Navigated and individual α-peak-frequency-guided transcranial magnetic stimulation in male patients with treatment-refractory schizophrenia.

BACKGROUND: Previous electroencephalography (EEG) studies have indicated altered brain oscillatory α-band activity in schizophrenia, and treatment with repetitive transcranial magnetic stimulation (rTMS) using individualized α-frequency has shown therapeutic effects. Magnetic resonance imaging-based neuronavigation methods allow stimulation of a specific cortical region and improve targeting of rTMS; therefore, we sought to study the efficacy of navigated, individual α-peak-frequency-guided rTMS (αTMS) on treatment-refractory schizophrenia. METHODS: We recruited medication-refractory male patients with schizophrenia or schizoaffective disorder in this doubleblind, sham-controlled study. We randomized patients to a 3-week course of either active αTMS or sham stimulation applied to the left dorsolateral prefrontal cortex (DLPFC). We assessed participants with the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impression Scale (CGI) at baseline and after treatment. We conducted a follow-up assessment with the PANSS 3 months after intervention. RESULTS: We included 44 patients. After treatment, we observed a significantly higher PANSS total score (p = 0.029), PANSS general psychopathology score (p = 0.027) and PANSS 5-factor model cognitive-disorganized factor score (p = 0.011) in the αTMS group than the sham group. In addition, the CGI-Improvement score was significantly higher among those who received αTMS compared with sham stimulation (p = 0.048). LIMITATIONS: The limited number of study participants included only male patients. Depression was not formally evaluated. CONCLUSION: Navigated αTMS to the left DLPFC reduced total, general psychopathological, and cognitive-disorganized symptoms of schizophrenia. These results provide evidence for the therapeutic efficacy of individual α-peak-frequency-guided rTMS in treatment-refractory schizophrenia. CLINICAL TRIAL REGISTRATION: NCT01941251; ClinicalTrials.gov.

Associations between physical fitness and cerebellar gray matter volume in adolescents.

Despite the importance of the developing cerebellum on cognition, the associations between physical fitness and cerebellar volume in adolescents remain unclear. We explored the associations of physical fitness with gray matter (GM) volume of VI, VIIb and Crus I & II, which are cerebellar lobules related to cognition, in 40 (22 females; 17.9 ± 0.8 year-old) adolescents, and whether the associations were sex-specific. Peak oxygen uptake (V̇O2peak ) and power were assessed by maximal ramp test on a cycle ergometer, muscular strength with standing long jump (SLJ), speed-agility with the shuttle-run test (SRT), coordination with the Box and Block Test (BBT) and neuromuscular performance index (NPI) as the sum of SLJ, BBT and SRT z-scores. Body composition was measured using a dual-energy X-ray absorptiometry. Cerebellar volumes were assessed by magnetic resonance imaging. V̇O2peak relative to lean mass was inversely associated with the GM volume of the cerebellum (standardized regression coefficient (ß) = -0.038, 95% confidence interval (CI) -0.075 to 0.001, p = 0.044). Cumulative NPI was positively associated with the GM volume of Crus I (ß = 0.362, 95% CI 0.045 to 0.679, p = 0.027). In females, better performance in SRT was associated with a larger GM volume of Crus I (ß = -0.373, 95% CI -0.760 to -0.028, p = 0.036). In males, cumulative NPI was inversely associated with the GM volume of Crus II (ß = -0.793, 95% CI -1.579 to -0.008 p = 0.048). Other associations were nonsignificant. In conclusion, cardiorespiratory fitness, neuromuscular performance and speed-agility were associated with cerebellar GM volume, and the strength and direction of associations were sex-specific.

Progressive myoclonic epilepsy type 1 (EPM1) patients present with abnormal 1H MRS brain metabolic profiles associated with cognitive function.

