Temporal hierarchy of cortical responses reflects core-belt-parabelt organization of auditory cortex in musicians.

Human auditory cortex (AC) organization resembles the core-belt-parabelt organization in nonhuman primates. Previous studies assessed mostly spatial characteristics; however, temporal aspects were little considered so far. We employed co-registration of functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) in musicians with and without absolute pitch (AP) to achieve spatial and temporal segregation of human auditory responses. First, individual fMRI activations induced by complex harmonic tones were consistently identified in four distinct regions-of-interest within AC, namely in medial Heschl's gyrus (HG), lateral HG, anterior superior temporal gyrus (STG), and planum temporale (PT). Second, we analyzed the temporal dynamics of individual MEG responses at the location of corresponding fMRI activations. In the AP group, the auditory evoked P2 onset occurred ~25 ms earlier in the right as compared with the left PT and ~15 ms earlier in the right as compared with the left anterior STG. This effect was consistent at the individual level and correlated with AP proficiency. Based on the combined application of MEG and fMRI measurements, we were able for the first time to demonstrate a characteristic temporal hierarchy ("chronotopy") of human auditory regions in relation to specific auditory abilities, reflecting the prediction for serial processing from nonhuman studies.

Tranexamic Acid for Intracerebral Hemorrhage in Patients on Non-Vitamin K Antagonist Oral Anticoagulants (TICH-NOAC): A Multicenter, Randomized, Placebo-Controlled, Phase 2 Trial.

BACKGROUND: Evidence-based hemostatic treatment for intracerebral hemorrhage (ICH) associated with non-vitamin K antagonist oral anticoagulants (NOACs) is lacking. Tranexamic acid (TXA) is an antifibrinolytic drug potentially limiting hematoma expansion. We aimed to assess the efficacy and safety of TXA in NOAC-ICH. METHODS: We performed a double-blind, randomized, placebo-controlled trial at 6 Swiss stroke centers. Patients with NOAC-ICH within 12 hours of symptom onset and 48 hours of last NOAC intake were randomized (1:1) to receive either intravenous TXA (1 g over 10 minutes followed by 1 g over 8 hours) or matching placebo in addition to standard medical care via a centralized Web-based procedure with minimization on key prognostic factors. All participants and investigators were masked to treatment allocation. Primary outcome was hematoma expansion, defined as ≥33% relative or ≥6 mL absolute volume increase at 24 hours and analyzed using logistic regression adjusted for baseline hematoma volume on an intention-to-treat basis. RESULTS: Between December 12, 2016, and September 30, 2021, we randomized 63 patients (median age, 82 years [interquartile range, 76-86]; 40% women; median hematoma volume, 11.5 [4.8-27.4] mL) of the 109 intended sample size before premature trial discontinuation due to exhausted funding. The primary outcome did not differ between TXA (n=32) and placebo (n=31) arms (12 [38%] versus 14 [45%]; adjusted odds ratio, 0.63 [95% CI, 0.22-1.82]; P=0.40). There was a signal for interaction with onset-to-treatment time (Pinteraction=0.024), favoring TXA when administered within 6 hours of symptom onset. Between the TXA and placebo arms, the proportion of participants who died (15 [47%] versus 13 [42%]; adjusted odds ratio, 1.07 [0.37-3.04]; P=0.91) or had major thromboembolic complications within 90 days (4 [13%] versus 2 [6%]; odds ratio, 1.86 [0.37-9.50]; P=0.45) did not differ. All thromboembolic events occurred at least 2 weeks after study treatment, exclusively in participants not restarted on oral anticoagulation. CONCLUSIONS: In a smaller-than-intended NOAC-ICH patient sample, we found no evidence that TXA prevents hematoma expansion, but there were no major safety concerns. Larger trials on hemostatic treatments targeting an early treatment window are needed for NOAC-ICH. REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT02866838.

Increased Ipsilateral Posterior Cerebral Artery P2-Segment Flow Velocity Predicts Hemodynamic Impairment.

