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.

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).

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.

Maturation changes the excitability and effective connectivity of the frontal lobe: A developmental TMS-EEG study.

The combination of transcranial magnetic stimulation with simultaneous electroencephalography (TMS-EEG) offers direct neurophysiological insight into excitability and connectivity within neural circuits. However, there have been few developmental TMS-EEG studies to date, and they all have focused on primary motor cortex stimulation. In the present study, we used navigated high-density TMS-EEG to investigate the maturation of the superior frontal cortex (dorsal premotor cortex [PMd]), which is involved in a broad range of motor and cognitive functions known to develop with age. We demonstrated that reactivity to frontal cortex TMS decreases with development. We also showed that although frontal cortex TMS elicits an equally complex TEP waveform in all age groups, the statistically significant between-group differences in the topography of the TMS-evoked peaks and differences in current density maps suggest changes in effective connectivity of the right PMd with maturation. More generally, our results indicate that direct study of the brain's excitability and effective connectivity via TMS-EEG co-registration can also be applied to pediatric populations outside the primary motor cortex, and may provide useful information for developmental studies and studies on developmental neuropsychiatric disorders.

Functional and structural asymmetry in primary motor cortex in Asperger syndrome: a navigated TMS and imaging study.

Motor functions are frequently impaired in Asperger syndrome (AS). In this study, we examined the motor cortex structure and function using navigated transcranial magnetic stimulation (nTMS) and voxel-based morphometry (VBM) and correlated the results with the box and block test (BBT) of manual dexterity and physical activity in eight boys with AS, aged 8-11 years, and their matched controls. With nTMS, we found less focused cortical representation areas of distinct hand muscles in AS. There was hemispheric asymmetry in the motor maps, silent period duration and active MEP latency in the AS group, but not in controls. Exploratory VBM analysis revealed less gray matter in the left postcentral gyrus, especially in the face area, and less white matter in the precentral area in AS as compared to controls. On the contrary, in the right leg area, subjects with AS displayed an increased density of gray matter. The structural findings of the left hemisphere correlated negatively with BBT score in controls, whereas the structure of the right hemisphere in the AS group correlated positively with motor function as assessed by BBT. These preliminary functional (neurophysiological and behavioral) findings are indicative of asymmetry, and co-existing structural alterations may reflect the motor impairments causing the deteriorations in manual dexterity and other motor functions commonly encountered in children with AS.

Association of the N100 TMS-evoked potential with attentional processes: A motor cortex TMS-EEG study.

The most thoroughly studied transcranial magnetic stimulation (TMS)-evoked electroencephalogram (EEG) potential (TEP), N100, is often defined as a measure of cortical inhibition. We explored the association of the N100 amplitude with attention in 51 young healthy adults. Navigated TMS with simultaneous EEG registering was applied over the left primary motor cortex at the intensity of 110% of the resting motor threshold. Attention was assessed with the Paced Auditory Serial Addition Test (PASAT). We found a negative Pearson correlation (p = .023, r = -0.317) between the left centroparietal N100 amplitude and the PASAT score. Of the participants, the 17 with the highest PASAT scores and 17 with the lowes scores were selected for further analysis, in which a significant between-group difference in the left centroparietal N100 was found (p = .017). The topographic specificity of this finding was further confirmed with linear mixed model (LMM) analysis, in which significant differences were detected in the N100 amplitude; most prominently in the left centroparietal region (p = .001). A smaller N100 amplitude was associated with better performance in the attention task. Our findings suggest that the GABA-B-ergic TEP N100 is associated with attentional processes and thus represents cortical inhibition beyond motor inhibition.

Heavy alcohol use in adolescence is associated with altered cortical activity: a combined TMS-EEG study.

