Stimulation Frequency Research Articles

Repetitive transcranial magnetic stimulation frequency influences the hemodynamic responses in patients with disorders of consciousness.

Repetitive transcranial magnetic stimulation (rTMS) emerges as a promising non-invasive neuromodulation technique for the treatment of patients with disorders of consciousness (DOC). The selection of rTMS parameters significantly influences the clinical therapeutic effects. However, the differences in spatiotemporal responsiveness of the brain under different rTMS stimulation frequencies remain unclear. In this pilot study, functional near-infrared spectroscopy (fNIRS) was used to evaluate the spatiotemporal differences in hemodynamic responses elicited by rTMS at different frequencies (1, 5, 10, 15, and 20Hz) over left dorsolateral prefrontal cortex (F3). The results showed that the distribution patterns of the rTMS-evoked hemodynamic responses varied across different frequencies, indicating that rTMS frequency influences the hemodynamic responses in patients with DOC. Specifically, 10Hz rTMS evoked strong positive hemodynamic responses over the frontal cortex, particularly in the right dorsolateral prefrontal cortex (R-DLPFC). Additionally, 20Hz rTMS produced largepositive hemodynamic responses over the motor-related cortex, especially the right premotor cortex (R-PreM) and right primary sensorimotor cortex (PSMC). The current findings suggested that fNIRS can be used as a promising tool for evaluating the effects of rTMS in patients with DOC. Moreover, it provides useful guidance for the personalized design of rTMS parameters in a clinical environment.

Characterization of preclinical models to investigate spinal cord stimulation for neuropathic pain: a systematic review and meta-analysis.

Despite advancements in preclinical and clinical spinal cord stimulation (SCS) research, the mechanisms of SCS action remain unclear. This may result from challenges in translatability of findings between species. Our systematic review (PROSPERO: CRD42023457443) aimed to comprehensively characterize the important translational components of preclinical SCS models, including stimulating elements and stimulation specifications. Databases (Embase, PubMed, Web of Science, and WikiStim) were searched on October 5, 2023, identifying 78 studies meeting the search criteria. We conducted a post hoc meta-analysis, including subgroup analyses and meta-regression, to assess SCS efficacy on mechanical hypersensitivity in rats subjected to neuropathic pain. Although monopolar electrodes were predominantly used as stimulating elements until 2013, quadripolar paddle and cylindrical leads gained recent popularity. Most research was conducted using 50 Hz and 200 µs stimulation. Motor threshold (MT) estimation was the predominant strategy to determine SCS intensity, which was set to 71.9% of MT on average. Our analysis revealed a large effect size for SCS (Hedge g = 1.13, 95% CI: [0.93, 1.32]) with similar magnitudes of effect between conventional (≤100 Hz) and nonconventional SCS paradigms while sham SCS had nonsignificant effect size. In addition, different stimulation intensity, frequency, and electrode design did not affect effect size. The risk of bias was assessed using Systematic Review Centre for Laboratory animal Experimentation criteria and was unclear, and only the frequency subgroup analysis showed publication bias. In summary, our review characterizes the critical components of preclinical SCS models and provides recommendations to improve reproducibility and translatability, thereby advancing the scientific foundation for SCS research.

Frequency-dependent phase entrainment of cortical cell types during tACS: computational modeling evidence