PURPOSE: Progressive myoclonic epilepsy, type 1A (EPM1, Unverricht-Lundborg disease), is a rare neurodegenerative autosomal recessive disorder characterized by stimulus-sensitive and action myoclonus and tonic-clonic epileptic seizures. Patients develop neurological symptoms, including ataxia, intention tremor, and dysarthria, over time, with relatively limited and nonspecific MRI atrophy findings. The effects of the disease on brain metabolism are largely unknown. METHOD: Eighteen EPM1 patients (9 M, 9F) underwent clinical evaluation and neuropsychological testing, which included the assessment of intellectual ability, verbal memory, and psychomotor and executive functions. Magnetic resonance spectroscopy (MRS) and imaging (MRI) were performed on a 1.5 T MRI system. 2D MRS chemical shift imaging (CSI) maps (TE = 270) were obtained from the following regions of the brain: basal ganglia, thalamus, insula, splenium, and occipital white and gray matter, and N-acetyl-aspartate (NAA)-, choline (Cho)-, and lactate (Lac)-to-creatine (Cr) ratios were analyzed. Ten healthy age-and sex-matched subjects (5M, 5F) were used as controls for MRS. RESULTS: We found significant brain metabolic changes involving lactate, NAA, and choline, which are widespread in the basal ganglia, thalamic nuclei, insula, and occipital areas of EPM1 patients. Changes, especially in the right insula, basal ganglia, and thalamus, were associated with intellectual abilities and impairment of the psychomotor and executive functions of EPM1 patients. CONCLUSION: Multiple brain metabolic alterations suggest the presence of neurodegeneration associated with EPM1 progression. The changes in metabolite ratios are associated with the neurocognitive dysfunction caused by the disease. However, the role of MRS findings in understanding pathophysiology of EPM1 warrants further studies.

Cortical thickness is inversely associated with transcranial magnetic stimulation-evoked N45 potential among young adults whose heavy drinking began in adolescence.

BACKGROUND: Adolescence is a particularly vulnerable stage of development in terms of the deleterious effects of alcohol. Both lower gray matter (GM) volume and greater GABAergic activity have been associated with chronic alcohol consumption during adolescence. However, the association between these measures has not been investigated. METHODS: In this exploratory study, we compared 26 young adults with a 10year history of heavy alcohol consumption with 21 controls who used little or no alcohol. Simultaneous transcranial magnetic stimulation and electroencephalography were used to assess transcranial magnetic stimulation-evoked N45 potentials, reflecting a balance between GABAergic inhibition and N-methyl-D-aspartate (NMDA) receptor-mediated glutaminergic excitation in the brain. GM thickness was measured from magnetic resonance images and GM and N45 potentials were then correlated. RESULTS: Cortical thickness was significantly lower in several brain regions in the heavy-drinking group than the light-drinking group. The N45 amplitude was significantly larger frontally in the heavy-drinking group. Among heavy drinkers, there were several statistically significant correlations between thinner GM and larger frontal N45 amplitudes that were not detectable in the light-drinking group. The strongest correlations were detected in the frontal and parietal lobes, especially in the left superior frontal gyrus and the left supramarginal gyrus, and in both hemispheres in the superior parietal lobes. CONCLUSIONS: These findings show that a thinner cortex and greater inhibitory neurotransmission are correlated in certain brain regions among young, long-term heavy alcohol users. Studies are needed to explore the possible causal mechanisms underlying these effects.

Dynamic contrast-enhanced MRI to characterize angiogenesis in primary epithelial ovarian cancer: An exploratory study.

PURPOSE: Angiogenesis is essential for tumor growth. Currently, there are no established imaging biomarkers to show angiogenesis in tumor tissue. The aim of this prospective study was to evaluate whether semiquantitative and pharmacokinetic DCE-MRI perfusion parameters could be used to assess angiogenesis in epithelial ovarian cancer (EOC). METHOD: We enrolled 38 patients with primary EOC treated in 2011-2014. DCE-MRI was performed with a 3.0 T imaging system before the surgical treatment. Two different sizes of ROI were used to evaluate semiquantitative and pharmacokinetic DCE perfusion parameters: a large ROI (L-ROI) covering the whole primary lesion on one plane and a small ROI (S-ROI) covering a small solid, highly enhancing focus. Tissue samples from tumors were collected during the surgery. Immunohistochemistry was used to measure the expression of vascular endothelial growth factor (VEGF), its receptors (VEGFRs) and to analyse microvascular density (MVD) and the number of microvessels. RESULTS: VEGF expression correlated inversely with Ktrans (L-ROI, r = -0.395 (p = 0.009), S-ROI, r = -0.390, (p = 0.010)), Ve (L-ROI, r = -0.395 (p = 0.009), S-ROI, r = -0.412 (p = 0.006)) and Vp (L-ROI, r = -0.388 (p = 0.011), S-ROI, r = -0.339 (p = 0.028)) values in EOC. Higher VEGFR-2 correlated with lower DCE parameters Ktrans (L-ROI, r = -0.311 (p = 0.040), S-ROI, r = -0.337 (p = 0.025)) and Ve (L-ROI, r = -0.305 (p = 0.044), S-ROI, r = -0.355 (p = 0.018)). We also found that MVD and the number of microvessels correlated positively with AUC, Peak and WashIn values. CONCLUSIONS: We observed that several DCE-MRI parameters correlated with VEGF and VEGFR-2 expression and MVD. Thus, both semiquantitative and pharmacokinetic perfusion parameters of DCE-MRI represent promising tools for the assessment of angiogenesis in EOC.