BACKGROUND AND PURPOSE: Increased Transcranial Doppler flow velocity in the ipsilateral P2-segment of the posterior cerebral artery (PCA-P2: cm/second) is associated with recurrent cerebrovascular events in patients with unilateral internal carotid artery occlusion. However, its predictive value and correlation with hemodynamic impairment in an overall stroke patient cohort remains to be determined. METHODS: Transcranial doppler PCA-P2 flow velocity was measured in 88 patients with symptomatic unilateral steno-occlusive disease who also underwent blood oxygenation-level dependent cerebrovascular reactivity imaging (blood oxygenation-level dependent [BOLD]-cerebrovascular reactivity [CVR]). A multivariate linear regression was used to evaluate the independent correlation between the ipsilateral PCA-P2 flow velocity measurements and hemispheric BOLD-CVR. Follow-up BOLD-CVR imaging data, available in 25 patients, were used to evaluate the temporal evolution of the BOLD-CVR and PCA-P2 flow velocity association using a mixed-effect model. Furthermore, a transcranial doppler cutoff for hemodynamic failure stage 2 was determined. RESULTS: The ipsilateral systolic PCA-P2 flow velocity strongly correlated with hemispheric BOLD-CVR (R=0.79; R2=0.61), which remained unchanged when evaluating the follow-up data. Using a PCA-P2 systolic flow velocity cutoff value of 85 cm/second, patients with BOLD-CVR based hemodynamic failure stage 2 were diagnosed with an area under the curve of 95. CONCLUSIONS: In patients with symptomatic unilateral steno-occlusive disease, increased ipsilateral transcranial doppler PCA-P2 systolic flow velocity independently correlates with BOLD-CVR based hemodynamic failure. A cutoff value of 85 cm/second appears to indicate hemodynamic failure stage 2, but this finding needs to be validated in an independent patient cohort.

Crossed Cerebellar Diaschisis in Patients With Symptomatic Unilateral Anterior Circulation Stroke Is Associated With Hemodynamic Impairment in the Ipsilateral MCA Territory.

BACKGROUND: In patients with steno-occlusive disease, recent findings suggest that hemodynamic alterations may also be associated with crossed cerebellar diaschisis (CCD) rather than a functional disruption alone. PURPOSE: To use a quantitative multiparametric hemodynamic MRI to gain a better understanding of hemodynamic changes related to CCD in patients with unilateral anterior circulation stroke. STUDY TYPE: Prospective cohort study. POPULATION: Twenty-four patients (25 datasets) with symptomatic unilateral anterior circulation stroke. FIELD STRENGTH/SEQUENCE: 3T/two sequences: single-shot (echo-planar imaging) EPI sequence and T2* gradient echo perfusion-weighted imaging study. ASSESSMENT: The presence of CCD was inferred from the cerebellar asymmetry index (CAI) of the blood oxygenation-level dependent cerebrovascular reactivity (BOLD-CVR) exam, which was calculated from the mean BOLD-CVR and standard deviation of the CAI of the healthy control group. For all perfusion-weighted (PW)-MRI parameters, the cerebellar and middle cerebral artery (MCA) territory asymmetry indices were calculated. STATISTICAL TESTS: Independent Student's t-test to compare the variables from the CCD positive(+) and CCD negative(-) groups and analysis of covariance (ANCOVA) to statistically control the effect of covariates (infarct volume and time since ischemia onset). RESULTS: CCD was present in 33% of patients. In the MCA territory of the affected hemisphere, BOLD-CVR was significantly more impaired in the CCD(+) group as compared to the CCD(-) group (mean BOLD-CVR ± SD [%BOLD signal/ΔmmHgCO2 ]: -0.03 ± 0.12 vs. 0.11 ± 0.13, P < 0.05). Moreover, the mean transit time (MTT) (asymmetry index (%) CCD(+) vs. CCD(-): 28 ± 23 vs. 4 ± 11, P < 0.05) and time to peak (TTP) (10 ± 10 vs. 2 ± 5, P < 0.05) in the MCA territory of the affected hemisphere were significantly prolonged, while cerebral blood volume was, on average, increased in the CCD(+) group (25 ± 15 vs. 4 ± 19, P < 0.05). DATA CONCLUSION: Our findings show that, in patients with symptomatic unilateral anterior circulation stroke, CCD is associated with hemodynamic impairment in the ipsilateral MCA territory, which further supports the concept of a vascular component of CCD. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 3.

