Changes In Neural Excitability Research Articles

Acute Effects of Strength and Skill Training on the Cortical and Spinal Circuits of Contralateral Limb

Unilateral strength and skill training increase strength and performance in the contralateral untrained limb, a phenomenon known as cross-education. Recent evidence suggests that similar neural mechanisms might be responsible for the increase in strength and skill observed in the untrained hand after unimanual training. The aims of this study were to: investigate whether a single session of unimanual strength and skill (force-tracking) training increased strength and skill in the opposite hand; measure ipsilateral (untrained) brain (via transcranial magnetic stimulation, TMS) and spinal (via the monosynaptic reflex) changes in excitability occurring after training; measure ipsilateral (untrained) pathway-specific changes in neural excitability (via TMS-conditioning of the monosynaptic reflex) occurring after training. Participants (N = 13) completed a session of unimanual strength (ballistic isometric wrist flexions) and skill (force-tracking wrist flexions) training on two separate days. Strength increased after training in the untrained hand (p = 0.025) but not in the trained hand (p = 0.611). Force-tracking performance increased in both the trained (p = 0.007) and untrained (p = 0.010) hand. Corticospinal excitability increased after force-tracking and strength training (p = 0.027), while spinal excitability was not affected (p = 0.214). TMS-conditioned monosynaptic reflex increased after force-tracking (p = 0.001) but not strength training (p = 0.689), suggesting a possible role of polysynaptic pathways in the increase of cortical excitability observed after training. The results suggest that cross-education of strength and skill at the acute stage is supported by increased excitability of the untrained motor cortex. New & Noteworthy: A single session of isometric wrist flexion strength and skill straining increased strength and skill in the untrained limb. The excitability of the untrained motor cortex increased after strength and skill training. TMS-conditioned H-reflexes increased after skill but not strength training in the untrained hand, indicating that polysynaptic pathways in the increase of cortical excitability observed after skill training.

Automated Multimodal Stimulation and Simultaneous Neuronal Recording from Multiple Small Organisms.

Fluorescent genetically encoded calcium indicators have contributed greatly to our understanding of neural dynamics from the level of individual neurons to entire brain circuits. However, neural responses may vary due to prior experience, internal states, or stochastic factors, thus generating the need for methods that can assess neural function across many individuals at once. Whereas most recording techniques examine a single animal at a time, we describe the use of wide-field microscopy to scale up neuronal recordings to dozens of Caenorhabditis elegans or other sub-millimeter-scale organisms at once. Open-source hardware and software allow great flexibility in programming fully automated experiments that control the intensity and timing of various stimulus types, including chemical, optical, mechanical, thermal, and electromagnetic stimuli. In particular, microfluidic flow devices provide precise, repeatable, and quantitative control of chemosensory stimuli with sub-second time resolution. The NeuroTracker semi-automated data analysis pipeline then extracts individual and population-wide neural responses to uncover functional changes in neural excitability and dynamics. This paper presents examples of measuring neuronal adaptation, temporal inhibition, and stimulus crosstalk. These techniques increase the precision and repeatability of stimulation, allow the exploration of population variability, and are generalizable to other dynamic fluorescent signals in small biosystems from cells and organoids to whole organisms and plants.

Priming locomotor training with transspinal stimulation in people with spinal cord injury: study protocol of a randomized clinical trial

