Role of visceral fat on postoperative complications and relapse in patients with Crohn's disease after ileocecal resection: Is it overrated?

INTRODUCTION: The role of visceral fat in disease development, particularly in Crohn´s disease (CD), is significant. However, its preoperative prognostic value for postoperative complications and CD relapse after ileocecal resection (ICR) remains unknown. This study aims to assess the predictive potential of preoperatively measured visceral and subcutaneous fat in postoperative complications and CD recurrence using magnetic resonance imaging (MRI). The primary endpoint was postoperative anastomotic leakage of the ileocolonic anastomosis, with secondary endpoints evaluating postoperative complications according to the Clavien Dindo classification and CD recurrence at the anastomosis. METHODS: We conducted a retrospective analysis of 347 CD patients who underwent ICR at our tertiary referral center between 2010 and 2020. We included 223 patients with high-quality preoperative MRI scans, recording demographics, postoperative outcomes, and CD recurrence rates at the anastomosis. To assess adipose tissue distribution, we measured total fat area (TFA), visceral fat area (VFA), subcutaneous fat area (SFA), and abdominal circumference (AC) at the lumbar 3 (L3) level using MRI cross-sectional images. Ratios of these values were calculated. RESULTS: None of the radiological variables showed an association with anastomotic leakage (TFA p = 0.932, VFA p = 0.982, SFA p = 0.951, SFA/TFA p = 0.422, VFA/TFA p = 0.422), postoperative complications, or CD recurrence (TFA p = 0.264, VFA p = 0.916, SFA p = 0.103, SFA/TFA p = 0.059, VFA/TFA p = 0.059). CONCLUSIONS: Radiological visceral obesity variables were associated with postoperative outcomes or clinical recurrence in CD patients undergoing ICR. Preoperative measurement of visceral fat measurement is not specific for predicting postoperative complications or CD relapse.

A prospective observational trial evaluating factors predictive of accurate endotracheal tube positioning in neonates and small infants.

BACKGROUND: There is a high incidence of endotracheal tube malposition in neonates and small infants. Yet, verification of accurate endotracheal tube location via radiographic imaging involves radiation exposure. AIMS: This study aimed to identify demographic and clinical parameters associated with accurate endotracheal tube positioning. METHODS: We conducted a prospective single-center study with term and preterm neonates and small infants between January 2018 and November 2019. We investigated correlations between ten variables and accurate endotracheal tube position. RESULTS: One hundred and sixty eight nasal intubations in 139 patients (weight 390-5000 g) were analyzed. An accurate tube position was confirmed by radiographic imaging in 71.4% of the intubations. The endotracheal tube was high in 8.3% and low in 20.2% of the cases. Male gender was the only variable that significantly correlated with an accurate endotracheal tube position (OR 2.5; 95% CI: 1.3, 5.0; P = .010). CONCLUSION: So far, no parameter has proven to be able to predict accurate endotracheal tube position in neonates reliably. These findings emphasize the indispensability of postintubation imaging in neonates and small infants.

Functional lesional neurosurgery for tremor: back to the future?

For nearly a century, functional neurosurgery has been applied in the treatment of tremor. While deep brain stimulation has been in the focus of academic interest in recent years, the establishment of incisionless technology, such as MRI-guided high-intensity focused ultrasound, has again stirred interest in lesional approaches.In this article, we will discuss the historical development of surgical technique and targets, as well as the technological state-of-the-art of conventional and incisionless interventions for tremor due to Parkinson's disease, essential and dystonic tremor and tremor related to multiple sclerosis (MS) and midbrain lesions. We will also summarise technique-inherent advantages of each technology and compare their lesion characteristics. From this, we identify gaps in the current literature and derive future directions for functional lesional neurosurgery, in particularly potential trial designs, alternative targets and the unsolved problem of bilateral lesional treatment. The results of a systematic review and meta-analysis of the consistency, efficacy and side effect rate of lesional treatments for tremor are presented separately alongside this article.

