Plasticity in neurological disorders and challenges for noninvasive brain stimulation (NBS)

There has been considerable interest in trialing NBS in a range of neurological conditions, and in parallel the range of NBS techniques available continues to expand. Underpinning this is the idea that NBS modulates neuroplasticity and that plasticity is an important contributor to functional recovery after brain injury and to the pathophysiology of neurological disorders. However while the evidence for neuroplasticity and its varied mechanisms is strong, the relationship to functional outcome is less clear and the clinical indications remain to be determined. To be maximally effective, the application of NBS techniques will need to be refined to take into account the diversity of neurological symptoms, the fundamental differences between acute, longstanding and chronic progressive disease processes, and the differential part played by functional and dysfunctional plasticity in diseases of the brain and spinal cord

NeuroMeasure: A Software Package for Quantification of Cortical Motor Maps Using Frameless Stereotaxic Transcranial Magnetic Stimulation

The recent enhanced sophistication of non-invasive mapping of the human motor cortex using MRI-guided Transcranial Magnetic Stimulation (TMS) techniques, has not been matched by refinement of methods for generating maps from motor evoked potential (MEP) data, or in quantifying map features. This is despite continued interest in understanding cortical reorganization for natural adaptive processes such as skill learning, or in the case of motor recovery, such as after lesion affecting the corticospinal system. With the observation that TMS-MEP map calculation and quantification methods vary, and that no readily available commercial or free software exists, we sought to establish and make freely available a comprehensive software package that advances existing methods, and could be helpful to scientists and clinician-researchers. Therefore, we developed NeuroMeasure, an open source interactive software application for the analysis of TMS motor cortex mapping data collected from Nexstim® and BrainSight®, two commonly used neuronavigation platforms. NeuroMeasure features four key innovations designed to improvemotor mapping analysis: de-dimensionalization of the mapping data, fitting a predictive model, reporting measurements to characterize the motor map, and comparing those measurements between datasets. This software provides a powerful and easy to use workflow for characterizing and comparing motor maps generated with neuronavigated TMS. The software can be downloaded on our github page: https://github.com/EdwardsLabNeuroSci/NeuroMeasure. AIM This paper aims to describe a software platform for quantifying and comparing maps of the human primarymotor cortex, using neuronavigated transcranialmagnetic stimulation, for the purpose of studying brain plasticity in health and diseas

Neuromeasure: A software package for quantification of cortical motor maps using frameless stereotaxic transcranial magnetic stimulation

The recent enhanced sophistication of non-invasive mapping of the human motor cortex using MRI-guided Transcranial Magnetic Stimulation (TMS) techniques, has not been matched by refinement of methods for generating maps from motor evoked potential (MEP) data, or in quantifying map features. This is despite continued interest in understanding cortical reorganization for natural adaptive processes such as skill learning, or in the case of motor recovery, such as after lesion affecting the corticospinal system. With the observation that TMS-MEP map calculation and quantification methods vary, and that no readily available commercial or free software exists, we sought to establish and make freely available a comprehensive software package that advances existing methods, and could be helpful to scientists and clinician-researchers. Therefore, we developed NeuroMeasure, an open source interactive software application for the analysis of TMS motor cortex mapping data collected from Nexstim® and BrainSight®, two commonly used neuronavigation platforms. NeuroMeasure features four key innovations designed to improve motor mapping analysis: de-dimensionalization of the mapping data, fitting a predictive model, reporting measurements to characterize the motor map, and comparing those measurements between datasets. This software provides a powerful and easy to use workflow for characterizing and comparing motor maps generated with neuronavigated TMS. The software can be downloaded on our github page: https://github.com/EdwardsLabNeuroSci/NeuroMeasure Aim This paper aims to describe a software platform for quantifying and comparing maps of the human primary motor cortex, using neuronavigated transcranial magnetic stimulation, for the purpose of studying brain plasticity in health and disease

