduction: Circulating microRNAs are promising biomarkers for multiple sclerosis (MS). Our aim was to correlate serum microRNA levels with various magnetic resonance imaging (MRI) parameters. Methods: We recruited 50 MS patients and measured cervical spine and cerebral white matter lesions together with regional brain volumes. Microstructural changes in the white matter were investigated with diffusion tensor imaging. Magnetic resonance spectroscopy was performed to measure cerebral metabolites. Functional connectivity within the default mode network was examined with resting-state functional MRI. On the day of the MRI measurements, we collected serum samples and carried out quantitative analysis of ten pre-selected microRNAs using droplet digital PCR. Results: Serum level of miR-143.3p could differentiate between MS subtypes and had lower levels in progressive MS types. We found significant associations between microRNA levels and MRI measures: (1) higher miR-92a.3p and miR-486.5p levels were associated with greater total white matter lesion volumes within the cervical spine, (2) decreased miR-142.5p levels was associated with reduced total creatinine concentration and (3) miR-92a.3p, miR-142.5p and miR-486.5p levels were associated with functional connectivity strengths between specific nodes of the default mode network. Specifically, we found a negative association between miR-92a.3p and miR-486.5p levels and connectivity strength between the lateral temporal cortex and posterior inferior parietal lobule, and a positive association between miR-142.5p level and connectivity strength between the retrosplenial cortex and temporal pole. However, miRNA levels were not associated with regional brain volumes. Conclusion: We provide here further evidence that circulating microRNAs may show correlation with both structural and functional neuroimaging outcomes in patients with MS.

Gray Matter Changes Following Mild COVID-19: An MR Morphometric Study in Healthy Young People.

BACKGROUND: Although COVID-19 is primarily an acute respiratory infection, 5%-40% of patients develop late and prolonged symptoms with frequent neurological complaints, known as long COVID syndrome. The presentation of the disease suggests that COVID infection may cause functional and/or morphological central nervous system alterations, but studies published in the literature report contradictory findings. PURPOSE: To investigate the chronic effects of COVID-19 on cerebral grey matter in a group of young patients without comorbidities, with mild course of COVID infection and no medical complaints at the time of examination. STUDY TYPE: Prospective. POPULATION: Thirty-eight young (age = 26.6 ± 5.0 years; male/female = 14/24), adult participants who recovered from mild COVID infection without a history of clinical long COVID and 37 healthy control subjects (age = 25.9 ± 2.8 years; male/female = 14/23). FIELD STRENGTH/SEQUENCE: Three Tesla, 3D T1-weighted magnetization-prepared rapid gradient-echo, 2D T2-weighted turbo spin-echo. ASSESSMENT: MRI-based morphometry and volumetry along with neuropsychological testing and self-assessed questionnaire. STATISTICAL TESTS: Fisher's exact test, Mann-Whitney U-test, and multiple linear regression analyses were used to assess differences between COVID and healthy control groups. P < 0.05 was used as cutoff for significance. RESULTS: In the COVID group, significantly lower bilateral mean cortical thickness (left/right-hemisphere: 2.51 ± 0.06 mm vs. 2.56 ± 0.07 mm, η2 p = 0.102/2.50 ± 0.06 mm vs. 2.54 ± 0.07 mm, η2 p = 0.101), lower subcortical gray matter (57881 ± 3998 mm3 vs. 60470 ± 5211 mm3 , η2 p = 0.100) and lower right olfactory bulb volume (52.28 ± 13.55 mm3 vs. 60.98 ± 15.8 mm3 , η2 p = 0.078) were found. In patients with moderate to severe anosmia, cortical thickness was significantly lower bilaterally, as compared to patients without olfactory function loss (left/right-hemisphere: 2.50 ± 0.06 mm vs. 2.56 ± 0.05 mm, η2 = 0.173/2.49 ± 0.06 mm vs. 2.55 ± 0.05 mm, η2 = 0.189). Using further exploratory analysis, significantly reduced cortical thickness was detected locally in the right lateral orbitofrontal cortex in the COVID group (2.53 ± 0.10 mm vs. 2.60 ± 0.09 mm, η2 p = 0.112). DATA CONCLUSION: Even without any subjective or objective neurological complaints at the time of the MR scan, subjects in the COVID group showed gray matter alterations in cortical thickness and subcortical gray matter volume. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 3.