BackgroundThe seemingly simple tasks of standing and walking require continuous integration of complex spinal reflex circuits between descending motor commands and ascending sensory inputs. Spinal cord injury greatly impairs standing and walking ability, but both improve with locomotor training. However, even after multiple locomotor training sessions, abnormal muscle activity and coordination persist. Thus, locomotor training alone cannot fully optimize the neuronal plasticity required to strengthen the synapses connecting the brain, spinal cord, and local circuits and potentiate neuronal activity based on need. Transcutaneous spinal cord (transspinal) stimulation alters motoneuron excitability over multiple segments by bringing motoneurons closer to threshold, a prerequisite for effectively promoting spinal locomotor network neuromodulation and strengthening neural connectivity of the injured human spinal cord. Importantly, whether concurrent treatment with transspinal stimulation and locomotor training maximizes motor recovery after spinal cord injury is unknown.MethodsForty-five individuals with chronic spinal cord injury are receiving 40 sessions of robotic gait training primed with 30 Hz transspinal stimulation at the Thoracic 10 vertebral level. Participants are randomized to receive 30 min of active or sham transspinal stimulation during standing or active transspinal stimulation while supine followed by 30 min of robotic gait training. Over the course of locomotor training, the body weight support, treadmill speed, and leg guidance force are adjusted as needed for each participant based on absence of knee buckling during the stance phase and toe dragging during the swing phase. At baseline and after completion of all therapeutic sessions, neurophysiological recordings registering corticospinal and spinal neural excitability changes along with clinical assessment measures of standing and walking, and autonomic function via questionnaires regarding bowel, bladder, and sexual function are taken.DiscussionThe results of this mechanistic randomized clinical trial will demonstrate that tonic transspinal stimulation strengthens corticomotoneuronal connectivity and dynamic neuromodulation through posture-dependent corticospinal and spinal neuroplasticity. We anticipate that this mechanistic clinical trial will greatly impact clinical practice because, in real-world clinical settings, noninvasive transspinal stimulation can be more easily and widely implemented than invasive epidural stimulation. Additionally, by applying multiple interventions to accelerate motor recovery, we are employing a treatment regimen that reflects a true clinical approach.Trial registrationClinicalTrials.gov NCT04807764. Registered on March 19, 2021.

Reliability of transcranial magnetic stimulation evoked potentials to detect the effects of theta-burst stimulation of the prefrontal cortex

BackgroundTranscranial magnetic stimulation (TMS) with simultaneous electroencephalography (EEG) is a novel method for assessing cortical properties outside the motor region. Theta burst stimulation (TBS), a form of repetitive TMS, can non-invasively modulate cortical excitability and has been increasingly used to treat psychiatric disorders by targetting the dorsolateral prefrontal cortex (DLPFC). The TMS-evoked potentials (TEPs) and local mean field power (LMFP) analyses have been used to evaluate local cortical excitability changes after TBS. However, it remains unclear whether TEPs can detect the neuromodulatory effects of TBS. ObjectivesTo confirm the reliability of TEP components and LMFP within and between sessions and to measure changes in neural excitability induced by intermittent (iTBS) and continuous TBS (cTBS) applied to the left DLPFC. MethodsTest-retest reliability of TEPs/LMFP and TBS-induced changes in cortical excitability were assessed in twenty-four healthy participants by stimulating the DLPFC in five separate sessions, once with sham and twice with iTBS and cTBS. EEG responses were recorded of 100 single TMS pulses before and after TBS, and the reproducibility measures were quantified with the concordance correlation coefficient (CCC). ResultsThe N100 and P200 components presented substantial reliability within the baseline block (CCCs>0.8) and moderate concordance between sessions (CCCmax> 0.6). Both N40 and P60 TEP amplitudes showed little concordance between sessions. Similar results were achieved using LMFP responses. Changes in TEP amplitudes after iTBS were marginally reliable for N100 (CCCmax = 0.52), P200 (CCCmax = 0.47) and P60 (CCCmax = 0.40), presenting only fair levels of concordance at specific time points. LMFP changes showed poor reproducibility after iTBS and cTBS. ConclusionsThe present findings show that only the N100 and P200 components had good concordance between sessions. The reliability of earlier TEP components and LMF responses may have been affected by a sub-optimal removal of TMS-related artefacts. The poor reliability in detecting changes in neural excitability induced by TBS indicates that TEPs/LMFP do not provide a precise estimate of the changes in excitability in the DLPFC or, alternatively, that TBS did not induce consistent changes in neural excitability.