Long-term alcohol use affects cognitive and neurophysiological functioning as well as structural brain development. Combining simultaneous electroencephalogram (EEG) recording with transcranial magnetic stimulation (TMS) enables direct, in vivo exploration of cortical excitability and assessment of effective and functional connectivity. In the central nervous system, the effects of alcohol are particularly mediated by alterations in gamma-aminobutyric acid (GABA)ergic neurotransmission, and TMS-evoked potentials (TEPs) N45 and N100 in EEG are known to reflect GABAergic function. However, no previous studies have examined the effects of long-term alcohol use in adolescence on TEPs. In this study, a total of 27 young adults with heavy alcohol use in adolescence and 25 age-matched, gender-matched and education-matched controls with little or no alcohol use participated in TMS-EEG measurements. The motor cortex (M1) was stimulated with an intensity of 90 percent of the resting motor threshold of the abductor pollicis brevis muscle. No significant differences were found in the resting motor threshold, TEP latencies or neuropsychological functioning between the groups. We observed an increase in the global mean field power in the time window of 54- to 75-millisecond post-TMS, as well as significant topographical differences in the P60 and N100 in those with a history of heavy drinking. Furthermore, there was a marked increase in the GABAergic N45 amplitude in alcohol users. These findings suggest that long-term alcohol use in adolescence, even when not meeting the diagnostic criteria for a disorder, is associated with changes in connectivity and cortical excitability.

Bifrontal active and sham rTMS in treatment-resistant unipolar major depression.

BACKGROUND AND AIM: Prevention of the recurrence of major depression and its residual symptoms requires effective treatment. Our aim was to study the effects of bifrontal active rTMS controlled by sham rTMS in treatment-resistant unipolar major depressive disorder (MDD). METHODS: Thirty-seven patients with treatment-resistant MDD were randomized into two groups. One group received a total of 30 sessions of active bifrontal rTMS (10 Hz rTMS on left dorsolateral prefrontal cortex (DLPFC) and 1 Hz rTMS on right DLPFC) and the other group received bilateral sham rTMS on five days a week for six weeks. RESULTS: Depressive symptoms significantly improved in both the groups, but without a significant group difference. Furthermore, patients with psychotic depression improved similarly to those with moderate or severe depression. CONCLUSIONS: The results of present study indicate a large sham effect of stimulation treatment. The intensive structured treatment protocol may explain the positive outcome in both the groups. It is important to recognize, appreciate, and utilize placebo effects as a significant means of rehabilitation in psychiatric care.

Development of cortical motor circuits between childhood and adulthood: A navigated TMS-HdEEG study.

Motor functions improve during childhood and adolescence, but little is still known about the development of cortical motor circuits during early life. To elucidate the neurophysiological hallmarks of motor cortex development, we investigated the differences in motor cortical excitability and connectivity between healthy children, adolescents, and adults by means of navigated suprathreshold motor cortex transcranial magnetic stimulation (TMS) combined with high-density electroencephalography (EEG). We demonstrated that with development, the excitability of the motor system increases, the TMS-evoked EEG waveform increases in complexity, the magnitude of induced activation decreases, and signal spreading increases. Furthermore, the phase of the oscillatory response to TMS becomes less consistent with age. These changes parallel an improvement in manual dexterity and may reflect developmental changes in functional connectivity. Hum Brain Mapp 38:2599-2615, 2017. © 2017 Wiley Periodicals, Inc.

Sensorimotor cortex excitability and connectivity in Alzheimer's disease: A TMS-EEG Co-registration study.

Several studies have shown that, in spite of the fact that motor symptoms manifest late in the course of Alzheimer's disease (AD), neuropathological progression in the motor cortex parallels that in other brain areas generally considered more specific targets of the neurodegenerative process. It has been suggested that motor cortex excitability is enhanced in AD from the early stages, and that this is related to disease's severity and progression. To investigate the neurophysiological hallmarks of motor cortex functionality in early AD we combined transcranial magnetic stimulation (TMS) with electroencephalography (EEG). We demonstrated that in mild AD the sensorimotor system is hyperexcitable, despite the lack of clinically evident motor manifestations. This phenomenon causes a stronger response to stimulation in a specific time window, possibly due to locally acting reinforcing circuits, while network activity and connectivity is reduced. These changes could be interpreted as a compensatory mechanism allowing for the preservation of sensorimotor programming and execution over a long period of time, regardless of the disease's progression. Hum Brain Mapp 37:2083-2096, 2016. © 2016 Wiley Periodicals, Inc.

