Transcranial magnetic stimulation in cognitive neuroscience--virtual lesion, chronometry, and functional connectivity

Fifteen years after its introduction by Anthony Barker, transcranial magnetic stimulation (TMS) appears to be 'coming of age' in cognitive neuroscience and promises to reshape the way we investigate brain-behavior relations. Among the many methods now available for imaging the activity of the human brain, magnetic stimulation is the only technique that allows us to interfere actively with brain function. As illustrated by several experiments over the past couple of years, this property of TMS allows us to investigate the relationship between focal cortical activity and behavior, to trace the timing at which activity in a particular cortical region contributes to a given task, and to map the functional connectivity between brain regions.     

经颅磁刺激:生理、心理、脑成像及其临床应用

非侵入性的经颅磁刺激 (TranscranialMagneticStimulation ,TMS)可以无痛地产生感应性电流来激活皮层 ,从而改变大脑内的生理过程。通过改变TMS的参数可以观测到不同的生理和心理效应。TMS对大脑的不同的调节方式体现在对感觉的调节、对认知功能和行为表现的促进或抑制上。TMS还可以与神经病学、精神病学和药理学研究相结合。无框架的TMS立体定位技术可以提高用于解剖定位的TMS以及用于指引脑外科手术的准确性。最后 ,中医针灸的理论也可以用于理解TMS在脑内调节作用的频率效应     

Transcranial magnetic stimulation and cognitive neuroscience

Transcranial magnetic stimulation has been used to investigate almost all areas of cognitive neuroscience. This article discusses the most important (and least understood) considerations regarding the use of transcranial magnetic stimulation for cognitive neuroscience and outlines advances in the use of this technique for the replication and extension of findings from neuropsychology. We also take a more speculative look forward to the emerging development of strategies for combining transcranial magnetic stimulation with other brain imaging technologies and methods in the cognitive neurosciences.     

Transcranial magnetic stimulation as an antioxidant

In the last decades, different transcranial magnetic stimulation protocols have been developed as a therapeutic tool against neurodegenerative and psychiatric diseases, although the biochemical, molecular and cellular mechanisms underlying these effects are not well known. Recent data show that those magnetic stimulation protocols showing beneficial effects could trigger an anti-oxidant action that would favour, at least partially, their therapeutic effect. We have aimed to review the molecular effects related to oxidative damage induced by this therapeutic strategy, as well as from them addressing a broader definition of the anti-oxidant concept.     

Transcranial magnetic stimulation: a primer

Transcranial magnetic stimulation (TMS) is a technique for noninvasive stimulation of the human brain. Stimulation is produced by generating a brief, high-intensity magnetic field by passing a brief electric current through a magnetic coil. The field can excite or inhibit a small area of brain below the coil. All parts of the brain just beneath the skull can be influenced, but most studies have been of the motor cortex where a focal muscle twitch can be produced, called the motor-evoked potential. The technique can be used to map brain function and explore the excitability of different regions. Brief interference has allowed mapping of many sensory, motor, and cognitive functions. TMS has some clinical utility, and, because it can influence brain function if delivered repetitively, it is being developed for various therapeutic purposes.     

Transcranial magnetic stimulation intensities in cognitive paradigms

Background

Transcranial magnetic stimulation (TMS) has become an important experimental tool for exploring the brain''s functional anatomy. As TMS interferes with neural activity, the hypothetical function of the stimulated area can thus be tested. One unresolved methodological issue in TMS experiments is the question of how to adequately calibrate stimulation intensities. The motor threshold (MT) is often taken as a reference for individually adapted stimulation intensities in TMS experiments, even if they do not involve the motor system. The aim of the present study was to evaluate whether it is reasonable to adjust stimulation intensities in each subject to the individual MT if prefrontal regions are stimulated prior to the performance of a cognitive paradigm.

Methods and Findings

Repetitive TMS (rTMS) was applied prior to a working memory task, either at the ‘fixed’ intensity of 40% maximum stimulator output (MSO), or individually adapted at 90% of the subject''s MT. Stimulation was applied to a target region in the left posterior middle frontal gyrus (pMFG), as indicated by a functional magnetic resonance imaging (fMRI) localizer acquired beforehand, or to a control site (vertex). Results show that MT predicted the effect size after stimulating subjects with the fixed intensity (i.e., subjects with a low MT showed a greater behavioral effect). Nevertheless, the individual adaptation of intensities did not lead to stable effects.

Conclusion

Therefore, we suggest assessing MT and account for it as a measure for general cortical TMS susceptibility, even if TMS is applied outside the motor domain.     