The effects of 72 h of dynamic ankle immobilization on neural excitability and lower extremity kinematics

BackgroundAnkle injuries can foster maladaptive changes in nervous system function that predisposes patients to subsequent injury. Patients are often placed in a dynamic boot immobilizer (BI) following injury; however, little is known about the effects of this treatment on neuromechanical function. Research questionWe aimed to determine the effect of 72 h of BI-use on neural excitability and lower extremity joint motion in a healthy cohort. MethodsTwelve uninjured individuals (20.8 ± 1.4 yrs, 1.7 ± 0.1 m, 75.2 ± 9.9 kg) participated in this crossover study. Neural excitability and lower extremity kinematics were assessed before and after 72 h of BI or compression sock (CS) use. Neural excitability was assessed via the Hoffmann (H) reflex and transcranial magnetic stimulation of the motor cortex by measuring muscle activation at the tibialis anterior, peroneus longus, and soleus of the immobilized extremity. Three-dimensional lower extremity joint angles were assessed while participants walked on a treadmill. Repeated-measures analyses of variance detected changes in neural excitability and peak joint angles across time-points and testing conditions, while statistical parametric mapping (SPM) was implemented to determine continuous joint angle changes (α = 0.05). ResultsPre-BI to post-BI, HMax:MMax ratio (F = 6.496; p = 0.031) significantly decreased. The BI did not alter resting motor threshold (F = 0.601; p = 0.468), or motor evoked potential amplitudes (F > 2.82; p > 0.608). Significant changes in peak knee and hip angles in the frontal and transverse planes were observed (p < 0.05), with no changes at the ankle. SPM analyses revealed significant hip and knee changes in range of motion (p < 0.05). SignificanceDecreased measures of reflex but not corticospinal excitability suggest that BI-use for 72 h unloaded the joint enough to generate peripheral changes, but not the CNS, as has been described in casting models. Further, kinematic changes were observed in proximal lower extremity joints, likely due to swing-phase adaptations while wearing the BI.

Nonlinear interaction between stimulation intensity and initial brain state: Evidence for the facilitatory/suppressive range model of online TMS effects

The effects of online Transcranial Magnetic Stimulation (TMS) can qualitatively vary as a function of brain state. For example, TMS intensities which normally impair performance can have a facilitatory effect if the targeted neuronal representations are in a suppressed state. These phenomena have been explained in terms of the existence of distinct facilitatory and suppressive ranges as a function of TMS intensity which are shifted by changes in neural excitability. We tested this model by applying TMS at a low (60 % of phosphene threshold) or high (120 % of phosphene threshold) intensity during a priming paradigm. Our results show that state-dependent TMS effects vary qualitatively as a function of TMS intensity. Whereas the application of TMS at 120 % of participants’ phosphene threshold impaired performance on fully congruent trials (in effect, reducing the benefit of priming), TMS applied at a lower intensity (60 % of phosphene threshold), facilitated performance on congruent trials. These results demonstrate that behavioral effects of TMS reflect a nonlinear interaction between initial activation state and TMS intensity. They also provide support for the existence of facilitatory/suppressive ranges of TMS effects which shift when neural excitability changes.

One Thing Leads to Another: Anticipating Visual Object Identity Based on Associative-Memory Templates.