Incidentally detected enhancing lesions found in breast MRI: analysis of apparent diffusion coefficient and T2 signal intensity significantly improves specificity.

OBJECTIVES: To evaluate the value of adding T2- and diffusion-weighted imaging (DWI) to the BI-RADS® classification in MRI-detected lesions. METHODS: This retrospective study included 112 consecutive patients who underwent 3.0T structural breast MRI with T2- and DWI on the basis of EUSOMA recommendations. Morphological and kinetic features, T2 signal intensity (T2 SI) and apparent diffusion coefficient (ADC) findings were assessed. RESULTS: Thirty-three (29.5 %) patients (mean age 57.0 ± 12.7 years) had 36 primarily MRI-detected incidental lesions of which 16 (44.4 %) proved to be malignant. No single morphological or kinetic feature was associated with malignancy. Both low T2 SI (P = 0.009) and low ADC values (≤0.87 × 10-3 mm2s-1, P < 0.001) yielded high specificity (80.0 %/80.0 %). The BI-RADS classification supplemented with information from DWI and T2-WI improved the diagnostic performance of the BI-RADS classification as sensitivity remained 100 % and specificity improved from 30 % to 65.0 %. The numbers of false positive lesions declined from 39 % (N = 14) to 19 % (N = 7). CONCLUSION: MRI-detected incidental lesions may be challenging to characterize as they have few specific malignancy indicating features. The specificity of MRI can be improved by incorporating T2 SI and ADC values into the BI-RADS assessment. KEY POINTS: • MRI-detected incidental lesions have few specific malignancy indicating features. • ≥ 1 suspicious morphologic or kinetic feature may warrant biopsy. • T2 signal intensity and DWI assessment are feasible in primarily MRI-detected lesions. • T2 SI and DWI assessment improve the BI-RADS specificity in MRI-detected lesions.

Correlation analysis of demographic and anthropometric factors, hip flexion angle and conus medullaris displacement with unilateral and bilateral straight leg raise.

PURPOSE: It has been shown that the conus medullaris displaces significantly and consistently in response to both unilateral and bilateral SLRs. Point of interest is represented by whether the magnitude of this displacement can be predicted in asymptomatic subjects. The purpose was to investigate whether any correlations existed between demographic and anthropometric factors and hip flexion angle with magnitude of conus medullaris displacement with the unilateral and bilateral SLR. This was done following the notion that there is the possibility that cord movement may contain aspects of predictability in asymptomatic subjects. METHODS: Using the same methods as in our previous MRI studies, we further investigated whether any correlations existed between age, height, weight, BMI or hip flexion angle and magnitude of conus medullaris displacement with the unilateral and bilateral SLR. RESULTS: Moderate to strong positive correlation was found between degree of hip flexion and magnitude of conus medullaris caudal displacement with unilateral and bilateral SLRs and CuMeD. A negligible inverse correlation between subjects' height and magnitude of conus medullaris displacement in response to unilateral SLR was found, while no correlation (r < 0.1) emerged with bilateral SLR and CuMeD. No correlation was found for other values such as age, weight or BMI. CONCLUSIONS: The data show that in in vivo and structurally intact asymptomatic volunteers, the degree of hip flexion may have strong predictive values for magnitude of neural displacement in response to unilateral and bilateral SLRs. This provides further justification to its quantification in clinical settings. Magnitude of conus medullaris displacement in response to unilateral and bilateral SLRs is not likely to be predicted from easily clinically collectable measures such as age, height, weight and BMI. This study offers information relevant to investigation of prediction of neuromechanical responses in neurodynamic tests.

White matter degeneration with Unverricht-Lundborg progressive myoclonus epilepsy: a translational diffusion-tensor imaging study in patients and cystatin B-deficient mice.