White matter hyperintensities associated with impulse control disorders in Parkinson's Disease.

Impulse control disorders (ICDs) in Parkinson's disease (PD) are increasingly recognized as clinically significant non-motor features that potentially impair the quality of life. White matter hyperintensities (WMHs), detected by magnetic resonance imaging, are frequently observed in PD and can be associated with both motor- and certain non-motor symptoms. Given the limited number of non-motor features studied in this context, our aim was to reveal the potential association between the severity of WMHs and ICDs in PD. Fluid-attenuated inversion recovery magnetic resonance images were retrospectively evaluated in 70 patients with PD (48 males; 59.3 ± 10.1 years). The severity of WMHs was assessed by Fazekas scores and by the volume and number of supratentorial WMHs. ICDs were evaluated using the modified Minnesota Impulsive Disorders Interview. Significant interaction between age and the severity of WMHs was present for ICDs. In our younger patients (< 60.5 years), severity of WMHs was positively associated with ICDs (p = 0.004, p = 0.021, p < 0.001 and p < 0.001, respectively for periventricular white matter and total Fazekas scores and the volume and number of WMHs). Our study supports the hypothesis that WMHs of presumed vascular origin may contribute to ICDs in PD. Future prospective studies are needed to assess the prognostic relevance of this finding.

Post-reperfusion acute MR diffusion in stroke is a potential predictor for clinical outcome in rats.

Middle cerebral artery occlusion (MCAO) models show substantial variability in outcome, introducing uncertainties in the evaluation of treatment effects. Early outcome predictors would be essential for prognostic purposes and variability control. We aimed to compare apparent diffusion coefficient (ADC) MRI data obtained during MCAO and shortly after reperfusion for their potentials in acute-phase outcome prediction. Fifty-nine male rats underwent a 45-min MCAO. Outcome was defined in three ways: 21-day survival; 24 h midline-shift and neurological scores. Animals were divided into two groups: rats surviving 21 days after MCAO (survival group, n = 46) and rats dying prematurely (non-survival/NS group, n = 13). At reperfusion, NS group showed considerably larger lesion volume and lower mean ADC of the initial lesion site (p < 0.0001), while during occlusion there were no significant group differences. At reperfusion, each survival animal showed decreased lesion volume and increased mean ADC of the initial lesion site compared to those during occlusion (p < 10-6), while NS group showed a mixed pattern. At reperfusion, lesion volume and mean ADC of the initial lesion site were significantly associated with 24 h midline-shift and neurological scores. Diffusion MRI performed soon after reperfusion has a great impact in early-phase outcome prediction, and it works better than the measurement during occlusion.

Emotional face expression recognition in problematic Internet use and excessive smartphone use: task-based fMRI study.

Growing literature indicates that problematic Internet use (PIU) and excessive smartphone use (ESU) are associated with breakdown of functional brain networks. The effects of PIU&ESU on emotional face expression (EFE) recognition are not well understood, however behavioural investigations and fMRI studies of different addiction forms indicated the impairment of this function. The Facial Emotion Recognition Paradigm was used to probe cortico-limbic responses during EFE recognition. Combined fMRI and psychophysiological analysis were implemented to measure EFE-related functional brain changes in PIU&ESU. Self-reported questionnaires were used to assess PIU&ESU. Positive associations were found between the extent of PIU&ESU and functional connections related to emotional cognitive control and social brain networks. Our findings highlight the involvement of social functioning, especially EFE recognition in PIU&ESU. Therefore, we emphasize that besides the brain's executive and reward systems, the social brain network might be the next candidate to be involved in the pathogenesis of PIU&ESU.

The neural correlates of mental fatigue and reward processing: A task-based fMRI study.

