Our understanding of human visual perception generally rests on the assumption that conscious visual states represent the interaction of spatial structures in the environment and our nervous system. This assumption is questioned by circumstances where conscious visual states can be triggered by external stimulation which is not primarily spatially defined. Here, subjective colors and forms are evoked by flickering light while the precise nature of those experiences varies over flicker frequency and phase. What’s more, the occurrence of one (...) subjective experience appears to be associated with the occurrence of others. While these data indicate that conscious visual experience may be evoked directly by particular variations in the flow of spatially unstructured light over time, it must be assumed that the systems responsible are essentially temporal in character and capable of representing a variety of visual forms and colors, coded in different frequencies or at different phases of the same processing rhythm. (shrink)

BackgroundIndividuals who use methamphetamine for a long period of time may experience decreased inhibition and increased impulsivity. In order to reduce impulsivity or improve inhibitory control ability, high-frequency repetitive transcranial magnetic stimulation has attracted much attention of researchers. Recent studies on addiction have shown that rTMS can stimulate different brain regions to produce different therapeutic effects. Recent work also suggests that HF-rTMS over right dorsolateral prefrontal cortex does not affect the impulsivity of patients with alcohol use disorder; while (...) HF-rTMS over left DLPFC could improve the impulsivity of patients with alcohol use disorder and cigarette smokers. However, it should be noted that empirical studies applying HF-rTMS over left DLPFC of patients with MA use disorders are still lacking.MethodsTwenty-nine patients with MAUD underwent five sessions of HF-rTMS on the left DLPFC per week for 4 consecutive weeks. The cue-induced craving and stop-signal and NoGo task were assessed pre-rTMS and post-rTMS. In addition, 29 healthy controls were recruited. There was no rTMS intervention for the controls, the performance of the stop-signal and NoGo task was evaluated on them.ResultsIn total, HF-rTMS of the left DLPFC significantly decreased MA-dependent patients’ cue-induced craving and stop-signal reaction time. For SSRT, the pre-test of experimental group was significantly higher than the score of control group. In the experimental group, the pre-test score was significantly higher than the post-test score. For Go and stop-signal delay, the pre-test scores of the experimental group was significantly lower than the scores of the control group. No significant difference was found between the pre-test and the post-test scores of the experimental group.ConclusionAdd-on HF-rTMS of left DLPFC may be an effective intervention for reducing impulsivity and cue-induced craving of patients with MAUD. Future research with a control group of MAUD that does not undergo the treatment is needed to confirm the effectiveness. (shrink)

Synchronous oscillations are ubiquitous throughout the cortex, but the frequency of oscillations differs from area to area. To elucidate the mechanistic architectures underlying various rhythmic activities, we tested whether spontaneous neural oscillations in different local cortical areas and large-scale networks can be phase-entrained by direct perturbation with distinct frequencies of repetitive transcranial magnetic stimulation. While recording the electroencephalogram, we applied single-pulse TMS and rTMS at 5, 11, and 23 Hz over the motor or visual cortex. We assessed local (...) and global modulation of phase dynamics using the phase-locking factor. sp-TMS to the motor and the visual cortex triggered a transient increase in PLF in distinct frequencies that peaked at 21 and 8 Hz, respectively. rTMS at 23 Hz over the motor cortex and 11 Hz over the visual cortex induced a prominent and progressive increase in PLF that lasted for a few cycles after the termination of rTMS. Moreover, the local increase in PLF propagated to other cortical areas. These results suggest that distinct cortical areas have area-specific oscillatory frequencies, and the manipulation of oscillations in local areas impacts other areas through the large-scale oscillatory network with the corresponding frequency specificity. We speculate that rTMS that is close to area-specific frequencies enables direct manipulation of brain dynamics and is thus useful for investigating the causal roles of synchronous neural oscillations. Moreover, this technique could be used to treat clinical symptoms associated with impaired oscillations and synchrony. (shrink)

