Circadian functional changes of pain-processing brainstem nuclei and implications for cluster headache: A 7 Tesla imaging study.

BACKGROUND: Pain thresholds and primary headaches, including cluster headache attacks, have circadian rhythmicity. Thus, they might share a common neuronal mechanism. OBJECTIVE: This study aimed to elucidate how the modulation of nociceptive input in the brainstem changes from noon to midnight. Insights into the mechanism of these fluctuations could allow for new hypotheses about the pathophysiology of cluster headache. METHODS: This repeated measure observational study was conducted at the University Hospital Zurich from December 2019 to November 2022. Healthy adults between 18 and 85 years of age were eligible. All participants were examined at noon and midnight. We tested the pain threshold on both sides of the foreheads with quantitative sensory testing, assessed tiredness levels, and obtained high-field (7 Tesla) and high-resolution functional magnetic resonance imaging (MRI) at each visit. Functional connectivity was assessed at the two visits by performing a region-of-interest analysis. We defined nuclei in the brainstem implicated in processing nociceptive input as well as the thalamus and suprachiasmatic nucleus as the region-of-interest. RESULTS: Ten people were enrolled, and seven participants were included. First, we did not find statistically significant differences between noon and midnight of A-delta-mediated pain thresholds (median mechanical pain threshold at noon: left 9.2, right 9.2; at night: left 6.5, right 6.1). Second, after correction for a false discovery rate, we found changes in the mechanical pain sensitivity to have a statistically significant effect on changes in the functional connectivity between the left parabrachial nucleus and the suprachiasmatic nucleus (T = -40.79). CONCLUSION: The MRI data analysis suggested that brain stem nuclei and the hypothalamus modulate A-delta-mediated pain perception; however, these changes in pain perception did not lead to statistically significantly differing pain thresholds between noon and midnight. Hence, our findings shed doubt on our hypothesis that the physiologic circadian rhythmicity of pain thresholds could drive the circadian rhythmicity of cluster headache attacks.

The longitudinal influence of tDCS on occipital GABA and glutamate/glutamine levels in episodic migraineurs.

This study investigated differences in the concentration of gamma-aminobutyric acid (GABA) and the combination of glutamine and glutamate (as GLX) in the early visual cortex of patients with episodic migraine and the influence of transcranial direct current stimulation (tDCS) on GABA and GLX. In this single-blind, sham-controlled trial, we randomly assigned patients with episodic migraine to receive daily anodal tDCS or sham stimulation. In addition, we included healthy controls. We acquired proton MR spectroscopy data of the visual cortex with 3 Tesla MRI at baseline and from migraine patients directly after the stimulation period and 4 months later. In 22 migraineurs and 25 controls, the GABA and the GLX concentrations did not differ at baseline between the groups. tDCS resulted in reduced concentrations of GABA but not GLX or the migraine frequency directly after the stimulation period, but not 4 months later. The changes in the levels of GABA in the early visual cortex of patients with episodic migraine in the interictal period suggest an effect of tDCS that allowed for subsequent changes in the migraine frequency. However, we might have missed relevant variations in the concentrations of these neurotransmitters during the follow-up period, as changes in migraine frequency appeared after the first MRI and disappeared before the second.

Impact of age on mechanical thrombectomy and clinical outcome in patients with acute ischemic stroke.

BACKGROUND AND PURPOSE: Mechanical thrombectomy is less effective in patients aged 80 years or older. Our goal was to better understand the impact of age in general on recanalization rates and clinical outcome. METHODS: We performed a retrospective analysis of our prospective database of adult patients with acute ischemic stroke due to large vessel occlusions, who had undergone mechanical thrombectomy between 2019 and mid-2021. The cohort was categorized into five age groups: 18 - 49, 50 - 59, 60 - 69, 70 - 79 and ≥ 80 years. Our primary outcome measure was clinical outcome at three months after mechanical thrombectomy, measured by the mRS score. Secondary outcomes were procedure times and rates of successful recanalization, defined by mTICI ≥ 2b. RESULTS: Data of 264 patients were analyzed. There were no significant differences in procedure times (p = 0.46) or in rates of successful recanalization (p = 0.49) between age groups. There was a significant association of age and mRS score at three months (p < 0.0001): From youngest to oldest group, odds of functional independence (mRS ≤ 2) decreased (80.0% vs. 21.3%) and odds of death (mRS 6) increased (13.3% vs. 57.3%). Increasing age was significantly associated with lower rates of functional independence (OR 0.93; [95% CI 0.90 - 0.95]), higher rates of care dependency (OR 1.04; [95% CI 1.01 - 1.07]) and higher mortality rates (OR 1.06; [95% CI 1.04 - 1.09]). CONCLUSION: Higher age had no significant impact on recanalization times or recanalization rates but was strongly associated with worse clinical outcome after mechanical thrombectomy.