Developmental models of motor-evoked potential features by transcranial magnetic stimulation across age groups from childhood to adulthood.

To derive the maturation of neurophysiological processes from childhood to adulthood reflected by the change of motor-evoked potential (MEP) features. 38 participants were recruited from four groups (age mean in years [SD in months], number (males)): children (7.3 [4.2], 7(4)), preadolescents (10.3 [6.9], 10(5)), adolescents (15.3 [9.8], 11(5)), and adults (26.9 [46.2], 10(5)). The navigated transcranial magnetic stimulation was performed on both hemispheres at seven stimulation intensity (SI) levels from sub- to supra-threshold and targeted to the representative cortical area of abductor pollicis brevis muscle. MEPs were measured from three hand- and two forearm-muscles. The input-output (I/O) curves of MEP features across age groups were constructed using linear mixed-effect models. Age and SI significantly affected MEP features, whereas the stimulated side had a minor impact. MEP size and duration increased from childhood to adulthood. MEP onset- and peak-latency dropped in adolescence, particularly in hand muscles. Children had the smallest MEPs with the highest polyphasia, whereas I/O curves were similar among preadolescents, adolescents, and adults. This study illustrates some of the changing patterns of MEP features across the ages, suggesting developing patterns of neurophysiological processes activated by TMS, and to motivate studies with larger sample size.

Greater increases in intratumoral apparent diffusion coefficients after chemoradiotherapy predict better overall survival of patients with cervical cancer.

PURPOSE: To evaluate whether 1) the intratumoral apparent diffusion coefficients (ADCs) change during cervical cancer treatment and 2) the pretreatment ADC values or their change after treatment predict the treatment outcome or overall survival of patients with cervical cancer. METHODS: We retrospectively enrolled 52 patients with inoperable cervical cancer treated with chemoradiotherapy, who had undergone diffusion weighted MRI before treatment and post external beam radiotherapy (EBRT) and concurrent chemotherapy. A subgroup of patients (n = 28) underwent altogether six consecutive diffusion weighted MRIs; 1) pretreatment, 2) post-EBRT and concurrent chemotherapy; 3-5) during image-guided brachytherapy (IGBT) and 6) after completing the whole treatment course. To assess interobserver and intertechnique reproducibility two observers independently measured the ADCs by drawing freehand a large region of interest (L-ROI) covering the whole tumor and three small ROIs (S-ROIs) in areas with most restricted diffusion. RESULTS: Reproducibility was equally good for L-ROIs and S-ROIs. The pretreatment ADCs were higher in L-ROIs (883 mm2/s) than in S-ROIs (687 mm2/s, P < 0.001). The ADCs increased significantly between the pretreatment and post-EBRT scans (L-ROI: P < 0.001; S-ROI: P = 0.001). The ADCs remained significantly higher than pretreatment values during the whole IGBT. Using S-ROIs, greater increases in ADCs between pretreatment and post-EBRT MRI predicted better overall survival (P = 0.018). CONCLUSION: ADC values significantly increase during cervical cancer treatment. Greater increases in ADC values between pretreatment and post-EBRT predicted better overall survival using S-ROIs. Standardized methods for timing and delineation of ADC measurements are advocated in future studies.

Neoadjuvant chemotherapy induces an elevation of tumour apparent diffusion coefficient values in patients with ovarian cancer.

