Hebbian activity-dependent plasticity in white matter

Synaptic plasticity is required for learning and follows Hebb's Rule, the computational principle underpinning associative learning. In recent years, a complementary type of brain plasticity has been identified in myelinated axons, which make up the majority of brain's white matter. Like synaptic plasticity, myelin plasticity is required for learning, but it is unclear whether it is Hebbian or whether it follows different rules. Here, we provide evidence that white matter plasticity operates following Hebb's Rule in humans. Across two experiments, we find that co-stimulating cortical areas to induce Hebbian plasticity leads to relative increases in cortical excitability and associated increases in a myelin marker within the stimulated fiber bundle. We conclude that Hebbian plasticity extends beyond synaptic changes, and can be observed in human white matter fibers.

Low-Frequency rTMS over Contralesional M1 Increases Ipsilesional Cortical Excitability and Motor Function with Decreased Interhemispheric Asymmetry in Subacute Stroke: A Randomized Controlled Study

Objective. To determine the long-term effects of low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) over the contralesional M1 preceding motor task practice on the interhemispheric asymmetry of the cortical excitability and the functional recovery in subacute stroke patients with mild to moderate arm paresis. Methods. Twenty-four subacute stroke patients were randomly allocated to either the experimental or control group. The experimental group underwent rTMS over the contralesional M1 (1 Hz), immediately followed by 30 minutes of motor task practice (10 sessions within 2 weeks). The controls received sham rTMS and the same task practice. Following the 2-week intervention period, the task practice was continued twice weekly for another 10 weeks in both groups. Outcomes were evaluated at baseline (T0), at the end of the 2-week stimulation period (T1), and at 12-week follow-up (T2). Results. The MEP (paretic hand) and interhemispheric asymmetry, Fugl-Meyer motor assessment, Action Research Arm Test, and box and block test scores improved more in the experimental group than controls at T1 ( p < 0.05 ). The beneficial effects were largely maintained at T2. Conclusion. LF-rTMS over the contralesional M1 preceding motor task practice was effective in enhancing the ipsilesional cortical excitability and upper limb function with reducing interhemispheric asymmetry in subacute stroke patients with mild to moderate arm paresis. Significance. Adding LF-rTMS prior to motor task practice may reduce interhemispheric asymmetry of cortical excitabilities and promote upper limb function recovery in subacute stroke with mild to moderate arm paresis.

BDNF polymorphism and inter hemispheric balance of motor cortex excitability: a preliminary study

Preclinical studies have demonstrated that Brain-Derived Neurotrophic Factor (BDNF) plays a crucial role in the homeostatic regulation of cortical excitability and excitation/inhibition balance. Using transcranial magnetic stimulation (TMS) techniques we investigated whether BDNF polymorphism could influence cortical excitability of the left and right primary motor cortex in healthy humans. Twenty-nine participants were recruited and genotyped for the presence of the BDNF Val66Met polymorphism, namely homozygous for the valine allele (Val/Val), heterozygotes (Val/Met), and homozygous for the methionine allele (Met/Met). Blinded to the latter, we evaluated inhibitory and facilitatory circuits of the left (LH) and right motor cortex (RH) by measuring resting (RMT) and active motor threshold (AMT), short interval intracortical inhibition (SICI) and intracortical facilitation (ICF). For each neurophysiological metric we also considered the inter-hemispheric balance expressed by the Laterality Index (LI). Val/Val participants (n= 21) exhibited an overall higher excitability of the LH compared to the RH, as probed by lower motor thresholds, lower SICI and higher ICF. Val/Val participants displayed positive LI, especially for AMT and ICF (all p< 0.05), indicating higher LH excitability and more pronounced inter-hemispheric excitability imbalance as compared to Met carriers. Our preliminary results suggest that BDNF Val66Met polymorphism might influence interhemispheric balance of motor cortex excitability.

Top-down contribution to motor network reorganization during action preparation

It is unclear whether the Bereitschaftspotential (BP) recorded in humans during action preparation mirrors motor areas activation escalation, or if its early and late phases reflect the engagement of different functional networks. Here, we aimed at recording the TMS evoked-potentials (TEP) stimulating the supplementary motor area (SMA) to assess whether and how cortical excitability and functional connectivity of this region change as the BP increases. We hypothesize that, at later stages, the SMA functional network should become more connected to regions relevant for the implementation of the final motor plan. We performed TMS-EEG recordings on fourteen healthy subjects during the performance of a visuomotor Go/No-go task, eliciting and recording cortical activity and functional connectivity at -700 ms and -300 ms before the onset of visual stimuli over the SMA. When approaching stimulus onset, and thus BP peak, the SMA increased its functional connectivity with movement-related structures in the gamma and alpha bands, indicating a regional top-down preparation to implement the motor act. Beta-band connectivity, instead, was maintained constant for the whole BP time-course, being potentially related to sustained attention required by the experimental task. These findings reveal that the BP is not a mere result of increased activation of the SMA, but the functional networks in which this region is involved qualitatively changes over time, becoming more related to the execution of the motor act.