Objective. Transcranial alternating current stimulation (tACS) enables non-invasive modulation of brain activity, holding promise for clinical and research applications. Yet, it remains unclear how the stimulation frequency differentially impacts various neuron types. Here, we aimed to quantify the frequency-dependent behavior of key neocortical cell types.Approach. We used both detailed (anatomical multicompartments) and simplified (three compartments) single-cell modeling approaches based on the Hodgkin-Huxley formalism to study neocortical excitatory and inhibitory cells under various tACS intensities and frequencies within the 5-50 Hz range at rest and during basal 10 Hz activity.Main results. L5 pyramidal cells (PCs) exhibited the highest polarizability at direct current, ranging from 0.21 to 0.25 mm and decaying exponentially with frequency. Inhibitory neurons displayed membrane resonance in the 5-15 Hz range with lower polarizability, although bipolar cells had higher polarizability. Layer 5 PC demonstrated the highest entrainment close to 10 Hz, which decayed with frequency. In contrast, inhibitory neurons entrainment increased with frequency, reaching levels akin to PC. Results from simplified models could replicate phase preferences, while amplitudes tended to follow opposite trends in PC.Significance. tACS-induced membrane polarization is frequency-dependent, revealing observable resonance behavior. Whilst optimal phase entrainment of sustained activity is achieved in PC when tACS frequency matches endogenous activity, inhibitory neurons tend to be entrained at higher frequencies. Consequently, our results highlight the potential for precise, cell-specific targeting for tACS.

Deep brain stimulation-entrained gamma oscillations in chronic home recordings in Parkinson's disease.

In Parkinson's disease, invasive brain recordings show that dopaminergic medication can induce narrowband gamma rhythms in the motor cortex and subthalamic nucleus, which co-fluctuate with dyskinesia scores. Deep brain stimulation can entrain these gamma oscillations to a subharmonic stimulation frequency. However, the incidence of entrainment during chronic therapeutic stimulation, its relationship to the basal ganglia stimulation site, and its effect on dyskinesia remain unknown. Determine whether the behavioral effects and statistical properties of levodopa-induced gamma oscillations are altered when entrained with deep brain stimulation. We used a sensing-enabled deep brain stimulator system, attached to both motor cortex and subthalamic (n=15) or pallidal (n=5) leads, to record 993 hours of multisite field potentials, with 656 hours recorded prior to initiating stimulation. 13 subjects (20 hemispheres) with Parkinson's disease (1/13 female, mean age 59±9 years) streamed data while at home on their usual antiparkinsonian medication. Recordings during stimulation occurred at least five months after initiating stimulation. Cortical entrained gamma oscillations were detected in 4/5 hemispheres undergoing pallidal stimulation and 12/15 hemispheres undergoing subthalamic stimulation. Entraining levodopa-induced gamma oscillations at either site reduced their prodyskinetic effects. Cortical entrained gamma oscillations had reduced variance in peak frequency, increased spectral power, and higher variance in spectral power than levodopa-induced gamma oscillations. Stimulation-entrained gamma oscillations are functionally and physiologically distinct from levodopa-induced gamma oscillations that occur in the absence of deep brain stimulation. Understanding the discrepancies between types of gamma oscillations may improve programming protocols.

Transcutaneous electrical acupoint stimulation for hypertension complicated by anxiety or sleep disorders: a pilot randomized controlled trial.

Hypertension is often accompanied by anxiety and sleep disorders, which further complicate the disease. This study aimed to evaluate the feasibility and effectiveness of transcutaneous electrical acupoint stimulation (TEAS) in patients with hypertension and anxiety or sleep disorders. Eligible participants were randomly assigned to the 10Hz TEAS, 2Hz TEAS, or routine treatment groups in a 1:1:1 ratio. Participants continued their routine treatment during the trial, while those in the two TEAS groups received 12 sessions of 30-min TEAS treatment with different stimulation frequencies. The feasibility parameters were successful screening probability, enrollment rate, and dropout rate. The primary outcome was the change in office systolic blood pressure from baseline to week four. Secondary outcomes included changes in office diastolic blood pressure, heart rate, Pittsburgh Sleep Quality Index score, and Generalized Anxiety Disorder 7-item scale score from baseline to week four. Eighty-eight participants (age 58.0 [51.0, 63.0] years; 49 women) were randomized. The successful screening probability was 56.1%, the enrollment rate was 3.1 participants per week, and the dropout rate was 14.8%. The change in office systolic blood pressure from baseline to week four was -2.8 ± 13.6mm Hg, -6.4 ± 10.0mm Hg, and -7.2 ± 11.2mm Hg, respectively, in the 10Hz TEAS, 2Hz TEAS, and routine treatment groups (P=0.332). No significant differences were noted, except for a change in the Pittsburgh Sleep Quality Index score (P=0.014). Both 10Hz (P=0.024) and 2Hz TEAS (P=0.039) significantly improved sleep quality compared to routine treatment. In patients with hypertension having anxiety or sleep disorders, this study did not demonstrate the superiority of TEAS over routine treatment but did show an improvement in sleep quality and a downward trend in diastolic blood pressure. Therefore, a largescale trial is warranted.