Descending pain modulatory efficiency in healthy subjects is related to structure and resting connectivity of brain regions.

The descending pain modulatory system in humans is commonly investigated using conditioned pain modulation (CPM). Whilst variability in CPM efficiency, i.e., inhibition and facilitation, is normal in healthy subjects, exploring the inter-relationship between brain structure, resting-state functional connectivity (rsFC) and CPM readouts will provide greater insight into the underlying CPM efficiency seen in healthy individuals. Thus, this study combined CPM testing, voxel-based morphometry (VBM) and rsFC to identify the neural correlates of CPM in a cohort of healthy subjects (n =40), displaying pain inhibition (n = 29), facilitation (n = 10) and no CPM effect (n = 1). Clusters identified in the VBM analysis were implemented in the rsFC analysis alongside key constituents of the endogenous pain modulatory system. Greater pain inhibition was related to higher volume of left frontal cortices and stronger rsFC between the motor cortex and periaqueductal grey. Conversely, weaker pain inhibition was related to higher volume of the right frontal cortex - coupled with stronger rsFC to the primary somatosensory cortex, and rsFC between the amygdala and posterior insula. Overall, healthy subjects showed higher volume and stronger rsFC of brain regions involved with descending modulation, while the lateral and medial pain systems were related to greater pain inhibition and facilitation during CPM, respectively. These findings reveal structural alignments and functional interactions between supraspinal areas involved in CPM efficiency. Ultimately understanding these underlying variations and how they may become affected in chronic pain conditions, will advance a more targeted subgrouping in pain patients for future cross-sectional studies investigating endogenous pain modulation.

Increased structural covariance in brain regions for number processing and memory in children with developmental dyscalculia.

Developmental dyscalculia (DD) is a developmental learning disability associated with deficits in processing numerical and mathematical information. Several studies demonstrated functional network alterations in DD. Yet, there are no studies, which examined the structural network integrity in DD. We compared whole-brain maps of volume based structural covariance between 19 (4 males) children with DD and 18 (4 males) typically developing children. We found elevated structural covariance in the DD group between the anterior intraparietal sulcus to the middle temporal and frontal gyrus (p < 0.05, corrected). A hippocampus subfield analysis showed higher structural covariance in the DD group for area CA3 to the parahippocampal and calcarine sulcus, angular gyrus and anterior part of the intraparietal sulcus as well as to the lingual gyrus. Lower structural covariance in this group was seen for the subiculum to orbitofrontal gyrus, anterior insula and middle frontal gyrus. In contrast, the primary motor cortex (control region) revealed no difference in structural covariance between groups. Our results extend functional magnetic resonance studies by revealing abnormal gray matter integrity in children with DD. These findings thus indicate that the pathophysiology of DD is mediated by both structural and functional abnormalities in a network involved in number processing and memory function.

The impact of levamisole and alcohol on white matter microstructure in adult chronic cocaine users.

Previous brain imaging studies with chronic cocaine users (CU) using diffusion tensor imaging (DTI) mostly focused on fractional anisotropy to investigate white matter (WM) integrity. However, a quantitative interpretation of fractional anisotropy (FA) alterations is often impeded by the inherent limitations of the underlying tensor model. A more fine-grained measure of WM alterations could be achieved by measuring fibre density (FD). This study investigates this novel DTI metric comparing 23 chronic CU and 32 healthy subjects. Quantitative hair analysis was used to determine intensity of cocaine and levamisole exposure-a cocaine adulterant with putative WM neurotoxicity. We first assessed the impact of cocaine use, levamisole exposure and alcohol use on group differences in WM integrity. Compared with healthy controls, all models revealed cortical reductions of FA and FD in CU. At the within-patient group level, we found that alcohol use and levamisole exposure exhibited regionally different FA and FD alterations than cocaine use. We found mostly negative correlations of tract-based WM associated with levamisole and weekly alcohol use. Specifically, levamisole exposure was linked with stronger WM reductions in the corpus callosum than alcohol use. Cocaine use duration correlated negatively with FA and FD in some regions. Yet, most of these correlations did not survive a correction for multiple testing. Our results suggest that chronic cocaine use, levamisole exposure and alcohol use were all linked to significant WM impairments in CU. We conclude that FD could be a sensitive marker to detect the impact of the use of multiple substances on WM integrity in cocaine but also other substance use disorders.