Precision targeting of specific white matter bundles that traverse the subcallosal cingulate has been linked to efficacy of deep brain stimulation for treatment resistant depression. Methods to confirm optimal target engagement in this heterogenous region are now critical to establish an objective treatment protocol. As yet unexamined are the time-frequency features of the SCC evoked potential, including spectral power and phase-clustering. We examined these spectral features—evoked power and phase clustering—in a sample of TRD patients with implanted SCC stimulators. (...) Electroencephalogram was recorded during wakeful rest. Location of electrical stimulation in the SCC target region was the experimental manipulation. EEG was analyzed at the surface level with an average reference for a cluster of frontal sensors and at a time window identified by prior study. Morlet wavelets generated indices of evoked power and inter-trial phase clustering. Enhanced phase clustering at theta frequency was observed in every subject and was significantly correlated with SCC-EP magnitude, but only during left SCC stimulation. Stimulation to dorsal SCC evinced stronger phase clustering than ventral SCC. There was a weak correlation between phase clustering and white matter density. An increase in evoked delta power was also coincident with SCC-EP, but was less consistent across participants. DBS evoked time-frequency features index mm-scale changes to the location of stimulation in the SCC target region and correlate with structural characteristics implicated in treatment optimization. Results also imply a shared generative mechanism between evoked potentials evinced by electrical stimulation and evoked potentials evinced by auditory/visual stimuli and behavioral tasks. Understanding how current injection impacts downstream cortical activity is essential to building new technologies that adapt treatment parameters to individual differences in neurophysiology. (shrink)

ObjectivesSeveral studies have examined the effects of repetitive transcranial magnetic stimulation (rTMS) on associative memory (AM) but findings were inconsistent. Here, we aimed to test whether twice-daily rTMS could significantly improve AM.MethodsIn this single-blind, sham-controlled experiment, 40 participants were randomized to receive twice-daily sham or real rTMS sessions for five consecutive days (a total of 16,000 pulses). The stimulation target in left inferior parietal lobule (IPL) exhibiting peak functional connectivity to the left hippocampus was individually defined for each (...) participant. Participants completed both a picture-cued word association task and Stroop test at baseline and 1 day after the final real or sham rTMS session. Effects of twice-daily rTMS on AM and Stroop test performance were compared using two-way repeated measures analysis of variance with main factors Group (real vs. sham) and Time (baseline vs. post-rTMS).ResultsThere was a significant Group × Time interaction effect. AM score was significantly enhanced in the twice-daily real group after rTMS, but this difference could not survive the post hoc analysis after multiple comparison correction. Further, AM improvement in the twice-daily real group was not superior to a previously reported once-daily rTMS group receiving 8,000 pulses. Then, we combined the twice- and once-daily real groups, and found a significant Group × Time interaction effect. Post hoc analysis indicated that the AM score was significantly enhanced in the real group after multiple comparisons correction.ConclusionOur prospective experiment did not show significant rTMS effect on AM, but this effect may become significant if more participants could be recruited as revealed by our retrospective analysis. (shrink)