Transcranial magnetic stimulation for the treatment of central post-stroke pain

Transcranial magnetic stimulation (TMS) is a new technique that results in neuron excitation using alternating magnetic fields. According to recent reports, high-frequency TMS could be an effective treatment for drug-resistant central post-stroke pain (CPSP). The present case report describes the clinical observation of two patients with CPSP with different lesion localisations and volumes. High frequency (10 Hz) TMS of the primary motor cortex of the affected hemisphere was used in each patient. After stimulation, we recorded a significant reduction in pain on a visual analogue scale (VAS). However, after the end of treatment with TMS, pain gradually returned to previous levels after 3–4 months.     

GenRev: exploring functional relevance of genes in molecular networks

We introduce GenRev, a network-based software package developed to explore the functional relevance of genes generated as an intermediate result from numerous high-throughput technologies. GenRev searches for optimal intermediate nodes (genes) for the connection of input nodes via several algorithms, including the Klein-Ravi algorithm, the limited kWalks algorithm and a heuristic local search algorithm. Gene ranking and graph clustering analyses are integrated into the package. GenRev has the following features. (1) It provides users with great flexibility to define their own networks. (2) Users are allowed to define each gene's importance in a subnetwork search by setting its score. (3) It is standalone and platform independent. (4) It provides an optimization in subnetwork search, which dramatically reduces the running time. GenRev is particularly designed for general use so that users have the flexibility to choose a reference network and define the score of genes. GenRev is freely available at http://bioinfo.mc.vanderbilt.edu/GenRev.html.     

Transcranial magnetic stimulation during resistance training of the tibialis anterior muscle.

During the first few weeks of resistance training, maximal voluntary contraction (MVC) force increases at a faster rate than can be accounted for by increases in protein synthesis. This early increase in MVC force has been attributed to neural mechanisms but the sources have not been identified. The purpose of this study was to measure changes in cortical excitability with transcranial magnetic stimulation during 4 weeks of resistance training of the tibialis anterior muscle. Ten individuals performed 6 sets of 10 MVCs 3 times per week for 4 weeks and ten participated as a control group. There were no changes in any parameters tested in the control group over the 4 weeks. In the training group, TA muscle strength increased significantly by 10% at week 2 and by 18% at week 4. As hypothesized, cortical excitability during resistance training also increased. The amplitude of the TA surface EMG motor evoked potential elicited by TMS during a low-level contraction increased by 32% after training with no change in the M-wave. These data indicate that there may be an increase in cortical excitability during the first few weeks of resistance training of the TA muscle.     

Transcranial magnetic stimulation in research of emotion in the healthy and patients with epilepsy

The main aim of this work was by using transcranial magnetic stimulation to investigate mechanisms of interhemispheric organization the emotion in the healthy and patients with epilepsy. The research was carried out on three groups: the first and second groups of healthy and third group of the patients with idiopatical epilepsy. The first and third groups received transcranial magnetic stimulation on right and left frontalis area. The second group was control (sham transcranial magnetic stimulation). Is shown, that transcranial magnetic stimulation of right frontalis area increases the examining time on negative photos and decreases on positive photos. Transcranial magnetic stimulation of left frontalis area in the healthy and patients with epilepsy increases the examining time on positive photos and decreases on negative photos. The right hemisphere at the healthy and patients with epilepsy in the greater degree is connected to negative marks of emotions, and left hemisphere with positive marks of emotions.     

Transcranial magnetic stimulation: studying the brain-behaviour relationship by induction of 'virtual lesions'.

Transcranial magnetic stimulation (TMS) provides a non-invasive method of induction of a focal current in the brain and transient modulation of the function of the targeted cortex. Despite limited understanding about focality and mechanisms of action, TMS provides a unique opportunity of studying brain-behaviour relations in normal humans. TMS can enhance the results of other neuroimaging techniques by establishing the causal link between brain activity and task performance, and by exploring functional brain connectivity.     

Shear field mapping in actin networks by using magnetic tweezers

An improved magnetic bead microrheometer based on phase contrast microscopy allowing high resolution measurements of local deformations within macromolecular networks is applied to study local viscoelastic properties of cross-linked actin networks. By embedding non-magnetic colloidal beads as probes into the networks, the spatial variation of the strain field within cross-linked actin networks can be mapped. Moreover, the Poisson ratio and shear modulus can be measured locally.     