Neurochemical profiles of the anterior temporal lobe predict response of repetitive transcranial magnetic stimulation on semantic processing

The effect of repetitive transcranial magnetic stimulation can vary considerably across individuals, but the reasons for this still remain unclear. Here, we investigated whether the response to continuous theta-burst stimulation (cTBS) – an effective protocol for decreasing cortical excitability – related to individual differences in glutamate and GABA neurotransmission. We applied cTBS over the anterior temporal lobe (ATL), a hub for semantic representation, to explore the relationship between the baseline neurochemical profiles in this region and the response to this stimulation. Our experiments revealed that non-responders (subjects who did not show an inhibitory effect of cTBS on subsequent semantic performance) had higher excitatory-inhibitory balance (glutamate + glutamine/GABA ratio) in the ATL, which led to up-regulated task-induced regional activity as well as increased ATL-connectivity with other semantic regions compared to responders. These results disclose that the baseline neurochemical state of a cortical region can be a significant factor in predicting responses to cTBS.

Respiration aligns perception with neural excitability

Recent studies from the field of interoception have highlighted the link between bodily and neural rhythms during action, perception, and cognition. The mechanisms underlying functional body-brain coupling, however, are poorly understood, as are the ways in which they modulate behaviour. We acquired respiration and human magnetoencephalography (MEG) data from a near-threshold spatial detection task to investigate the trivariate relationship between respiration, neural excitability, and performance. Respiration was found to significantly modulate perceptual sensitivity as well as posterior alpha power (8 - 13 Hz), a well-established proxy of cortical excitability. In turn, alpha suppression prior to detected vs undetected targets underscored the behavioural benefits of heightened excitability. Notably, respiration-locked excitability changes were maximised at a respiration phase lag of around -30° and thus temporally preceded performance changes. In line with interoceptive inference accounts, these results suggest that respiration actively aligns sampling of sensory information with transient cycles of heightened excitability to facilitate performance.

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

Background: Transcranial 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) analysis has been used to evaluate cortical excitability changes after TBS. However, it remains unclear whether TEPs can detect the neuromodulatory effects of TBS. Objectives: To confirm the reliability of TEP components within and between sessions and to measure changes in neural excitability induced by intermittent (iTBS) and continuous TBS (cTBS) applied to the left DLPFC. Methods: Test-retest reliability of TEPs 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). Results: The N100 and P200 components presented substantial reliability within the baseline block (CCCs>0.8) and moderate concordance between sessions (CCCmax≈0.7). Both N40 and P60 TEP amplitudes showed little concordance between sessions. 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. Conclusions: The present findings show that only the N100 and P200 components had good concordance between sessions. The reliability of earlier components may have been affected by TMS-evoked artefacts. The poor reliability to detect changes in neural excitability induced by TBS indicates that TEPs 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.

Effects of a single session of cathodal transcranial direct current stimulation primed intermittent theta-burst stimulation on heart rate variability and cortical excitability measures

Objectives: Transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) have been used as neuromodulators in neuropsychiatric conditions. This study is aimed to find the effects of a single session of priming cathodal tDCS with intermittent theta-burst stimulation (iTBS) over left dorsolateral prefrontal cortex on heart rate variability (HRV) and cortical excitability parameters before and after perturbation. Materials and Methods: The neuromodulatory techniques used in the study were Cathodal tDCS for 20 min followed by iTBS for 3 min on the left dorsolateral prefrontal cortex (DLPFC). HRV variables and TMS parameters were recorded before and after this intervention of combined neuromodulation in 31 healthy volunteers (20 males and 11 females; age range of 19–35 years with Mean ± SD = 24.2 ± 4.7 years). Results: The results showed an overall increase in cortical excitability and parasympathetic dominance in healthy volunteers. Other measures of cortical excitability and HRV did not change significantly following single session of combined neuromodulation. Conclusion: This study showed that there is an overall increase in cortical excitability and parasympathetic dominance in the cohort of healthy volunteers following a combination of neuromodulation involving cathodal tDCS followed by iTBS over left DLPFC. Future studies exploring the effects of other possible combinations with sham stimulation could be carried out to explore the utility of dual stimulation as add-on therapy in disorders.