Chronic low-frequency rTMS of primary motor cortex diminishes exercise training-induced gains in maximal voluntary force in humans.

Although there is consensus that the central nervous system mediates the increases in maximal voluntary force (maximal voluntary contraction, MVC) produced by resistance exercise, the involvement of the primary motor cortex (M1) in these processes remains controversial. We hypothesized that 1-Hz repetitive transcranial magnetic stimulation (rTMS) of M1 during resistance training would diminish strength gains. Forty subjects were divided equally into five groups. Subjects voluntarily (Vol) abducted the first dorsal interosseus (FDI) (5 bouts x 10 repetitions, 10 sessions, 4 wk) at 70-80% MVC. Another group also exercised but in the 1-min-long interbout rest intervals they received rTMS [Vol+rTMS, 1 Hz, FDI motor area, 300 pulses/session, 120% of the resting motor threshold (rMT)]. The third group also exercised and received sham rTMS (Vol+Sham). The fourth group received only rTMS (rTMS_only). The 37.5% and 33.3% gains in MVC in Vol and Vol+Sham groups, respectively, were greater (P = 0.001) than the 18.9% gain in Vol+rTMS, 1.9% in rTMS_only, and 2.6% in unexercised control subjects who received no stimulation. Acutely, within sessions 5 and 10, single-pulse TMS revealed that motor-evoked potential size and recruitment curve slopes were reduced in Vol+rTMS and rTMS_only groups and accumulated to chronic reductions by session 10. There were no changes in rMT, maximum compound action potential amplitude (M(max)), and peripherally evoked twitch forces in the trained FDI and the untrained abductor digiti minimi. Although contributions from spinal sources cannot be excluded, the data suggest that M1 may play a role in mediating neural adaptations to strength training.

Polychlorinated trityl radicals for dynamic nuclear polarization: the role of chlorine nuclei

Polychlorinated trityl radicals bearing carboxylate substituents are water soluble persistent radicals that can be used for dynamic nuclear polarization. In contrast to other trityl radicals, the polarization mechanism differs from the classical solid effect. DFT calculations performed to rationalize this behaviour support the hypothesis that polarization is transferred from the unpaired electron to chlorine nuclei and from these to carbon by spin diffusion. The marked differences observed between neutral and anionic forms of the radical will be discussed.

Long-lived States in an intrinsically disordered protein domain

Long-lived states (LLS) are relaxation-favoured eigenstates of J-coupled magnetic nuclei. LLS were measured, along with classical 1H and 15 N relaxation rate constants, in aminoacids of the N-terminal Unique domain of the c-Src kinase (USrc), which is disordered in vitro under physiological conditions. The relaxation rates of LLS are a probe for motions and interactions in biomolecules. LLS of the aliphatic protons of glycines, with lifetimes ca. four times longer than their spin-lattice relaxation times, are reported for the first time in an intrinsically disordered protein domain (IDP). LLS relaxation experiments were integrated with 2D spectroscopy methods, further adapting them for studies on proteins.

Memòria, reorganització cerebral evidenciada amb fMRI i hipocamp

Aquesta pretén ser una revisió general dels processos cognitius normals i de la capacitat de reorganització cerebral en cas de dany cerebral adquirit (lesions i malalties neurodegeneratives).

Neurophysiological changes during shortening osteotomies of the spine.

