Magnetic Resonance Imaging Session Research Articles

Neuroplasticity induced by general anaesthesia: study protocol for a randomised cross-over clinical trial exploring the effects of sevoflurane and propofol on the brain \u2013 A 3-T magnetic resonance imaging study of healthy volunteers

BackgroundAlthough used extensively worldwide, the effects of general anaesthesia on the human brain remain largely elusive. Moreover, general anaesthesia may contribute to serious conditions or adverse events such as postoperative cognitive dysfunction and delirium. To understand the basic mechanisms of general anaesthesia, this project aims to study and compare possible de novo neuroplastic changes induced by two commonly used types of general anaesthesia, i.e. inhalation anaesthesia by sevoflurane and intravenously administered anaesthesia by propofol. In addition, we wish to to explore possible associations between neuroplastic changes, neuropsychological adverse effects and subjective changes in fatigue and well-being.MethodsThis is a randomised, participant- and assessor-blinded, cross-over clinical trial. Thirty healthy volunteers (male:female ratio 1:1) will be randomised to general anaesthesia by either sevoflurane or propofol. Multimodal magnetic resonance imaging (MRI) of the brain will be performed before and after general anaesthesia and repeated after 1 and 8 days. Each magnetic resonance imaging session will be accompanied by cognitive testing and questionnaires on fatigue and well-being. After a wash-out period of 4 weeks, the volunteers will receive the other type of anaesthetic (sevoflurane or propofol), followed by the same series of tests. Primary outcomes: changes in T1-weighted 3D anatomy and diffusion tensor imaging. Secondary outcomes: changes in resting-state functional magnetic resonance imaging, fatigue, well-being, cognitive function, correlations between magnetic resonance imaging findings and the clinical outcomes (questionnaires and cognitive function). Exploratory outcomes: changes in cerebral perfusion and oxygen metabolism, lactate, and response to visual stimuli.DiscussionTo the best of our knowledge, this is the most extensive and advanced series of studies with head-to-head comparison of two widely used methods for general anaesthesia. Recruitment was initiated in September 2019.Trial registrationApproved by the Research Ethics Committee in the Capital Region of Denmark, ref. H-18028925 (6 September 2018). EudraCT and Danish Medicines Agency: 2018-001252-35 (23 March 2018). www.clinicaltrials.gov, ID: NCT04125121. Retrospectively registered on 10 October 2019.

Birth weight is associated with adolescent brain development: A multimodal imaging study in monozygotic twins.

Previous research has shown that the prenatal environment, commonly indexed by birth weight (BW), is a predictor of morphological brain development. We previously showed in monozygotic (MZ) twins associations between BW and brain morphology that were independent of genetics. In the present study, we employed a longitudinal MZ twin design to investigate whether variations in prenatal environment (as indexed by discordance in BW) are associated with resting‐state functional connectivity (rs‐FC) and with structural connectivity. We focused on the limbic and default mode networks (DMNs), which are key regions for emotion regulation and internally generated thoughts, respectively. One hundred and six healthy adolescent MZ twins (53 pairs; 42% male pairs) followed longitudinally from birth underwent a magnetic resonance imaging session at age 15. Graph theoretical analysis was applied to rs‐FC measures. TrackVis was used to determine track count as an indicator of structural connectivity strength. Lower BW twins had less efficient limbic network connectivity as compared to their higher BW co‐twin, driven by differences in the efficiency of the right hippocampus and right amygdala. Lower BW male twins had fewer tracks connecting the right hippocampus and right amygdala as compared to their higher BW male co‐twin. There were no associations between BW and the DMN. These findings highlight the possible role of unique prenatal environmental influences in the later development of efficient spontaneous limbic network connections within healthy individuals, irrespective of DNA sequence or shared environment.

