Transcranial Direct Current Stimulation Enhances Neuroplasticity and Accelerates Motor Recovery in a Stroke Mouse Model.

BACKGROUND: More effective strategies are needed to promote poststroke functional recovery. Here, we evaluated the impact of bihemispheric transcranial direct current stimulation (tDCS) on forelimb motor function recovery and the underlying mechanisms in mice subjected to focal ischemia of the motor cortex. METHODS: Photothrombotic stroke was induced in the forelimb brain motor area, and tDCS was applied once per day for 3 consecutive days, starting 72 hours after stroke. Grid-walking, single pellet reaching, and grip strength tests were conducted to assess motor function. Local field potentials were recorded to evaluate brain connectivity. Western immunoblotting, ELISA, quantitative real-time polymerase chain reaction, and Golgi-Cox staining were used to uncover tDCS-mediated stroke recovery mechanisms. RESULTS: Among our results, tDCS increased the rate of motor recovery, anticipating it at the early subacute stage. In this window, tDCS enhanced BDNF (brain-derived neurotrophic factor) expression and dendritic spine density in the peri-infarct motor cortex, along with increasing functional connectivity between motor and somatosensory cortices. Treatment with the BDNF TrkB (tropomyosin-related tyrosine kinase B) receptor inhibitor, ANA-12, prevented tDCS effects on motor recovery and connectivity as well as the increase of spine density, pERK (phosphorylated extracellular signal-regulated kinase), pCaMKII (phosphorylated calcium/calmodulin-dependent protein kinase II), pMEF (phosphorylated myocyte-enhancer factor), and PSD (postsynaptic density)-95. The tDCS-promoted rescue was paralleled by enhanced plasma BDNF level, suggesting its potential role as circulating prognostic biomarker. CONCLUSIONS: The rate of motor recovery is accelerated by tDCS applied in the subacute phase of stroke. Anticipation of motor recovery via vicariate pathways or neural reserve recruitment would potentially enhance the efficacy of standard treatments, such as physical therapy, which is often delayed to a later stage when plastic responses are progressively lower.

Activity of hippocampal, amygdala, and neocortex during the Rey auditory verbal learning test: an event-related potential study in epileptic patients.

OBJECTIVE: Previous evidence in epileptic subjects has shown that theta (about 4-7Hz) and gamma rhythms (about 40-45Hz) of hippocampus, amygdala, and neocortex were temporally synchronized during the listening of repeated words successfully remembered (Babiloni et al., 2009). Here we re-analyzed those electroencephalographic (EEG) data to test whether a parallel increase in amplitude of late positive event-related potentials takes place. METHODS: Intracerebral electroencephalographic (EEG) activity had been recorded in five subjects with drug-resistant temporal lobe epilepsy, undergoing pre-surgical evaluation. During the recording of the intracerebral EEG activity, the subjects performed a computerized version of the Rey auditory verbal learning test (RAVLT). They heard the same list of 15 common words for five times. Each time, immediately after the listening of the list, the subjects were required to repeat as many words as they could recall. RESULTS: We found that late positive event-related potentials (ERPs) peaking at about 350ms post-stimulus in amygdala, hippocampus, and occipital-temporal cortex had a higher amplitude during the listening of the repeated words that were subsequently recalled than for those that were not recalled. CONCLUSIONS: Late positive ERPs reflect a functional mechanism implemented in a human brain network spanning amygdala, hippocampus, and occipital-temporal cortex which is at the basis of the memorization processes of verbal materials. SIGNIFICANCE: This ERP component is a promising neuromarker of successful memorization of repeated words in humans.

"Neural efficiency" of athletes' brain for upright standing: a high-resolution EEG study.

"Neural efficiency" hypothesis posits that neural activity is reduced in experts. Here we tested the hypothesis that compared with non-athletes, elite athletes are characterized by a reduction of cortical activation during an engaging upright standing. EEG (56 channels; Be-plus Eb-Neuro and stabilogram (RGM) data were simultaneously recorded in 10 elite karate, 10 elite fencing athletes, and 12 non-athletes during a simple bipodalic (standard Romberg) and a more engaging monopodalic upright standing. Balance was indexed by body "sway area". The EEG data were spatially enhanced by surface Laplacian estimation. Cortical activity was indexed by task-related power decrease (TRPD) of EEG alpha power (8-12Hz) during monopodalic referenced to bipodalic condition. The body "sway area" was larger during the monopodalic than bipodalic upright standing in all groups. Low-frequency alpha TRPD (about 8-10Hz) was lower in amplitude in the karate and fencing athletes than in the non-athletes at left central, right central, middle parietal, and right parietal areas (p<0.01). Similarly, the amplitude of high-frequency alpha TRPD (10-12Hz) was lower in the karate and fencing athletes than in the non-athletes at right frontal, left central, right central, and middle parietal areas (p<0.03). These results suggest that during monopodalic referenced to less engaging bipodalic condition, the power decrease (i.e. the desynchronization) of cortical activity at alpha rhythms is largely reduced in elite athletes than in non-athletes, in line with the "neural efficiency" hypothesis. The present study extends our understanding of the physiological mechanisms at the basis of the "neural efficiency" for engaging upright standing in elite athletes.