Probabilistic associations between stimuli afford memory templates that guide perception through proactive anticipatory mechanisms. A great deal of work has examined the behavioral consequences and human electrophysiological substrates of anticipation following probabilistic memory cues that carry spatial or temporal information to guide perception. However, less is understood about the electrophysiological substrates linked to anticipating the sensory content of events based on recurring associations between successive events. Here, we demonstrate behavioral and electrophysiological signatures of using associative-memory templates to guide perception, while equating spatial and temporal anticipation (experiments 1 and 2), as well as target probability and response demands (experiment 2). By recording the electroencephalogram in the two experiments (N = 55; 24 females), we show that two markers in human electrophysiology implicated in spatial and temporal anticipation also contribute to the anticipation of perceptual identity, as follows: attenuation of alpha-band oscillations and the contingent negative variation (CNV). Together, our results show that memory-guided identity templates proactively impact perception and are associated with anticipatory states of attenuated alpha oscillations and the CNV. Furthermore, by isolating object-identity anticipation from spatial and temporal anticipation, our results suggest a role for alpha attenuation and the CNV in specific visual content anticipation beyond general changes in neural excitability or readiness.SIGNIFICANCE STATEMENT Probabilistic associations between stimuli afford memory templates that guide perception through proactive anticipatory mechanisms. The current work isolates the behavioral benefits and electrophysiological signatures of memory-guided identity-based anticipation, while equating anticipation of space, time, motor responses, and task relevance. Our results show that anticipation of the specific identity of a forthcoming percept impacts performance and is associated with states of attenuated alpha oscillations and the contingent negative variation, extending previous work implicating these neural substrates in spatial and temporal preparatory attention. Together, this work bridges fields of attention, memory, and perception, providing new insights into the neural mechanisms that support complex attentional templates.

Role of spinal glial cells in excitability of wide dynamic range neurons and the development of neuropathic pain with the L5 spinal nerve transection in the rats: Behavioral and electrophysiological study

The activation of glial cells affects the neuronal excitability in the spinal cord. Therefore, in this study, we tried to find out the modulatory role of spinal glial cells in the excitability of wide dynamic range (WDR) neurons, induction of the long-term potentiation (LTP) and development of neuropathic pain by L5 spinal nerve transection model in the rats. Forty-eight adult male Wistar rats were used to measure the paw withdrawal threshold to mechanical stimuli and also, to carry out the spinal extracellular single unit recording experiments. In these experiments, spinal nerve ligation (SNL) and a daily injection of propentofylline (1 mg/kg, ip) as a glial cell inhibitor agent, 1 h following nerve ligation during 7-day post-SNL period, were performed. Our findings showed that the mechanical allodynia, and synaptically-evoked firing were caused LTP in the Aδ-fiber, C-fiber and lesser in the Aβ-fiber after high frequency stimulation. Daily injection of propentofylline considerably decreased LTP induction in the Aδ- and C-fibers (P < .001). It was concluded that glial cell activation mediates LTP induction in the spinal cord following peripheral nerve injury. It seems that pain modulatory role of glial cells is partly parallel to changes in neural excitability of the WDR neurons in the dorsal horn of spinal cord.

Application of Tetrode Technology for Analysis of Changes in Neural Excitability of Medial Vestibular Nucleus by Acute Arterial Hypotension

Objectives Excitability o medial vestibular nucleus (MVN) in the brainstem can be affected by changes in the arterial blood pressure. Several animal studies have demonstrated that acute hypotension results in the alteration of multiunit activities and expression of cFos protein in the MVN. In the field of extracellular electrophysiological recording, tetrode technology and spike sorting algorithms can easily identify single unit activity from multiunit activities in the brain. However, detailed properties of electrophysiological changes in single unit of the MVN during acute hypotension have been unknown. Methods Therefore, we applied tetrode techniques and electrophysiological characterization methods to know the effect of acute hypotension on single unit activities of the MVN of rats. Results Twoor3typesofunitcouldbeclassifiedaccordingtothemorphologyofspikes and firing properties of neurons. Acute hypotension elicited 4 types of changes in spontaneous firing of single unit in the MVN. Most of these neurons showed excitatory responses for about within 1 minute after the induction of acute hypotension and then returned to the baseline activity 10 minutes after the injection of sodium nitroprusside. There was also gradual increase in spontaneous firing in some units. In contrast small proportion of units showed rapid reduction of firing rate just after acute hypotension. Conclusions Therefore, application of tetrode technology and spike sorting algorithms is another method for the monitoring of electrical activity of vestibular nuclear during acute hypotension. Keywords: Medial vestibular nucleus; Acute arterial hypotension; Tetrode electrode; Spike sorting; Neuronal firing 중심 단어: ë‚´ì¸¡ì „ì •í•µ, 급성 ì €í˜ˆì••, í ŒíŠ¸ë¡œë“œ ì „ê·¹, 스파이크 분류, ì‹ ê²½ 흥분