Machine-learning-based outcome prediction in stroke patients with middle cerebral artery-M1 occlusions and early thrombectomy.

BACKGROUND AND PURPOSE: Clinical outcomes vary substantially among individuals with large vessel occlusion (LVO) stroke. A small infarct core and large imaging mismatch were found to be associated with good recovery. The aim of this study was to investigate whether those imaging variables would improve individual prediction of functional outcome after early (<6 h) endovascular treatment (EVT) in LVO stroke. METHODS: We included 222 patients with acute ischemic stroke due to middle cerebral artery (MCA)-M1 occlusion who received EVT. As predictors, we used clinical variables and region of interest (ROI)-based magnetic resonance imaging features. We developed different machine-learning models and quantified their prediction performance according to the area under the receiver-operating characteristic curves and the Brier score. RESULTS: The rate of successful recanalization was 78%, with 54% patients having a favorable outcome (modified Rankin scale score 0-2). Small infarct core was associated with favorable functional outcome. Outcome prediction improved only slightly when imaging was added to patient variables. Age was the driving factor, with a sharp decrease in likelihood of favorable functional outcome above the age of 78 years. CONCLUSIONS: In patients with MCA-M1 occlusion strokes referred to EVT within 6 h of symptom onset, infarct core volume was associated with outcome. However, ROI-based imaging variables led to no significant improvement in outcome prediction at an individual patient level when added to a set of clinical predictors. Our study is in concordance with current practice, where imaging mismatch or collateral readouts are not recommended as factors for excluding patients with MCA-M1 occlusion for early EVT.

Large and Small Cerebral Vessel Involvement in Severe COVID-19: Detailed Clinical Workup of a Case Series.

BACKGROUND AND PURPOSE: Case series indicating cerebrovascular disorders in coronavirus disease 2019 (COVID-19) have been published. Comprehensive workups, including clinical characteristics, laboratory, electroencephalography, neuroimaging, and cerebrospinal fluid findings, are needed to understand the mechanisms. METHODS: We evaluated 32 consecutive critically ill patients with COVID-19 treated at a tertiary care center from March 9 to April 3, 2020, for concomitant severe central nervous system involvement. Patients identified underwent computed tomography, magnetic resonance imaging, electroencephalography, cerebrospinal fluid analysis, and autopsy in case of death. RESULTS: Of 32 critically ill patients with COVID-19, 8 (25%) had severe central nervous system involvement. Two presented with lacunar ischemic stroke in the early phase and 6 with prolonged impaired consciousness after termination of analgosedation. In all but one with delayed wake-up, neuroimaging or autopsy showed multiple cerebral microbleeds, in 3 with additional subarachnoid hemorrhage and in 2 with additional small ischemic lesions. In 3 patients, intracranial vessel wall sequence magnetic resonance imaging was performed for the first time to our knowledge. All showed contrast enhancement of vessel walls in large cerebral arteries, suggesting vascular wall pathologies with an inflammatory component. Reverse transcription-polymerase chain reactions for SARS-CoV-2 in cerebrospinal fluid were all negative. No intrathecal SARS-CoV-2-specific IgG synthesis was detectable. CONCLUSIONS: Different mechanisms of cerebrovascular disorders might be involved in COVID-19. Acute ischemic stroke might occur early. In a later phase, microinfarctions and vessel wall contrast enhancement occur, indicating small and large cerebral vessels involvement. Central nervous system disorders associated with COVID-19 may lead to long-term disabilities. Mechanisms should be urgently investigated to develop neuroprotective strategies.

Crossed Cerebellar Diaschisis in Patients with Diffuse Glioma Is Associated with Impaired Supratentorial Cerebrovascular Reactivity and Worse Clinical Outcome.