The neural correlates of the visual consciousness in schizophrenia: an fMRI study

In the current literature, two distinct and opposite models are suggested to explain the consciousness disorders in schizophrenia. The first one suggests that consciousness disorders rely on a low-level processing deficit, when the second model suggests that consciousness disorders rely on disruption in the ability to consciously access information, with preserved unconscious processing. The current study aims to understand the mechanisms associated with visual consciousness disorder in order to pave the road that will settle the debate regarding these hypotheses. During a functional magnetic resonance imaging session, 19 healthy participants (HC) and 15 patients with schizophrenia (SCZ) performed a visual detection task to compare the neural substrates associated with the conscious access to the visual inputs. The visual detection threshold was significantly higher in SCZ than in HC [t(32) = 3.37, p = 0.002]. Whole-brain ANOVA demonstrated that around the visual detection threshold patients with SCZ failed to activate a large network of brain areas compared to HC. (1) During conscious vision, HC engaged more the left cuneus and the right occipital cortex than patients with SCZ, (2) during unconscious vision, HC engaged a large network that patients with SCZ failed to activate, and finally, (3) during the access to consciousness process, patients with SCZ failed to activate the anterior cingulate cortex. These results suggest that the consciousness disorders in schizophrenia rely on specific dysfunctions depending on the consciousness stage. The disorders of the conscious vision are associated with dysfunction of occipital areas while the ones associated with unconscious vision rely on a large widespread network. Finally, the conscious access to the visual inputs is impaired by a dysfunction of the anterior cingulate cortex. The current study suggests that none of the two suggested models can explain consciousness disorders in schizophrenia. We suggest that there is an alternative model supporting that the conscious access to visual inputs is due to a disengagement of the supragenual anterior cingulate during the unconscious processing of the visual inputs associated with a sensory deficit.

Higher Adherence to the Mediterranean Diet Is Associated With Preserved White Matter Integrity and Altered Structural Connectivity.

The Mediterranean diet (MedDiet) has been associated with cognitive performance. Yet, controlled trials have yielded contradictory results. To tackle this controversy, a comprehensive multimodal analysis of the association of the MedDiet with cognitive performance and brain structure in normative aging is still necessary. Here, community dwellers ≥50 years from a cohort study on normative aging (n = 76) underwent a (i) magnetic resonance imaging session with two acquisitions: structural and diffusion-weighted imaging (DWI); (ii) neuropsychological battery of tests focusing on memory and executive functioning; and (iii) dietary assessment through the Mediterranean Diet Assessment Screener (MEDAS, score range: 0–14, scores ≥10 indicate high adherence to the Mediterranean diet) 18 months prior to the brain imaging and neuropsychological assessment. We found that high adherence to the MedDiet (MEDAS ≥10) was associated with higher values of fractional anisotropy and lower diffusivity values in the brain white matter. Similarly, high adherence to the MedDiet was associated with higher structural connectivity between left hemisphere brain regions. Specifically, the amygdala, lingual, olfactory, middle occipital gyrus, and calcarine areas. No association was found between high adherence to the MedDiet and total brain volumes or hypointensities. Higher adherence to the MedDiet was positively associated with executive functioning scores. These results suggest that high adherence to the MedDiet positively associates with brain health, specifically with executive function scores and white matter integrity of bundles related to the processing and integration of taste, reward, and decision making. These findings seem to support the view that the MedDiet should be part of recommendations to promote a healthy brain.

Diffusion Tensor Imaging in Contact and Non-Contact University-Level Sport Athletes.

Subconcussive hits to the head and physical fitness both have been associated with alterations in white matter (WM) microstructure in partly overlapping areas of the brain. The aim of the present study was to determine whether WM damage associated with repeated exposure to subconcussive hits to the head in university level contact sports athletes is modulated by high levels of fitness. To this end, 72 students were recruited: 24 athletes practicing a varsity contact sport (A-CS), 24 athletes practicing a varsity non-contact sport (A-NCS), and 24 healthy non-athletes (NA). Participants underwent a magnetic resonance imaging session that included diffusion-weighted imaging. Between-groups, statistical analyses were performed with diffusion tensor imaging measures extracted by tractometry of sections of the corpus callosum and the corticospinal tract. Most significant effects were found in A-NCS who exhibited higher fractional anisotropy (FA) values than A-CS in almost all segments of the corpus callosum and in the corticospinal tract. The A-NCS also showed higher FA compared with NA in the anterior regions of the corpus callosum and the corticospinal tracts. No group difference was found between the A-CS and the NA groups. These data suggest that repeated subconcussive hits to the head lead to anisotropic changes in the WM that may counteract the beneficial effects associated with high levels of fitness.