Increasing time spent on the task (i.e., the time-on-task (ToT) effect) often results in mental fatigue. Typical effects of ToT are decreasing levels of task-related motivation and the deterioration of cognitive performance. However, a massive body of research indicates that the detrimental effects can be reversed by extrinsic motivators, for example, providing rewards to fatigued participants. Although several attempts have been made to identify brain areas involved in mental fatigue and related reward processing, the neural correlates are still less understood. In this study, we used the psychomotor vigilance task to induce mental fatigue and blood oxygen-level-dependent functional magnetic resonance imaging to investigate the neural correlates of the ToT effect and the reward effect (i.e., providing extra monetary reward after fatigue induction) in a healthy young sample. Our results were interpreted in a recently proposed neurocognitive framework. The activation of the right middle frontal gyrus, right insula and right anterior cingulate gyrus decreased as fatigue emerged and the cognitive performance dropped. However, after providing an extra reward, the cognitive performance, as well as activation of these areas, increased. Moreover, the activation levels of all of the mentioned areas were negatively associated with reaction times. Our results confirm that the middle frontal gyrus, insula and anterior cingulate cortex play crucial roles in cost-benefit evaluations, a potential background mechanism underlying fatigue, as suggested by the neurocognitive framework.

Age-related decline in circulating IGF-1 associates with impaired neurovascular coupling responses in older adults.

Impairment of moment-to-moment adjustment of cerebral blood flow (CBF) to the increased oxygen and energy requirements of active brain regions via neurovascular coupling (NVC) contributes to the genesis of age-related cognitive impairment. Aging is associated with marked deficiency in the vasoprotective hormone insulin-like growth factor-1 (IGF-1). Preclinical studies on animal models of aging suggest that circulating IGF-1 deficiency is causally linked to impairment of NVC responses. The present study was designed to test the hypotheses that decreases in circulating IGF-1 levels in older adults also predict the magnitude of age-related decline of NVC responses. In a single-center cross-sectional study, we enrolled healthy young (n = 31, 11 female, 20 male, mean age: 28.4 + / - 4.2 years) and aged volunteers (n = 32, 18 female, 14 male, mean age: 67.9 + / - 4.1 years). Serum IGF-1 level, basal CBF (phase contrast magnetic resonance imaging (MRI)), and NVC responses during the trail making task (with transcranial Doppler sonography) were assessed. We found that circulating IGF-1 levels were significantly decreased with age and associated with decreased basal CBF. Age-related decline in IGF-1 levels predicted the magnitude of age-related decline in NVC responses. In conclusion, our study provides additional evidence in support of the concept that age-related circulating IGF-1 deficiency contributes to neurovascular aging, impairing CBF and functional hyperemia in older adults.

Language processing in Internet use disorder: Task-based fMRI study.

Internet use disorder (IUD) is generally conceptualized as a fast-growing behavioral addiction. Several structural and functional brain alterations have been revealed in this condition, but previous behavioral studies indicated that language systems may also be impaired. We used a silent word generation task to induce brain activation in Broca's area and other parts of the language system. Blood-oxygen-level-dependent activation analysis and psychophysiological interaction analysis were applied to assess functional brain changes. IUD was measured by the Problematic Internet Use Questionnaire and two additional questions concerning usage time and subjective rating of addiction. According to our key findings, areas strongly related to the default mode network were altered in IUD during the task. Moreover, Broca's area showed altered functional connectivity with other language network and occipital areas in IUD. These findings may address the neural background of decreased verbal fluency performance previously reported in the literature, and we emphasize that beside the brain's reward and inhibitory control systems, the language system is the next candidate to be involved in the pathogenesis of IUD.

Emotional Intelligence Not Only Can Make Us Feel Negative, but Can Provide Cognitive Resources to Regulate It Effectively: An fMRI Study.

Neuroscientists have formulated the model of emotional intelligence (EI) based on brain imaging findings of individual differences in EI. The main objective of our study was to operationalize the advantage of high EI individuals in emotional information processing and regulation both at behavioral and neural levels of investigation. We used a self-report measure and a cognitive reappraisal task to demonstrate the role of EI in emotional perception and regulation. Participants saw pictures with negative or neutral captions and shifted (reappraised) from negative context to neutral while we registered brain activation. Behavioral results showed that higher EI participants reported more unpleasant emotions. The Utilization of emotions scores negatively correlated with the valence ratings and the subjective difficulty of reappraisal. In the negative condition, we found activation in hippocampus (HC), parahippocampal gyrus, cingulate cortex, insula and superior temporal lobe. In the neutral context, we found elevated activation in vision-related areas and HC. During reappraisal (negative-neutral) condition, we found activation in the medial frontal gyrus, temporal areas, vision-related regions and in cingulate gyrus. We conclude that higher EI is associated with intensive affective experiences even if emotions are unpleasant. Strong skills in utilizing emotions enable one not to repress negative feelings but to use them as source of information. High EI individuals use effective cognitive processes such as directing attention to relevant details; have advantages in allocation of cognitive resources, in conceptualization of emotional scenes and in building emotional memories; they use visual cues, imagination and executive functions to regulate negative emotions effectively.