Cardiac muscle contracts more efficiently at lower contraction frequencies.

This study investigated how contraction frequency impacts the mechano-energetics of cardiac muscle performing mechanical work. Left-ventricular trabeculae were isolated from rat hearts and mounted in our work-loop calorimeter to assess their function at physiological temperature (37°C) across three stimulation frequencies, 2 Hz, 3.5 Hz and 5Hz, in a randomised sequence. Each trabecula was subjected to two experimental protocols: work-loop contractions under a range of afterloads and isometric contractions under a range of muscle lengths. Two contraction protocols allowed the partition of the various components of energy expenditure during cardiac contraction. By simultaneously measuring force-length work and heat output, mechanical efficiency was calculated over a range of afterloads to determine the peak value. Our findings revealed that force production, activation heat (energy associated with Ca2+ cycling) and cross-bridge heat were unaffected by stimulation frequency. Trabeculae produced greater work output per twitch at 2 Hz and 3.5Hz than at 5Hz. Positive correlations among work output, shortening extent and mechanical efficiency were detected. From these findings it was concluded that the higher work output at lower frequencies is associated with greater extent of shortening, which correlates to greater mechanical efficiency. This study highlights the mechano-energetic advantage of ventricular trabeculae in terms of increased work output and energy efficiency gained from operating at lower contraction frequencies, supporting the notion that heart rate reduction produces direct benefits on cardiac energetics.

Correlation of zero echo time functional MRI with neuronal activity in rats.

Zero echo time (zero-TE) pulse sequences provide a quiet and artifact-free alternative to conventional functional magnetic resonance imaging (fMRI) pulse sequences. The fast readouts (<1 ms) utilized in zero-TE fMRI produce an image contrast with negligible contributions from blood oxygenation level-dependent (BOLD) mechanisms, yet the zero-TE contrast is highly sensitive to brain function. However, the precise relationship between the zero-TE contrast and neuronal activity has not been determined. Therefore, we aimed to derive a function to model the temporal dynamics of the zero-TE fMRI signal in response to neuronal activity. Furthermore, we examined the correlation of zero-TE fMRI with neuronal activity across stimulation frequencies. To these ends, we performed simultaneous electrophysiological recordings and zero-TE fMRI in rats subjected to whisker stimulation. The presented impulse response function provides a basis for the statistical modeling of neuronal activity-induced changes in the zero-TE fMRI signal. The temporal characteristics of the zero-TE fMRI response were found to be consistent with the previously postulated non-BOLD hemodynamic origin of the functional contrast. The zero-TE fMRI signal was well predicted by electrophysiological recordings, although systematic stimulation-dependent residuals were also observed, suggesting nonlinearities in neurovascular coupling. We conclude that zero-TE fMRI provides a robust proxy for neuronal activity.

