Evoked Electroencephalographic Research Articles

Breakdown of TMS evoked EEG signal propagation within the default mode network in Alzheimer’s disease

BackgroundThe neural activity of the Default Mode Network (DMN) is disrupted in patients with In Alzheimer’s disease (AD). ObjectivesWe used a novel multimodal approach to track neural signal propagation within the DMN in AD patients. MethodsTwenty mild to moderate AD patients were recruited. We used transcranial magnetic stimulation (TMS) pulses to probe with a millisecond time resolution the propagation of evoked electroencephalography (EEG) signal following the neural activation of the Precuneus (PC), which is a key hub area of the DMN. Moreover, functional and structural magnetic resonance imaging (MRI) data were collected to reconstruct individual features of the DMN. ResultsIn AD patients a probe TMS pulse applied over the PC evokes an increased local activity unmasking underlying hyperexcitability. In contrast, the EEG evoked neural signal did not propagate efficiently within the DMN showing a remarkable breakdown of signal propagation. fMRI and structural tractography showed that impaired signal propagation was related to the same connectivity matrices derived from DMN BOLD signal and transferred by specific white matter bundles forming the cingulum. These features were not detectable stimulating other areas (left dorsolateral prefrontal cortex) or for different networks (fronto-parietal network). Finally, connectivity breakdown was associated with cognitive impairment, as measured with the Clinical Dementia Rating Scale sum of boxes (CDR-SB). ConclusionsTMS-EEG in AD shows both local hyperexcitability and a lack of signal propagation within the DMN. These neurophysiological features also correlate with structural and cognitive attributes of the patients. SignificanceNeuronavigated TMS-EEG may be used as a novel neurophysiological biomarker of DMN connectivity in AD patients.

Examination of associations between psychopathy and neural reinforcement sensitivity theory constructs.

We investigated psychopathy from the neurobiological perspective of reinforcement sensitivity theory (RST). In contrast to previous semantically derived self-report scales, we operationalised RST systems neurally with evoked electroencephalography (EEG). Participants were from a community sample weighted towards externalising psychopathology. We compared the Carver & White Behavioural Inhibition System (BIS)/Behavioural Approach System (BAS) scales with EEG responses associated with RST's systems of goal conflict (aka 'behavioural inhibition'), repulsion/outcome conflict (aka 'fight/flight/freeze') and attraction (aka 'approach'). Bivariate correlations and multiple regression analysis yielded results generally consistent with past literature for associations between psychopathy and the self-report BIS/BAS scales. There were some differences from self-report associations with neural measures of RST. With EEG measures, (1) no meaningful associations were observed between any psychopathy scales and the attraction system; (2) affective-interpersonal traits of psychopathy were negatively associated with goal conflict; (3) disinhibition-behavioural traits of psychopathy were negatively associated with goal conflict but, unexpectedly, positively associated with outcome conflict. These results indicate frontal-temporal-limbic circuit dysfunction in psychopathy as specific domains were linked to neural deficits in goal conflict processing, but there was no evidence for deficits in attraction-related processes.

NeuroDM: Decoding and visualizing human brain activity with EEG-guided diffusion model

Background and Objective:Brain–Computer Interface (BCI) technology has recently been advancing rapidly, bringing significant hope for improving human health and quality of life. Decoding and visualizing visually evoked electroencephalography (EEG) signals into corresponding images plays a crucial role in the practical application of BCI technology. The recent emergence of diffusion models provides a good modeling basis for this work. However, the existing diffusion models still have great challenges in generating high-quality images from EEG, due to the low signal-to-noise ratio and strong randomness of EEG signals. The purpose of this study is to address the above-mentioned challenges by proposing a framework named NeuroDM that can decode human brain responses to visual stimuli from EEG-recorded brain activity. Methods:In NeuroDM, an EEG-Visual-Transformer (EV-Transformer) is used to extract the visual-related features with high classification accuracy from EEG signals, then an EEG-Guided Diffusion Model (EG-DM) is employed to synthesize high-quality images from the EEG visual-related features. Results:We conducted experiments on two EEG datasets (one is a forty-class dataset, and the other is a four-class dataset). In the task of EEG decoding, we achieved average accuracies of 99.80% and 92.07% on two datasets, respectively. In the task of EEG visualization, the Inception Score of the images generated by NeuroDM reached 15.04 and 8.67, respectively. All the above results outperform existing methods. Conclusions:The experimental results on two EEG datasets demonstrate the effectiveness of the NeuroDM framework, achieving state-of-the-art performance in terms of classification accuracy and image quality. Furthermore, our NeuroDM exhibits strong generalization capabilities and the ability to generate diverse images.