BACKGROUND CONTEXT: Kyphotic deformities with sagittal imbalance of the spine can be treated with spinal osteotomies. Those procedures are known to have a high incidence of neurological complications, in particular at the thoracic level. Motor evoked potentials (MEPs) have been widely used in helping to avoid major neurological deficits postoperatively. Previous reports have shown that a significant proportion of such cases present with important transcranial MEP (Tc-MEP) changes during surgery with some of them being predictive of postoperative deficits. PURPOSE: Our aim was to study Tc-MEP changes in a consecutive series of patients and correlate them with clinical parameters and radiological changes. STUDY DESIGN/SETTING: Retrospective case notes study from a prospective patient register. PATIENT SAMPLE: Eighteen patients undergoing posterior shortening osteotomies (nine at thoracic and nine at lumbar levels) for kyphosis of congenital, degenerative, inflammatory, or post-traumatic origin were included. OUTCOME MEASURES: Loss of at least 80% of Tc-MEP signal expressed as the area under the curve percentual change, of at least one muscle. METHODS: We studied the relation between outcome measure (80% Tc-MEP loss in at least one muscle group) and amount of posterior vertebral body shortening as well as angular correction measured on computed tomography scans, occurrence of postoperative deficits, intraoperative blood pressure at the time of the osteotomy, and hemoglobin (Hb) change. RESULTS: All patients showed significant Tc-MEP changes. In particular, greater than 80% MEP loss in at least one muscle group was observed in five of nine patients in the thoracic group and four of nine patients in the lumbar group. No surgical maneuver was undertaken as a result of this loss in an effort to improve motor responses other than verifying the stability of the construct and the extent of the decompression. Four patients developed postoperative deficits of radicular origin, three of them recovering fully at 3 months. No relation was found between intraoperative blood pressure, Hb changes, and Tc-MEP changes. Severity of Tc-MEP loss did not correlate with postoperative deficits. Shortening of more than 10 mm was linked to more severe Tc-MEP changes in the thoracic group. CONCLUSIONS: Transcranial MEP changes during spinal shortening procedures are common and do not appear to predict severe postoperative deficits. Total loss of Tc-MEP (not witnessed in our series) might require a more drastic approach with possible reversal of the correction and wake-up test.

Meta-structure correlation in protein space unveils different selection rules for folded and intrinsically disordered proteins

The number of existing protein sequences spans a very small fraction of sequence space. Natural proteins have overcome a strong negative selective pressure to avoid the formation of insoluble aggregates. Stably folded globular proteins and intrinsically disordered proteins (IDP) use alternative solutions to the aggregation problem. While in globular proteins folding minimizes the access to aggregation prone regions IDPs on average display large exposed contact areas. Here, we introduce the concept of average meta-structure correlation map to analyze sequence space. Using this novel conceptual view we show that representative ensembles of folded and ID proteins show distinct characteristics and responds differently to sequence randomization. By studying the way evolutionary constraints act on IDPs to disable a negative function (aggregation) we might gain insight into the mechanisms by which function - enabling information is encoded in IDPs.

Auditory spatio-temporal brain dynamics and their consequences for multisensory interactions in humans.

Recent multisensory research has emphasized the occurrence of early, low-level interactions in humans. As such, it is proving increasingly necessary to also consider the kinds of information likely extracted from the unisensory signals that are available at the time and location of these interaction effects. This review addresses current evidence regarding how the spatio-temporal brain dynamics of auditory information processing likely curtails the information content of multisensory interactions observable in humans at a given latency and within a given brain region. First, we consider the time course of signal propagation as a limitation on when auditory information (of any kind) can impact the responsiveness of a given brain region. Next, we overview the dual pathway model for the treatment of auditory spatial and object information ranging from rudimentary to complex environmental stimuli. These dual pathways are considered an intrinsic feature of auditory information processing, which are not only partially distinct in their associated brain networks, but also (and perhaps more importantly) manifest only after several tens of milliseconds of cortical signal processing. This architecture of auditory functioning would thus pose a constraint on when and in which brain regions specific spatial and object information are available for multisensory interactions. We then separately consider evidence regarding mechanisms and dynamics of spatial and object processing with a particular emphasis on when discriminations along either dimension are likely performed by specific brain regions. We conclude by discussing open issues and directions for future research.

Cardiac motion estimation by joint alignment of tagged MRI sequences

Image registration has been proposed as an automatic method for recovering cardiac displacement fields from Tagged Magnetic Resonance Imaging (tMRI) sequences. Initially performed as a set of pairwise registrations, these techniques have evolved to the use of 3D+t deformation models, requiring metrics of joint image alignment (JA). However, only linear combinations of cost functions defined with respect to the first frame have been used. In this paper, we have applied k-Nearest Neighbors Graphs (kNNG) estimators of the -entropy (H ) to measure the joint similarity between frames, and to combine the information provided by different cardiac views in an unified metric. Experiments performed on six subjects showed a significantly higher accuracy (p < 0.05) with respect to a standard pairwise alignment (PA) approach in terms of mean positional error and variance with respect to manually placed landmarks. The developed method was used to study strains in patients with myocardial infarction, showing a consistency between strain, infarction location, and coronary occlusion. This paper also presentsan interesting clinical application of graph-based metric estimators, showing their value for solving practical problems found in medical imaging.