Neural Working Memory Changes During a Spaceflight Analog With Elevated Carbon Dioxide: A Pilot Study.

Spaceflight missions to the International Space Station (ISS) expose astronauts to microgravity, radiation, isolation, and elevated carbon dioxide (CO2), among other factors. Head down tilt bed rest (HDBR) is an Earth-based analog for spaceflight used to study body unloading, fluid shifts, and other factors unrelated to gravitational changes. While in space, astronauts need to use mental rotation strategies to facilitate their adaptation to the ISS environment. Therefore, spatial working memory is essential for crewmember performance. Although the effects of HDBR on spatial working memory have recently been studied, the results are still inconclusive. Here, we expand upon past work and examine the effects of HDBR with elevated CO2 (HDBR + CO2) on brain activation patterns during spatial working memory performance. In addition, we compare brain activation between 30 days of HDBR + CO2 and 70 days of HDBR to test the isolated effect of CO2. Eleven subjects (6 males, 5 females; mean age = 34 ± 8 years) underwent six functional magnetic resonance imaging (fMRI) sessions pre-, during, and post-HDBR + CO2. During the HDBR + CO2 intervention, we observed decreasing activation in the right middle frontal gyrus and left regions of the cerebellum, followed by post-intervention recovery. We detected several correlations between brain and behavioral slopes of change with the HDBR + CO2 intervention. For example, greater increases in activation in frontal, temporal and parietal regions were associated with larger spatial working memory improvements. Comparing the HDBR + CO2 group to data from our previous 70-day HDBR study, we found greater decreases in activation in the right hippocampus and left inferior temporal gyrus for the HDBR + CO2 group over the course of the intervention. Together, these findings increase our understanding of the neural mechanisms of HDBR, elevated levels of CO2 and spaceflight-related changes in spatial working memory performance.

MRI Measurement of Upper Cervical Spinal Cord Cross-Sectional Area in Children.

Neurological and neurodegenerative diseases can affect the spinal cord (SC) of pediatric patients. Magnetic resonance imaging (MRI) allows for in vivo quantification of SC atrophy via cross-sectional area (CSA). The study of CSA values in the general population is important to disentangle disease-related changes from intersubject variability. This study aimed at providing normative values for cervical CSA in children, extending our previous work performed with adults. Seventy-eight children (age 7-17 years) were selected from a Developmental Dyslexia study. All subjects underwent a 3T brain MRI session and any incidental findings were reported on the scans. A sagittal 1 mm3 3-dimensional T1 -weighted brain acquisition extended to the upper cervical cord was used to measure CSA at C2-C3, as well as spinal canal area and skull volume (V-scale). These three metrics were linearly fitted as a function of age to extract trends and percentage annual changes. Sex differences of CSA were assessed using least squares regression analyses, adjusting for age. We tested normalization strategies proven to be effective in reducing the intersubject variability of adults' CSA. CSA changed as a function of age at a faster rate when compared with skull volume (CSA: 1.82% increase, V-scale: .60% reduction). Sex had a statistically significant effect on CSA. Normalization methods based on canal area and skull volume reduced the CSA intersubject variability up to 16.84%. We present CSA normative values in a large cohort of children, reporting on sources of intersubject variability and how to reduce them applying normalization methods previously developed.

Impact of Cochlear Implant With Diametric Magnet on Imaging Access, Safety, and Clinical Care.