Crossed cerebellar diaschisis (CCD) can be associated with impaired cerebrovascular reactivity (CVR) and poor clinical outcome, but whether this holds true for patients with diffuse glioma is unknown. With blood oxygenation level-dependent (BOLD)-CVR imaging, we determined the presence of CCD in patients with diffuse glioma and investigated its relationship with cerebrovascular reactivity and clinical outcome. For eighteen enrolled subjects (nineteen datasets) with diffuse glioma, CCD was deferred from BOLD-CVR using a predetermined cerebellar asymmetry index (CAI) cutoff value of 6.0%. A FET-PET study was done as a verification of the CCD diagnosis. BOLD-CVR values as well as clinical performance scores (i.e., Karnofsky performance score (KPS), disability rating scale (DRS), and modified Rankin scale (mRS)) by BOLD-CVR scan at 3-month clinical follow-up were assessed and compared for the CCD-positive and CCD-negative group. CCD was present in 26.3% of subjects and strongly associated with impaired BOLD-CVR of the affected (i.e., the hemisphere harboring the glioma) and unaffected supratentorial hemisphere (CCD(+) vs. CCD(-): 0.08 ± 0.11 vs. 0.18 ± 0.04; p = 0.007 and 0.08 ± 0.12 vs. 0.19 ± 0.04; p = 0.007, respectively). This finding was independent of tumor volume (p = 0.48). Furthermore, poorer initial (by scan) clinical performance scores at follow-up were found for the CCD(+) group. The presence of crossed cerebellar diaschisis in patients with diffuse glioma is associated with impaired supratentorial cerebrovascular reactivity and worse clinical outcome.

Assessment of the impact of sex in intensity, skin flares and central processing of histaminergic itch-A pilot study.

Itch is the commonest skin-related symptom, and sex differences are increasingly recognised as important determinants in stratified medicine, but only little is known about sex differences in itch. Questionnaire-based studies indicated that women perceive itch as more intensive and bothersome in comparison with men. However, data of studies using standardised itch models to objectify sex differences are scarce and inconsistent. To determine sex differences in intensity, skin flares and central processing of histaminergic itch, we compared 15 female and 15 male healthy subjects in a double-blinded, within-subject, placebo-controlled study using a histamine skin prick itch model (histamine 1% applied onto the volar forearm) and functional MRI. We found trends in higher mean itch intensity (0.58 VAS, CI 95% 0.004-1.19, P = .056) and maximum itch intensity (men 3.93 VAS ± 0.39 SD at 3 minutes, women 4.73 VAS ± 0.31 SD at 4 minutes, P = .073) in women paralleled by a trend in a stronger positive correlation between itch intensity and blood oxygen level-dependent (BOLD) activity in brain structures identified during itch in comparison with men (rs in women: .46, P = .08, rs in men: .07, P = .79). The erythema and wheal following histamine skin pricking were (non-significantly) larger in men, indicating that higher mean itch intensities on the right volar forearm in women may not be explained by more intense flares. The comparison of the activation patterns between the sexes revealed increased activity in men compared to women in the left middle temporal gyrus (temporooccipital part)/lateral occipital cortex. Thus, our findings indicate that histaminergic itch perception and central itch processing differ between the sexes under standardised conditions.

Preferential spinal cord volume loss in primary progressive multiple sclerosis.

BACKGROUND: Little is known on longer term changes of spinal cord volume (SCV) in primary progressive multiple sclerosis (PPMS). OBJECTIVE: Longitudinal evaluation of SCV loss in PPMS and its correlation to clinical outcomes, compared to relapse-onset multiple sclerosis (MS) subtypes. METHODS: A total of 60 MS age-, sex- and disease duration-matched patients (12 PPMS, each 24 relapsing-remitting (RRMS) and secondary progressive MS (SPMS)) were analysed annually over 6 years of follow-up. The upper cervical SCV was measured on 3D T1-weighted magnetization-prepared rapid gradient-echo (MPRAGE) images using a semi-automatic software (CORDIAL), along with the total brain volume (TBV), brain T2 lesion volume (T2LV) and Expanded Disability Status Scale (EDSS). RESULTS: PPMS showed faster SCV loss over time than RRMS ( p < 0.01) and by trend ( p = 0.066) compared with SPMS. In contrast to relapse-onset MS, in PPMS SCV loss progressed independent of TBV and T2LV changes. Moreover, in PPMS, SCV was the only magnetic resonance imaging (MRI) measurement associated with EDSS increase over time ( p < 0.01), as opposed to RRMS and SPMS. CONCLUSION: SCV loss is a strong predictor of clinical outcomes in PPMS and has shown to be faster and independent of brain MRI metrics compared to relapse-onset MS.