[Focused ultrasound ablation as tremor treatment]. / Fokussierter Ultraschall in der Behandlung von Tremor.

BACKGROUND: The development of high-intensity magnetic resonance imaging (MRI)-guided focused ultrasound (MRIgFUS) ablation has widened the spectrum of interventional techniques for stereotactic functional neurosurgery of lesions. This has resulted in novel incisionless intervention approaches for the therapy of tremor disorders. The safety and efficacy is documented by recent study data. OBJECTIVES: This article encompasses a description of the technological basis and typical course of MRIgFUS interventions, a comparison to alternative open or incisionless surgical techniques as well as a review of the current evidence base for MRIgFUS ablation in the context of lesional interventions to treat tremor. MATERIAL AND METHODS: Narrative literature review and comparison. RESULTS: Depending on the surgical target and tremor etiology published trials of MRIgFUS ablation report a reduction of tremor intensity of up to 80% after 6-12 months follow-up without the disadvantages of open brain surgery. CONCLUSION: The MRIgFUS functional neurosurgery is conducted only at a limited number of treatment sites. First data on lesions of the thalamic ventral intermediary nucleus (V.im.) as well as subthalamic fiber tracts have been published. These results indicate an effective and safe treatment of tremor disorders by MRIgFUS ablation. Incisionless lesional surgery using MRIgFUS is a significant addition to the interventional armamentarium for functional stereotactic neurosurgery and a potentially valuable alternative to established interventional therapy options for tremor disorders.

Effect of patent ductus arteriosus and patent foramen ovale on left ventricular stroke volume measurement by electrical velocimetry in comparison to transthoracic echocardiography in neonates.

This prospective single-center observational study compared impedance cardiography [electrical velocimetry (EV)] with transthoracic echocardiography (TTE, based on trans-aortic flow) and analyzed the influence of physiological shunts, such as patent ductus arteriosus (PDA) or patent foramen ovale (PFO), on measurement accuracy. Two hundred and ninety-one triplicate simultaneous paired left ventricular stroke volume (LVSV) measurements by EV (LVSVEV) and TTE (LVSVTTE) in 99 spontaneously breathing neonates (mean weight 3270 g; range 1227-4600 g) were included. For the whole cohort, the mean absolute LVSVEV was 5.5 mL, mean LVSVTTE was 4.9 mL, resulting in an absolute Bland-Altman bias of -0.7 mL (limits of agreement LOA -3.0 to 1.7 mL), relative bias -12.8 %; mean percentage error MPE 44.9 %; true precision TPEV 33.4 % (n = 99 aggregated data points). In neonates without shunts (n = 32): mean LVSVEV 5.0 mL, mean LVSVTTE 4.6 mL, Bland-Altman bias -0.4 mL (LOA -2.8 to 2.0 mL), relative bias -8.2 %; MPE 50.7 %; TPEV 40.9 %. In neonates with shunts (PDA and/or PFO; n = 67): mean LVSVEV 5.8 mL, mean LVSVTTE 5.0 mL, bias -0.8 mL (LOA -3.1 to 1.5 mL), relative bias -14.8 %, MPE 41.9 %, TPEV 29.3 %. Accuracy was affected by PDA and/or PFO, with a significant increase in the relative difference in LVSVEV versus LVSVTTE: Subjects without shunts -2.9 % (n = 91), PFO alone -9.6 % (n = 125), PDA alone -14.0 % (n = 12), and PDA and PFO -18.5 % (n = 63). Physiological shunts (PDA and/or PFO) in neonates affect measurement accuracy and cause overestimation of LVSVEV compared with LVSVTTE.

Subcortical glutamate mediates the reduction of short-range functional connectivity with age in a developmental cohort.