OBJECTIVES: Multiparametric magnetic resonance imaging (mMRI) is the modality of choice in the imaging of ovarian cancer (OC). We aimed to investigate the feasibility of different types of regions of interest (ROIs) in the measurement of apparent diffusion coefficient (ADC) values of diffusion-weighted imaging in OC patients treated with neoadjuvant chemotherapy (NACT). METHODS: We retrospectively enrolled 23 consecutive patients with advanced OC who had undergone NACT and mMRI. Seventeen of them had been imaged before and after NACT. Two observers independently measured the ADC values in both ovaries and in the metastatic mass by drawing on a single slice of (1) freehand large ROIs (L-ROIs) covering the solid parts of the whole tumour and (2) three small round ROIs (S-ROIs). The side of the primary ovarian tumour was defined. We evaluated the interobserver reproducibility and statistical significance of the change in tumoural pre- and post-NACT ADC values. Each patient's disease was defined as platinum-sensitive, semi-sensitive, or resistant. The patients were deemed either responders or non-responders. RESULTS: The interobserver reproducibility of the L-ROI and S-ROI measurements ranged from good to excellent (ICC range: 0.71-0.99). The mean ADC values were significantly higher after NACT in the primary tumour (L-ROI p < 0.001, S-ROIs p < 0.01), and the increase after NACT was associated with sensitivity to platinum-based chemotherapy. The changes in the ADC values of the omental mass were associated with a response to NACT. CONCLUSION: The mean ADC values of the primary tumour increased significantly after NACT in the OC patients, and the amount of increase in omental mass was associated with the response to platinum-based NACT. Our study indicates that quantitative analysis of ADC values with a single slice and a whole tumour ROI placement is a reproducible method that has a potential role in the evaluation of NACT response in patients with OC. TRIAL REGISTRATION: Retrospectively registered (institutional permission code: 5302501; date of the permission: 31.7.2020).

The effect of shunt surgery on corticospinal excitability in idiopathic normal pressure hydrocephalus: a transcranial magnetic stimulation study.

BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) is a multifactorial disease presenting with a classical symptom triad of cognitive decline, gait disturbance and urinary incontinence. The symptoms can be alleviated with shunt surgery but the etiology of the symptoms remains unclear. Navigated transcranial magnetic stimulation (nTMS) was applied to characterize corticospinal excitability and cortical motor function before and after shunt surgery in order to elucidate the pathophysiology of iNPH. We also aimed to determine, whether nTMS could be applied as a predictive tool in the pre-surgical work-up of iNPH. METHODS: 24 patients with possible or probable iNPH were evaluated at baseline, after cerebrospinal fluid drainage test (TAP test) and three months after shunt surgery (follow-up). Symptom severity was evaluated on an iNPH scale and with clinical tests (walking test, Box & Block test, grooved pegboard). In the nTMS experiments, resting motor threshold (RMT), silent period (SP), input-output curve (IO-curve), repetition suppression (RS) and mapping of cortical representation areas of hand and foot muscles were assessed. RESULTS: After shunt surgery, all patients showed improved performance in gait and upper limb function. The nTMS parameters showed an increase in the RMTs (hand and foot) and the maximum value of the IO-curve increased in subject with a good surgical outcome. The improvement in gait correlated with an increase in the maximum value of the IO-curve. SP, RS and mapping remained unchanged. CONCLUSION: The excitability of the motor cortex and the corticospinal tract increased in iNPH patients after shunt surgery. A favorable clinical outcome of shunt surgery is associated with a higher ability to re-form and maintain neuronal connectivity.

Association between breast cancer's prognostic factors and 3D textural features of non-contrast-enhanced T1 weighted breast MRI.