Evoked EEG Responses to TMS Targeting Regions Outside the Primary Motor Cortex and Their Test–Retest Reliability

Transcranial magnetic stimulation (TMS)–evoked electroencephalography (EEG) potentials (TEPs) provide unique insights into cortical excitability and connectivity. However, confounding EEG signals from auditory and somatosensory co-stimulation complicate TEP interpretation. Our optimized sham procedure established with TMS of primary motor cortex (Gordon in JAMA 245:118708, 2021) differentiates direct cortical EEG responses to TMS from those caused by peripheral sensory inputs. Using this approach, this study aimed to investigate TEPs and their test–retest reliability when targeting regions outside the primary motor cortex, specifically the left angular gyrus, supplementary motor area, and medial prefrontal cortex. We conducted three identical TMS–EEG sessions one week apart involving 24 healthy participants. In each session, we targeted the three areas separately using a figure-of-eight TMS coil for active TMS, while a second coil away from the head produced auditory input for sham TMS. Masking noise and electric scalp stimulation were applied in both conditions to achieve matched EEG responses to peripheral sensory inputs. High test–retest reliability was observed in both conditions. However, reliability declined for the ‘cleaned’ TEPs, resulting from the subtraction of evoked EEG response to the sham TMS from those to the active, particularly for latencies > 100 ms following the TMS pulse. Significant EEG differences were found between active and sham TMS at latencies < 90 ms for all targeted areas, exhibiting distinct spatiotemporal characteristics specific to each target. In conclusion, our optimized sham procedure effectively reveals EEG responses to direct cortical activation by TMS in brain areas outside primary motor cortex. Moreover, we demonstrate the impact of peripheral sensory inputs on test–retest reliability of TMS-EEG responses.

Single-trial visually evoked potentials predict both individual choice and market outcomes

A central assumption in the behavioral sciences is that choice behavior generalizes enough across individuals that measurements from a sampled group can predict the behavior of the population. Following from this assumption, the unit of behavioral sampling or measurement for most neuroimaging studies is the individual; however, cognitive neuroscience is increasingly acknowledging a dissociation between neural activity that predicts individual behavior and that which predicts the average or aggregate behavior of the population suggesting a greater importance of individual differences than is typically acknowledged. For instance, past work has demonstrated that some, but not all, of the neural activity observed during value-based decision-making is able to predict not just individual subjects’ choices but also the success of products on large, online marketplaces—even when those two behavioral outcomes deviate from one another—suggesting that some neural component processes of decision-making generalize to aggregate market responses more readily across individuals than others do. While the bulk of such research has highlighted affect-related neural responses (i.e. in the nucleus accumbens) as a better predictor of group-level behavior than frontal cortical activity associated with the integration of more idiosyncratic choice components, more recent evidence has implicated responses in visual cortical regions as strong predictors of group preference. Taken together, these findings suggest a role of neural responses during early perception in reinforcing choice consistency across individuals and raise fundamental scientific questions about the role sensory systems in value-based decision-making processes. We use a multivariate pattern analysis approach to show that single-trial visually evoked electroencephalographic (EEG) activity can predict individual choice throughout the post-stimulus epoch; however, a nominally sparser set of activity predicts the aggregate behavior of the population. These findings support an account in which a subset of the neural activity underlying individual choice processes can scale to predict behavioral consistency across people, even when the choice behavior of the sample does not match the aggregate behavior of the population.