Objectives/HypothesisReview safety and effectiveness of magnetic resonance imaging (MRI) of patients implanted with a cochlear implant (CI) containing a diametric magnet housed within the undersurface of the device.Study DesignRetrospective chart review with additional review of MRI at a tertiary‐care children's hospital.MethodsSeven patients with mean age of 8.4 years (range = 1.3–19 years) with a diametric magnet in situ during MRI. The intervention comprised one or more sessions of 1.5 T or 3.0 T MRI without a head wrap. The main outcome measures were the occurrence of magnet‐related complications including discomfort and magnet displacement, use of anesthesia or sedation, and clinical usefulness of MRI studies.ResultsSeven CI recipients underwent 17 episodes of 1.5 or 3.0 T MRI with an in situ diametric magnet. Thirteen of 17 (76%) MRI sessions were completed in awake patients. No patients had device‐related discomfort. No magnet‐related complications occurred. Thirteen of 14 (93%) brain studies were clinically useful despite artifacts.ConclusionsThe diametric magnet enabled MRI with magnet in situ without the discomfort or magnet displacement associated with removable axial magnets. The reduction in MRI magnet‐related complications occurred because torque is not directed perpendicular and outward from the plane of the magnet, and the magnet is securely contained within its housing. The design of this device increased access and reduced the need for sedation or anesthesia.Level of Evidence4 Laryngoscope, 131:E952–E956, 2021

Emotional experience in patients with clinically isolated syndrome and early multiple sclerosis.

Evidence suggests that there are changes in the processing of emotional information (EP) in people with multiple sclerosis (MS). It is unclear which functional domains of EP are affected, whether these changes are secondary to other MS-related neuropsychological or psychiatric symptoms and if EP changes are present in early MS. The aim of the study was to investigate EP in patients with early MS (clinically isolated syndrome and early relapsing/remitting MS) and healthy controls (HCs). A total of 29 patients without neuropsychological or psychiatricdeficits and 29 matched HCs were presented with pictures from the International Affective Picture System with negative, positive or neutral content. Participants rated the induced emotion regarding valence and arousal using nine-level Likert scales. A speeded recognition test assessed memory for the emotional stimuli and for the emotional modulation of response time. A subgroup of participants was tested during a magnetic resonance imaging (MRI) session. Patients in the MRI subgroup rated the experience induced by pictures with positive or negative emotional content significantly more weakly than HCs. Further, these patients were significantly less aroused when watching the pictures from the International Affective Picture System. There were no effects in the non-MRI subgroup or effects on emotional memory or response times. Emotional processing changes may be present in early MS in the form of flattened emotional experience on both the valence and arousal dimensions. These changes do not appear to be secondary to neuropsychological or psychiatric deficits. The fact that emotional flattening was only found in the MRI setting suggests that EP changes may be unmasked within stressful environments and points to the potential yet underestimated impact of the MRI setting on behavioral outcomes.

Medial Orbitofrontal De-Activation During Tonic Cold Pain Stimulation: A fMRI Study Examining the Opponent-Process Theory.

BackgroundWhile the concomitant administration of painful and rewarding stimuli tends to reduce the perception of one another, recent evidence shows that pleasant pain relief is experience after the interruption of noxious stimuli. On neurobiological grounds, these opponent processes should translate into decreased activity in brain reward regions during nociceptive stimulation and increased activity in these regions after its interruption. While growing evidence supports the latter assumption, evidence is lacking in humans in support of the former.MethodsTwenty-six healthy individuals underwent a functional magnetic resonance imaging (fMRI) session during which they were administered a cold pain stimulation, using a novel paradigm which consisted in a cold gel applied on the right foot of participants.ResultsAfter the interruption of noxious stimulation, participants experienced significant levels of pleasant pain relief. During cold pain stimulation, brain activations were observed in key regions of the pain matrix (eg, thalamus, primary somatosensory cortex and insula). Conversely, the medial orbitofrontal cortex was found to be de-activated. Medial orbitofrontal de-activations were negatively correlated with subclinical pain symptoms.DiscussionOur results show that a key brain reward region (eg, medial orbitofrontal cortex) is de-activated during cold pain stimulation, a result which is consistent with one of the central assumptions of the opponent-process theory. On methodological grounds, our results show that the cold gel applied to the foot can be used to trigger activations in the pain matrix, and that the interruption of the cold pressor test elicits significant levels of pleasant pain relief. fMRI studies on pain–reward interactions in chronic pain patients are warranted.

Grey-Matter Thickness of the Left But Not the Right Primary Visual Area Correlates with Autism Traits in Typically Developing Adults.