Schizophrenia is a serious mental illness characterized by a disconnection between brain regions. Transcranial magnetic stimulation is a non-invasive brain intervention technique that can be used as a new and safe treatment option for patients with schizophrenia with drug-refractory symptoms, such as negative symptoms and cognitive impairment. However, the therapeutic effects of transcranial magnetic stimulation remain unclear and would be investigated using non-invasive tools, such as functional connectivity. A longitudinal design was adopted to investigate the alteration in FC (...) dynamics using a dynamic functional connectivity approach in patients with schizophrenia following high-frequency repeated transcranial magnetic stimulation with the target at the left dorsolateral prefrontal cortex. Two groups of schizophrenia inpatients were recruited. One group received a 4-week high-frequency rTMS together with antipsychotic drugs, while the other group only received antipsychotic drugs. Resting-state functional magnetic resonance imaging and psychiatric symptoms were obtained from the patients with schizophrenia twice at baseline and after 4-week treatment. The dynamics was evaluated using voxel- and region-wise FC temporal variability resulting from fMRI data. The pattern classification technique was used to verify the clinical application value of FC temporal variability. For the voxel-wise FC temporary variability, the repeated measures ANCOVA analysis showed significant treatment × time interaction effects on the FC temporary variability between the left DLPFC and several regions, including the thalamus, cerebellum, precuneus, and precentral gyrus, which are mainly located within the cortico-thalamo-cerebellar circuit. For the ROI-wise FC temporary variability, our results found a significant interaction effect on the FC among CTCC. rTMS intervention led to a reduced FC temporary variability. In addition, higher alteration in FC temporal variability between left DLPFC and right posterior parietal thalamus predicted a higher remission ratio of negative symptom scores, indicating that the decrease of FC temporal variability between the brain regions was associated with the remission of schizophrenia severity. The support vector regression results suggested that the baseline pattern of FC temporary variability between the regions in CTCC could predict the efficacy of high-frequency rTMS intervention on negative symptoms in schizophrenia. These findings confirm the potential relationship between the reduction in whole-brain functional dynamics induced by high-frequency rTMS and the improvement in psychiatric scores, suggesting that high-frequency rTMS affects psychiatric symptoms by coordinating the heterogeneity of activity between the brain regions. Future studies would examine the clinical utility of using functional dynamics patterns between specific brain regions as a biomarker to predict the treatment response of high-frequency rTMS. (shrink)

The vestibulo-ocular reflex plays an important role in controlling the gaze at a visual target. Although patients with vestibular hypofunction aim to improve their VOR function, some retain dysfunction for a long time. Previous studies have explored the effects of direct current stimulation on vestibular function; however, the effects of random noise stimulation on eye–head coordination have not previously been tested. Therefore, we aimed to clarify the effects of high frequency noisy vestibular stimulation on eye–head coordination (...) related to VOR function. Thirteen healthy young adult participants with no serious disease took part in our study. The current amplitude and density used were 0.4 mA and 0.2 mA/cm2, respectively, with a random noise frequency of 100–640 Hz. The electrodes were located on both mastoid processes. The stimulus duration and fade in/out duration were 600 and 10 s, respectively. Subjects oscillated their head horizontally, gazing at the fixation point, at 1 Hz for 30 repetitions. The coordination of eye–head movements was measured by eye-tracking and a motion capture system. Peak-to-peak angles for eye and head movement and deviation of the visual line from the fixation target revealed no significant differences between HF-nVS and sham. The lag time between the eye and head movement with HF-nVS post-stimulation was significantly shorter than that of the sham. We found that HF-nVS can reduce the lag time between eye and head movement and improve coordination, contributing to a clear retinal image. This technique could be applied as a form of VOR training for patients with vestibular hypofunction. (shrink)

ObjectivePrevious studies have demonstrated altered brain activity in strabismic amblyopia. In this study, low-frequency repetitive transcranial magnetic stimulation was applied in children with strabismic amblyopia after they had undergone strabismus surgery. The effect of rTMS was investigated by measuring the changes of brain features using the amplitude of low-frequency fluctuation.Materials and MethodsIn this study, 21 SA patients were recruited based on their age, weight, and sex. They all had SA in their left eyes and they received rTMS (...) treatment one month after strabismus surgery. Their vision before and after surgery were categorized as pre-rTMS and post-rTMS. All participants received rTMS treatment, underwent magnetic resonance imaging, and their data were analyzed using the repeated measures t-test. The team used correlation analysis to explore the relationship between logMAR visual acuity and ALFF.ResultsPre- versus post-rTMS values of ALFF were significantly different within individuals. In the POT group, ALFF values were significantly decreased in the Angular_R, Parietal_Inf_L, and Cingulum_Mid_R while ALFF values were significantly increased in the Fusiform_R and Frontal_Inf_Orb_L compared to the PRT stage.ConclusionOur data showed that ALFF recorded from some brain regions was changed significantly after rTMS in strabismic amblyopes. The results may infer the pathological basis of SA and demonstrate that visual function may be improved using rTMS in strabismic amblyopic patients. (shrink)