Local field potential phase modulates the evoked response to electrical stimulation in visual cortex

Objective.Development of cortical visual prostheses requires optimization of evoked responses to electrical stimulation to reduce charge requirements and improve safety, efficiency, and efficacy. One promising approach is timing stimulation to the local field potential (LFP), where action potentials have been found to occur preferentially at specific phases. To assess the relationship between electrical stimulation and the phase of the LFP, we recorded action potentials from primary (V1) and secondary (V2) visual cortex in marmosets while delivering single-pulse electrical microstimulation at different phases of the LFP.Approach.A 64-channel 4 shank probe was inserted into V1 and V2. Microstimulation (single biphasic pulse, 10µA and 200µs per phase) was applied to selected channels in V1, and action potentials recorded simultaneously in V1 and V2. Microstimulation pulses were jittered in time to randomize the phase of the LFP at the time of stimulation.Results.We found frequency-specific phase modulation in a subset of units, where microstimulation in V1 evokes a higher firing rate in both V1 and V2 when delivered at specific phases of the LFP. We characterize phase modulation in terms of the preferred phase and frequency of V1 stimulation for responses in both V1 and V2, and effect size as a function of phase estimation accuracy.Significance.Phase modulation could reduce charge requirements for neural activation, reducing the volume of activated tissue and improving the safety, efficacy, and specificity of cortical visual prostheses. Phase modulation could allow cortical visual prostheses to stimulate using more simultaneous electrodes, with improved neural specificity, and, potentially, targeting downstream cortical activation.

The boost of force in unfused tetanic contractions at variable interpulse intervals in fast motor units of the rat medial gastrocnemius

Previously, boost and sag effects seen in unfused tetanic contractions have been studied exclusively at constant stimulation frequency. However, intervals between successive discharges of motoneurons vary during voluntary movements. We therefore aimed to test whether the extra-efficient force production at the onset of contraction (boost) occurs during stimulation with variable intervals, and to what extent it depends on the level of interpulse interval (IPI) variability and history of stimulation. Four sets of three repeated unfused tetani (the first set with constant IPIs at 35 Hz; the other three sets with mean frequency 35 Hz and variable IPIs 28 ± 2 ms, ± 5 ms, and ± 7 ms, respectively) were recorded with 3 min breaks in fast fatigable and fast fatigue-resistant motor units of the rat medial gastrocnemius. We show that boost occurred in the first tetanic contraction of each set for stimulation at both constant and variable IPIs in two fast types of motor units; additionally, it was present in different IPIs variability for a given range. Mathematical decomposition of first (sagging) and second (non-sagging) tetanic contractions into twitch-like responses to successive stimuli in the tested IPIs variability showed that the changes underlying boost are pattern independent. This implies that boost probably occurs in daily activity when motoneurons fire with an unstable firing rate. The effect may therefore contribute to the development and regulation of force in voluntary daily activities, especially in short powerful contractions.

Cortical Acetylcholine Response to Deep Brain Stimulation of the Basal Forebrain in Mice.

Deep brain stimulation (DBS) using electrical stimulation of neuronal tissue in the basal forebrain to enhance release of the neurotransmitter acetylcholine is under consideration to improve executive function in patients with dementia. While some small studies indicate a positive response in the clinical setting, the relationship between DBS and acetylcholine pharmacokinetics is incompletely understood. We examined the cortical acetylcholine response to different stimulation parameters of the basal forebrain. 2-photon in vivo imaging was combined with deep brain stimulation in C57BL/6J mice. Stimulating electrodes were implanted in the subpallidal basal forebrain, and the ipsilateral somatosensory cortex was imaged. Acetylcholine activity was determined using the GRABACh-3.0 acetylcholine receptor sensor, and blood vessels were visualized with Texas red. Experiments manipulating stimulation frequency demonstrated that integrated acetylcholine induced fluorescence was insensitive to frequency with the same number of pulses, and that maximum peak levels were achieved with frequencies from 60 to 130 Hz. Altering pulse train length indicated that longer stimulation resulted in higher peaks and more activation with sublinear summation. The acetylcholinesterase inhibitor, donepezil, increased the peak response to 10s of stimulation at 60Hz, and the integrated response increased 57% with the 2 mg/kg dose, and 126% with the 4 mg/kg dose. Acetylcholine levels returned to baseline with a time constant of 14 to 18 seconds. Donepezil increases total acetylcholine receptor activation associated with DBS but did not change temporal kinetics. The long time constants observed in the cerebral cortex add to the evidence supporting volume and synaptic neurotransmission.