Organization and plasticity of auditory spatial representations

Spatial hearing refers to a set of abilities enabling us to determine the location of sound sources, redirect our attention toward relevant acoustic events, and recognize separate sound sources in noisy environments. Determining the location of sound sources plays a key role in the way in which humans perceive and interact with their environment. Deficits in sound localization abilities are observed after lesions to the neural tissues supporting these functions and can result in serious handicaps in everyday life. These deficits can, however, be remediated (at least to a certain degree) by the surprising capacity of reorganization that the human brain possesses following damage and/or learning, namely, the brain plasticity. In this thesis, our aim was to investigate the functional organization of auditory spatial functions and the learning-induced plasticity of these functions. Overall, we describe the results of three studies. The first study entitled "The role of the right parietal cortex in sound localization: A chronometric single pulse transcranial magnetic stimulation study" (At et al., 2011), study A, investigated the role of the right parietal cortex in spatial functions and its chronometry (i.e. the critical time window of its contribution to sound localizations). We concentrated on the behavioral changes produced by the temporarily inactivation of the parietal cortex with transcranial magnetic stimulation (TMS). We found that the integrity of the right parietal cortex is crucial for localizing sounds in the space and determined a critical time window of its involvement, suggesting a right parietal dominance for auditory spatial discrimination in both hemispaces. In "Distributed coding of the auditory space in man: evidence from training-induced plasticity" (At et al., 2013a), study B, we investigated the neurophysiological correlates and changes of the different sub-parties of the right auditory hemispace induced by a multi-day auditory spatial training in healthy subjects with electroencephalography (EEG). We report a distributed coding for sound locations over numerous auditory regions, particular auditory areas code specifically for precise parts of the auditory space, and this specificity for a distinct region is enhanced with training. In the third study "Training-induced changes in auditory spatial mismatch negativity" (At et al., 2013b), study C, we investigated the pre-attentive neurophysiological changes induced with a training over 4 days in healthy subjects with a passive mismatch negativity (MMN) paradigm. We showed that training changed the mechanisms for the relative representation of sound positions and not the specific lateralization themselves and that it changed the coding in right parahippocampal regions. - L'audition spatiale désigne notre capacité à localiser des sources sonores dans l'espace, de diriger notre attention vers les événements acoustiques pertinents et de reconnaître des sources sonores appartenant à des objets distincts dans un environnement bruyant. La localisation des sources sonores joue un rôle important dans la façon dont les humains perçoivent et interagissent avec leur environnement. Des déficits dans la localisation de sons sont souvent observés quand les réseaux neuronaux impliqués dans cette fonction sont endommagés. Ces déficits peuvent handicaper sévèrement les patients dans leur vie de tous les jours. Cependant, ces déficits peuvent (au moins à un certain degré) être réhabilités grâce à la plasticité cérébrale, la capacité du cerveau humain à se réorganiser après des lésions ou un apprentissage. L'objectif de cette thèse était d'étudier l'organisation fonctionnelle de l'audition spatiale et la plasticité induite par l'apprentissage de ces fonctions. Dans la première étude intitulé « The role of the right parietal cortex in sound localization : A chronometric single pulse study » (At et al., 2011), étude A, nous avons examiné le rôle du cortex pariétal droit dans l'audition spatiale et sa chronométrie, c'est-à- dire le moment critique de son intervention dans la localisation de sons. Nous nous sommes concentrés sur les changements comportementaux induits par l'inactivation temporaire du cortex pariétal droit par le biais de la Stimulation Transcrânienne Magnétique (TMS). Nous avons démontré que l'intégrité du cortex pariétal droit est cruciale pour localiser des sons dans l'espace. Nous avons aussi défini le moment critique de l'intervention de cette structure. Dans « Distributed coding of the auditory space : evidence from training-induced plasticity » (At et al., 2013a), étude B, nous avons examiné la plasticité cérébrale induite par un entraînement des capacités de discrimination auditive spatiale de plusieurs jours. Nous avons montré que le codage des positions spatiales est distribué dans de nombreuses régions auditives, que des aires auditives spécifiques codent pour des parties données de l'espace et que cette spécificité pour des régions distinctes est augmentée par l'entraînement. Dans « Training-induced changes in auditory spatial mismatch negativity » (At et al., 2013b), étude C, nous avons examiné les changements neurophysiologiques pré- attentionnels induits par un entraînement de quatre jours. Nous avons montré que l'entraînement modifie la représentation des positions spatiales entraînées et non-entrainées, et que le codage de ces positions est modifié dans des régions parahippocampales.