Effects of transcranial direct current stimulation on gait in people with Parkinson\u2019s disease: study protocol for a randomized, controlled clinical trial

BackgroundGait difficulties are common and frequently devastating to people with Parkinson’s disease (PD). These difficulties are often followed by an increased risk of falls, leading to injury, hospitalization and mortality. The dysfunction in the basal ganglia-thalamocortical motor circuits and reduced activity in the premotor and primary motor cortices has raised interest in transcranial direct current stimulation (tDCS) as an adjunct intervention in PD. tDCS might provide a potentially safe and non-invasive treatment by modulating cortical excitability and behavioural outcomes. The aim of this study is to compare the effects of different monopolar and bipolar montages of tDCS administered to the motor cortex and cerebellum on gait speed in PD.MethodsThis study will be conducted in a randomized, double-blind cross-over design. Eighteen participants diagnosed with Parkinson’s disease will receive anodal and sham tDCS (1 mA, 20 min, 10 × 4 cm2) over the premotor and primary motor cortices with the cathode over the cerebellum during treadmill walking. Three montages will be applied over three sessions and compared: anodal tDCS with a small active cathode (4 × 4 cm2); anodal tDCS with a large, functionally inert cathode (10 × 10 cm2); and sham tDCS. The primary outcome measure is gait speed, and secondary outcome measures include gait parameters (temporospatial, segmental, kinematic), the Timed Up and Go test and lower limb muscle activity patterns as measured by electromyography.DiscussionThis study will investigate the short-term effects of anodal tDCS over the premotor and primary motor cortices on gait abilities using monopolar and bipolar montages in people with PD. The outcomes will inform future studies aimed at inducing longer-lasting changes in neural excitability and performance using multisession tDCS designs in PD.Trial registrationAustralian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12618000063213. Registered on 17 January 2018. Retrospectively registered.

Common framework for “virtual lesion” and state-dependent TMS: The facilitatory/suppressive range model of online TMS effects on behavior

The behavioral effects of Transcranial Magnetic Stimulation (TMS) are often nonlinear; factors such as stimulation intensity and brain state can modulate the impact of TMS on observable behavior in qualitatively different manner. Here we propose a theoretical framework to account for these effects. In this model, there are distinct intensity ranges for facilitatory and suppressive effects of TMS – low intensities facilitate neural activity and behavior whereas high intensities induce suppression. The key feature of the model is that these ranges are shifted by changes in neural excitability: consequently, a TMS intensity, which normally induces suppression, can have a facilitatory effect if the stimulated neurons are being inhibited by ongoing task-related processes or preconditioning. For example, adaptation reduces excitability of adapted neurons; the outcome is that TMS intensities which inhibit non-adapted neurons induce a facilitation on adapted neural representations, leading to reversal of adaptation effects. In conventional “virtual lesion” paradigms, similar effects occur because neurons not involved in task-related processes are inhibited by the ongoing task. The resulting reduction in excitability can turn high intensity “inhibitory” TMS to low intensity “facilitatory” TMS for these neurons, and as task-related neuronal representations are in the inhibitory range, the outcome is a reduction in signal-to-noise ratio and behavioral impairment.

Using Biophysical Models to Understand the Effect of tDCS on Neurorehabilitation: Searching for Optimal Covariates to Enhance Poststroke Recovery.