The brain-computer interface of steady-state visual evoked potential is one of the fundamental ways of human-computer communication. The main challenge is that there may be a nonlinear relationship between different SSVEP in other states. For improving the performance of SSVEP BCI, a novel CNN algorithm model is proposed in this study. Based on the discrete Fourier transform to calculate the signal's power spectral density, we perform zero-padding in the signal's time domain to improve its performance on the PSD and make (...) it more refined. In this way, the frequency point interval in the PSD of the SSVEP is consistent with the minimum gap between the stimulation frequency. Combining the nonlinear transformation capabilities of CNN in deep learning, a zero-padding frequency domain convolutional neural network model is proposed. Extensive experiments based on the SSVEP dataset validate the effectiveness of our method. The study verifies that the proposed ZPFDCNN method can improve the effectiveness of the SSVEP-based high-speed BCI ITR. It has massive potential in the application of BCI. (shrink)

It has been well documented that the auditory system in the superior temporal cortex is responsible for processing basic auditory sound features, such as sound frequency and intensity, while the prefrontal cortex is involved in higher-order auditory functions, such as language processing and auditory episodic memory. The temporal auditory cortex has vast forward anatomical projections to the prefrontal auditory cortex, connecting with the lateral, medial, and orbital parts of the prefrontal cortex. The connections between the auditory cortex and the (...) prefrontal cortex thus help in localizing, recognizing, and comprehending external auditory inputs. In addition, the medial prefrontal cortex (MPFC) is believed to be a core region of episodic memory retrieval and is one of the most important regions in the default mode network (DMN). However, previous neural evidence with regard to the comparison between basic auditory processing and auditory episodic memory retrieval mainly comes from fMRI studies. The specific neural networks and the corresponding critical frequency bands of neuronal oscillations underlying the two auditory functions remain unclear. In the present study, we reported results of direct cortical stimulations during stereo-electro-encephalography (SEEG) recording in a patient with drug-resistant epilepsy. Electrodes covered the superior temporal gyrus, the operculum and the insula cortex of bilateral hemispheres, the prefrontal cortex, the parietal lobe, the anterior and middle cingulate cortex, and the amygdala of the left hemisphere. Two types of auditory hallucinations were evoked with direct cortical stimulations, which were consistent with the habitual seizures. The noise hallucinations, i.e., “I could hear buzzing noises in my head,” were evoked with the stimulation of the superior temporal gyrus. The episodic memory hallucinations “I could hear a young woman who was dressed in a red skirt saying: What is the matter with you?,” were evoked with the stimulation of MPFC. The patient described how she had met this young woman when she was young and that the woman said the same sentence to her. Furthermore, by analyzing the high gamma power (HGP) induced by direct electrical stimulation, two dissociable neural networks underlying the two types of auditory hallucinations were localized. Taken together, the present results confirm the hierarchical processing of auditory information by showing the different involvements of the primary auditory cortex vs. the prefrontal cortex in the two types of auditory hallucinations. (shrink)

Single-pulse and repetitive transcranial magnetic stimulation are used in clinical practice for diagnostic and therapeutic purposes. However, rTMS-based therapies that lead to a significant and sustained reduction in neuropsychiatric symptoms remain scarce. While it is generally accepted that the stimulation frequency plays a crucial role in producing the therapeutic effects of rTMS, less attention has been dedicated to determining the role of the electric field strength. Conventional threshold-based intensity selection approaches, such as the resting motor threshold, produce (...) variable stimulation intensities and electric fields across participants and cortical regions. Insufficient standardization of electric field strength may contribute to the variability of rTMS effects and thus therapeutic success. Computational approaches that can prospectively optimize the electric field and standardize it across patients and cortical targets may overcome some of these limitations. Here, we discuss these approaches and propose that electric field standardization will be instrumental for translational science frameworks aimed at deciphering the subcellular, cellular, and network mechanisms of rTMS. Advances in understanding these mechanisms will be important for optimizing rTMS-based therapies in psychiatry. (shrink)