Diagnosis of adult-onset MELAS syndrome in a 63-year-old patient with suspected recurrent strokes - a case report.

BACKGROUND: Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) is a mitochondrial cytopathy caused by mutations in mitochondrial DNA. Clinical manifestation is typically before the age of 40. CASE PRESENTATION: We present the case of a 63-year-old female in whom the symptoms of MELAS were initially misdiagnosed as episodes of recurrent ischemic strokes. Brain imaging including MRI, clinical and laboratory findings that lent cues to the diagnosis of MELAS are discussed. In addition, MRI findings in MELAS in comparison to imaging mimics of MELAS are presented. CONCLUSIONS: This case underscores the importance of considering MELAS as a potential cause of recurrent stroke-like events if imaging findings are untypical for cerebral infarction, even among middle-aged patients with vascular risk factors.

Vascular Anatomy Predicts the Risk of Cerebral Ischemia in Patients Randomized to Carotid Stenting Versus Endarterectomy.

BACKGROUND AND PURPOSE: Complex vascular anatomy might increase the risk of procedural stroke during carotid artery stenting (CAS). Randomized controlled trial evidence that vascular anatomy should inform the choice between CAS and carotid endarterectomy (CEA) has been lacking. METHODS: One-hundred eighty-four patients with symptomatic internal carotid artery stenosis who were randomly assigned to CAS or CEA in the ICSS (International Carotid Stenting Study) underwent magnetic resonance (n=126) or computed tomographic angiography (n=58) at baseline and brain magnetic resonance imaging before and after treatment. We investigated the association between aortic arch configuration, angles of supra-aortic arteries, degree, length of stenosis, and plaque ulceration with the presence of ≥1 new ischemic brain lesion on diffusion-weighted magnetic resonance imaging (DWI+) after treatment. RESULTS: Forty-nine of 97 patients in the CAS group (51%) and 14 of 87 in the CEA group (16%) were DWI+ (odds ratio [OR], 6.0; 95% confidence interval [CI], 2.9-12.4; P<0.001). In the CAS group, aortic arch configuration type 2/3 (OR, 2.8; 95% CI, 1.1-7.1; P=0.027) and the degree of the largest internal carotid artery angle (≥60° versus <60°; OR, 4.1; 95% CI, 1.7-10.1; P=0.002) were both associated with DWI+, also after correction for age. No predictors for DWI+ were identified in the CEA group. The DWI+ risk in CAS increased further over CEA if the largest internal carotid artery angle was ≥60° (OR, 11.8; 95% CI, 4.1-34.1) than if it was <60° (OR, 3.4; 95% CI, 1.2-9.8; interaction P=0.035). CONCLUSIONS: Complex configuration of the aortic arch and internal carotid artery tortuosity increase the risk of cerebral ischemia during CAS, but not during CEA. Vascular anatomy should be taken into account when selecting patients for stenting. CLINICAL TRIAL REGISTRATION: URL: http://www.isrctn.com/ISRCTN25337470. Unique identifier: ISRCTN25337470.

Parietal lobe critically supports successful paired immediate and single-item delayed memory for targets.