Supraspinal nociceptive networks in neuropathic pain after spinal cord injury.

Neuropathic pain following spinal cord injury involves plastic changes along the whole neuroaxis. Current neuroimaging studies have identified grey matter volume (GMV) and resting-state functional connectivity changes of pain processing regions related to neuropathic pain intensity in spinal cord injury subjects. However, the relationship between the underlying neural processes and pain extent, a complementary characteristic of neuropathic pain, is unknown. We therefore aimed to reveal the neural markers of widespread neuropathic pain in spinal cord injury subjects and hypothesized that those with greater pain extent will show higher GMV and stronger connectivity within pain related regions. Thus, 29 chronic paraplegic subjects and 25 healthy controls underwent clinical and electrophysiological examinations combined with neuroimaging. Paraplegics were demarcated based on neuropathic pain and were thoroughly matched demographically. Our findings indicate that (a) spinal cord injury subjects with neuropathic pain display stronger connectivity between prefrontal cortices and regions involved with sensory integration and multimodal processing, (b) greater neuropathic pain extent, is associated with stronger connectivity between the posterior insular cortex and thalamic sub-regions which partake in the lateral pain system and (c) greater intensity of neuropathic pain is related to stronger connectivity of regions involved with multimodal integration and the affective-motivational component of pain. Overall, this study provides neuroimaging evidence that the pain phenotype of spinal cord injury subjects is related to the underlying function of their resting brain.

Considering non-bladder aetiologies of overactive bladder: a functional neuroimaging study.

OBJECTIVES: To better understand the neuropathophysiology of overactive bladder (OAB) in women by characterising supraspinal activity in response to bladder distention and cold stimulation. SUBJECTS/PATIENTS AND METHODS: We recruited 24 female participants, 12 with OAB (median [interquartile range, IQR] age 40 [32-42] years) and 12 healthy controls (HCs) without lower urinary tract (LUT) symptoms (median [IQR] age 34 [28-44] years), and assessed LUT and cognitive function through neuro-urological examination, 3-day bladder diary, urodynamic investigation, and questionnaires. Functional magnetic resonance (MR) imaging using a 3-T scanner was performed in all participants during automated, repetitive bladder filling and draining (block design) with 100 mL body temperature (37 °C) saline using a MR-compatible and MR-synchronised infusion-drainage device until strong desire to void (HIGH-FILLING/DRAINING) and bladder filling with cold saline (4 °C, i.e. COLD). Whole-brain and region-of-interest analyses were conducted using Statistical Parametric Mapping, version 12. RESULTS: Significant between-group differences were found for 3-day bladder diary variables (i.e. voiding frequency/24 h, P < 0.001; voided volume/void, P = 0.04; and urinary incontinence [UI] episodes/24 h, P = 0.007), questionnaire scores (International Consultation on Incontinence Questionnaire-Female LUT symptoms [overall, filling, and UI scores, all P < 0.001]; the Overactive Bladder Questionnaire short form [symptoms and quality-of-life scores, both P < 0.001]; the Hospital Anxiety and Depression Scale [anxiety P = 0.004 and depression P = 0.003 scores]), as well as urodynamic variables (strong desire to void, P = 0.02; maximum cystometric capacity, P = 0.007; and presence of detrusor overactivity, P = 0.002). Age, weight and cognitive function (i.e. Mini-Mental State Examination, P = 1.0) were similar between groups (P > 0.05). In patients with OAB, the HIGH task elicited activity in the superior temporal gyrus, ventrolateral prefrontal cortex (VLPFC), and mid-cingulate cortex; and the COLD task elicited activity in the VLPFC, cerebellum, and basal ganglia. Compared to HCs, patients with OAB showed significantly stronger cerebellar activity during HIGH-FILLING and significantly less activity in the insula and VLPFC during HIGH-DRAINING. CONCLUSIONS: The present findings suggest a sensory processing and modulation deficiency in our OAB group, probably as part of their underlying pathophysiology, as they lacked activity in essential sensory processing areas, such as the insula. Instead, accessory areas, such as the cerebellum, showed significantly stronger activation compared to HCs, presumably supporting pelvic-floor motor activity to prevent UI. The novel findings of the present study provide physiological evidence of the necessity to consider non-bladder aetiologies of bladder symptoms.

Long-Term Effects of Self-Administered Transcranial Direct Current Stimulation in Episodic Migraine Prevention: Results of a Randomized Controlled Trial.