Posibilidades diagnósticas de la Tomografía por Emisión de Positrones (PET): Aplicaciones en la patología oncológica bucal y maxilofacial

Se describen los principios de la tomografía por emisión de positrones (PET) como procedimiento diagnóstico de reciente introducción en el campo de las Ciencias de la Salud. Las aplicaciones clínicas principales se dan en un grupo concreto de especialidades: la cardiología, neurología, psiquiatría y sobre todo la oncología. La tomografía por emisión de positrones es una técnica de diagnóstico por la imagen no invasiva de uso clínico. Se trata de una excelente herramienta para el estudio de la estadificación y la posible malignización de los tumores de cabeza y cuello, la detección de metástasis y linfoadenopatías no valorables clínicamente, así como para el diagnóstico de recidivas tumorales. El único trazador que tiene aplicación clínica es la fluor-desoxiglucosa- F18 o FDG. La PET detecta la intensa acumulación de FDG que se produce en los tumores malignos, debido al mayor índice glicolítico que tienen las células neoplásicas. Con la introducción de sistemas híbridos que combinan la tomografía computadorizada o la resonancia magnética con la tomografía por emisión de positrones, se está produciendo un importante avance en el diagnóstico y el seguimiento de la patología oncológica de cabeza y cuello.

Intraoperative cerebral perfusion in geriatric patients

Background: It is unknown whether cerebral perfusion in geriatric and younger patients under general anaesthesia differs. Methods: We compared 2 groups of patients undergoing elective major non-cardiac surgery under standardized general anaesthesia (thiopental, sevoflurane, fentanyl, atracurium). Group 1: 18-40 yrs (n = 20), Group 2: >65 yrs (n = 37). Cerebral perfusion was investigated with transcranial Doppler and near-infrared spectroscopy (NIRS). Arterial blood pressure was monitored continuously with a Finapres device. Mx, an index allowing continuous monitoring of cerebrovascular autoregulation based on the changes in mean arterial blood pressure (MAP) and cerebral blood flow velocity was calculated. Data are shown as mean } SD. Results: MAP (86 } 9.6 vs 79 } 10.9 mm Hg, p = 0.02), end-tidal concentration of sevoflurane (1.9 } 0.3 vs 1.6 } 0.3%, p <0.01), and the cerebral tissue oxygenation index measured by NIRS (72 } 4 vs 68 } 5%, p = 0.01), were significantly lower in Group 2. The end-tidal concentration of O2 was significantly higher in Group 2 (46 } 4 vs 48 } 4% p = 0.04). There were no significant differences between Group 1 and 2 for cerebral blood flow velocity (41 } 10 vs 43 } 18 cm/s), end tidal CO2 (4.7 } 0.3 vs 4.6 } 0.3 kPa) and cerebrovascular autoregulation (Mx 0.42 } 0.2 vs 0.48 } 0.2). In Group 1 35% and in Group 2 43% of the patients had an index of autoregulation suggesting disturbed cerebrovascular autoregulation (p = n.s.). Conclusions: In elderly patients under general anaesthesia with sevoflurane the cerebral tissue oxygenation index was significantly lower than in younger patients despite higher end-tidal oxygen concentrations. Our data suggest subtle differences in cerebral perfusion between geriatric and younger

Brain functional abnormality in schizo-affective disorder: an fMRI study.

Background.Schizo-affective disorder has not been studied to any significant extent using functional imaging. The aim of this study was to examine patterns of brain activation and deactivation in patients meeting strict diagnostic criteria for the disorder. METHOD: Thirty-two patients meeting research diagnostic criteria (RDC) for schizo-affective disorder (16 schizomanic and 16 schizodepressive) and 32 matched healthy controls underwent functional magnetic resonance imaging (fMRI) during performance of the n-back task. Linear models were used to obtain maps of activations and deactivations in the groups. RESULTS: Controls showed activation in a network of frontal and other areas and also deactivation in the medial frontal cortex, the precuneus and the parietal cortex. Schizo-affective patients activated significantly less in prefrontal, parietal and temporal regions than the controls, and also showed failure of deactivation in the medial frontal cortex. When task performance was controlled for, the reduced activation in the dorsolateral prefrontal cortex (DLPFC) and the failure of deactivation of the medial frontal cortex remained significant. CONCLUSIONS: Schizo-affective disorder shows a similar pattern of reduced frontal activation to schizophrenia. The disorder is also characterized by failure of deactivation suggestive of default mode network dysfunction.