Does the audiogram shape influence the intracochlear recording of Electrocochleography during and after cochlear implantation?

During cochlear implant (CI) surgery, it is desirable to perform intraoperative measurements such as Electrocochleography (ECochG) to monitor the inner ear function and thereby to support the preservation of residual hearing. However, a significant challenge arises as the recording location of intracochlear ECochG via the CI electrode changes during electrode insertion. This study aimed to investigate the relationships between intracochlear ECochG recordings, the position of the recording contact within the cochlea relative to its anatomy, and the implications for frequency and residual hearing preservation. Intraoperative ECochG recordings were conducted using the CI electrode (MED-EL) during the insertion of hearing preservation electrodes and after the insertion process. Recordings were continuously conducted using the most apical electrode (contact 1) during insertion. After insertion, the recordings were performed on all different electrode contacts. The electrode location in the cochlea during insertion was estimated using mathematical models and preoperative clinical imaging, while the postoperative electrode position was determined using postoperative clinical imaging. The study involved 10 adult CI recipients. In those with good low-frequency hearing, an increase in signal amplitude was observed, with the highest amplitudes closest to the stimulation frequency generators, and no phase change was observed. Conversely, patients with flat hearing loss exhibited a second peak with an opposite phase in the medial area of the cochlea. This study is the first to suggest that the pattern of the preoperative audiogram may influence the ECochG outcomes measured intraoperatively. Specifically, the ECochG responses during insertion appeared to behave as expected with good low-frequency hearing, while with flat hearing loss there appear to be further effects. These findings indicate that this approach can provide valuable information for the interpretation of intracochlearly recorded ECochG signals.

Subthalamic nucleus deep brain stimulation in the beta frequency range boosts cortical beta oscillations and slows down movement.

Recordings from Parkinson's disease (PD) patients typically show strong beta-band oscillations (13-35Hz), which can be modulated by deep brain stimulation (DBS). While high-frequency DBS (>100Hz) ameliorates motor symptoms and reduces beta activity in basal ganglia and motor cortex, the effects of low-frequency DBS (<30Hz) are less clear. Clarifying these effects is relevant for the debate about the role of beta oscillations in motor slowing, which might be causal or epiphenomenal. Here, we investigated how subthalamic nucleus (STN) beta-band DBS affects cortical beta oscillations and motor performance. We recorded the magnetoencephalogram of 14 PD patients (9 males) with DBS implants while on their usual medication. Following a baseline recording (DBS off), we applied bipolar DBS at beta frequencies (10, 16, 20, 26, and 30Hz) via the left electrode in a cyclic fashion, turning stimulation on (5s) and off (3s) repeatedly. For each frequency, cyclic stimulation was applied at rest and during right hand finger tapping. In the baseline recording, we observed a negative correlation between the strength of hemispheric beta power lateralization and the tap rate. Importantly, beta-band DBS accentuated the lateralization and reduced the tap rate proportionally. The change in lateralization was specific to the alpha/beta range (8-26Hz), outlasted stimulation and did not depend on the stimulation frequency, suggesting a remote induced response rather than entrainment. Our study demonstrates that cortical beta oscillations can be manipulated by STN beta-band DBS. Importantly, this manipulation appears to have consequences for motor performance, supporting a causal role of beta oscillations in motor control.Significance Statement The slowing of movement in Parkinson's disease is known to be related to pathologically enhanced neural oscillations in the beta range (13-35Hz). Whether these oscillations are the cause of motor slowing, however, remains debated. Here, we stimulated the brains of Parkinson patients in the beta range, using their implanted deep brain stimulator. Consistent with a causal effect, stimulation slowed down finger tapping. Additionally, the subcortical stimulation affected the hemispheric balance of beta oscillations in the remote motor cortices. The stronger the shift, the stronger was the slowing. These results suggest that subcortical beta-band stimulation causes motor slowing by boosting motor cortical beta oscillations, indicating that beta oscillations might indeed be "a bad boy in Parkinson's disease".