We examined whether functional and structural variability in the primary visual area (V1) correlated with autism traits. Twenty-nine participants (16 males; MAge = 26.4years, SDAge = 4.0years) completed the autism-spectrum quotient (AQ) questionnaire prior to a magnetic resonance imaging session. The total AQ scores was used to assess the degree of self-reported autism traits. The average functional activation in V1 to visual stimulation and its average grey-matter thickness were calculated. There were no correlations between functional activation in V1 and autism traits. Conversely, grey-matter thickness of the left but not the right V1 correlated with autism traits. We conclude that structural changes in the left V1 could be a marker for the presence of autism traits.

Incidental or Intentional? Different Brain Responses to One's Own Action Sounds in Hurdling vs. Tap Dancing.

Most human actions produce concomitant sounds. Action sounds can be either part of the action goal (GAS, goal-related action sounds), as for instance in tap dancing, or a mere by-product of the action (BAS, by-product action sounds), as for instance in hurdling. It is currently unclear whether these two types of action sounds—incidental or intentional—differ in their neural representation and whether the impact on the performance evaluation of an action diverges between the two. We here examined whether during the observation of tap dancing compared to hurdling, auditory information is a more important factor for positive action quality ratings. Moreover, we tested whether observation of tap dancing vs. hurdling led to stronger attenuation in primary auditory cortex, and a stronger mismatch signal when sounds do not match our expectations. We recorded individual point-light videos of newly trained participants performing tap dancing and hurdling. In the subsequent functional magnetic resonance imaging (fMRI) session, participants were presented with the videos that displayed their own actions, including corresponding action sounds, and were asked to rate the quality of their performance. Videos were either in their original form or scrambled regarding the visual modality, the auditory modality, or both. As hypothesized, behavioral results showed significantly lower rating scores in the GAS condition compared to the BAS condition when the auditory modality was scrambled. Functional MRI contrasts between BAS and GAS actions revealed higher activation of primary auditory cortex in the BAS condition, speaking in favor of stronger attenuation in GAS, as well as stronger activation of posterior superior temporal gyri and the supplementary motor area in GAS. Results suggest that the processing of self-generated action sounds depends on whether we have the intention to produce a sound with our action or not, and action sounds may be more prone to be used as sensory feedback when they are part of the explicit action goal. Our findings contribute to a better understanding of the function of action sounds for learning and controlling sound-producing actions.

An Improved Multi-Modal based Machine Learning Approach for the Prognosis of Alzheimer’s disease

Alzheimer’s disease (AD) is the most common type of neurological disorder that leads to the brain’s cell death overtime. It is one of the major important causes of memory loss and cognitive decline in elderly subjects around the globe. Early detection and streamlining of diagnostic practices are the prime domains of the interest to the healthcare community. Machine learning (ML) algorithms and numerous multivariate data exploratory tools have been extensively used in the field of AD research. The primary purpose of this study is to present an automated classification system to retrieve information patterns. We proposed a five-stage ML pipeline, where each stage was further categorized in different sub-levels. The study relied on the Open Access Series of Imaging Studies (OASIS) database of MRI (Magnetic Resonance Imaging) brain images for the analysis. The dataset comprised of 343 MRI sessions involving 150 subjects. Three different scores namely, MMSE (Mini-Mental State Examination), CDR (Clinical Dementia Rating), and ASF (Atlas Scaling Factor) were used in the analysis. The proposed ML pipeline constitutes a classifier system along with data transformation and feature selection techniques that have been embedded inside an experimental and data analysis design. Performance metrics for Random Forest (RF) classifier showed the highest output in the classification accuracy.

Longitudinal Magnetic Resonance Imaging as a Potential Correlate in the Diagnosis of Alzheimer Disease: Exploratory Data Analysis