BACKGROUND: Migraine is a multifactorial neurovascular disorder, which affects about 12% of the general population. In episodic migraine, the visual cortex revealed abnormal processing, most likely due to decreased preactivation level. Transcranial direct current stimulation (tDCS) is able to modify cortical excitability and might result in an alleviation of migraine occurrence if used repetitively. OBJECTIVE: To test the hypothesis that self-administered anodal tDCS over the visual cortex significantly decreases the number of monthly migraine days in episodic migraine. MATERIALS AND METHODS: The study was single-blind, randomized, and sham-controlled. Inclusion criteria were age 18-80 years and an ICHD-3 diagnosis of episodic migraine. Exclusion criteria were pregnancy, presence of a neurodegenerative disorder, a contraindication against MRI examinations, and less than two migraine days during the 28-day baseline period. Patients in whom the baseline period suggested chronic migraine were excluded. After baseline, participants applied daily either verum (anodal-1 mA to 20 min) or sham tDCS (anodal-1 mA to 30 sec) at Oz (reference Cz electrode) for 28 days. Headache diaries were used to record the number of migraine days at baseline, during the stimulation period, and during four subsequent 28-day periods. RESULTS: Twenty-eight patients were included; two were excluded after the baseline period because less than two migraine days occurred; three were excluded because their headache diaries suggested the diagnosis of chronic migraine. Twenty-three datasets were taken for further analysis. Compared to sham tDCS (n = 12), verum tDCS (n = 11) resulted in a lower number of migraine days (p = 0.010) across all follow-up periods. We found no significant change in total headache days (p = 0.165), anxiety (p = 0.884), or depression scores (p = 0.535). No serious adverse events occurred; minor side effects were similar in both groups. CONCLUSIONS: This study provides Class II evidence that self-administered anodal tDCS over the visual cortex in episodic migraine results in a significantly lower number of monthly migraine days. However, it has neither an immediate nor a long-term effect.

Tracking tDCS induced grey matter changes in episodic migraine: a randomized controlled trial.

BACKGROUND: Occipital transcranial direct current stimulation (tDCS) is an effective and safe treatment for migraine attack prevention. Structural brain alterations have been found in migraineurs in regions related to pain modulation and perception, including occipital areas. However, whether these structural alterations can be dynamically modulated through tDCS treatment is understudied. OBJECTIVE: To track longitudinally grey matter volume changes in occipital areas in episodic migraineurs during and up to five months after occipital tDCS treatment in a single-blind, and sham-controlled study. METHODS: 24 episodic migraineurs were randomized to either receive verum or sham occipital tDCS treatment for 28 days. To investigate dynamic grey matter volume changes patients underwent structural MRI at baseline (prior to treatment), 1.5 months and 5.5 months (after completion of treatment). 31 healthy controls were scanned with the same MRI protocol. Morphometry measures assessed rate of changes over time and between groups by means of tensor-based morphometry. RESULTS: Before treatment, migraineurs reported 5.6 monthly migraine days on average. A cross-sectional analysis revealed grey matter volume increases in the left lingual gyrus in migraineurs compared to controls. Four weeks of tDCS application led to a reduction of 1.9 migraine days/month and was paralleled by grey matter volume decreases in the left lingual gyrus in the treatment group; its extent overlapping with that seen at baseline. CONCLUSION: This study shows that migraineurs have increased grey matter volume in the lingual gyrus, which can be modified by tDCS. Tracking structural plasticity in migraineurs provides a potential neuroimaging biomarker for treatment monitoring. TRIAL REGISTRATION: ClinicalTrials.gov , NCT03237754 . Registered 03 August 2017 - retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03237754 .

Structural brain network characteristics in patients with episodic and chronic migraine.

BACKGROUND: Migraine is a primary headache disorder that can be classified into an episodic (EM) and a chronic form (CM). Network analysis within the graph-theoretical framework based on connectivity patterns provides an approach to observe large-scale structural integrity. We test the hypothesis that migraineurs are characterized by a segregated network. METHODS: 19 healthy controls (HC), 17 EM patients and 12 CM patients were included. Cortical thickness and subcortical volumes were computed, and topology was analyzed using a graph theory analytical framework and network-based statistics. We further used support vector machines regression (SVR) to identify whether these network measures were able to predict clinical parameters. RESULTS: Network based statistics revealed significantly lower interregional connectivity strength between anatomical compartments including the fronto-temporal, parietal and visual areas in EM and CM when compared to HC. Higher assortativity was seen in both patients' group, with higher modularity for CM and higher transitivity for EM compared to HC. For subcortical networks, higher assortativity and transitivity were observed for both patients' group with higher modularity for CM. SVR revealed that network measures could robustly predict clinical parameters for migraineurs. CONCLUSION: We found global network disruption for EM and CM indicated by highly segregated network in migraine patients compared to HC. Higher modularity but lower clustering coefficient in CM is suggestive of more segregation in this group compared to EM. The presence of a segregated network could be a sign of maladaptive reorganization of headache related brain circuits, leading to migraine attacks or secondary alterations to pain.