Artificial Taste: Advances and Innovative Applications in Healthcare

Background: Scientists have recently developed a technology that induces artificial taste through electronic stimulation. However, scattered reports have made it difficult to comprehensively understand the technology’s details and appreciate its potential applications in healthcare. To address these gaps, a meta-review was conducted. We re-viewed the current literatures on the technology behind artificial taste. Targeted original research papers were analyzed, with data extracted to address five key aspects: interface design, stimulation parameters, sensation verification results, applications to health problems, and potential side effects in human subjects. Results: A total of 19 relevant papers were identified. Eight studies focused on tongue-tip electrode interfaces, while others integrated technology into eating utensils. Eleven studies examined stimulation frequencies (50–1000 Hz), with five altering temperature and two changing water color to enhance taste perception. Only six studies reported verification results, showing that most participants perceived sour and salty tastes, mild bitter responses, and unreliable sweet evocation. Sixteen papers discussed applications in healthcare (dietary and weight management), entertainment (food and beverage sampling), and education. Side effects included reduced sensitivity after repeated trials and occasional discomfort from excessive stimulation, though no immediate tissue damage was reported. Conclusions: Artificial taste technology offers an innovative approach to managing food and beverage intake without compromising taste sensations. When applied on a large scale, it holds significant potential for regulating eating behaviors and providing novel strategies for addressing chronic health issues associated with diet.

Dynamic retinal vessel analysis with flicker light stimulation: Higher stimulation frequencies lead to higher vascular responses

Aims/Purpose: Dynamic retinal vessel analysis (DVA) with flicker light is an established method of retinal vessel analysis. Stimulation is generally performed according to a standard protocol at 12.5 Hz. Technologically, a full‐field shutter is used, which is located in the illumination path. In 2002, Polak et al. investigated the flicker‐induced vascular response at different frequencies (2–64Hz). This showed that from frequencies &gt; 4Hz, smaller responses tend to result. However, current developments in light stimulation are moving towards spatio‐temporal stimulators. We therefore used a spatial light modulator (SLM) in a DVA setup. In this work, we investigated vascular responses at a lower and higher stimulation frequency compared to 12.5Hz. The dilation maxima were determined and compared.Methods: We studied 12 subjects (7w, 5m, 26.6 ± 3.7yr, 1 eye). We measured two primary vessels each: a superior temporal artery and a vein. All subjects were free of ocular and systemic diseases. A high‐power LED (515nm) and a transmissive liquid crystal display (Sony LCX017AL) were connected to a mydriatic fundus camera. The SLM was controlled via standard graphics card and a customized software. The field of view was set to 30°. Each subject was measured two times. One measurement was carried out at 3.75Hz and one at 30Hz flicker frequency, randomized among the subjects. As in Polak et al. (2002), measurements were taken with 60s baseline, 60s flicker stimulation. Decay measurement was 120s. The pause time between two measurements was 15min. The mean value and standard deviation were calculated for each stimulation frequency and vessel type. The differences were tested for normal distribution and either the paired t‐test or the Wilcoxon signed‐rank test was performed.Results: All subjects were able to successfully complete the study (n = 12). Arteries showed a mean maximum dilatation of 2.8 ± 1.2% at 3.75Hz and 4.0 ± 1.6% at 30Hz (p = 0.023, Cohen's d = 0.765). Veins showed 2.8 ± 1.7% at 3.75Hz and 4.4 ± 2.5% at 30Hz (p = 0.005, Cohen's d = 1.015).Conclusions: We successfully performed a study on the generation of different flicker frequencies using a transmissive liquid crystal display. The results are contrary to those of Polak et al. (2002). Other parameters need to be compared in further studies.