Background Alzheimer disease (AD) is a degenerative progressive brain disorder where symptoms of dementia and cognitive impairment intensify over time. Numerous factors exist that may or may not be related to the lifestyle of a patient that result in a higher risk for AD. Diagnosing the disorder in its beginning period is important, and several techniques are used to diagnose AD. A number of studies have been conducted on the detection and diagnosis of AD. This paper reports the empirical study performed on the longitudinal-based magnetic resonance imaging (MRI) Open Access Series of Brain Imaging dataset. Furthermore, the study highlights several factors that influence the prediction of AD. Objective This study aimed to correlate the effect of various factors such as age, gender, education, and socioeconomic background of patients with the development of AD. The effect of patient-related factors on the severity of AD was assessed on the basis of MRI features, Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR), estimated total intracranial volume (eTIV), normalized whole brain volume (nWBV), and Atlas Scaling Factor (ASF). Methods In this study, we attempted to establish the role of longitudinal MRI in an exploratory data analysis (EDA) of AD patients. EDA was performed on the dataset of 150 patients for 343 MRI sessions (mean age 77.01 [SD 7.64] years). The T1-weighted MRI of each subject on a 1.5-Tesla Vision (Siemens) scanner was used for image acquisition. Scores of three features, MMSE, CDR, and ASF, were used to characterize the AD patients included in this study. We assessed the role of various features (ie, age, gender, education, socioeconomic status, MMSE, CDR, eTIV, nWBV, and ASF) on the prognosis of AD. Results The analysis further establishes the role of gender in the prevalence and development of AD in older people. Moreover, a considerable relationship has been observed between education and socioeconomic position on the progression of AD. Also, outliers and linearity of each feature were determined to rule out the extreme values in measuring the skewness. The differences in nWBV between CDR=0 (nondemented), CDR=0.5 (very mild dementia), and CDR=1 (mild dementia) are significant (ie, P<.01). Conclusions A substantial correlation has been observed between the pattern and other related features of longitudinal MRI data that can significantly assist in the diagnosis and determination of AD in older patients.

Association between Anterior Cingulate Neurochemical Concentration and Individual Differences in Hypnotizability.

Hypnosis is the oldest form of Western psychotherapy and a powerful evidence-based treatment for numerous disorders. Hypnotizability is variable between individuals; however, it is a stable trait throughout adulthood, suggesting that neurophysiological factors may underlie hypnotic responsiveness. One brain region of particular interest in functional neuroimaging studies of hypnotizability is the anterior cingulate cortex (ACC). Here, we examined the relationships between the neurochemicals, GABA, and glutamate, in the ACC and hypnotizability in healthy individuals. Participants underwent a magnetic resonance imaging (MRI) session, whereby T1-weighted anatomical and MEGA-PRESS spectroscopy scans were acquired. Voxel placement over the ACC was guided by a quantitative meta-analysis of functional neuroimaging studies of hypnosis. Hypnotizability was assessed using the Hypnotic Induction Profile (HIP), and self-report questionnaires to assess absorption (TAS), dissociation (DES), and negative affect were completed. ACC GABA concentration was positively associated with HIP scores such that the higher the GABA concentration, the more hypnotizable an individual. An exploratory analysis of questionnaire subscales revealed a negative relationship between glutamate and the absorption and imaginative involvement subscale of the DES. These results provide a putative neurobiological basis for individual differences in hypnotizability and can inform our understanding of treatment response to this growing psychotherapeutic tool.

Radiomics from magnetic resonance imaging may be used to predict the progression of white matter hyperintensities and identify associated risk factors.

The progression of white matter hyperintensities (WMH) varies considerably in adults. In this study, we aimed to predict the progression and related risk factors of WMH based on the radiomics of whole-brain white matter (WBWM). A retrospective analysis was conducted on 141 patients with WMH who underwent two consecutive brain magnetic resonance (MR) imaging sessions from March 2014 to May 2018. The WBWM was segmented to extract and score the radiomics features at baseline. Follow-up images were evaluated using the modified Fazekas scale, with progression indicated by scores ≥ 1. Patients were divided into progressive (n = 65) and non-progressive (n = 76) groups. The progressive group was subdivided into any WMH (AWMH), periventricular WMH (PWMH), and deep WMH (DWMH). Independent risk factors were identified using logistic regression. The area under the curve (AUC) values for the radiomics signatures of the training sets were 0.758, 0.749, and 0.775 for AWMH, PWMH, and DWMH, respectively. The AUC values of the validation set were 0.714, 0.697, and 0.717, respectively. Age and hyperlipidemia were independent predictors of progression for AWMH. Age and body mass index (BMI) were independent predictors of progression for DWMH, while hyperlipidemia was an independent predictor of progression for PWMH. After combining clinical factors and radiomics signatures, the AUC values were 0.848, 0.863, and 0.861, respectively, for the training set, and 0.824, 0.818, and 0.833, respectively, for the validation set. MRI-based radiomics of WBWM, along with specific risk factors, may allow physicians to predict the progression of WMH. • Radiomics features detected by magnetic resonance imaging may be used to predict the progression of white matter hyperintensities. • Radiomics may be used to identify risk factors associated with the progression of white matter hyperintensities. • Radiomics may serve as non-invasive biomarkers to monitor white matter status.