Individual differences in the experience of body ownership are related to cortical thickness.

The widely used rubber hand illusion (RHI) paradigm provides insight into how the brain manages conflicting multisensory information regarding bodily self-consciousness. Previous functional neuroimaging studies have revealed that the feeling of body ownership is linked to activity in the premotor cortex, the intraparietal areas, the occipitotemporal cortex, and the insula. The current study investigated whether the individual differences in the sensation of body ownership over a rubber hand, as measured by subjective report and the proprioceptive drift, are associated with structural brain differences in terms of cortical thickness in 67 healthy young adults. We found that individual differences measured by the subjective report of body ownership are associated with the cortical thickness in the somatosensory regions, the temporo-parietal junction, the intraparietal areas, and the occipitotemporal cortex, while the proprioceptive drift is linked to the premotor area and the anterior cingulate cortex. These results are in line with functional neuroimaging studies indicating that these areas are indeed involved in processes such as cognitive-affective perspective taking, visual processing of the body, and the experience of body ownership and bodily awareness. Consequently, these individual differences in the sensation of body ownership are pronounced in both functional and structural differences.

Osteopontin levels are associated with late-time lower regional brain volumes in multiple sclerosis.

Osteopontin (OPN) is a proinflammatory marker produced by systemic immune and central nervous system (CNS) resident cells. We examined, if the level of OPN in the cerebrospinal fluid (CSF) and blood is associated with late-time regional brain volumes and white matter (WM) lesion load in MS. Concentrations of OPN in blood and CSF were related to MRI findings 10.1 ± 2.0 years later in 46 patients with MS. OPN concentration was measured by ELISA, while regional brain volumes and lesion load was assessed by magnetic resonance imaging (MRI) using 3D MPRAGE sequence and automated MR volumetry. OPN measured in the CSF was associated with several regional brain volumes and WM lesion load measured 10.1 ± 2.0 years later. CSF OPN concentration correlated with long-term enlargement of lateral- and inferior lateral ventricles and the elevation of gross CSF volume, in conjunction with the reduction of several cortical/subcortical gray matter and WM volumes. Serum OPN showed no long-term association with regional brain volumes. OPN measured from the CSF but not from the serum was associated with lower regional brain volumes measured a decade later, indicating the primary role of inflammation within the CNS in developing long-term brain related alterations.

Muscle damage in response to a single bout of high intensity concentric exercise in patients with Pompe disease.

BACKGROUND: In Pompe disease, resistance exercise could be an effective treatment to delay motor function impairment, however, the acute effects of this exercise modality are unclear. METHODS: In a prospective cohort study, we compared responses to a single bout of resistance exercise by serum markers of muscle damage and quantitative muscle magnetic resonance imaging (MRI) in patients (n=12) and age- and gender-matched healthy controls (n=12). Participants performed 50 maximal effort concentric knee flexions on a dynamometer. RESULTS: Twenty-four hours after exercise, levels of serum creatine kinase, lactate dehydrogenase and myoglobin increased in controls. In contrast, only myoglobin level increased in patients. All elevated serum markers declined by 48 hours after exercise in both groups. Mild soreness developed at 24 hours, which disappeared at 48 hours in both groups. In controls, MRI R2* relaxation rate reduced immediately and 24 hours after exercise, indicating increased water content and muscle perfusion. In patients, exercise had no effect on R2* values. The resistance exercise did not induce acute strength deficit in patients, rather, patients increased their strength by 24 hours. When serum marker changes were normalized to the magnitude of knee flexor tension developed during exercise, lactate dehydrogenase response was greater in patients. CONCLUSIONS: Late-onset Pompe disease did not exacerbate exercise-induced muscle damage, however, lactate dehydrogenase may be monitored to screen high responders during high intensity resistance exercise interventions.