A new method to evaluate staircase phenomenon in skeletal muscle using piezoelectric sensor.

The staircase phenomenon, which refers to the increases in the force of contraction with repetitive stimulation of the muscle, has been studied for many years, but the method is difficult and not widely used. Our objective was to evaluate the staircase phenomenon in skeletal muscle using a piezoelectric sensor. Thirty-five subjects without neuromuscular diseases (normal controls), 11 patients with Becker muscular dystrophy (BMD), and 19 patients with myotonic dystrophy type 1 (MyD) were studied. Compound muscle action potential (CMAP) and movement-related potential (MRP) waveforms were recorded using piezoelectric sensors during repetitive stimulation of the median nerve, and the amplitudes and durations were measured. Excitation-contraction (E-C) coupling time (ECCT) was calculated from the difference between onset latencies of CMAP and MRP. In normal controls, MRP amplitude ratio (relative to baseline) increased significantly with increase in stimulation duration and with increase in stimulation frequency. In BMD and MyD, however, MRP amplitude ratio did not change significantly with increase in stimulation duration. Especially, in MyD, there was no change in MRP amplitude ratio with increase in frequency. Staircase phenomenon abnormalities can be evaluated easily using piezoelectric sensors, indicating their potential utility for evaluating E-C coupling impairment in myopathies. Piezoelectric sensors may be a useful tool to evaluate staircase phenomenon in skeletal muscle.

Adenosine deficiency facilitates CA1 synaptic hyperexcitability in the presymptomatic phase of a knockin mouse model of Alzheimer disease.

The disease's trajectory of Alzheimer disease (AD) is associated with and negatively correlated to hippocampal hyperexcitability. Here, we show that during the asymptomatic stage in a knockin (KI) mouse model of Alzheimer disease (APPNL-G-F/NL-G-F; APPKI), hippocampal hyperactivity occurs at the synaptic compartment, propagates to the soma, and is manifesting at low frequencies of stimulation. We show that this aberrant excitability is associated with a deficient adenosine tone, an inhibitory neuromodulator, driven by reduced levels of CD39/73 enzymes, responsible for the extracellular ATP-to-adenosine conversion. Both pharmacologic (adenosine kinase inhibitor) and non-pharmacologic (ketogenic diet) restorations of the adenosine tone successfully normalize hippocampal neuronal activity. Our results demonstrated that neuronal hyperexcitability during the asymptomatic stage of a KI model of Alzheimer disease originated at the synaptic compartment and is associated with adenosine deficient tone. These results extend our comprehension of the hippocampal vulnerability associated with the asymptomatic stage of Alzheimer disease.

Simulation Study of Envelope Wave Electrical Nerve Stimulation Based on a Real Head Model.

In recent years, the modulation of brain neural activity by applied electromagnetic fields has become a hot spot in neuroscience research. Transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS) are two common non-invasive neuromodulation techniques. However, conventional tACS has limited stimulation effects in the deeper parts of the brain. In this study, a method of low and medium frequency envelope wave neurostimulation is proposed, and its effectiveness and safety are evaluated by simulation and human experiment. First, we built a real head model from head MRI image data and used the finite element method to calculate the current distribution of the envelope wave in the brain. Then, a single-compartment neuron model was constructed in NEURON software to simulate the action potential generation of neurons under different frequencies of electrical stimulation. Finally, a human experiment was conducted to investigate the threshold of human perception of envelope wave electrical stimulation. The results show that envelope wave can both increase the depth of stimulation and induce neurons to generate effective action potentials. In envelope wave electrical stimulation, the optimal modulating wave frequency was 50 Hz, and the carrier frequency was 2 kHz-3 kHz. This method is expected to play an important role in the non-invasive treatment of neurological and psychiatric disorders.

Intermodulation frequencies reveal common neural assemblies integrating facial and vocal fearful expressions.