Marked changes in brain physiology and structure take place between childhood and adulthood, including changes in functional connectivity and changes in the balance between main excitatory and inhibitory neurotransmitters glutamate (Glu) and GABA. The balance of these neurotransmitters is thought to underlie neural activity in general and functional connectivity networks in particular, but so far no studies have investigated the relationship between human development related differences in these neurotransmitters and concomitant changes in functional connectivity. GABA+/H2O and Glu/H2O levels were acquired in a group of healthy children, adolescents, and adults in a subcortical (basal ganglia) region, as well as in a frontal region in adolescents and adults. Our results showed higher GABA+/Glu with age in both the subcortical and the frontal voxel, which were differentially associated with significantly lower Glu/H2O with age in the subcortical voxel and by significantly higher GABA+/H2O with age in the frontal voxel. Using a seed-to-voxel analysis, we were further able to show that functional connectivity between the putamen (seed) and other subcortical structures was lower with age. Lower subcortical Glu/H2O with age mediated the lower connectivity in the dorsal putamen. Based on these results, and the potential role of Glu in synaptic pruning, we suggest that lower Glu mediates a reduction of local connectivity during human development.

Identification of nuclear genes affecting 2-Deoxyglucose resistance in Schizosaccharomyces pombe.

2-Deoxyglucose (2-DG) is a toxic glucose analog. To identify genes involved in 2-DG toxicity in Schizosaccharomyces pombe, we screened a wild-type overexpression library for genes which render cells 2-DG resistant. A gene we termed odr1, encoding an uncharacterized hydrolase, led to strong resistance and altered invertase expression when overexpressed. We speculate that Odr1 neutralizes the toxic form of 2-DG, similar to the Saccharomyces cerevisiae Dog1 and Dog2 phosphatases which dephosphorylate 2-DG-6-phosphate synthesized by hexokinase. In a complementary approach, we screened a haploid deletion library to identify 2-DG-resistant mutants. This screen identified the genes snf5, ypa1, pas1 and pho7 In liquid medium, deletions of these genes conferred 2-DG resistance preferentially under glucose-repressed conditions. The deletion mutants expressed invertase activity more constitutively than the control strain, indicating defects in the control of glucose repression. No S. cerevisiae orthologs of the pho7 gene is known, and no 2-DG resistance has been reported for any of the deletion mutants of the other genes identified here. Moreover, 2-DG leads to derepressed invertase activity in S. pombe, while in S. cerevisiae it becomes repressed. Taken together, these findings suggest that mechanisms involved in 2-DG resistance differ between budding and fission yeasts.

Histidine degradation via an aminotransferase increases the nutritional flexibility of Candida glabrata.

The ability to acquire nutrients during infections is an important attribute in microbial pathogenesis. Amino acids are a valuable source of nitrogen if they can be degraded by the infecting organism. In this work, we analyzed histidine utilization in the fungal pathogen of humans Candida glabrata. Hemiascomycete fungi, like C. glabrata or Saccharomyces cerevisiae, possess no gene coding for a histidine ammonia-lyase, which catalyzes the first step of a major histidine degradation pathway in most other organisms. We show that C. glabrata instead initializes histidine degradation via the aromatic amino acid aminotransferase Aro8. Although ARO8 is also present in S. cerevisiae and is induced by extracellular histidine, the yeast cannot use histidine as its sole nitrogen source, possibly due to growth inhibition by a downstream degradation product. Furthermore, C. glabrata relies only on Aro8 for phenylalanine and tryptophan utilization, since ARO8, but not its homologue ARO9, was transcriptionally activated in the presence of these amino acids. Accordingly, an ARO9 deletion had no effect on growth with aromatic amino acids. In contrast, in S. cerevisiae, ARO9 is strongly induced by tryptophan and is known to support growth on aromatic amino acids. Differences in the genomic structure of the ARO9 gene between C. glabrata and S. cerevisiae indicate a possible disruption in the regulatory upstream region. Thus, we show that, in contrast to S. cerevisiae, C. glabrata has adapted to use histidine as a sole source of nitrogen and that the aromatic amino acid aminotransferase Aro8, but not Aro9, is the enzyme required for this process.