Pain-related gamma band activity is dependent on the features of nociceptive stimuli: a comparison of laser and contact heat.

Painful contact heat and laser stimulation offer an avenue to characterize nociceptive pathways involved in acute pain processing, by way of evoked potentials. Direct comparisons of radiant laser and contact heat are limited, particularly in context of examining time-frequency responses to stimulation. This is important in light of recent evidence to suggest that gamma band oscillations (GBOs) represent a functionally heterogeneous measure of pain. The purpose of the current study was to investigate differences in GBOs generated in response to laser and contact heat stimulation of the nondominant forearm. Following intensity matching to pain ratings, evoked electroencephalography (EEG) responses to laser and contact heat stimulation were examined in the time-frequency domain in the same participants (19 healthy adults) across two sessions. At ∼200 ms, both contact heat and laser stimulation resulted in significant, group-level event-related synchronization (ERS) in the low gamma band (i.e., 30-60 Hz) in central electrode locations (Cc, Cz, Ci). Laser stimulation also generated ERS in the 60-100 Hz range (i.e., high gamma), at ∼200 ms, while contact heat led to a significant period of desynchronization in the high gamma range between 400 and 600 ms. Both contact heat and laser GBOs were stronger on the central electrodes contralateral to the stimulated forearm, indicative of primary somatosensory cortex involvement. Based on our findings, and taken in conjunction with previous studies, laser and contact heat stimulation generate characteristically different responses in the brain, with only the former leading to high-frequency GBOs characteristic of painful stimuli.NEW & NOTEWORTHY Despite matching pain perception between noxious laser and contact heat stimuli, we report notable differences in gamma band oscillations (GBO), measured via electroencephalography. GBOs produced following contact heat more closely resembled that of nonnoxious stimuli, while GBOs following laser stimuli were in line with previous reports. Taken together, laser and contact heat stimulation generate characteristically different responses in the brain, with only the former leading to high-frequency GBOs characteristic of painful stimuli.

TMS-EEG signatures of glutamatergic neurotransmission in human cortex

Neuronal activity in the brain reflects an excitation–inhibition balance that is regulated predominantly by glutamatergic and GABAergic neurotransmission, and often disturbed in neuropsychiatric disorders. Here, we tested the effects of a single oral dose of two anti-glutamatergic drugs (dextromethorphan, an NMDA receptor antagonist; perampanel, an AMPA receptor antagonist) and an L-type voltage-gated calcium channel blocker (nimodipine) on transcranial magnetic stimulation (TMS)-evoked electroencephalographic (EEG) potentials (TEPs) and TMS-induced oscillations (TIOs) in 16 healthy adults in a pseudorandomized, double-blinded, placebo-controlled crossover design. Single-pulse TMS was delivered to the hand area of left primary motor cortex. Dextromethorphan increased the amplitude of the N45 TEP, while it had no effect on TIOs. Perampanel reduced the amplitude of the P60 TEP in the non-stimulated hemisphere, and increased TIOs in the beta-frequency band in the stimulated sensorimotor cortex, and in the alpha-frequency band in midline parietal channels. Nimodipine and placebo had no effect on TEPs and TIOs. The TEP results extend previous pharmaco-TMS-EEG studies by demonstrating that the N45 is regulated by a balance of GABAAergic inhibition and NMDA receptor-mediated glutamatergic excitation. In contrast, AMPA receptor-mediated glutamatergic neurotransmission contributes to propagated activity reflected in the P60 potential and midline parietal induced oscillations. This pharmacological characterization of TMS-EEG responses will be informative for interpreting TMS-EEG abnormalities in neuropsychiatric disorders with pathological excitation–inhibition balance.