Brain functional abnormality in schizo-affective disorder: an fMRI study.

Background.Schizo-affective disorder has not been studied to any significant extent using functional imaging. The aim of this study was to examine patterns of brain activation and deactivation in patients meeting strict diagnostic criteria for the disorder. METHOD: Thirty-two patients meeting research diagnostic criteria (RDC) for schizo-affective disorder (16 schizomanic and 16 schizodepressive) and 32 matched healthy controls underwent functional magnetic resonance imaging (fMRI) during performance of the n-back task. Linear models were used to obtain maps of activations and deactivations in the groups. RESULTS: Controls showed activation in a network of frontal and other areas and also deactivation in the medial frontal cortex, the precuneus and the parietal cortex. Schizo-affective patients activated significantly less in prefrontal, parietal and temporal regions than the controls, and also showed failure of deactivation in the medial frontal cortex. When task performance was controlled for, the reduced activation in the dorsolateral prefrontal cortex (DLPFC) and the failure of deactivation of the medial frontal cortex remained significant. CONCLUSIONS: Schizo-affective disorder shows a similar pattern of reduced frontal activation to schizophrenia. The disorder is also characterized by failure of deactivation suggestive of default mode network dysfunction.

Brain functional abnormality in schizo-affective disorder: an fMRI study.

Background.Schizo-affective disorder has not been studied to any significant extent using functional imaging. The aim of this study was to examine patterns of brain activation and deactivation in patients meeting strict diagnostic criteria for the disorder. METHOD: Thirty-two patients meeting research diagnostic criteria (RDC) for schizo-affective disorder (16 schizomanic and 16 schizodepressive) and 32 matched healthy controls underwent functional magnetic resonance imaging (fMRI) during performance of the n-back task. Linear models were used to obtain maps of activations and deactivations in the groups. RESULTS: Controls showed activation in a network of frontal and other areas and also deactivation in the medial frontal cortex, the precuneus and the parietal cortex. Schizo-affective patients activated significantly less in prefrontal, parietal and temporal regions than the controls, and also showed failure of deactivation in the medial frontal cortex. When task performance was controlled for, the reduced activation in the dorsolateral prefrontal cortex (DLPFC) and the failure of deactivation of the medial frontal cortex remained significant. CONCLUSIONS: Schizo-affective disorder shows a similar pattern of reduced frontal activation to schizophrenia. The disorder is also characterized by failure of deactivation suggestive of default mode network dysfunction.

Prognostic value of cortically induced motor evoked activity by TMS in chronic stroke: caveats from a very revealing single clinical case

Background: We report the case of a chronic stroke patient (62 months after injury) showing total absence of motor activity evoked by transcranial magnetic stimulation (TMS) of spared regions of the left motor cortex, but near-to-complete recovery of motor abilities in the affected hand. Case presentation: Multimodal investigations included detailed TMS based motor mapping, motor evoked potentials (MEP), and Cortical Silent period (CSP) as well as functional magnetic resonance imaging (fMRI) of motor activity, MRI based lesion analysis and Diffusion Tensor Imaging (DTI) Tractography of corticospinal tract (CST). Anatomical analysis revealed a left hemisphere subinsular lesion interrupting the descending left CST at the level of the internal capsule. The absence of MEPs after intense TMS pulses to the ipsilesional M1, and the reversible suppression of ongoing electromyographic (EMG) activity (indexed by CSP) demonstrate a weak modulation of subcortical systems by the ipsilesional left frontal cortex, but an inability to induce efficient descending volleys from those cortical locations to right hand and forearm muscles. Functional MRI recordings under grasping and finger tapping patterns involving the affected hand showed slight signs of subcortical recruitment, as compared to the unaffected hand and hemisphere, as well as the expected cortical activations. Conclusions: The potential sources of motor voluntary activity for the affected hand in absence of MEPs are discussed. We conclude that multimodal analysis may contribute to a more accurate prognosis of stroke patients.