Based on increased user experience during stimulation, frequency-modulated steady-state visual evoked potentials have been suggested as an improved stimulation method for brain-computer interfaces. Adapting such a novel stimulation paradigm requires in-depth analyses of all different stimulation parameters and their influence on brain responses as well as the user experience during the stimulation. In the current manuscript, we assess the influence of different values for the modulation index, which determine the spectral distribution in the (...) class='Hi'>stimulation signal on FM-SSVEPs. We visually stimulated 14 participants at different target frequencies with four different values for the modulation index. Our results reveal that changing the modulation index in a way that elevates the stimulation power in the targeted sideband leads to increased FM-SSVEP responses. There is, however, a tradeoff with user experience as increased modulation indices also lead to increased perceived flicker intensity as well as decreased stimulation comfort in our participants. Our results can guide the choice of parameters in future FM-SSVEP implementations. (shrink)

The vestibular system encodes motion and orientation of the head in space and is essential for negotiating in and interacting with the world. Recently, random waveform electric vestibular stimulation has become an increasingly common means of probing the vestibular system. However, many of the methods used to analyze the behavioral response to this type of stimulation assume a linear relationship between frequencies in the stimulus and its associated response. Here we examine this stimulus-response frequency linearity to determine (...) the validity of this assumption. Forty-five university-aged subjects stood on a force-plate for 4 min while receiving vestibular stimulation. To determine the linearity of the stimulus-response relationship we calculated the cross-frequency power coupling between a 0 and 25 Hz bandwidth limited white noise stimulus and induced postural responses, as measured using the horizontal forces acting at the feet. Ultimately, we found that, on average, the postural response to a random stimulus is linear across stimulation frequencies. This result supports the use of analysis methods that depend on the assumption of stimulus-response frequency linearity, such as coherence and gain, which are commonly used to analyze the body’s response to random waveform electric stimuli. (shrink)

The literature on deep brain stimulation (DBS) and adaptive DBS (aDBS) raises concerns that these technologies may affect personality, mood, and behavior. We conducted semi-structured interviews with researchers (n = 23) involved in developing next-generation DBS systems, exploring their perspectives on ethics and policy topics including whether DBS/aDBS can cause such changes. The majority of researchers reported being aware of personality, mood, or behavioral (PMB) changes in recipients of DBS/aDBS. Researchers offered varying estimates of the frequency of PMB (...) changes. A smaller majority reported changes in personality specifically. Some expressed reservations about the scientific status of the term ‘personality,’ while others used it freely. Most researchers discussed negative PMB changes, but a majority said that DBS/aDBS can also result in positive changes. Several researchers viewed positive PMB changes as part of the therapeutic goal in psychiatric applications of DBS/aDBS. Finally, several discussed potential causes of PMB changes other than the device itself. (shrink)