Impedance cardiography (electrical velocimetry) and transthoracic echocardiography for non-invasive cardiac output monitoring in pediatric intensive care patients: a prospective single-center observational study.

INTRODUCTION: Electrical velocimetry (EV) is a type of impedance cardiography, and is a non-invasive and continuously applicable method of cardiac output monitoring. Transthoracic echocardiography (TTE) is non-invasive but discontinuous. METHODS: We compared EV with TTE in pediatric intensive care patients in a prospective single-center observational study. Simultaneous, coupled, left ventricular stroke volume measurements were performed by EV using an Aesculon® monitor and TTE (either via trans-aortic valve flow velocity time integral [EVVTI], or via M-mode [EVMM]). H0: bias was less than 10% and the mean percentage error (MPE) was less than 30% in Bland-Altman analysis between EV and TTE. If appropriate, data were logarithmically transformed prior to Bland-Altman analysis. RESULTS: A total of 72 patients (age: 2 days to 17 years; weight: 0.8 to 86 kg) were analyzed. Patients were divided into subgroups: organ transplantation (OTX, n = 28), sepsis or organ failure (SEPSIS, n = 16), neurological patients (NEURO, n = 9), and preterm infants (PREM, n = 26); Bias/MPE for EVVTI was 7.81%/26.16%. In the EVVTI subgroup analysis for OTX, NEURO, and SEPSIS, bias and MPE were within the limits of H0, whereas the PREM subgroup had a bias/MPE of 39.00%/46.27%. Bias/MPE for EVMM was 8.07%/37.26% where the OTX and NEURO subgroups were within the range of H0, but the PREM and SEPSIS subgroups were outside the range. Mechanical ventilation, non-invasive continuous positive airway pressure ventilation, body weight, and secondary abdominal closure were factors that significantly affected comparison of the methods. CONCLUSIONS: This study shows that EV is comparable with aortic flow-based TTE for pediatric patients.

Association between early administration of high-dose erythropoietin in preterm infants and brain MRI abnormality at term-equivalent age.

IMPORTANCE: Premature infants are at risk of developing encephalopathy of prematurity, which is associated with long-term neurodevelopmental delay. Erythropoietin was shown to be neuroprotective in experimental and retrospective clinical studies. OBJECTIVE: To determine if there is an association between early high-dose recombinant human erythropoietin treatment in preterm infants and biomarkers of encephalopathy of prematurity on magnetic resonance imaging (MRI) at term-equivalent age. DESIGN, SETTING, AND PARTICIPANTS: A total of 495 infants were included in a randomized, double-blind, placebo-controlled study conducted in Switzerland between 2005 and 2012. In a nonrandomized subset of 165 infants (n=77 erythropoietin; n=88 placebo), brain abnormalities were evaluated on MRI acquired at term-equivalent age. INTERVENTIONS: Participants were randomly assigned to receive recombinant human erythropoietin (3000 IU/kg; n=256) or placebo (n=239) intravenously before 3 hours, at 12 to 18 hours, and at 36 to 42 hours after birth. MAIN OUTCOMES AND MEASURES: The primary outcome of the trial, neurodevelopment at 24 months, has not yet been assessed. The secondary outcome, white matter disease of the preterm infant, was semiquantitatively assessed from MRI at term-equivalent age based on an established scoring method. The resulting white matter injury and gray matter injury scores were categorized as normal or abnormal according to thresholds established in the literature by correlation with neurodevelopmental outcome. RESULTS: At term-equivalent age, compared with untreated controls, fewer infants treated with recombinant human erythropoietin had abnormal scores for white matter injury (22% [17/77] vs 36% [32/88]; adjusted risk ratio [RR], 0.58; 95% CI, 0.35-0.96), white matter signal intensity (3% [2/77] vs 11% [10/88]; adjusted RR, 0.20; 95% CI, 0.05-0.90), periventricular white matter loss (18% [14/77] vs 33% [29/88]; adjusted RR, 0.53; 95% CI, 0.30-0.92), and gray matter injury (7% [5/77] vs 19% [17/88]; adjusted RR, 0.34; 95% CI, 0.13-0.89). CONCLUSIONS AND RELEVANCE: In an analysis of secondary outcomes of a randomized clinical trial of preterm infants, high-dose erythropoietin treatment within 42 hours after birth was associated with a reduced risk of brain injury on MRI. These findings require assessment in a randomized trial designed primarily to assess this outcome as well as investigation of the association with neurodevelopmental outcomes. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00413946.