Hippocampal, amygdala, and neocortical synchronization of theta rhythms is related to an immediate recall during rey auditory verbal learning test.

It is well known that theta rhythms (3-8 Hz) are the fingerprint of hippocampus, and that neural activity accompanying encoding of words differs according to whether the items are later remembered or forgotten ["subsequent memory effect" (SME)]. Here, we tested the hypothesis that temporal synchronization of theta rhythms among hippocampus, amygdala, and neocortex is related to immediate memorization of repeated words. To address this issue, intracerebral electroencephalographic (EEG) activity was recorded in five subjects with drug-resistant temporal lobe epilepsy (TLE), under presurgical monitoring routine. During the recording of the intracerebral EEG activity, the subjects performed a computerized version of Rey auditory verbal learning test (RAVLT), a popular test for the clinical evaluation of the immediate and delayed memory. They heard the same list of 15 common words for five times. Each time, immediately after listening the list, the subjects were required to repeat as many words as they could recall. Spectral coherence of the intracerebral EEG activity was computed in order to assess the temporal synchronization of the theta (about 3-8 Hz) rhythms among hippocampus, amygdala, and temporal-occipital neocortex. We found that theta coherence values between amygdala and hippocampus, and between hippocampus and occipital-temporal cortex, were higher in amplitude during successful than unsuccessful immediate recall. A control analysis showed that this was true also for a gamma band (40-45 Hz). Furthermore, these theta and gamma effects were not observed in an additional (control) subject with drug-resistant TLE and a wide lesion to hippocampus. In conclusion, a successful immediate recall to the RAVLT was associated to the enhancement of temporal synchronization of the theta (gamma) rhythms within a cerebral network including hippocampus, amygdala, and temporal-occipital neocortex.

Functional cortico-muscular coupling during upright standing in athletes and nonathletes: a coherence electroencephalographic-electromyographic study.

We tested the hypothesis that functional cortico-muscular coupling of brain rhythms is implied in the control of lower limb muscles for upright standing. Electroencephalographic (EEG; Be-plus Eb-Neuro) and electromyographic (EMG) data were recorded in 18 fencing and 19 karate elite athletes, 14 karate amateurs, and 9 non-athletes, during quiet upright standing with open and closed eyes conditions. Cortico-muscular coupling was evaluated by computing EEG-EMG spectral coherence and directed transfer function (DTF). Body sway area did not differ among the groups. In non-athletes, the EEG-EMG coherence (gastrocnemius lateralis) at centro-parietal and parasylvian alpha rhythms (about 8-12 Hz) was higher during the open than closed eyes condition. This was not true in the elite athletes. At the same alpha rhythms, the sport amateurs presented values halfway between the non-athletes and elite athletes. Finally, the DTF was higher for cortico-muscular than muscular-cortical direction. These results suggest that visual information affects cortico-muscular coherence at 8-12 Hz in non-athletes and amateur athletes but not in elite athletes. In elite athletes, this might be due to a long training for the control of equilibrium based on proprioceptive and tactile inputs.

Functional coupling between anterior prefrontal cortex (BA10) and hand muscle contraction during intentional and imitative motor acts.

The present study tested the hypothesis that functional cortico-muscular coupling is a putative physiological mechanism by which Brodmann area 10 (BA10) of anterior prefrontal cortex controls subjects' behavior. Intracerebral stereo electroencephalographic (SEEG) data were recorded from BA10 of epilepsy subjects in the course of pre-surgical monitoring. During the SEEG recordings, these subjects were engaged in three conditions: the execution of intentional hand muscle contractions as triggered by auditory stimuli ("EXE"); the execution of the same muscle contractions as an imitation of a person seated in front of the subject ("IMI"); and the mere observation of the hand muscle contractions performed by that person ("OBS"). SEEG frequency bands of interest were theta (4-7 Hz), alpha (8-12 Hz), beta 1 (13-21 Hz), beta 2 (22-30 Hz), and gamma (31-45 Hz). Results showed that functional cortico-muscular coupling at gamma band was higher in amplitude during the intentional muscle contraction ("EXE") than the other conditions ("IMI" and "OBS"). Instead, cortico-muscular coupling at theta band was higher in amplitude during the imitative muscle contraction ("IMI") than the other conditions ("EXE" and "OBS"). In parallel, there was an increase of SEEG gamma band power during the intentional muscle contraction and an increase of SEEG theta band power during its imitation. The present results suggest that anterior prefrontal cortex (BA10) might control subjects' behavior by means of functional cortico-muscular coupling at selective frequency bands (theta and wide gamma rhythms).