Network-based fMRI-neurofeedback training of sustained attention.

The brain regions supporting sustained attention (sustained attention network; SAN) and mind-wandering (default-mode network; DMN) have been extensively studied. Nevertheless, this knowledge has not yet been translated into advanced brain-based attention training protocols. Here, we used network-based real-time functional magnetic resonance imaging (fMRI) to provide healthy individuals with information about current activity levels in SAN and DMN. Specifically, 15 participants trained to control the difference between SAN and DMN hemodynamic activity and completed behavioral attention tests before and after neurofeedback training. Through training, participants improved controlling the differential SAN-DMN feedback signal, which was accomplished mainly through deactivating DMN. After training, participants were able to apply learned self-regulation of the differential feedback signal even when feedback was no longer available (i.e., during transfer runs). The neurofeedback group improved in sustained attention after training, although this improvement was temporally limited and rarely exceeded mere practice effects that were controlled by a test-retest behavioral control group. The learned self-regulation and the behavioral outcomes suggest that neurofeedback training of differential SAN and DMN activity has the potential to become a non-invasive and non-pharmacological tool to enhance attention and mitigate specific attention deficits.

Visual snow syndrome: a review on diagnosis, pathophysiology, and treatment.

PURPOSE OF REVIEW: Visual snow is considered a disorder of central visual processing resulting in a perturbed perception of constant bilateral whole-visual field flickering or pixelation. When associated with additional visual symptoms, it is referred to as visual snow syndrome. Its pathophysiology remains elusive. This review highlights the visual snow literature focusing on recent clinical studies that add to our understanding of its clinical picture, pathophysiology, and treatment. RECENT FINDINGS: Clinical characterization of visual snow syndrome is evolving, including a suggested modification of diagnostic criteria. Regarding pathophysiology, two recent studies tested the hypothesis of dysfunctional visual processing and occipital cortex hyperexcitability using electrophysiology. Likewise, advanced functional imaging shows promise to allow further insights into disease mechanisms. A retrospective study now provides Class IV evidence for a possible benefit of lamotrigine in a minority of patients. SUMMARY: Scientific understanding of visual snow syndrome is growing. Major challenges remain the subjective nature of the disease, its overlap with migraine, and the lack of quantifiable outcome measures, which are necessary for clinical trials. In that context, refined perceptual assessment, objective electrophysiological parameters, as well as advanced functional brain imaging studies, are promising tools in the pipeline.

Test-Retest Reliability of the Brain Metabolites GABA and Glx With JPRESS, PRESS, and MEGA-PRESS MRS Sequences in vivo at 3T.

BACKGROUND: The optimization of magnetic resonance spectroscopy (MRS) sequences allows improved diagnosis and prognosis of neurological and psychological disorders. Thus, to assess the test-retest and intersequence reliability of such MRS sequences in quantifying metabolite concentrations is of clinical relevance. PURPOSE: To evaluate the test-retest and intersequence reliability of three MRS sequences to estimate GABA and Glx = Glutamine+Glutamate concentrations in the human brain. STUDY TYPE: Prospective. SUBJECTS: Eighteen healthy participants were scanned twice (range: 1 day to 1 week between the two sessions) with identical protocols. FIELD STRENGTH/SEQUENCE: 3T using a 32-channel SENSE head coil in the PCC region; PRESS, JPRESS, and MEGA-PRESS sequences. ASSESSMENT: Metabolite concentrations were estimated using LCModel (for PRESS and MEGA-PRESS) and ProFit2 (for JPRESS). STATISTICAL TESTS: The test-retest reliability was evaluated by Wilcoxon signed-rank tests, Pearson's r correlation coefficients, intraclass-correlation coefficients (ICC), coefficients of variation (CV), and by Bland-Altman (BA) plots. The intersequence reliability was assessed with Wilcoxon signed-rank tests, Pearson's r correlation coefficients, and BA plots. RESULTS: For GABA, only the MEGA-PRESS sequence showed a moderate test-retest correlation (r = 0.54, ICC = 0.5, CV = 8.8%) and the BA plots indicated good agreement (P > 0.05) for all sequences. JPRESS provided less precise results and PRESS was insensitive to GABA. For Glx, the r and ICC values for PRESS (r = 0.87, ICC = 0.9, CV = 2.9%) and MEGA-PRESS (r = 0.70, ICC = 0.7, CV = 5.3%) reflect higher correlations, compared with JPRESS (r = 0.39, ICC = 0.4, CV = 20.1%). DATA CONCLUSION: MEGA-PRESS and JPRESS are suitable for the reliable detection of GABA, the first being more precise. The three sequences included in the study can measure Glx concentrations. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2020;51:1181-1191.