Print-specific multimodal brain activation in kindergarten improves prediction of reading skills in second grade.

Children who are poor readers usually experience troublesome school careers and consequently often suffer from secondary emotional and behavioural problems. Early identification and prediction of later reading problems thus are critical in order to start targeted interventions for those children with an elevated risk for emerging reading problems. In this study, behavioural precursors of reading were assessed in nineteen (aged 6.4 ± 0.3 years) non-reading kindergarteners before training letter-speech sound associations with a computerized game (Graphogame) for eight weeks. The training aimed to introduce the basic principles of letter-speech sound correspondences and to initialize the sensitization of specific brain areas to print. Event-related potentials (ERP) and functional magnetic resonance imaging (fMRI) data were recorded during an explicit word/symbol processing task after the training. Reading skills were assessed two years later in second grade. The focus of this study was on clarifying whether electrophysiological and fMRI data of kindergarten children significantly improve prediction of future reading skills in 2nd grade over behavioural data alone. Based on evidence from previous studies demonstrating the importance of initial print sensitivity in the left occipito-temporal visual word form system (VWFS) for learning to read, the first pronounced difference in processing words compared to symbols in the ERP, an occipito-temporal negativity (N1: 188-281 ms) along with the corresponding functional activation in the left occipito-temporal VWFS were defined as potential predictors. ERP and fMRI data in kindergarteners significantly improved the prediction of reading skills in 2nd grade over behavioural data alone. Together with the behavioural measures they explained up to 88% of the variance. An additional discriminant analysis revealed a remarkably high accuracy in classifying normal (n=11) and poor readers (n=6). Due to the key limitation of the study, i.e. the small group sizes, the results of our prediction analyses should be interpreted with caution and regarded as preliminary despite cross-validation. Nevertheless our results indicate the potential of combining neuroimaging and behavioural measures to improve prediction at an early stage, when literacy skills are acquired and interventions are most beneficial.

Developmental changes of functional and directed resting-state connectivities associated with neuronal oscillations in EEG.

Several studies demonstrated that resting-state EEG power differs tremendously between school-aged children and adults. Low-frequency oscillations (delta and theta, <7 Hz) are dominant in children but become less prominent in the adult brain, where higher-frequency alpha oscillations (8-12 Hz) dominate the mature brain rhythm. However, this assessment of developmental effects with EEG power mapping is restricted to the scalp level and blind to the information flow between brain regions, thus limiting insights about brain development. In contrast dynamic source synchronization provides a tool to study inter-regional directionality on the cortical and sub-cortical source level. In this study we investigated functional and directed connectivities (information flow) with renormalized partial directed coherence during resting state EEG (eyes open and eyes closed) recordings in 17 school-aged children and 17 young adults. First, we found higher spectral mean source power in children relative to adults, irrespective of the examined frequency band and resting state. We further found that coherence values were stronger in adults compared to children in all frequency bands. The directed within-group coherence analysis indicated information flow from frontal to parietal sources in children, while information flow from parietal to frontal was observed in adults. In addition, significant thalamocortical connectivity was unidirectional (i.e., outflow to cortical regions) in adults, but bidirectional in children. Group comparison confirmed the results of the single subject analyses for both functional and directed connectivities. Our results suggest that both functional and directed connectivities are sensitive to brain maturation as the distribution and directionality of functional connections differ between the developing and adult brains.