Stroke is a leading cause of worldwide disability, and up to 75% of survivors suffer from some degree of arm paresis. Recently, rehabilitation of stroke patients has focused on recovering motor skills by taking advantage of use-dependent neuroplasticity, where high-repetition of goal-oriented movement is at times combined with non-invasive brain stimulation, such as transcranial direct current stimulation (tDCS). Merging the two approaches is thought to provide outlasting clinical gains, by enhancing synaptic plasticity and motor relearning in the motor cortex primary area. However, this general approach has shown mixed results across the stroke population. In particular, stroke location has been found to correlate with the likelihood of success, which suggests that different patients might require different protocols. Understanding how motor rehabilitation and stimulation interact with ongoing neural dynamics is crucial to optimize rehabilitation strategies, but it requires theoretical and computational models to consider the multiple levels at which this complex phenomenon operate. In this work, we argue that biophysical models of cortical dynamics are uniquely suited to address this problem. Specifically, biophysical models can predict treatment efficacy by introducing explicit variables and dynamics for damaged connections, changes in neural excitability, neurotransmitters, neuromodulators, plasticity mechanisms, and repetitive movement, which together can represent brain state, effect of incoming stimulus, and movement-induced activity. In this work, we hypothesize that effects of tDCS depend on ongoing neural activity and that tDCS effects on plasticity may be also related to enhancing inhibitory processes. We propose a model design for each step of this complex system, and highlight strengths and limitations of the different modeling choices within our approach. Our theoretical framework proposes a change in paradigm, where biophysical models can contribute to the future design of novel protocols, in which combined tDCS and motor rehabilitation strategies are tailored to the ongoing dynamics that they interact with, by considering the known biophysical factors recruited by such protocols and their interaction.

P151 Repetitive Transcranial Magnetic Stimulation: A call for better data

Introduction The experimental science to inform application of Repetitive Transcranial Magnetic Stimulation (rTMS) is inconsistent. Evidence is strongly based on measurements of motor-evoked potentials (MEPs) which are indirect measures of cortical changes. It is still unclear whether rTMS achieves its effects through plasticity, changes in neural excitability, control of gene expression or another route. Objectives We approached this work as computational physicists. Our aim was to analyze rTMS literature to identify underlying trends. Specifically: 1. Which parameters (e.g. number of pulses, repetition rate) are important? 2. How does the MEP relate to changes in the cortex? 3. What science must be included in a numerical model of the MEP and rTMS? Materials & methods We identified 92 rTMS publications reporting data from 164 experiments. Often, data were poorly recorded and key information was absent. With non-bursting protocols, we identified only 39 publications (76 experiments) which unambiguously gave the rTMS frequency, the number of pulses applied, the pulse intensity and the effect on the MEP. We used principal component analysis to identify which parameters most affected the MEP. We tried to repeat this for bursting protocols; but were prevented by lack of variation in the reported protocols. We used an existing neural field model to study the effect on the MEP of changes in cortical excitability and connection strengths. Results Results are in line with existing dogma: >5 Hz rTMS leads to an increase in MEP; Conclusion Overall, we need better data. Many experiments are poorly reported. Key information is missing or ambiguous. The MEP is an inconvenient and indirect measure of the effect of rTMS. It is often poorly defined and recorded. One needs to 1. record it and report it rigorously and quantitatively, and 2. develop better numerical models of MEPs. Bursting experiments have focused on too few possibilities (e.g. 5 Hz theta-burst stimulation or quadripulse) to unlock underlying science.

Spontaneous Neural Oscillations Bias Perception by Modulating Baseline Excitability.

Spontaneous fluctuations of brain activity explain why a faint sensory stimulus is sometimes perceived and sometimes not. The prevailing view is that heightened neural excitability, indexed by decreased α oscillations, promotes better perceptual performance. Here, we provide evidence that heightened neural excitability instead reflects a state of biased perception, during which a person is more likely to see a stimulus, whether or not it is actually present. Therefore, we propose that changes in neural excitability leave the precision of sensory processing unaffected. These results establish the link between spontaneous brain activity and the variability in human perception.

