Large-scale brain networks are often described using resting-state functional magnetic resonance imaging (fMRI). However, the blood oxygenation level-dependent (BOLD) signal provides an indirect measure of neuronal firing and reflects slow-evolving hemodynamic activity that fails to capture the faster timescale of normal physiological function. Here we used fMRI-guided transcranial magnetic stimulation (TMS) and simultaneous electroencephalography (EEG) to characterize individual brain dynamics within discrete brain networks at high temporal resolution. TMS was used to induce controlled perturbations to individually defined nodes of the default mode network (DMN) and the dorsal attention network (DAN). Source-level EEG propagation patterns were network-specific and highly reproducible across sessions 1 month apart. Additionally, individual differences in high-order cognitive abilities were significantly correlated with the specificity of TMS propagation patterns across DAN and DMN, but not with resting-state EEG dynamics. Findings illustrate the potential of TMS-EEG perturbation-based biomarkers to characterize network-level individual brain dynamics at high temporal resolution, and potentially provide further insight on their behavioral significance.

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Recovery of lower-limb function after spinal cord injury (SCI) likely depends on transmission in the corticospinal pathway. Here, we examined whether paired corticospinal-motoneuronal stimulation (PCMS) changes transmission at spinal synapses of lower-limb motoneurons in humans with chronic incomplete SCI and aged-matched controls. We used 200 pairs of stimuli where corticospinal volleys evoked by transcranial magnetic stimulation (TMS) over the leg representation of the motor cortex were timed to arrive at corticospinal-motoneuronal synapses of the tibialis anterior (TA) muscle 2 ms before antidromic potentials evoked in motoneurons by electrical stimulation of the common peroneal nerve (PCMS+) or when antidromic potentials arrived 15 or 28 ms before corticospinal volleys (PCMS-) on separate days. Motor evoked potentials (MEPs) elicited by TMS and electrical stimulation were measured in the TA muscle before and after each stimulation protocol. After PCMS+, the size of MEPs elicited by TMS and electrical stimulation increased for up to 30 min in control and SCI participants. Notably, this was accompanied by increases in TA electromyographic activity and ankle dorsiflexion force in both groups, suggesting that this plasticity has functional implications. After PCMS-, MEPs elicited by TMS and electrical stimulation were suppressed if afferent input from the common peroneal nerve reduced TA MEP size during paired stimulation in both groups. In conclusion, PCMS elicits spike-timing-dependent changes at spinal synapses of lower-limb motoneurons in humans and has potential to improve lower-limb motor output following SCI. Approaches that aim to enhance corticospinal transmission to lower-limb muscles following spinal cord injury (SCI) are needed. We demonstrate that paired corticomotoneuronal stimulation (PCMS) can enhance plasticity at spinal synapses of lower-limb motoneurons in humans with and without SCI. We propose that PCMS has potential for improving motor output in leg muscles in individuals with damage to the corticospinal tract.

Transcranial magnetic stimulation (TMS)-evoked potentials (TEPs), recorded using electroencephalography (EEG), reflect a combination of TMS-induced cortical activity and multi-sensory responses to TMS. The auditory evoked potential (AEP) is a high-amplitude sensory potential—evoked by the “click” sound produced by every TMS pulse—that can dominate the TEP and obscure observation of other neural components. The AEP is peripherally evoked and therefore should not be stimulation site specific. We address the problem of disentangling the peripherally evoked AEP of the TEP from components evoked by cortical stimulation and ask whether removal of AEP enables more accurate isolation of TEP. We hypothesized that isolation of the AEP using Independent Components Analysis (ICA) would reveal features that are stimulation site specific and unique individual features. In order to improve the effectiveness of ICA for removal of AEP from the TEP, and thus more clearly separate the transcranial-evoked and non-specific TMS-modulated potentials, we merged sham and active TMS datasets representing multiple stimulation conditions, removed the resulting AEP component, and evaluated performance across different sham protocols and clinical populations using reduction in Global and Local Mean Field Power (GMFP/LMFP) and cosine similarity analysis. We show that removing AEPs significantly reduced GMFP and LMFP in the post-stimulation TEP (14 to 400 ms), driven by time windows consistent with the N100 and P200 temporal characteristics of AEPs. Cosine similarity analysis supports that removing AEPs reduces TEP similarity between subjects and reduces TEP similarity between stimulation conditions. Similarity is reduced most in a mid-latency window consistent with the N100 time-course, but nevertheless remains high in this time window. Residual TEP in this window has a time-course and topography unique from AEPs, which follow-up exploratory analyses suggest could be a modulation in the alpha band that is not stimulation site specific but is unique to individual subject. We show, using two datasets and two implementations of sham, evidence in cortical topography, TEP time-course, GMFP/LMFP and cosine similarity analyses that this procedure is effective and conservative in removing the AEP from TEP, and may thus better isolate TMS-evoked activity. We show TEP remaining in early, mid and late latencies. The early response is site and subject specific. Later response may be consistent with TMS-modulated alpha activity that is not site specific but is unique to the individual. TEP remaining after removal of AEP is unique and can provide insight into TMS-evoked potentials and other modulated oscillatory dynamics.

To date, no systematic research investigating cortical correlates of performance changes in dual tasking has been reported in the elderly population. Thus, we monitored whole-scalp cortical activations (EEG) during both single task and posture-cognition dual tasking with the main goal of understanding cortical activity modulations underlying age-related differences on posture-cognition dual tasking conditions. Postural and cognitive data analyses showed that elderly people had decreased cognitive performance even during challenging single cognitive tasks. Working memory impairments in the elderly group can be observed when a challenging cognitive task is performed in any postural condition, while postural control performance differences only became significant during challenging dual task conditions. Behavioral performance results, in general, indicate that elderly subjects may adopt a non-automated conscious control strategy and prioritize postural performance over cognitive performance to maintain upright stance only when the cognitive load is low. EEG analyses showed increased delta, theta and gamma oscillations, primarily over frontal, central-frontal, central and central-parietal cortices during dual tasking conditions. We found that delta oscillations were more responsive to challenging postural conditions presumably related to cortical representations of changing sensory conditions in postural tasks. Theta rhythms, on the other hand, were more responsive to cognitive task difficulty in both groups, with more pronounced increases in younger subjects which may underlie neural correlates of high-level cognitive computations including encoding and retrieval. Gamma oscillations also increased in the elderly primarily over central and central-parietal cortices during challenging postural tasks, indicating increased allocation of attentional sources to postural tasks.

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The modulation of perturbation-evoked potential (PEP) N1 as a function of different biomechanical characteristics of perturbation has been investigated before. However, it remains unknown whether the PEP N1 modulation contributes to the shaping of the functional postural response. To improve this understanding, we examined the modulation of functional postural response in relation to the PEP N1 response in ten healthy young subjects during unpredictable perturbations to their upright stance-translations of the support surface in a forward or backward direction at two different amplitudes of constant speed. Using independent components from the fronto-central region, obtained from subject-specific head models created from the MRI, our results show that the latency of onset of the functional postural response after the PEP N1 response was faster for forward than backward perturbations at a constant speed but was not affected by the speed of perturbation. Further, our results reinforce some of the previous findings that suggested that the N1 peak amplitude and peak latency are both modulated by the speed of perturbation but not by the direction of the perturbation. Our results improve the understanding of the relation between characteristics of perturbation and the neurophysiology of reactive balance control and may have implications for the design of brain-machine interfaces for populations with a higher risk of falls.