OBJECTIVES: The aim of this exploratory study was to evaluate whether three-dimensional texture analysis (3D-TA) features of non-contrast-enhanced T1 weighted MRI associate with traditional prognostic factors and disease-free survival (DFS) of breast cancer. METHODS: 3D-T1 weighted images from 78 patients with 81 malignant histopathologically verified breast lesions were retrospectively analysed using standard-size volumes of interest. Grey-level co-occurrence matrix (GLCM)-based features were selected for statistical analysis. In statistics the Mann-Whitney U and the Kruskal-Wallis tests, the Cox proportional hazards model and the Kaplan-Meier method were used. RESULTS: Tumours with higher histological grade were significantly associated with higher contrast (1 voxel: p = 0.033, 2 voxels: p = 0.036). All the entropy parameters showed significant correlation with tumour grade (p = 0.015-0.050) but there were no statistically significant associations between other TA parameters and tumour grade. The Nottingham Prognostic Index (NPI) was correlated with contrast and sum entropy parameters. A higher sum variance TA parameter was a significant predictor of shorter DFS. CONCLUSION: Texture parameters, assessed by 3D-TA from non-enhanced T1 weighted images, indicate tumour heterogeneity but have limited independent prognostic value. However, they are associated with tumour grade, NPI, and DFS. These parameters could be used as an adjunct to contrast-enhanced TA parameters. ADVANCES IN KNOWLEDGE: 3D-TA of non-contrast enhanced T1 weighted breast MRI associates with tumour grade, NPI, and DFS. The use of non-contrast 3D-TA parameters in adjunct with contrast-enhanced 3D-TA parameters warrants further research.

TMS-EEG Biomarkers of Amnestic Mild Cognitive Impairment Due to Alzheimer's Disease: A Proof-of-Concept Six Years Prospective Study.

Background: Early and affordable identification of subjects with amnestic mild cognitive impairment (aMCI) who will convert to Alzheimer's disease (AD) is a major scientific challenge. Objective: To investigate the neurophysiological hallmarks of sensorimotor cortex function in aMCI under the hypothesis that some may represent the plastic rearrangements induced by neurodegeneration, hence predictors of future conversion to AD. We sought to determine (1) whether the sensorimotor network shows peculiar alterations in patients with aMCI and (2) if sensorimotor network alterations predict long-term disease progression at the individual level. Methods: We studied several transcranial magnetic stimulation (TMS)-electroencephalogram (EEG) parameters of the sensorimotor cortex in a group of patients with aMCI and followed them for 6 years. We then identified aMCI who clinically converted to AD [prodromal to AD-MCI (pAD-MCI)] and those who remained cognitively stable [non-prodromal to AD-MCI (npAD-MCI)]. Results: Patients with aMCI showed reduced motor cortex (M1) excitability and disrupted EEG synchronization [decreased intertrial coherence (ITC)] in alpha, beta and gamma frequency bands compared to the control subjects. The degree of alteration in M1 excitability and alpha ITC was comparable between pAD-MCI and npAD-MCI. Importantly, beta and gamma ITC impairment in the stimulated M1 was greater in pAD-MCI than npAD-MCI. Furthermore, an additional parameter related to the waveform shape of scalp signals, reflecting time-specific alterations in global TMS-induced activity [stability of the dipolar activity (sDA)], discriminated npAD-MCI from MCI who will convert to AD. Discussion: The above mentioned specific cortical changes, reflecting deficit of synchronization within the cortico-basal ganglia-thalamo-cortical loop in aMCI, may reflect the pathological processes underlying AD. These changes could be tested in larger cohorts as neurophysiological biomarkers of AD.

Atlas-informed computational processing pipeline for individual targeting of brain areas for therapeutic navigated transcranial magnetic stimulation.

OBJECTIVE: Navigated transcranial magnetic stimulation (nTMS) is targeted at different cortical sites for diagnostic, therapeutic, and neuroscientific purposes. Correct identification of the cortical target areas is important for achieving desired effects, but it is challenging when no direct responses arise upon target area stimulation. We aimed at utilizing atlas-based marking of cortical areas for nTMS targeting to present a convenient, rater-independent method for overlaying the individual target sites with brain anatomy. METHODS: We developed a pipeline, which fits a brain atlas to the individual brain and enables visualization of the target areas during the nTMS session. We applied the pipeline to our previous nTMS data, focusing on depression and schizophrenia patients. Furthermore, we included examples of Tourette syndrome and tinnitus therapies, as well as neurosurgical and motor mappings. RESULTS: In depression and schizophrenia patients, the visually selected dorsolateral prefrontal cortex (DLPFC) targets were close to the border between atlas areas A9/46 and A8. In the other areas, the atlas-based areas were in agreement with the treatment targets. CONCLUSIONS: The atlas-based target areas agreed well with the cortical targets selected by experts during the treatments. SIGNIFICANCE: Overlaying atlas information over the navigation view is a convenient and useful add-on for improving nTMS targeting.