The essential role of creativity has been highlighted in several human knowledge areas. Regarding the neural underpinnings of creativity, there is evidence about the role of left dorsolateral prefrontal cortex (DLPFC) and left inferior frontal gyrus (IFG) on divergent thinking (DT) and convergent thinking (CT). Transcranial stimulation studies suggest that the left DLPFC is associated with both DT and CT, whereas left IFG is more related to DT. However, none of the previous studies have targeted both hubs simultaneously and (...) compared transcranial direct current stimulation (tDCS) and random noise stimulation (tRNS). Additionally, given the relationship between cognitive flexibility and creativity, we included it in order to check if the improvement in creativity may be mediated by cognitive flexibility. In this double-blind, between-subjects study, 66 healthy participants were randomly assigned to one of three groups (N = 22) that received a transcranial direct current stimulation (tDCS), transcranial random noise stimulation (tRNS), or sham for 20 min. The tDCS group received 1.5 mA with the anode over the left DLPFC and cathode over the left IFG. Locations in tRNS group were the same and they received 1.5 mA of high frequency tRNS (100–500 Hz). Divergent thinking was assessed before (baseline) and during stimulation with unusual uses (UU) and picture completion (PC) subtests from Torrance Creative thinking Test, whereas convergent thinking was evaluated with the remote association test (RAT). Stroop test was included to assess cognitive flexibility. ANCOVA results of performance under stimulation (controlling for baseline performance) showed that there were significant differences in PC (F = 3.35, p = 0.042, np2 = 0.10) but not in UU (F = 0.61, p = 0.546) and RAT (F = 2.65, p = 0.079) scores. Post-hoc analyses showed that tRNS group had significantly higher scores compared to sham (p = 0.004) in PC. More specifically, tRNS showed higher performance in fluency (p = 0.012) and originality (p = 0.021) dimensions of PC compared to sham. Regarding cognitive flexibility, we did not find any significant effect of any of the stimulation groups (F = 0.34, p = 0.711). Therefore, no further mediation analyses were performed. Finally, the group that received tDCS reported more adverse effects than sham group (F = 3.46, p = 0.035). Altogether, these results suggest that tRNS may have some advantages over tDCS in DT. (shrink)

Cranial electrical stimulation has been applied at various current levels in both adults and children with neurological conditions with seemingly promising but somewhat inconsistent results. Stimulation-induced spatial electric fields within a specific brain region are likely a significant contributing factor for the biological effects. Although several simulation models have been used to predict EF distributions in the brain, these models actually have not been validated by in vivo CES-induced EF measurements in the live human brain. This study directly (...) measured the CES-induced voltage changes with implanted stereotactic-electroencephalographic electrodes in twenty-one epilepsy participants and then compared these measured values with the simulated ones obtained from the personalized models. In addition, we further investigated the influence of stimulation frequency, intensity, electrode montage and age on EFs in parts of participants. We found both measured voltages and EFs obtained in vivo are highly correlated with the predicted ones in our cohort. In white matter and gray matter, the measured voltages linearly increased when the stimulation intensity increased from 5 to 500 μA but showed no significant changes with changing stimulation frequency from 0.5 to 200 Hz. Electrode montage, but not age, significantly affects the distribution of the EFs. Our in vivo measurements demonstrate that the individualized simulation model can reliably predict the CES-induced EFs in both adults and children. It also confirms that the CES-induced EFs highly depend on the electrode montages and individual anatomical features. (shrink)

Recent advances in second-person neuroscience have allowed the underlying neural mechanisms involved in teaching-learning interactions to be better understood. Teaching is not merely a one-way transfer of information from teacher to student; it is a complex interaction that requires metacognitive and mentalizing skills to understand others’ intentions and integrate information regarding oneself and others. Physiotherapy involving therapists instructing patients on how to improve their motor skills is a clinical field in which teaching-learning interactions play a central role. Accumulating evidence suggests (...) that non-invasive brain stimulation modulates cognitive functions; however, NIBS approaches to teaching-learning interactions are yet to be utilized in rehabilitation. In this review, I evaluate the present research into NIBS and its role in enhancing metacognitive and mentalizing abilities; I then review hyperscanning studies of teaching-learning interactions and explore the potential clinical applications of NIBS in rehabilitation. Dual-brain stimulation using NIBS has been developed based on findings of brain-to-brain synchrony in hyperscanning studies, and it is delivered simultaneously to two individuals to increase inter-brain synchronized oscillations at the stimulated frequency. Artificial induction of brain-to-brain synchrony has the potential to promote instruction-based learning. The brain-to-brain interface, which induces inter-brain synchronization by adjusting the patient’s brain activity, using NIBS, to the therapist’s brain activity, could have a positive effect on both therapist-patient interactions and rehabilitation outcomes. NIBS based on second-person neuroscience has the potential to serve as a useful addition to the current neuroscientific methods used in complementary interventions for rehabilitation. (shrink)