Performing MRI Scans on Cochlear Implant and Auditory Brainstem Implant Recipients: Review of 14.5 Years Experience.

To assess the complication rate of magnetic resonance imaging (MRI) using 1.5 T scanners on cochlear implant (CI) and auditory brainstem implant (ABI) recipients over 14.5 years. Prospective study conducted in a tertiary referral center for cochlear and auditory brainstem implantation, including patients with neurofibromatosis 2. The primary outcome was complications related to MRI scanning in implant recipients, including failure to complete MRI sessions. The secondary outcome was magnet void size due to MRI scanning with magnet in situ. Ninety-seven patients (21 ABI recipients, 76 CI recipients of whom 23 were bilateral) underwent a total of 428 MRI sessions consisting of 680 MRI procedures, which generated 2,601 MRI sequences (excluding localizers). Of these, 28/428 (6.5%) MRI sessions were performed with magnet removed, and the remaining 400/428 (93.4%) with the magnet in situ. The overall complication rate per session was 15/428 (3.5%). The majority of complications were accounted for by patient discomfort, in some cases requiring abandoning the scan session, but 5 magnet dislocations were also recorded. There were no cases of implant device failure or excessive demagnetization of the receiver stimulator magnet.For CI and ABI recipients, the implant caused large voids of around 110 mm × 60 mm with the magnet in situ which reduced to 60 mm × 30 mm when the magnet was removed. However, it was usually possible to visualize the internal acoustic meatus and cerebellopontine angle by positioning the implant package higher and further forward compared with conventional positioning. MRI scanning in ABI and CI recipients is generally safe and well tolerated without magnet removal, and carries a low rate of complications. However, patients should be fully informed of the possibility of discomfort, and precautions such as local anesthetic injection and head bandaging may reduce the likelihood of adverse events.

Neural Correlates of Vestibular Processing During a Spaceflight Analog With Elevated Carbon Dioxide (CO2): A Pilot Study

Astronauts return to Earth from spaceflight missions with impaired mobility and balance; recovery can last weeks postflight. This is due in large part to the altered vestibular signaling and sensory reweighting that occurs in microgravity. The neural mechanisms of spaceflight-induced vestibular changes are not well understood. Head-down-tilt bed rest (HDBR) is a common spaceflight analog environment that allows for study of body unloading, fluid shifts, and other consequences of spaceflight. Subjects in this context still show vestibular changes despite being in Earth’s gravitational environment, potentially due to sensory reweighting. Previously, we found evidence of sensory reweighting and reduced neural efficiency for vestibular processing in subjects who underwent a 70-day HDBR intervention. Here we extend this work by evaluating the impact of HDBR paired with elevated carbon dioxide (CO2) to mimic International Space Station conditions on vestibular neural processing. Eleven participants (6 males, 34 ± 8 years) completed 30 days of HDBR combined with 0.5% atmospheric CO2 (HDBR + CO2). Participants underwent six functional magnetic resonance imaging (fMRI) sessions pre-, during, and post- HDBR + CO2 while we measured brain activity in response to pneumatic skull taps (a validated method of vestibular stimulation). We also measured mobility and balance performance several times before and after the intervention. We found support for adaptive neural changes within the vestibular system during bed rest that subsequently recovered in several cortical and cerebellar regions. Further, there were multiple brain regions where greater pre- to post- deactivation was associated with reduced pre- to post- balance declines. That is, increased deactivation of certain brain regions associated with better balance post-HDBR + CO2. We also found that, compared to HDBR alone (n = 13 males; 29 ± 3 years) HDBR + CO2 is associated with greater increases in activation of multiple frontal, parietal, and temporal regions during vestibular stimulation. This suggests interactive or additive effects of bed rest and elevated CO2. Finally, we found stronger correlations between pre- to post- HDBR + CO2 brain changes and dependence on the visual system during balance for subjects who developed signs of Spaceflight-Associated Neuro-ocular Syndrome (SANS). Together, these findings have clear implications for understanding the neural mechanisms of bed rest and spaceflight-related changes in vestibular processing, as well as adaptation to altered sensory inputs.