The parietal lobe is important for successful recognition memory, but its role is not yet fully understood. We investigated the parietal lobes' contribution to immediate paired-associate memory and delayed item-recognition memory separately for hits (targets) and correct rejections (distractors). We compared the behavioral performance of 56 patients with known parietal and medial temporal lobe dysfunction (i.e. early Alzheimer's Disease) to 56 healthy control participants in an immediate paired and delayed single item object memory task. Additionally, we performed voxel-based morphometry analyses to investigate the functional-neuroanatomic relationships between performance and voxel-based estimates of atrophy in whole-brain analyses. Behaviorally, all participants performed better identifying targets than rejecting distractors. The voxel-based morphometry analyses associated atrophy in the right ventral parietal cortex with fewer correct responses to familiar items (i.e. hits) in the immediate and delayed conditions. Additionally, medial temporal lobe integrity correlated with better performance in rejecting distractors, but not in identifying targets, in the immediate paired-associate task. Our findings suggest that the parietal lobe critically supports successful immediate and delayed target recognition memory, and that the ventral aspect of the parietal cortex and the medial temporal lobe may have complementary preferences for identifying targets and rejecting distractors, respectively, during recognition memory.

Presurgical motor, somatosensory and language fMRI: Technical feasibility and limitations in 491 patients over 13 years.

OBJECTIVES: To analyse the long-term feasibility and limitations of presurgical fMRI in a cohort of tumour and epilepsy patients with different MR-scanners at 1.5 and 3.0 T. METHODS: Four hundred and ninety-one consecutive patients undergoing presurgical fMRI between 2000 and 2012 on five different MR-scanners using established paradigms and semi-automated data processing were included. Success rates of task performance and BOLD-activation were determined for motor and somatosensory somatotopic mapping and language localisation. Procedural success, failures and imaging artifacts were analysed. MR-field strengths were compared. RESULTS: Two thousand three hundred fifteen of 2348 (98.6 %) attempted paradigms (1033 motor, 1220 speech, 95 somatosensory) were successfully performed. 100 paradigms (4.3 %) were repetition runs. 23 speech, 6 motor and 2 sensory paradigms failed for non-compliance and technical issues. Most language paradigm failures were noted in overt sentence generation. Average significant BOLD-activation was higher for motor than language paradigms (95.8 vs. 81.6 %). Most language paradigms showed significantly higher activation rates at 3 T compared to 1.5 T, whereas no significant difference was found for motor paradigms. CONCLUSIONS: fMRI proved very robust for the presurgical localisation of the different motor and somatosensory body representations, as well as Broca's and Wernicke's language areas across different MR-scanners at 1.5 and 3.0 T over 13 years. KEY POINTS: • Standardised presurgical motor and language fMRI is robust across various MRI platforms. • Motor fMRI is less dependent on field strength than language fMRI. • fMRI task failures are relatively low and are reduced by paradigm repetition.

Reduced white matter integrity in amateur boxers.

INTRODUCTION: Professional boxing can lead to chronic traumatic encephalopathy, a variant of traumatic brain injury (TBI). Its occurrence in amateur boxers is a matter of debate since amateur boxing is considered to be less harmful due to more strict regulations. However, several studies using different methodological approaches have revealed subtle signs of TBI even in amateurs. Diffusion tensor imaging (DTI) is sensitive to microscopic white matter changes and has been proven useful in TBI when routine MR imaging often is unrevealing. METHODS: DTI, with tract-based spatial statistics (TBSS) together with neuropsychological examination of executive functions and memory, was used to investigate a collective of 31 male amateur boxers and 31 age-matched controls as well as a subgroup of 19 individuals, respectively, who were additionally matched for intellectual performance (IQ). RESULTS: All participants had normal findings in neurological examination and conventional MR. Amateur boxers did not show deficits in neuropsychological tests when their IQ was taken into account. Fractional anisotropy was significantly reduced, while diffusivity measures were increased along central white matter tracts in the boxers group. These changes were in part associated with the number of fights. CONCLUSIONS: TBSS revealed widespread white matter disturbance partially related to the individual fighting history in amateur boxers. These findings closely resemble those in patients with accidental TBI and indicate similar histological changes in amateur boxers.

Association between changes in cerebral grey matter volume and postoperative cognitive dysfunction in elderly patients: study protocol for a prospective observational cohort study.