Effective social communication depends on the integration of emotional expressions coming from the face and the voice. Although there are consistent reports on how seeing and hearing emotion expressions can be automatically integrated, direct signatures of multisensory integration in the human brain remain elusive. Here we implemented a multi-input electroencephalographic (EEG) frequency tagging paradigm to investigate neural populations integrating facial and vocal fearful expressions. High-density EEG was acquired in participants attending to dynamic fearful facial and vocal expressions tagged at different frequencies (fvis, faud). Beyond EEG activity at the specific unimodal facial and vocal emotion presentation frequencies, activity at intermodulation frequencies (IM) arising at the sums and differences of the harmonics of the stimulation frequencies (mfvis±nfaud) were observed, suggesting non-linear integration of the visual and auditory emotion information into a unified representation. These IM provide evidence that common neural populations integrate signal from the two sensory streams. Importantly, IMs were absent in a control condition with mismatched facial and vocal emotion expressions. Our results provide direct evidence from non-invasive recordings in humans for common neural populations that integrate fearful facial and vocal emotional expressions.

Optimal Word Reading Rate as Evidenced by Frequency-tagging Electrophysiology.

Fast periodic visual stimulation (FPVS) coupled with EEG has been used for a decade to measure word-selective neural responses in (a)typical adults and developmental readers. Here, we used this FPVS-EEG approach to evaluate suitable and optimal stimulation frequency rates for prelexical and lexical word-selective responses and relate these rates to typical reading speed and interindividual variability in reading performance. EEG was recorded in 41 healthy adults who viewed words inserted periodically (1 Hz) at four different stimulation frequency rates (4 Hz, 6 Hz, 10 Hz, and 20 Hz). At all these stimulation rates but the highest (20 Hz), we found typical left-lateralized, word-selective, occipito-temporal responses, larger for the prelexical (words in nonwords) than lexical (words in pseudowords) contrast. Although significant responses were found at all frequency rates, these responses were negligible at 20 Hz, without any evidence of left lateralization at this frequency. The largest occipito-temporal response was found at a 4-Hz base rate in both hemispheres for the prelexical contrast, with increased left lateralization for the lexical discrimination. Moreover, word-selective responses for this discrimination (lexical), only at 4 Hz, were related to reading speed. The optimal 4-Hz rate finding is in line with the mean reading speed for expert readers as assessed during text reading. Overall, these findings further validate and optimize the FPVS-EEG approach for rapid implicit measurement of word-selective neural responses.

The Modulatory Effects of Transcranial Alternating Current Stimulation on Brain Oscillatory Patterns in the Beta Band in Healthy Older Adults.

Background: In the last few years, transcranial alternating current stimulation (tACS) has attracted attention as a promising approach to interact with ongoing oscillatory cortical activity and, consequently, to enhance cognitive and motor processes. While tACS findings are limited by high variability in young adults' responses, its effects on brain oscillations in older adults remain largely unexplored. In fact, the modulatory effects of tACS on cortical oscillations in healthy aging participants have not yet been investigated extensively, particularly during movement. This study aimed to examine the after-effects of 20 Hz and 70 Hz High-Definition tACS on beta oscillations both during rest and movement. Methods: We recorded resting state EEG signals and during a handgrip task in 15 healthy older participants. We applied 10 min of 20 Hz HD-tACS, 70 Hz HD-tACS or Sham stimulation for 10 min. We extracted resting-state beta power and movement-related beta desynchronization (MRBD) values to compare between stimulation frequencies and across time. Results: We found that 20 Hz HD-tACS induced a significant reduction in beta power for electrodes C3 and CP3, while 70 Hz did not have any significant effects. With regards to MRBD, 20 Hz HD-tACS led to more negative values, while 70 Hz HD-tACS resulted in more positive ones for electrodes C3 and FC3. Conclusions: These findings suggest that HD-tACS can modulate beta brain oscillations with frequency specificity. They also highlight the focal impact of HD-tACS, which elicits effects on the cortical region situated directly beneath the stimulation electrode.