Neural activity in the hippocampus predicts individual visual short-term memory capacity.

Although the hippocampus had been traditionally thought to be exclusively involved in long-term memory, recent studies raised controversial explanations why hippocampal activity emerged during short-term memory tasks. For example, it has been argued that long-term memory processes might contribute to performance within a short-term memory paradigm when memory capacity has been exceeded. It is still unclear, though, whether neural activity in the hippocampus predicts visual short-term memory (VSTM) performance. To investigate this question, we measured BOLD activity in 21 healthy adults (age range 19-27 yr, nine males) while they performed a match-to-sample task requiring processing of object-location associations (delay period = 900 ms; set size conditions 1, 2, 4, and 6). Based on individual memory capacity (estimated by Cowan's K-formula), two performance groups were formed (high and low performers). Within whole brain analyses, we found a robust main effect of "set size" in the posterior parietal cortex (PPC). In line with a "set size × group" interaction in the hippocampus, a subsequent Finite Impulse Response (FIR) analysis revealed divergent hippocampal activation patterns between performance groups: Low performers (mean capacity = 3.63) elicited increased neural activity at set size two, followed by a drop in activity at set sizes four and six, whereas high performers (mean capacity = 5.19) showed an incremental activity increase with larger set size (maximal activation at set size six). Our data demonstrated that performance-related neural activity in the hippocampus emerged below capacity limit. In conclusion, we suggest that hippocampal activity reflected successful processing of object-location associations in VSTM. Neural activity in the PPC might have been involved in attentional updating.

Long-term neurodevelopmental outcome with hypoxic-ischemic encephalopathy.

OBJECTIVES: To determine the long-term neurodevelopmental outcome for children after hypoxic-ischemic encephalopathy (HIE) without major disability, and to examine neonatal injury patterns detected on cerebral magnetic resonance imaging (MRI) in relation to later deficits. STUDY DESIGN: Prospectively enrolled children with HIE and neonatal cerebral MRI data (n = 68) were examined at a mean age of 11.2 years (range, 8.2-15.7 years). Eleven children had a major disability (ie, cerebral palsy or mental retardation). Brain injury was scored according to the region and extent of injury. RESULTS: Children without major disability (n = 57) had lower full-scale and performance IQ scores compared with norms (P = .02 and .01, respectively), and the proportion of children with an IQ <85 was higher than expected (P = .04). Motor performance on the Zurich Neuromotor Assessment was affected in the pure motor, adaptive fine motor, and gross motor domains, as well as in the movement quality domain (all P < .001). Watershed injury pattern on neonatal MRI correlated with full-scale and verbal IQ scores (P = .006 and <.001, respectively), but neonatal MRI pattern did not correlate with motor performance in children without major disability. CONCLUSION: Children who sustained neonatal HIE without major disability are at increased risk for long-term intellectual, verbal, and motor deficits. The severity of watershed injury is correlated with later intellectual performance. Long-term follow-up examinations are necessary for early detection of neurodevelopmental impairment and early initiation of adequate therapies.

Comparison of temperature processing methods for monitoring focused ultrasound ablation in the brain.