Heavy drinking from adolescence to young adulthood is associated with an altered cerebellum.

Excessive alcohol use results in cerebellar damage in adults, but there has been less research on how alcohol use during adolescence affects the cerebellum. In this study, we observed that heavy drinking from adolescence to young adulthood was associated with altered volumes of cerebellar lobules. The study included two groups consisting of 33 heavy-drinking and 25 light-drinking participants. The heavy-drinking participants were highly functional young adults without alcohol use disorder, but with a history of regular heavy alcohol consumption. The participants were 13-18 years old at baseline and were followed for 10 years. At the age of 21-28 years, the participants underwent magnetic resonance imaging (MRI). From the MR images, the cerebellum was segmented into 12 lobules using the CERES pipeline. Heavy drinking did not influence the absolute cerebellar volume, but changes were observed in posterior cerebellar lobules associated with motor and cognitive functions. The absolute volume (p = 0.038) and gray matter volume (p = 0.034) of Crus II (hemispheres combined) were smaller in the heavy-drinking group. Furthermore, the relative volume of the right VIIIB lobule was larger in the HD group (p = 0.036). However, there were no differences in the absolute right VIIIB volumes (p = 0.198) between the groups. Our results suggest changes in the cerebellum in healthy young adults with a history of heavy drinking from adolescence. The exact implications and significance of these findings require further research.

Primary hand motor representation areas in healthy children, preadolescents, adolescents, and adults.

The development of the organization of the motor representation areas in children and adolescents is not well-known. This cross-sectional study aimed to provide an understanding for the development of the functional motor areas of the upper extremity muscles by studying healthy right-handed children (6-9 years, n = 10), preadolescents (10-12 years, n = 13), adolescents (15-17 years, n = 12), and adults (22-34 years, n = 12). The optimal representation site and resting motor threshold (rMT) for the abductor pollicis brevis (APB) were assessed in both hemispheres using navigated transcranial magnetic stimulation (nTMS). Motor mapping was performed at 110% of the rMT while recording the EMG of six upper limb muscles in the hand and forearm. The association between the motor map and manual dexterity (box and block test, BBT) was examined. The mapping was well-tolerated and feasible in all but the youngest participant whose rMT exceeded the maximum stimulator output. The centers-of-gravity (CoG) for individual muscles were scattered to the greatest extent in the group of preadolescents and centered and became more focused with age. In preadolescents, the CoGs in the left hemisphere were located more laterally, and they shifted medially with age. The proportion of hand compared to arm representation increased with age (p = 0.001); in the right hemisphere, this was associated with greater fine motor ability. Similarly, there was less overlap between hand and forearm muscles representations in children compared to adults (p<0.001). There was a posterior-anterior shift in the APB hotspot coordinate with age, and the APB coordinate in the left hemisphere exhibited a lateral to medial shift with age from adolescence to adulthood (p = 0.006). Our results contribute to the elucidation of the developmental course in the organization of the motor cortex and its associations with fine motor skills. It was shown that nTMS motor mapping in relaxed muscles is feasible in developmental studies in children older than seven years of age.

Severe Obstructive Sleep Apnea and Increased Cortical Amyloid-ß Deposition.