PURPOSE: To study white matter (WM) changes in patients with Unverricht-Lundborg progressive myoclonus epilepsy (EPM1) caused by mutations in the cystatin B gene and in the cystatin B-deficient (Cstb-/-) mouse model and to validate imaging findings with histopathologic analysis of mice. MATERIALS AND METHODS: Informed consent was obtained and the study was approved by an institutional ethics committee. Animal work was approved by the Animal Experiment Board of Finland. Diffusion-tensor imaging and tract-based spatial statistics (TBSS) were used to compare fractional anisotropic (FA) results and axial, radial, and mean diffusion among patients with EPM1 (n = 19) and control subjects (n = 18). Ex vivo diffusion-tensor imaging and TBSS were used to compare Cstb-/- mice (n = 9) with wild controls (n = 4). Areas of FA decrease in mice were characterized by means of immunohistochemical analysis and transmission electron microscopy. Student t test statistics were applied to report significant findings (threshold-free cluster enhancement, P < .05). RESULTS: Patients with EPM1 showed significantly (P < .05) reduced FA and increased radial and mean diffusion in all major WM tracts compared with those of control subjects, shown as global FA decrease along the TBSS skeleton (0.41 ± 0.03 vs 0.45 ± 0.02, respectively; P < 5 × 10(-6)). Cstb-/- mice exhibited significantly reduced FA (P < .05) and antimyelin basic protein staining. Transmission electron microscopy revealed degenerating axons in Cstb-/- mice vs controls (979 axons counted, 51 degenerating axons; 2.09 ± 0.29 per field vs 1072 axons counted, nine degenerating axons; 0.48 ± 0.19 per field; P = .002). CONCLUSION: EPM1 is characterized by widespread alterations in subcortical WM, the thalamocortical system, and the cerebellum, which result in axonal degeneration and WM loss. These data suggest that motor disturbances and other symptoms in patients with EPM1 involve not only the cortical system but also the thalamocortical system and cerebellum.

Alterations of motor cortical excitability and anatomy in Unverricht-Lundborg disease.

Unverricht-Lundborg disease is the most common form of progressive myoclonus epilepsies. In addition to generalized seizures, it is characterized by myoclonus, which usually is the most disabling feature of the disease. Classically, the myoclonus has been attributed to increased excitability of the primary motor cortex. However, inhibitory cortical phenomena have also been described along with anatomical alterations. We aimed to characterize the relationship between the excitability and anatomy of the motor cortex and their association with the severity of the clinical symptoms. Seventy genetically verified patients were compared with forty healthy controls. The symptoms were evaluated with the Unified Myoclonus Rating Scale. Navigated transcranial magnetic stimulation was applied to characterize the excitability of the primary motor cortex by determining the motor thresholds and cortical silent periods. In addition, the induced cortical electric fields were estimated using individual scalp-to-cortex distances measured from MRIs. A cortical thickness analysis was performed to elucidate possible disease-related anatomical alterations. The motor thresholds, cortical electric fields, and silent periods were significantly increased in the patients (P < 0.01). The silent periods correlated with the myoclonus scores (r = 0.48 to r = 0.49, P < 0.001). The scalp-to-cortex distance increased significantly with disease duration (r = 0.56, P < 0.001) and correlated inversely with cortical thickness. The results may reflect the refractory nature of the myoclonus and indicate a possible reactive cortical inhibitory mechanism to the underlying disease process. This is the largest clinical series on Unverricht-Lundborg disease and the first study describing parallel pathophysiological and structural alterations associated with the severity of the symptoms.

Cavum septum pellucidum and psychopathy.

The presence of cavum septum pellucidum (CSP) has been reported to be a neurodevelopmental marker of psychopathy. We scanned 26 violent offenders and 25 controls; 2 offenders and 2 controls had CSP (8% in both groups). Thus, the presence of CSP is not a common or a unique feature of antisocial personality disorder or psychopathy.

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.

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.

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.