Magnetic Resonance Spectroscopy following Mild Traumatic Brain Injury: A Systematic Review and Meta-Analysis on the Potential to Detect Posttraumatic Neurodegeneration.

INTRODUCTION: Traumatic brain injury (TBI) is the most relevant external risk factor for dementia and a major global health burden. Mild TBI (mTBI) contributes to up to 90% of all TBIs, and the classification "mild" often misrepresents the patient's burden who suffer from neuropsychiatric long-term sequelae. Magnetic resonance spectroscopy (MRS) allows in vivo detection of compromised brain metabolism although it is not routinely used after TBI. OBJECTIVE: Thus, we performed a systematic review and meta-analysis to elucidate if MRS has the potential to identify changes in brain metabolism in adult patients after a single mTBI with a negative routine brain scan (CCT and/or MRI scan) compared to aged- and sex-matched healthy controls (HC) during the acute or subacute postinjury phase (≤90 days after mTBI). METHODS: A comprehensive literature search was conducted from the first edition of electronic databases until January 31, 2020. Group analyses were performed per metabolite using a random-effects model. RESULTS: Four and 2 out of 5,417 articles met the inclusion criteria for the meta-analysis and systematic review, respectively. For the meta-analysis, 50 mTBI patients and 51 HC with a mean age of 31 and 30 years, respectively, were scanned using N-acetyl-aspartate (NAA), a marker for neuronal integrity. Glutamate (Glu), a marker for disturbed brain metabolism, choline (Cho), a marker for increased cell membrane turnover, and creatine (Cr) were used in 2 out of the 4 included articles. Regions of interests were the frontal lobe, the white matter around 1 cm above the lateral ventricles, or the whole brain. NAA was decreased in patients compared to HC with an effect size (ES) of -0.49 (95% CI -1.08 to 0.09), primarily measured in the frontal lobe. Glu was increased in the white matter in 22 mTBI patients compared to 22 HC (ES 0.79; 95% CI 0.17-1.41). Cho was decreased in 31 mTBI patients compared to 31 HC (ES -0.31; 95% CI -0.81 to 0.19). Cr was contradictory and, therefore, potentially not suitable as a reference marker after mTBI. CONCLUSIONS: MRS pinpoints changes in posttraumatic brain metabolism that correlate with cognitive dysfunction and, thus, might possibly help to detect mTBI patients at risk for unfavorable outcome or posttraumatic neurodegeneration early.

Reliability of supraspinal correlates to lower urinary tract stimulation in healthy participants - A fMRI study.

Previous functional neuroimaging studies provided evidence for a specific supraspinal network involved in lower urinary tract (LUT) control. However, data on the reliability of blood oxygenation level-dependent (BOLD) signal changes during LUT task-related functional magnetic resonance imaging (fMRI) across separate measurements are lacking. Proof of the latter is crucial to evaluate whether fMRI can be used to assess supraspinal responses to LUT treatments. Therefore, we prospectively assessed task-specific supraspinal responses from 20 healthy participants undergoing two fMRI measurements (test-retest) within 5-8 weeks. The fMRI measurements, conducted in a 3T magnetic resonance (MR) scanner, comprised a block design of repetitive bladder filling and drainage using an automated MR-compatible and MR-synchronized infusion-drainage device. Following transurethral catheterization and bladder pre-filling with body warm saline until participants perceived a persistent desire to void (START condition), fMRI was recorded during repetitive blocks (each 15 s) of INFUSION and WITHDRAWAL of 100 mL body warm saline into respectively from the bladder. BOLD signal changes were calculated for INFUSION minus START. In addition to whole brain analysis, we assessed BOLD signal changes within multiple 'a priori' region of interest (ROI), i.e. brain areas known to be involved in the LUT control from previous literature. To evaluate reliability of the fMRI results between visits, we applied different types of analyses: coefficient of variation (CV), intraclass correlation coefficient (ICC), Sørensen-Dice index, Bland-Altman method, and block-wise BOLD signal comparison. All participants completed the study without adverse events. The desire to void was rated significantly higher for INFUSION compared to START or WITHDRAWAL at both measurements without any effect of visit. At whole brain level, significant (p < 0.05, cluster corrected, k ≥ 41 voxels) BOLD signal changes were found for the contrast INFUSION compared to START in several brain areas. Overlap of activation maps from both measurements were observed in the orbitofrontal cortex, insula, ventrolateral prefrontal cortex (VLPFC), and inferior parietal lobe. The two highest ICCs, based on a ROI's mean beta weight, were 0.55 (right insular cortex) and 0.47 (VLPFC). Spatial congruency (Sørensen-Dice index) of all voxels within each ROI between measurements was highest in the insular cortex (left 0.55, right 0.44). In addition, the mean beta weight of the right insula and right VLPFC demonstrated the lowest CV and narrowest Bland and Altman 95% limits of agreement. In conclusion, the right insula and right VLPFC were revealed as the two most reliable task-specific ROIs using our automated, MR-synchronized protocol. Achieving high reliability using a viscero-sensory/interoceptive task such as repetitive bladder filling remains challenging and further endeavour is highly warranted to better understand which factors influence fMRI outcomes and finally to assess LUT treatment effects on the supraspinal level.