BACKGROUND: The suggested association between severe obstructive sleep apnea (OSA) and risk of Alzheimer's disease (AD) needs further study. Only few recent reports exist on associations between brain amyloid-ß (Aß) burden and severe OSA in middle-aged patients. OBJECTIVE: Examine the possible presence of cortical Aß accumulation in middle-aged patients with severe OSA. METHODS: We performed detailed multimodal neuroimaging in 19 cognitive intact patients (mean 44.2 years) with severe OSA (Apnea-Hypopnea Index >30 h-1). Known etiological factors for possible Aß accumulation were used as exclusion criteria. Aß uptake was studied with [11C]-PiB-PET, glucose metabolism with [18F]-FDG-PET, and structural imaging with 3.0T MRI. RESULTS: When analyzed individually, in [11C]-PiB-PET a substantial number (∼32%) of the patients exhibited statistically significant evidence of increased cortical Aß uptake based on elevated regional Z-score values, mostly seen bilaterally in the precuneus and posterior cingulum regions. Cortical glucose hypometabolism in [18F]-FDG-PET was seen in two patients. MRI did not show structural changes suggestive of AD-related pathology. CONCLUSION: Increased [11C]-PiB uptake was seen in middle-aged cognitively intact patients with severe OSA. These findings are similar to those described in cognitive unimpaired older OSA patients. The changes in cortical Aß uptake suggest that severe OSA itself may predispose to alterations related to AD already in middle-age. Aß clearance may be compromised without simultaneous evidence of metabolic or structural alterations. The results emphasize the importance of early diagnostics and proper treatment of severe OSA in cognitively intact middle-aged subjects, possibly diminishing the individual risk for later cognitive dysfunction.

Brain Response Induced with Paired Associative Stimulation Is Related to Repetition Suppression of Motor Evoked Potential.

Repetition suppression (RS), i.e., the reduction of neuronal activity upon repetition of an external stimulus, can be demonstrated in the motor system using transcranial magnetic stimulation (TMS). We evaluated the RS in relation to the neuroplastic changes induced by paired associative stimulation (PAS). An RS paradigm, consisting of 20 trains of four identical suprathreshold TMS pulses 1 s apart, was assessed for motor-evoked potentials (MEPs) in 16 healthy subjects, before and following (at 0, 10, and 20 min) a common PAS protocol. For analysis, we divided RS into two components: (1) the ratio of the second MEP amplitude to the first one in RS trains, i.e., the "dynamic" component, and (2) the mean of the second to fourth MEP amplitudes, i.e., the "stable" component. Following PAS, five subjects showed change in the dynamic RS component. However, nearly all the individuals (n = 14) exhibited change in the stable component (p < 0.05). The stable component was similar between subjects showing increased MEPs and those showing decreased MEPs at this level (p = 0.254). The results suggest the tendency of the brain towards a stable state, probably free from the ongoing dynamics, following PAS.

Corticospinal excitability in idiopathic normal pressure hydrocephalus: a transcranial magnetic stimulation study.

BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) is a neurodegenerative disease with an unknown etiology. Disturbed corticospinal inhibition of the motor cortex has been reported in iNPH and can be evaluated in a noninvasive and painless manner using navigated transcranial magnetic stimulation (nTMS). This is the first study to characterize the immediate impact of cerebrospinal fluid (CSF) drainage on corticospinal excitability. METHODS: Twenty patients with possible or probable iNPH (16 women and 4 men, mean age 74.4 years, range 67-84 years), presenting the classical symptom triad and radiological findings, were evaluated with motor function tests (10-m walk test, Grooved Pegboard and Box & Block test) and nTMS (silent period, SP, resting motor threshold, RMT and input-output curve, IO-curve). Evaluations were performed at baseline and repeated immediately after CSF drainage via lumbar puncture. RESULTS: At baseline, iNPH patients presented shorter SPs (p < 0.001) and lower RMTs (p < 0.001) as compared to normative values. Positive correlation was detected between SP duration and Box & Block test (rho = 0.64, p = 0.002) in iNPH patients. CSF drainage led to an enhancement in gait velocity (p = 0.002) and a steeper IO-curve slope (p = 0.049). CONCLUSIONS: Shorter SPs and lower RMTs in iNPH suggest impaired corticospinal inhibition and corticospinal hyperexcitability. The steeper IO-slope in patients who improve their gait velocity after CSF drainage may indicate a higher recovery potential. Corticospinal excitability correlated with the motor function of the upper limbs implying that the disturbance in motor performance in iNPH extends beyond the classically reported gait impairment.

The Image Fusion Technique for Cochlear Implant Imaging: A Study of its Application for Different Electrode Arrays.