A Role of Phase-Resetting in Coordinating Large Scale Neural Networks During Attention and Goal-Directed Behavior.

Short periods of oscillatory activation are ubiquitous signatures of neural circuits. A broad range of studies documents not only their circuit origins, but also a fundamental role for oscillatory activity in coordinating information transfer during goal directed behavior. Recent studies suggest that resetting the phase of ongoing oscillatory activity to endogenous or exogenous cues facilitates coordinated information transfer within circuits and between distributed brain areas. Here, we review evidence that pinpoints phase resetting as a critical marker of dynamic state changes of functional networks. Phase resets: (1) set a “neural context” in terms of narrow band frequencies that uniquely characterizes the activated circuits; (2) impose coherent low frequency phases to which high frequency activations can synchronize, identifiable as cross-frequency correlations across large anatomical distances; (3) are critical for neural coding models that depend on phase, increasing the informational content of neural representations; and (4) likely originate from the dynamics of canonical E-I circuits that are anatomically ubiquitous. These multiple signatures of phase resets are directly linked to enhanced information transfer and behavioral success. We survey how phase resets re-organize oscillations in diverse task contexts, including sensory perception, attentional stimulus selection, cross-modal integration, Pavlovian conditioning, and spatial navigation. The evidence we consider suggests that phase-resets can drive changes in neural excitability, ensemble organization, functional networks, and ultimately, overt behavior.

Formation and Dynamics of Waves in a Cortical Model of Cholinergic Modulation

Acetylcholine (ACh) is a regulator of neural excitability and one of the neurochemical substrates of sleep. Amongst the cellular effects induced by cholinergic modulation are a reduction in spike-frequency adaptation (SFA) and a shift in the phase response curve (PRC). We demonstrate in a biophysical model how changes in neural excitability and network structure interact to create three distinct functional regimes: localized asynchronous, traveling asynchronous, and traveling synchronous. Our results qualitatively match those observed experimentally. Cortical activity during slow wave sleep (SWS) differs from that during REM sleep or waking states. During SWS there are traveling patterns of activity in the cortex; in other states stationary patterns occur. Our model is a network composed of Hodgkin-Huxley type neurons with a M-current regulated by ACh. Regulation of ACh level can account for dynamical changes between functional regimes. Reduction of the magnitude of this current recreates the reduction in SFA the shift from a type 2 to a type 1 PRC observed in the presence of ACh. When SFA is minimal (in waking or REM sleep state, high ACh) patterns of activity are localized and easily pinned by network inhomogeneities. When SFA is present (decreasing ACh), traveling waves of activity naturally arise. A further decrease in ACh leads to a high degree of synchrony within traveling waves. We also show that the level of ACh determines how sensitive network activity is to synaptic heterogeneity. These regimes may have a profound functional significance as stationary patterns may play a role in the proper encoding of external input as memory and traveling waves could lead to synaptic regularization, giving unique insights into the role and significance of ACh in determining patterns of cortical activity and functional differences arising from the patterns.

Rhythmic auditory cortex activity at multiple timescales shapes stimulus-response gain and background firing.

The phase of low-frequency network activity in the auditory cortex captures changes in neural excitability, entrains to the temporal structure of natural sounds, and correlates with the perceptual performance in acoustic tasks. Although these observations suggest a causal link between network rhythms and perception, it remains unknown how precisely they affect the processes by which neural populations encode sounds. We addressed this question by analyzing neural responses in the auditory cortex of anesthetized rats using stimulus-response models. These models included a parametric dependence on the phase of local field potential rhythms in both stimulus-unrelated background activity and the stimulus-response transfer function. We found that phase-dependent models better reproduced the observed responses than static models, during both stimulation with a series of natural sounds and epochs of silence. This was attributable to two factors: (1) phase-dependent variations in background firing (most prominent for delta; 1-4 Hz); and (2) modulations of response gain that rhythmically amplify and attenuate the responses at specific phases of the rhythm (prominent for frequencies between 2 and 12 Hz). These results provide a quantitative characterization of how slow auditory cortical rhythms shape sound encoding and suggest a differential contribution of network activity at different timescales. In addition, they highlight a putative mechanism that may implement the selective amplification of appropriately timed sound tokens relative to the phase of rhythmic auditory cortex activity.