PURPOSE: To investigate the performance of different reconstruction methods for monitoring temperature changes during transcranial magnetic resonance imaging (MRI)-guided focused ultrasound (MRgFUS). MATERIALS AND METHODS: Four different temperature reconstruction methods were compared in volunteers (without heating) and patients undergoing transcranial MRgFUS: single baseline subtraction, multibaseline subtraction, hybrid single baseline/referenceless reconstruction, and hybrid multibaseline/referenceless reconstruction. Absolute temperature error and temporal temperature uncertainty of the different reconstruction methods were analyzed and compared. RESULTS: Absolute temperature errors and temporal temperature uncertainty were highest with single baseline subtraction and lowest with hybrid multibaseline/referenceless reconstruction in all areas of the brain. Pulsation of the brain and susceptibility changes from tongue motion or swallowing caused substantial temperature errors when single or multibaseline subtraction was used, which were much reduced when the referenceless component was added to the reconstruction. CONCLUSION: Hybrid multibaseline/referenceless thermometry accurately measures temperature changes in the brain with fewer artifacts and errors due to motion than pure baseline subtraction methods.

Back seat driving: hindlimb corticospinal neurons assume forelimb control following ischaemic stroke.

Whereas large injuries to the brain lead to considerable irreversible functional impairments, smaller strokes or traumatic lesions are often associated with good recovery. This recovery occurs spontaneously, and there is ample evidence from preclinical studies to suggest that adjacent undamaged areas (also known as peri-infarct regions) of the cortex 'take over' control of the disrupted functions. In rodents, sprouting of axons and dendrites has been observed in this region following stroke, while reduced inhibition from horizontal or callosal connections, or plastic changes in subcortical connections, could also occur. The exact mechanisms underlying functional recovery after small- to medium-sized strokes remain undetermined but are of utmost importance for understanding the human situation and for designing effective treatments and rehabilitation strategies. In the present study, we selectively destroyed large parts of the forelimb motor and premotor cortex of adult rats with an ischaemic injury. A behavioural test requiring highly skilled, cortically controlled forelimb movements showed that some animals recovered well from this lesion whereas others did not. To investigate the reasons behind these differences, we used anterograde and retrograde tracing techniques and intracortical microstimulation. Retrograde tracing from the cervical spinal cord showed a correlation between the number of cervically projecting corticospinal neurons present in the hindlimb sensory-motor cortex and good behavioural recovery. Anterograde tracing from the hindlimb sensory-motor cortex also showed a positive correlation between the degree of functional recovery and the sprouting of neurons from this region into the cervical spinal cord. Finally, intracortical microstimulation confirmed the positive correlation between rewiring of the hindlimb sensory-motor cortex and the degree of forelimb motor recovery. In conclusion, these experiments suggest that following stroke to the forelimb motor cortex, cells in the hindlimb sensory-motor area reorganize and become functionally connected to the cervical spinal cord. These new connections, probably in collaboration with surviving forelimb neurons and more complex indirect connections via the brainstem, play an important role for the recovery of cortically controlled behaviours like skilled forelimb reaching.

Brain sensitivity to print emerges when children learn letter-speech sound correspondences.

The acquisition of reading skills is a major landmark process in a human's cognitive development. On the neural level, a new functional network develops during this time, as children typically learn to associate the well-known sounds of their spoken language with unfamiliar characters in alphabetic languages and finally access the meaning of written words, allowing for later reading. A critical component of the mature reading network located in the left occipito-temporal cortex, termed the "visual word-form system" (VWFS), exhibits print-sensitive activation in readers. When and how the sensitivity of the VWFS to print comes about remains an open question. In this study, we demonstrate the initiation of occipito-temporal cortex sensitivity to print using functional MRI (fMRI) (n = 16) and event-related potentials (ERP) (n = 32) in a controlled, longitudinal training study. Print sensitivity of fast (<250 ms) processes in posterior occipito-temporal brain regions accompanied basic associative learning of letter-speech sound correspondences in young (mean age 6.4 +/- 0.08 y) nonreading kindergarten children, as shown by concordant ERP and fMRI results. The occipito-temporal print sensitivity thus is established during the earliest phase of reading acquisition in childhood, suggesting that a crucial part of the later reading network first adopts a role in mapping print and sound.

Brain state regulation during normal development: Intrinsic activity fluctuations in simultaneous EEG-fMRI.