NeuroMeasure: A Software Package for Quantification of Cortical Motor Maps Using Frameless Stereotaxic Transcranial Magnetic Stimulation

The recent enhanced sophistication of non-invasive mapping of the human motor cortex using MRI-guided Transcranial Magnetic Stimulation (TMS) techniques, has not been matched by refinement of methods for generating maps from motor evoked potential (MEP) data, or in quantifying map features. This is despite continued interest in understanding cortical reorganization for natural adaptive processes such as skill learning, or in the case of motor recovery, such as after lesion affecting the corticospinal system. With the observation that TMS-MEP map calculation and quantification methods vary, and that no readily available commercial or free software exists, we sought to establish and make freely available a comprehensive software package that advances existing methods, and could be helpful to scientists and clinician-researchers. Therefore, we developed NeuroMeasure, an open source interactive software application for the analysis of TMS motor cortex mapping data collected from Nexstim® and BrainSight®, two commonly used neuronavigation platforms. NeuroMeasure features four key innovations designed to improve motor mapping analysis: de-dimensionalization of the mapping data, fitting a predictive model, reporting measurements to characterize the motor map, and comparing those measurements between datasets. This software provides a powerful and easy to use workflow for characterizing and comparing motor maps generated with neuronavigated TMS. The software can be downloaded on our github page: https://github.com/EdwardsLabNeuroSci/NeuroMeasureAimThis paper aims to describe a software platform for quantifying and comparing maps of the human primary motor cortex, using neuronavigated transcranial magnetic stimulation, for the purpose of studying brain plasticity in health and disease

Long Lasting Modulation of Cortical Oscillations after Continuous Theta Burst Transcranial Magnetic Stimulation

Transcranial magnetic theta burst stimulation (TBS) differs from other high-frequency rTMS protocols because it induces plastic changes up to an hour despite lower stimulus intensity and shorter duration of stimulation. However, the effects of TBS on neuronal oscillations remain unclear. In this study, we used electroencephalography (EEG) to investigate changes of neuronal oscillations after continuous TBS (cTBS), the protocol that emulates long-term depression (LTD) form of synaptic plasticity. We randomly divided 26 healthy humans into two groups receiving either Active or Sham cTBS as control over the left primary motor cortex (M1). Post-cTBS aftereffects were assessed with behavioural measurements at rest using motor evoked potentials (MEPs) and at active state during the execution of a choice reaction time (RT) task in combination with continuous electrophysiological recordings. The cTBS-induced EEG oscillations were assessed using event-related power (ERPow), which reflected regional oscillatory activity of neural assemblies of θ (4–7.5 Hz), low α (8–9.5 Hz), µ (10–12.5 Hz), low β (13–19.5 Hz), and high β (20–30 Hz) brain rhythms. Results revealed 20-min suppression of MEPs and at least 30-min increase of ERPow modulation, suggesting that besides MEPs, EEG has the potential to provide an accurate cortical readout to assess cortical excitability and to investigate the interference of cortical oscillations in the human brain post-cTBS. We also observed a predominant modulation of β frequency band, supporting the hypothesis that cTBS acts more on cortical level. Theta oscillations were also modulated during rest implying the involvement of independent cortical theta generators over the motor network post cTBS. This work provided more insights into the underlying mechanisms of cTBS, providing a possible link between synchronised neural oscillations and LTD in humans

Neuroregeneration in neurodegenerative disorders

<p>Abstract</p> <p>Background</p> <p>Neuroregeneration is a relatively recent concept that includes neurogenesis, neuroplasticity, and neurorestoration - implantation of viable cells as a therapeutical approach.</p> <p>Discussion</p> <p>Neurogenesis and neuroplasticity are impaired in brains of patients suffering from Alzheimer's Disease or Parkinson's Disease and correlate with low endogenous protection, as a result of a diminished growth factors expression. However, we hypothesize that the brain possesses, at least in early and medium stages of disease, a "neuroregenerative reserve", that could be exploited by growth factors or stem cells-neurorestoration therapies.</p> <p>Summary</p> <p>In this paper we review the current data regarding all three aspects of neuroregeneration in Alzheimer's Disease and Parkinson's Disease.</p