BACKGROUND: Cognitive decline is frequently observed in elderly patients after major surgery. The pathophysiology of postoperative cognitive dysfunction (POCD) remains unclear. The aim of our investigation is to identify potential associations between brain volume change and POCD in elderly patients undergoing major surgery. METHODS: This is a prospective observational cohort study approved by the regional ethics board. We intend to compare specific brain volumes (hippocampus, lateral ventricle, total grey matter volume, regional cortical thickness) on magnetic resonance imaging and cognitive functions determined by a neuropsychological assessment battery in 70 study participants aged ≥65 years before and 3 and 12 months after major noncardiac surgery. Thirty volunteers will be included as matched nonsurgical controls. The primary endpoint of the study is the change in hippocampal volume over time in patients with and without POCD. The secondary endpoint is the correlation between the change in cerebral volume and cognitive function. We will follow the STROBE guidelines for reporting the results of observational studies. DISCUSSION: We hypothesize that surgery under general anesthesia is associated with a loss of cerebral grey matter, and that the degree of postoperative cognitive dysfunction correlates with the extent of atrophy in areas of the brain that are relevant for cognitive functions. The validation of reproducible anatomical biomarkers, such as the specific brain volumes examined in our cohort, may serve to evaluate the effect of preventive strategies and treatment interventions for POCD in follow-up studies. TRIAL REGISTRATION: Clinicaltrials.gov NCT02045004 . Registered 22 January 2014. Kofam.ch SNCTP000001751. Registered 21 April 2016 (retrospectively registered).

Comparison between balanced steady-state free precession and standard spoiled gradient echo magnetization transfer ratio imaging in multiple sclerosis: methodical and clinical considerations.

Different pathological processes like demyelination and axonal loss can alter the magnetisation transfer ratio (MTR) in brain tissue. The standard method to measure this effect is to scan the respective tissue twice, one with and one without a specific saturation pulse. A major drawback of this technique based on spoiled gradient echo (GRE) sequences relates to its long acquisition time due to the saturation pulses. Recently, an alternative concept for MT imaging based on balanced steady state free precession (bSSFP) has been proposed. Modification of the duration of the radiofrequency pulses for imaging allows scanning MT sensitive and non-sensitive images. The steady-state character of bSSFP with high intrinsic signal-to-noise ratio (SNR) allows three-dimensional (3D) whole brain MTR at high spatial resolution within short and thus clinically feasible acquisition times. In the present study, both bSSFP-MT and 2D GRE-MT imaging were used in a cohort of 31 patients with multiple sclerosis (MS) to characterize different normal appearing (NA) and pathological brain structures. Under the constraint of identical SNR and scan time, a 3.4 times higher voxel size could be achieved with bSSFP. This increased resolution allowed a more accurate delineation of the different brain structures, especially of cortex, hippocampus and MS lesions. In a multiple linear regression model, we found an association between MTR of cortical lesions and a clinical measure of disability (r= -0.407, p=0.035) in the bSSFP dataset only. The different relaxation weighting of the base images (T2/T1 in bSSFP, proton density in GRE) had no effects besides a larger spreading of the MTR values of the different NA structures. This was demonstrated by the nearly perfect linearity between the NA matter MTR of both techniques as well as in the absolute MTR differences between NA matter and the respective lesions.

Increased volume and function of right auditory cortex as a marker for absolute pitch.

Absolute pitch (AP) perception is the auditory ability to effortlessly recognize the pitch of any given tone without external reference. To study the neural substrates of this rare phenomenon, we developed a novel behavioral test, which excludes memory-based interval recognition and permits quantification of AP proficiency independently of relative pitch cues. AP- and non-AP-possessing musicians were studied with morphological and functional magnetic resonance imaging (fMRI) and magnetoencephalography. Gray matter volume of the right Heschl's gyrus (HG) was highly correlated with AP proficiency. Right-hemispheric auditory evoked fields were increased in the AP group. fMRI revealed an AP-dependent network of right planum temporale, secondary somatosensory, and premotor cortices, as well as left-hemispheric "Broca's" area. We propose the right HG as an anatomical marker of AP and suggest that a right-hemispheric network mediates AP "perception," whereas pitch "labeling" takes place in the left hemisphere.

PKCα is genetically linked to memory capacity in healthy subjects and to risk for posttraumatic stress disorder in genocide survivors.