Brain maturation in adolescence is mirrored by the EEG as a pronounced decrease in low frequency activity. This EEG power attenuation parallels reductions of structural and metabolic markers of neuronal maturation (i.e., gray matter loss and decrease of absolute cerebral glucose utilization). However, it is largely unknown what causes these electrophysiological changes, and how this functional reorganization relates to other functional measures such as the fMRI BOLD signal. In this study, we used simultaneously recorded EEG and fMRI to localize hemodynamic correlates of fluctuating EEG oscillations and to study the development of this EEG-BOLD coupling. Furthermore, the maturational EEG power attenuation was directly compared to BOLD signal power maturation. Both analyses were novel in their developmental perspective and aimed at providing a functional lead to EEG maturation. Data from 19 children, 18 adolescents and 18 young adults were acquired in 10 min eyes-open/eyes-closed resting states. Our results revealed that both EEG and BOLD amplitudes strongly decrease between childhood and adulthood, but their functional coupling remains largely unchanged. The global reduction of absolute amplitude of spontaneous slow BOLD signal fluctuation is a novel marker for brain maturation, and parallels the globally decreasing trajectories of EEG amplitudes, gray matter and glucose metabolism during adolescence. Further, the absence of thalamocortical EEG-BOLD coupling in children together with age-related normalized thalamic BOLD power increase indicated maturational changes in brain state regulation.

Transcranial magnetic resonance imaging-guided focused ultrasound: noninvasive central lateral thalamotomy for chronic neuropathic pain.

OBJECT: Recent technological developments open the field of therapeutic application of focused ultrasound to the brain through the intact cranium. The goal of this study was to apply the new transcranial magnetic resonance imaging-guided focused ultrasound (tcMRgFUS) technology to perform noninvasive central lateral thalamotomies (CLTs) as a treatment for chronic neuropathic pain. METHODS: In 12 patients suffering from chronic therapy-resistant neuropathic pain, tcMRgFUS CLT was proposed. In 11 patients, precisely localized thermal ablations of 3-4 mm in diameter were produced in the posterior part of the central lateral thalamic nucleus at peak temperatures between 51 ° C and 64 ° C with the aid of real-time patient monitoring and MR imaging and MR thermometry guidance. The treated neuropathic pain syndromes had peripheral (5 patients) or central (6 patients) origins and covered all body parts (face, arm, leg, trunk, and hemibody). RESULTS: Patients experienced mean pain relief of 49% at the 3-month follow-up (9 patients) and 57% at the 1-year follow-up (8 patients). Mean improvement according to the visual analog scale amounted to 42% at 3 months and 41% at 1 year. Six patients experienced immediate and persisting somatosensory improvements. Somatosensory and vestibular clinical manifestations were always observed during sonication time because of ultrasound-based neuronal activation and/or initial therapeutic effects. Quantitative electroencephalography (EEG) showed a significant reduction in EEG spectral overactivities. Thermal ablation sites showed sharply delineated ellipsoidal thermolesions surrounded by short-lived vasogenic edema. Lesion reconstructions (18 lesions in 9 patients) demonstrated targeting precision within a millimeter for all 3 coordinates. There was 1 complication, a bleed in the target with ischemia in the motor thalamus, which led to the introduction of 2 safety measures, that is, the detection of a potential cavitation by a cavitation detector and the maintenance of sonication temperatures below 60 ° C. CONCLUSIONS: The authors assert that tcMRgFUS represents a noninvasive, precise, and radiation-free neurosurgical technique for the treatment of neuropathic pain. The procedure avoids mechanical brain tissue shift and eliminates the risk of infection. The possibility of applying sonication thermal spots free from trajectory restrictions should allow one to optimize target coverage. The real-time continuous MR imaging and MR thermometry monitoring of targeting accuracy and thermal effects are major factors in optimizing precision, safety, and efficacy in an outpatient context.