Lateral geniculate nucleus volumetry at 3T and 7T: Four different optimized magnetic-resonance-imaging sequences evaluated against a 7T reference acquisition.

PURPOSE: The lateral geniculate nucleus (LGN) is an essential nucleus of the visual pathway, occupying a small volume (60-160 mm3) among the other thalamic nuclei. The reported LGN volumes vary greatly across studies due to technical limitations and due to methodological differences of volume assessment. Yet, structural and anatomical alterations in ophthalmologic and neurodegenerative pathologies can only be revealed by a precise and reliable LGN representation. To improve LGN volume assessment, we first implemented a reference acquisition for LGN volume determination with optimized Contrast to Noise Ratio (CNR) and high spatial resolution. Next, we compared CNR efficiency and rating reliability of 3D Magnetization Prepared Rapid Gradient Echo (MPRAGE) images using white matter nulled (WMn) and grey matter nulled (GMn) sequences and its subtraction (WMn-GMn) relative to the clinical standard Proton Density Turbo Spin Echo (PD 2D TSE) and the reference acquisition. We hypothesized that 3D MPRAGE should provide a higher CNR and volume determination accuracy than the currently used 2D sequences. MATERIALS AND METHODS: In 31 healthy subjects, we obtained at 3 and 7 T the following MR sequences: PD-TSE, MPRAGE with white/grey matter signal nulled (WMn/GMn), and a motion-corrected segmented MPRAGE sequence with a resolution of 0.4 × 0.4 × 0.4 mm3 (reference acquisition). To increase CNR, GMn were subtracted from WMn (WMn-GMn). Four investigators manually segmented the LGN independently. RESULTS: The reference acquisition provided a very sharp depiction of the LGN and an estimated mean LGN volume of 124 ±â€¯3.3 mm3. WMn-GMn had the highest CNR and gave the most reproducible LGN volume estimations between field strengths. Even with the highest CNR efficiency, PD-TSE gave inconsistent LGN volumes with the weakest reference acquisition correlation. The LGN WM rim induced a significant difference between LGN volumes estimated from WMn and GMn. WMn and GMn LGN volume estimations explained most of the reference acquisition volumes' variance. For all sequences, the volume rating reliability were good. On the other hand, the best CNR rating reliability, LGN volume and CNR correlations with the reference acquisition were obtained with GMn at 7 T. CONCLUSION: WMn and GMn MPRAGE allow reliable LGN volume determination at both field strengths. The precise location and identification of the LGN (volume) can help to optimize neuroanatomical and neurophysiological studies, which involve the LGN structure. Our optimized imaging protocol may be used for clinical applications aiming at small nuclei volumetric and CNR quantification.

Cerebral blood flow in striatal regions is associated with apathy in patients with schizophrenia.

BACKGROUND: Striatal dysfunction has been proposed as a pathomechanism for negative symptoms in schizophrenia. There is consensus that negative symptoms can be grouped into 2 dimensions: apathy and diminished expression. Recent studies suggest that different neural mechanisms underlie these dimensions, but the relationship between regional resting-state cerebral blood flow (rCBF) and negative symptom dimensions has not been investigated. METHODS: This study included 29 patients with schizophrenia and 20 healthy controls. We measured rCBF in the striatum using arterial spin labelling (ASL) MRI. We assessed negative symptoms using the Brief Negative Symptom Scale. RESULTS: In the ventral and dorsal striatum, rCBF was not different between patients with schizophrenia and controls. However, we did find a positive association between the severity of apathy and increased rCBF in the ventral and dorsal striatum in patients with schizophrenia. This effect was not present for diminished expression. LIMITATIONS: All patients were taking atypical antipsychotics, so an effect of antipsychotic medication on rCBF could not be excluded, although we did not find a significant association between rCBF and chlorpromazine equivalents. CONCLUSION: The main finding of this study was a specific association between increased striatal rCBF and the negative symptom dimension of apathy. Our results further support the separate assessment of apathy and diminished expression when investigating the neural basis of negative symptoms. The ASL technique can provide a direct and quantitative approach to investigating the role of rCBF changes in the pathophysiology of negative symptoms.