Leveraging enzyme structure-function relationships for functional inference and experimental design: the structure-function linkage database

The study of mechanistically diverse enzyme superfamilies-collections of enzymes that perform different overall reactions but share both a common fold and a distinct mechanistic step performed by key conserved residues-helps elucidate the structure-function relationships of enzymes. We have developed a resource, the structure-function linkage database (SFLD), to analyze these structure-function relationships. Unique to the SFLD is its hierarchical classification scheme based on linking the specific partial reactions (or other chemical capabilities) that are conserved at the superfamily, subgroup, and family levels with the conserved structural elements that mediate them. We present the results of analyses using the SFLD in correcting misannotations, guiding protein engineering experiments, and elucidating the function of recently solved enzyme structures from the structural genomics initiative. The SFLD is freely accessible at http://sfld.rbvi.ucsf.edu.     

Transcranial magnetic stimulation reveals attentional feedback to area V1 during serial visual search

Visual search tasks have been used to understand how, where and when attention influences visual processing. Current theories suggest the involvement of a high-level "saliency map" that selects a candidate location to focus attentional resources. For a parallel (or "pop-out") task, the first chosen location is systematically the target, but for a serial (or "difficult") task, the system may cycle on a few distractors before finally focusing on the target. This implies that attentional effects upon early visual areas, involving feedback from higher areas, should be visible at longer latencies during serial search. A previous study from Juan & Walsh (2003) had used Transcranial Magnetic Stimulation (TMS) to support this conclusion; however, only a few post-stimulus delays were compared, and no control TMS location was used. Here we applied TMS double-pulses (sub-threshold) to induce a transient inhibition of area V1 at every post-stimulus delay between 100 ms and 500 ms (50 ms steps). The search array was presented either at the location affected by the TMS pulses (previously identified by applying several pulses at supra-threshold intensity to induce phosphene perception), or in the opposite hemifield, which served as a retinotopically-defined control location. Two search tasks were used: a parallel (+ among Ls) and a serial one (T among Ls). TMS specifically impaired the serial, but not the parallel search. We highlight an involvement of V1 in serial search 300 ms after the onset; conversely, V1 did not contribute to parallel search at delays beyond 100 ms. This study supports the idea that serial search differs from parallel search by the presence of additional cycles of a select-and-focus iterative loop between V1 and higher-level areas.     

Towards functional phosphoproteomics by mapping differential phosphorylation events in signaling networks

Protein phosphorylation plays a central role in many signal transduction pathways that mediate biological processes. Novel quantitative mass spectrometry-based methods have recently revealed phosphorylation dynamics in animals, yeast, and plants. These methods are important for our understanding of how differential phosphorylation participates in translating distinct signals into proper physiological responses, and shifted research towards screening for potential cancer therapies and in-depth analysis of phosphoproteomes. In this review, we aim to describe current progress in quantitative phosphoproteomics. This emerging field has changed numerous static pathways into dynamic signaling networks, and revealed protein kinase networks that underlie adaptation to environmental stimuli. Mass spectrometry enables high-throughput and high-quality analysis of differential phosphorylation at a site-specific level. Although determination of differential phosphorylation between treatments is analogous to detecting differential gene expression, the large body of statistical techniques that has been developed for analysis of differential gene expression is not generally applied for detecting differential phosphorylation. We suggest possible improvements for analysis of quantitative phosphorylation by increasing the number of biological replicates and adapting statistical tests used for gene expression profiling and widely implemented in freely available software tools.     

Post-lesional cerebral reorganisation: Evidence from functional neuroimaging and transcranial magnetic stimulation

Reorganisation of cerebral representations has been hypothesised to underlie the recovery from ischaemic brain infarction. The mechanisms can be investigated non-invasively in the human brain using functional neuroimaging and transcranial magnetic stimulation (TMS). Functional neuroimaging showed that reorganisation is a dynamic process beginning after stroke manifestation. In the acute stage, the mismatch between a large perfusion deficit and a smaller area with impaired water diffusion signifies the brain tissue that potentially enables recovery subsequent to early reperfusion as in thrombolysis. Single-pulse TMS showed that the integrity of the cortico-spinal tract system was critical for motor recovery within the first four weeks, irrespective of a concomitant affection of the somatosensory system. Follow-up studies over several months revealed that ischaemia results in atrophy of brain tissue adjacent to and of brain areas remote from the infarct lesion. In patients with hemiparetic stroke activation of premotor cortical areas in both cerebral hemispheres was found to underlie recovery of finger movements with the affected hand. Paired-pulse TMS showed regression of perilesional inhibition as well as intracortical disinhibition of the motor cortex contralateral to the infarction as mechanisms related to recovery. Training strategies can employ post-lesional brain plasticity resulting in enhanced perilesional activations and modulation of large-scale bihemispheric circuits.