Evidence for high-fidelity timing-dependent synaptic plasticity of human motor cortex

A single transcranial magnetic stimulation (TMS) pulse typically evokes a short series of spikes in corticospinal neurons [known as indirect (I)-waves] which are thought to arise from transynaptic input. Delivering a second pulse at inter-pulse intervals (IPIs) corresponding to the timing of these I-waves leads to a facilitation of the response, and if stimulus pairs are delivered repeatedly, a persistent LTP-like increase in excitability can occur. This has been demonstrated at an IPI of 1.5 ms, which corresponds to the first I-wave interval, in an intervention referred to as ITMS (I-wave TMS), and it has been argued that this may have similarities with timing-dependent plasticity models. Consequently, we hypothesized that if the second stimulus is delivered so as not to coincide with I-wave timing, it should lead to LTD. We performed a crossover study in 10 subjects in which TMS doublets were timed to coincide (1.5-ms IPI, ITMS1.5) or not coincide (2-ms IPI, ITMS2) with I-wave firing. Single pulse motor-evoked potential (MEP) amplitude, resting motor threshold (RMT), and short-interval cortical inhibition (SICI) were measured from the first dorsal interosseous (FDI) muscle. After ITMS1.5 corticomotor excitability was increased by ∼60% for 15 min (P < 0.05) and returned to baseline by 20 min. Increasing the IPI by just 500 μs to 2 ms reversed the aftereffect, and MEP amplitude was significantly reduced (∼35%, P < 0.05) for 15 min before returning to baseline. This reduction was not associated with an increase in SICI, suggesting a reduction in excitatory transmission rather than an increase in inhibitory efficacy. RMT also remained unchanged, suggesting that these changes were not due to changes in membrane excitability. Amplitude-matching ITMS2 did not modulate excitability. The results are consistent with timing-dependent synaptic LTP/D-like effects and suggest that there are plasticity mechanisms operating in the human motor cortex with a temporal resolution of the order of a few hundreds of microseconds

Changes in corticomotor excitability and inhibition after exercise are influenced by hand dominance and motor demand

Previous studies on handedness have often reported functional asymmetries in corticomotor excitability (CME) associated with voluntary movement. Recently, we have shown that the degree of post-exercise corticomotor depression (PED) and increase in short-interval cortical inhibition (SICI) after a repetitive finger movement task was less when the task was performed at a maximal voluntary rate (MVR) than when it was performed at a submaximal sustainable rate (SR). In the current study, we have compared the time course of PED and SICI in the dominant (DOM) and nondominant (NDOM) hands after an MVR and SR finger movement task to determine the influence of hand dominance and task demand. We tracked motor-evoked potential (MEP) amplitude from the first dorsal interosseous muscle of the DOM and NDOM hand for 20 min after a 10-s index finger flexion-extension task at MVR and SR. For all hand-task combinations, we report a period of PED and increased SICI lasting for up to 8 min. We find that the least demanding task, one that involved index finger movement of the DOM hand at SR, was associated with the greatest change in PED and SICI from baseline (63.6&plusmn;5.7% and 79&plusmn;2%, P&lt;0.001, PED and SICI, respectively), whereas the most demanding task (MVR of the NDOM hand) was associated with the least change from baseline (PED: 88.1&plusmn;3.6%, SICI: 103&plusmn;2%; P&lt;0.001). Our findings indicate that the changes in CME and inhibition associated with repetitive finger movement are influenced both by handedness and the degree of demand of the motor task and are inversely related to task demand, being smallest for an MVR task of the NDOM hand and greatest for an SR task of the DOM hand. The findings provide additional evidence for differences in neuronal processing between the dominant and nondominant hemispheres in motor control