Interictal Hyperperfusion in the Higher Visual Cortex in Patients With Episodic Migraine.

BACKGROUND: Migraine pathophysiology is complex and probably involves cortical and subcortical alterations. Structural and functional brain imaging studies indicate alterations in the higher order visual cortex in patients with migraine. Arterial spin labeling magnetic resonance imaging (ASL-MRI) is a non-invasive imaging method for assessing changes in cerebral blood flow (CBF) in vivo. OBJECTIVE: To examine if interictal CBF differs between patients with episodic migraine (EM) with or without aura and healthy controls (HC). METHODS: We assessed interictal CBF using 2D pseudo-continuous ASL-MRI on a 3 Tesla Philips scanner (University Hospital Zurich, Switzerland) in EM (N = 17, mean age 32.7 ± 9.9, 13 females) and HC (N = 19, mean age 31.0 ± 9.3, 11 females). RESULTS: Compared to HC, EM showed exclusively hyperperfusion in the right MT+ and Cohen's d effect size was 0.99 (HC mean CBF ± SD: 33.1 ± 5.9 mL/100 g/minutes; EM mean CBF: 40.9 ± 9.4 mL/100 g/minutes). EM with aura (N = 13, MwA) revealed hyperperfusion compared to HC in the right MT+ and superior temporal gyrus. For MT, Cohen's d effect size was 1.34 (HC mean CBF ± SD: 33.1 ± 5.9 mL/100 g/minutes; MwA mean CBF: 43.3 ± 8.6 mL/100 g/minutes). For the superior temporal gyrus, Cohen's d effect size was 1.28 (HC mean CBF ± SD: 40.1 ± 4.9 mL/100 g/minutes; MwA mean CBF: 47.4 ± 6.4 mL/100 g/minutes). In EM, anxiety was positively associated with CBF in the parietal operculum and angular gyrus. CONCLUSIONS: Our results suggest that extrastriate brain regions probably involved in cortical spreading depression are associated with CBF changes in the interictal state. We conclude that ASL-MRI is a sensitive method to identify local neuro-functional abnormalities in CBF in patients with EM in the interictal state.

Movement disorders in genetically confirmed mitochondrial disease and the putative role of the cerebellum.

BACKGROUND: Mitochondrial disease can present as a movement disorder. Data on this entity's epidemiology, genetics, and underlying pathophysiology, however, is scarce. OBJECTIVE: The objective of this study was to describe the clinical, genetic, and volumetric imaging data from patients with mitochondrial disease who presented with movement disorders. METHODS: In this retrospective analysis of all genetically confirmed mitochondrial disease cases from three centers (n = 50), the prevalence and clinical presentation of video-documented movement disorders was assessed. Voxel-based morphometry from high-resolution MRI was employed to compare cerebral and cerebellar gray matter volume between mitochondrial disease patients with and without movement disorders and healthy controls. RESULTS: Of the 50 (30%) patients with genetically confirmed mitochondrial disease, 15 presented with hypokinesia (parkinsonism 3/15), hyperkinesia (dystonia 5/15, myoclonus 3/15, chorea 2/15), and ataxia (3/15). In 3 patients, mitochondrial disease presented as adult-onset isolated dystonia. In comparison to healthy controls and mitochondrial disease patients without movement disorders, patients with hypo- and hyperkinetic movement disorders had significantly more cerebellar atrophy and an atrophy pattern predominantly involving cerebellar lobules VI and VII. CONCLUSION: This series provides clinical, genetic, volumetric imaging, and histologic data that indicate major involvement of the cerebellum in mitochondrial disease when it presents with hyper- and hypokinetic movement disorders. As a working hypothesis addressing the particular vulnerability of the cerebellum to energy deficiency, this adds substantially to the pathophysiological understanding of movement disorders in mitochondrial disease. Furthermore, it provides evidence that mitochondrial disease can present as adult-onset isolated dystonia. © 2017 International Parkinson and Movement Disorder Society.