Theta Burst Transcranial Magnetic Stimulation of Fronto-Parietal Networks: Modulation by Mental State.

Transcranial magnetic stimulation (TMS) treats neuropsychiatric disorders, but effects of stimulation are highly state-dependent and in most therapeutic applications, mental state is not controlled. This exploratory proposal will test the broad hypothesis that when TMS, specifically intermittent theta burst stimulation (iTBS), is applied during a controlled mental state, network changes will be facilitated, compared to stimulation when mental state is uncontrolled. We will focus on the dorsolateral prefrontal cortex (dlPFC) and the associated fronto-parietal network (FPN), which subserves cognitive control, an important neural and behavioral target of therapeutic TMS. After a baseline functional magnetic resonance imaging (fMRI) session, iTBS will be administered to 40 healthy subjects in three sessions over three days in a within-subjects, cross-over design: (1) dlPFC stimulation by iTBS alone, (2) dlPFC stimulation by iTBS while simultaneously performing a cognitive task, and (3) vertex (control) iTBS stimulation. Immediately after each iTBS session, we will measure blood oxygenation level-dependent (BOLD) activation during a cognitive control task (“n-back” task) and during the resting state, using BOLD connectivity and arterial spin labeling (ASL). We will test hypotheses that persisting neural changes and performance enhancement induced by iTBS to the dlPFC, compared to iTBS to the vertex, will affect the FPN, and these effects will be modulated by whether or not subjects receive iTBS when they are engaged in a cognitive control task. Demonstrating this interaction between iTBS and mental state will lay critical groundwork for future studies to show how controlling mental state during TMS can improve therapeutic effects.Trial RegistrationClinicaltrials.gov NCT04010461.

The muscarinic M1 receptor modulates associative learning and memory in psychotic disorders

BackgroundPsychotic disorders are characterized by prominent deficits in associative learning and memory for which there are currently no effective treatments. Functional magnetic resonance imaging (fMRI) studies in psychotic disorders have identified deficits in fronto-temporal activation during associative learning and memory. The underlying pathology of these findings remains unclear. Postmortem data have suggested these deficits may be related to loss of muscarinic M1 receptor mediated signaling. This is supported by an in-vivo study showing improvements in these symptoms after treatment with the experimental M1/4 receptor agonist xanomeline. The current study tests whether reported deficits in fronto-temporal activation could be mediated by loss of M1 receptor signaling in psychotic disorders. MethodsTwenty-six medication-free subjects diagnosed with a psychotic disorder and 29 age-, gender-, and IQ-matched healthy controls underwent two functional magnetic resonance imaging (fMRI) sessions, one under placebo and one under selective M1 antagonist biperiden, while performing the paired associated learning task. M1 binding potentials (BPND) were measured in the dorsolateral prefrontal cortex (DLPFC) and hippocampus using 123I-IDEX single photon emission computed tomography. ResultsIn the subjects with psychotic disorders DLPFC hypoactivation was only found in the memory phase of the task. In both learning and memory phases of the task, M1 antagonism by biperiden elicited significantly greater hyperactivation of the parahippocampal gyrus and superior temporal gyrus in subjects with a psychotic disorders compared to controls. Greater hyperactivation of these areas after biperiden was associated with greater hippocampal M1 receptor binding during learning, with no association found with M1 receptor binding in the DLPFC. M1 receptor binding in the DLPFC was related to greater functional sensitivity to biperiden of the cingulate gyrus during the memory phase. ConclusionThe current study is the first to show differences in M1 receptor mediated functional sensitivity between subjects with a psychotic disorder and controls during a paired associate learning and memory task. Results point to subjects with psychotic disorders having a loss of M1 receptor reserve in temporal-limbic areas.