Premovement Changes in Corticospinal Excitability of the Biceps Brachii are Not Different Between Arm Cycling and an Intensity-Matched Tonic Contraction.

The purpose of this study was to determine if supraspinal and/or spinal motoneuron excitability of the biceps brachii were differentially modulated before: 1) arm cycling and 2) an intensity-matched tonic contraction. Surface EMG recordings of motor evoked potentials (MEPs) and cervicomedullary motor evoked potentials (CMEPs) were used to assess supraspinal and spinal motoneuron excitability, respectively. MEP amplitudes were larger and onset latencies shorter, before arm cycling and tonic contraction when compared with rest with no intent to move, but with no difference between motor outputs. CMEP amplitudes and onset latencies remained unchanged before cycling and tonic contraction compared with rest. Premovement enhancement of corticospinal excitability was due to an increase in supraspinal excitability that was not task-dependent. This suggests that a common neural drive is used to initiate both motor outputs with task-dependent changes in neural excitability only being evident once the motor outputs have begun.

TDCS to temporoparietal cortex during familiarisation enhances the subsequent phonological coherence of nonwords in immediate serial recall

Research has shown that direct current stimulation (tDCS) over left temporoparietal cortex – a region implicated in phonological processing – aids new word learning. The locus of this effect remains unclear since (i) experiments have not empirically separated the acquisition of phonological forms from lexical-semantic links and (ii) outcome measures have focused on learnt associations with a referent rather than phonological stability. We tested the hypothesis that left temporoparietal tDCS would strengthen the acquisition of phonological forms, even in the absence of the opportunity to acquire lexical-semantic associations. Participants were familiarised with nonwords paired with (i) photographs of concrete referents or (ii) blurred images where no clear features were visible. Nonword familiarisation proceeded under conditions of anodal tDCS and sham stimulation in different sessions. We examined the impact of these manipulations on the stability of the phonological trace in an immediate serial recall (ISR) task the following day, ensuring that any effects were due to the influence of tDCS on long-term learning and not a direct consequence of short-term changes in neural excitability. We found that only a few exposures to the phonological forms of nonwords were sufficient to enhance nonword ISR overall compared to entirely novel items. Anodal tDCS during familiarisation further enhanced the acquisition of phonological forms, producing a specific reduction in the frequency of phoneme migrations when sequences of nonwords were maintained in verbal short-term memory. More of the phonemes that were recalled were bound together as a whole correct nonword following tDCS. These data show that tDCS to left temporoparietal cortex can facilitate word learning by strengthening the acquisition of long-term phonological forms, irrespective of the availability of a concrete referent, and that the consequences of this learning can be seen beyond the learning task as strengthened phonological coherence in verbal short-term memory.

The interplay of intrinsic excitability and network topology in spatiotemporal pattern generation in neural networks

It is clear that spatiotemporal patterning in brain networks is a complex outcome of network physical connectivity and dynamical properties of interacting neurons, however characterization of this interaction remains elusive. These dynamical properties of the cells are affected/controlled by various neuromodulators secreted by the brain at various cognitive cycles or as a part of the response to the incoming stimuli. During sleep the brain cycles though distinct spatiotemporal patterns of neural activity. Acetylcholine (ACh) is a major regulatory factor of sleep states and plays an important role in the transition from slow wave sleep to waking or rapid eye movement sleep. Slow wave sleep is a slow oscillation in firing rate that travels through the cortical network and occurs when ACh levels are low [1]. At the cellular level, ACh causes changes in neural excitability by shifting the neural phase response curve (PRC)