Neuromagnetic functional coupling during dichotic listening of speech sounds.

The present magnetoencephalography (MEG) study tested the hypothesis of a phase synchronization (functional coupling) of cortical alpha rhythms (about 6-12 Hz) within a "speech" cortical neural network comprising bilateral primary auditory cortex and Wernicke's areas, during dichotic listening (DL) of consonant-vowel (CV) syllables. Dichotic stimulation was done with the CV-syllable pairs /da/-/ba/ (true DL, yielded by stimuli having high spectral overlap) and /da/-/ka/ (sham DL, obtained with stimuli having poor spectral overlap). Whole-head MEG activity (165 sensors) was recorded from 10 healthy right-handed non-musicians showing right ear advantage in a speech DL task. Functional coupling of alpha rhythms was defined as the spectral coherence at the following bands: alpha 1 (about 6-8 Hz), alpha 2 (about 8-10 Hz), and alpha 3 (about 10-12) with respect to the peak of individual alpha frequency. Results showed an inverse pattern of functional coupling: during DL of speech sounds, spectral coherence of the high-band alpha rhythms increased between left auditory and Wernicke's areas with respect to sham DL, whereas it decreased between left and right auditory areas. The increase of functional coupling within the left hemisphere would underlie the processing of the syllable presented to the right ear, which arrives to the left auditory cortex without the interference of the other syllable presented to the left ear. Conversely, the decrease of inter-hemispherical coupling of the high-band alpha might be due to the fact that the two auditory cortices do not receive the same information from the ears during DL. These results suggest that functional coupling of alpha rhythms can constitute a neural substrate for the lateralization of auditory stimuli during DL.

Visual event-related potentials in elite and amateur athletes.

In the present study, we tested the hypothesis that the neural synchronization estimated in visual cortex during visuo-spatial demands shows different features in elite karate athletes when compared to amateur karate athletes and non-athletes. EEG recordings (56 channels; EB-Neuro) were performed from 17 elite karate athletes, 14 amateur karate athletes, and 15 non-athletes, during the observation of pictures with basket and karate attacks. They clicked a right (left) keyboard button for basket or karate attacks at right (left) monitor side. Results pointed to no difference of late occipital VEPs/ERPs after basket versus karate attacks in the non-athletes (300-800 ms post-stimulus). In the amateur karate athletes, occipital VEPs/ERPs at 300-450 ms post-stimulus (P3-P4 components) were lower in amplitude for the karate than basket attacks. In the elite karate athletes, the occipital VEPs/ERPs further declined in amplitude at 300-450 ms post-stimulus (P3 and P4 components) and enhanced at about 800 ms post-stimulus ("N2" component) for the karate than basket attacks. A control study showed that in 10 elite fencers, the same was true for the fencing compared to the karate attacks. These results support the hypothesis that peculiar mechanisms of occipital neural synchronization can be observed in elite athletes during visuo-spatial demands, possibly to underlie sustained visuo-spatial attention and self-control.

Cortical alpha rhythms are correlated with body sway during quiet open-eyes standing in athletes: a high-resolution EEG study.

Electroencephalographic (EEG; Be-plus Eb-Neuro) and stabilogram (RGM) data were simultaneously recorded in 19 elite karate and 18 fencing athletes and in 10 non-athletes during quiet upright standing at open- and closed-eyes condition in order to investigate the correlation between cortical activity and body sway when the visual inputs are available for balance. Our working hypothesis is that, at difference of non-athletes, athletes are characterized by enhanced cortical information processing as indexed by the amplitude reduction of EEG oscillations at alpha rhythms (about 8-12 Hz) during open- referenced to closed-eyes condition (event-related desynchronization, ERD). Balance during quiet standing was indexed by body "sway area". Correlation between alpha ERD and event-related change of the sway area was computed by a non-parametric test (p<0.05). It was found that alpha ERD (10-12 Hz) is stronger in amplitude in the karate and fencing athletes than in the non-athletes at ventral centro-parietal electrodes of the right hemisphere (p<0.02). Furthermore, there was a statistically significant correlation in the karate athletes between right ventral centro-parietal alpha ERD and body sway area (r=0.61; p<0.008): specifically, the greater the alpha ERD, the greater the percentage reduction of the body sway area when the visual inputs were available. These results suggest that parasylvian alpha ERD of the right hemisphere may reflect the cortical information processing for the balance in elite athletes subjected to a long training for equilibrium control.