Strong memory of a traumatic event is thought to contribute to the development and symptoms of posttraumatic stress disorder (PTSD). Therefore, a genetic predisposition to build strong memories could lead to increased risk for PTSD after a traumatic event. Here we show that genetic variability of the gene encoding PKCα (PRKCA) was associated with memory capacity--including aversive memory--in nontraumatized subjects of European descent. This finding was replicated in an independent sample of nontraumatized subjects, who additionally underwent functional magnetic resonance imaging (fMRI). fMRI analysis revealed PRKCA genotype-dependent brain activation differences during successful encoding of aversive information. Further, the identified genetic variant was also related to traumatic memory and to the risk for PTSD in heavily traumatized survivors of the Rwandan genocide. Our results indicate a role for PKCα in memory and suggest a genetic link between memory and the risk for PTSD.

Label-fusion-segmentation and deformation-based shape analysis of deep gray matter in multiple sclerosis: the impact of thalamic subnuclei on disability.

Deep gray matter (DGM) atrophy has been reported in patients with multiple sclerosis (MS) already at early stages of the disease and progresses throughout the disease course. We studied DGM volume and shape and their relation to disability in a large cohort of clinically well-described MS patients using new subcortical segmentation methods and shape analysis. Structural 3D magnetic resonance images were acquired at 1.5 T in 118 patients with relapsing remitting MS. Subcortical structures were segmented using a multiatlas technique that relies on the generation of an automatically generated template library. To localize focal morphological changes, shape analysis was performed by estimating the vertex-wise displacements each subject must undergo to deform to a template. Multiple linear regression analysis showed that the volume of specific thalamic nuclei (the ventral nuclear complex) together with normalized gray matter volume explains a relatively large proportion of expanded disability status scale (EDSS) variability. The deformation-based displacement analysis confirmed the relation between thalamic shape and EDSS scores. Furthermore, white matter lesion volume was found to relate to the shape of all subcortical structures. This novel method for the analysis of subcortical volume and shape allows depicting specific contributions of DGM abnormalities to neurological deficits in MS patients. The results stress the importance of ventral thalamic nuclei in this respect.

White matter lesion filling improves the accuracy of cortical thickness measurements in multiple sclerosis patients: a longitudinal study.

BACKGROUND: Previous studies have demonstrated that white matter (WM) lesions bias automated brain tissue classifications and cerebral volume measurements. However, filling WM lesions using the intensity of neighbouring normal-appearing WM has been shown to increase the accuracy of automated volume measurements in the brain. In the present study, we investigate the influence of WM lesions on cortical thickness (CTh) measures and assessed the impact of lesion filling on both cross-sectional/longitudinal and global/regional measurements of CTh in multiple sclerosis (MS) patients. METHODS: Fifty MS patients were studied at baseline as well as after three and six years of follow-up. CTh was estimated using a fully automated pipeline (CIVET) on T1-weighted magnetic resonance images data acquired at 1.5 Tesla without (original) and with WM lesion filling (filled). WM lesions were semi-automatically segmented and then filled with the mean intensity of the neighbouring voxels. For both original and filled T1 images we investigated and compared the main CIVET's steps: tissue classification, surfaces generation and CTh measurement. RESULTS: On the original T1 images, the majority of WM lesion volume (72%) was wrongly classified as gray matter (GM). After lesion filling the accuracy of WM lesions classification improved significantly (p < 0.001, 94% of WM lesion volume correctly classified) as well as the WM surface generation (p < 0.0001). The mean CTh computed on the original T1 images, overall time points, was significantly thinner (p < 0.001) compared the CTh estimated on the filled T1 images. The vertex-wise longitudinal analysis performed on the filled T1 images showed an increased number of vertices in the fronto-temporal region with a significantly decrease of CTh over time compared the analysis performed on the original images. CONCLUSION: These results indicate that WM lesions bias the CTh estimation both cross-sectionally as well as longitudinally. The lesion filling approach significantly improved the accuracy of the regional CTh estimation and has an impact also on the global estimation of CTh.