OBJECTIVES: To investigate the benefits of the image fusion technique for precise postoperative assessment of intracochlear placement with six different electrode arrays. STUDY DESIGN: Consecutive retrospective case study. SETTINGS: Tertiary referral center. PATIENTS: Analyses of imaging data of 30 patients implanted with six different electrode arrays. INTERVENTIONS: Electrode reconstructions obtained from postoperative cone-beam computed tomography (CBCT) were overlaid onto preoperative magnetic resonance imaging (MRI) and/or high-resolution computed tomography (HRCT) registrations to create artefact-free images. MAIN OUTCOME MEASURES: Each electrode's intracochlear position was analyzed with the image fusion reconstructions and compared with the results obtained by CBCT alone. The electrode location was classified according to its position in relation to the basal membrane at four different insertion angles. RESULTS: In 40 out of 151 measurements (26.5%), the location grading obtained by CBCT alone changed after the assessment with the image fusion reconstructions. A significant association was found between deep insertions (over 360 degrees) and the effectiveness of image fusion (p = 0.019). The difference between the impact of the fusion technique for the basal turn versus the apical part was highly significant (p = 0.001). There was no significant difference between the effectiveness of the image fusion and the different electrodes. CONCLUSIONS: By utilizing an image fusion technique, a more accurate assessment of electrode placement could be achieved for all types of electrodes. Image fusion was especially beneficial for insertions beyond 360 degrees.

The effect of coil placement and orientation on the assessment of focal excitability in motor mapping with navigated transcranial magnetic stimulation.

BACKGROUND: Navigated transcranial magnetic stimulation (nTMS) is used for mapping muscle representations in the primary motor cortex. We used sulcus-aligned mapping and electric field (E-field) modeling to investigate the excitability of the motor hand area for further understanding the methodological limitations of nTMS. NEW METHOD: We studied 10 healthy volunteers to locate the cortical target eliciting the largest responses (the hotspot) in the first dorsal interosseous (FDI) muscle. Six additional targets were placed along the central sulcus at 5-mm distances. Resting motor thresholds (rMTs) and optimal coil orientations were determined at all targets, and a conventional motor mapping was conducted. The cortical E-fields, induced by stimulating the targets with rMT intensities and optimal coil orientations, were modeled in a realistic head geometry to estimate the activated cortical sites. RESULTS: The rMTs increased with increasing distance from the hotspot (p < 0.001). The greatest motor-evoked potential (MEP) amplitudes occurred with the coil perpendicular to the sulcus and with the coil pointing towards the hotspot or the center of gravity of the motor map. The E-field strengths at the hotspot (99±26 V/m) remained above previously estimated thresholds for activation. COMPARISON WITH EXISTING METHODS: Depending on the target location, optimal coil orientations may deviate significantly from the conventional perpendicular-to-sulcus angle, which is often assumed optimal. These orientations seem to maintain the E-field stable in the hand knob, regardless of the sulcal shape near the stimulated target. CONCLUSIONS: The coil orientation is crucial for the accuracy of motor mapping, and the apparent motor map may extend due to remote hotspot activation.

Effects of long-term adolescent alcohol consumption on white matter integrity and their correlations with metabolic alterations.

Alcohol-related white matter (WM) microstructural changes have not been fully elucidated in adolescents. We aimed to investigate influences of subclinical alcohol use during adolescence on WM microstructure and to characterize those with serum metabolic alterations. 35 moderate-to-heavy drinkers (15 males, 20 females) and 27 controls (12 males, 15 females) were selected based on their ten-year Alcohol Use Disorders Identification Test scores measured at three time points. Magnetic resonance imaging was conducted at endpoint time. Whole brain analysis of fractional anisotropy (FA) was performed. Diffusivity indices in the significant regions were computed for between-group comparisons and correlation analyses with serum metabolite concentrations. Decreased FA was found in moderate-to-heavy drinking men in anterior corpus callosum, superior/anterior corona radiata and right inferior fronto-occipital fasciculus, accompanied by increased radial diffusivity and a smaller area of reduced axial diffusivity, which correlated with serum metabolites playing roles in energy metabolism, myelination and axonal degeneration. No significant difference in FA was detected between female or mixed-gender moderate-to-heavy drinking subjects and controls, supporting gender differences in the relationship between adolescent alcohol use and neurodevelopmental trajectories. Future researches with longitudinal imaging data are warranted for comprehensive evaluation on potentially reversible effects of alcohol use over adolescent brain.