Pinging the brain with transcranial magnetic stimulation reveals cortical reactivity in time and space

BackgroundSingle-pulse transcranial magnetic stimulation (TMS) elicits an evoked electroencephalography (EEG) potential (TMS-evoked potential, TEP), which is interpreted as direct evidence of cortical reactivity to TMS. Thus, combining TMS with EEG can be used to investigate the mechanism underlying brain network engagement in TMS treatment paradigms. However, controversy remains regarding whether TEP is a genuine marker of TMS-induced cortical reactivity or if it is confounded by responses to peripheral somatosensory and auditory inputs. Resolving this controversy is of great significance for the field and will validate TMS as a tool to probe networks of interest in cognitive and clinical neuroscience. ObjectiveHere, we delineated the cortical origin of TEP by spatially and temporally localizing successive TEP components, and modulating them with transcranial direct current stimulation (tDCS) to investigate cortical reactivity elicited by single-pulse TMS and its causal relationship with cortical excitability. MethodsWe recruited 18 healthy participants in a double-blind, cross-over, sham-controlled design. We collected motor-evoked potentials (MEPs) and TEPs elicited by suprathreshold single-pulse TMS targeting the left primary motor cortex (M1). To causally test cortical and corticospinal excitability, we applied tDCS to the left M1. ResultsWe found that the earliest TEP component (P25) was localized to the left M1. The following TEP components (N45 and P60) were largely localized to the primary somatosensory cortex, which may reflect afferent input by hand-muscle twitches. The later TEP components (N100, P180, and N280) were largely localized to the auditory cortex. As hypothesized, tDCS selectively modulated cortical and corticospinal excitability by modulating the pre-stimulus mu-rhythm oscillatory power. ConclusionTogether, our findings provide causal evidence that the early TEP components reflect cortical reactivity to TMS.

Early and late signals of unexpected reward contribute to low extraversion and high disinhibition, respectively.

Like socio-economic status and cognitive abilities, personality traits predict important life outcomes. Traits that reflect unusually low or high approach motivations, such as low extraversion and high disinhibition, are linked to various forms of mental disorder. Similarly, the dopamine system is theoretically linked to approach motivation traits and to various forms of mental disorder. Identifying neural contributions to extremes of such traits should map to neural sources of psychopathology, with dopamine a prime candidate. Notably, dopamine cells fire in response to unexpected reward, which suggests that the size of non-invasive, scalp-recorded potentials evoked by unexpected reward could reflect sensitivity in approach motivation traits. Here, we evaluated the validity of evoked electroencephalography (EEG) responses to unexpected reward in a monetary gain/loss task to assess approach motivation traits in 137 participants, oversampled for externalizing psychopathology symptoms. We demonstrated that over the 0-400ms period in which feedback on the outcome was presented, responses evoked by unexpected reward contributed to all theoretically relevant approach motivation trait domains (disinhibition, extraversion and the behavioural activation system); and did so only at times when dopamine responses normally peak and reportedly code salience (70-100ms) and valuation (200-300ms). In particular, we linked "dopaminergic" salience and valuation to the psychopathology-related constructs of low extraversion (social anxiety) and high disinhibition (impulsivity) respectively, making the evoked potential components biomarker candidates for indexing aberrant processing of unexpected reward.

Portable neuromodulation induces neuroplasticity to re-activate motor function recovery from brain injury: a high-density MEG case study

BackgroundIn a recent high-profile case study, we used functional magnetic resonance imaging (fMRI) to monitor improvements in motor function related to neuroplasticity following rehabilitation for severe traumatic brain injury (TBI). The findings demonstrated that motor function improvements can occur years beyond current established limits. The current study extends the functional imaging investigation to characterize neuromodulation effects on neuroplasticity to further push the limits.MethodsCanadian Soldier Captain (retired) Trevor Greene (TG) survived a severe open-TBI when attacked with an axe during a 2006 combat tour in Afghanistan. TG has since continued intensive daily rehabilitation to recover motor function, experiencing an extended plateau using conventional physical therapy. To overcome this plateau, we paired translingual neurostimulation (TLNS) with the continuing rehabilitation program.ResultsCombining TLNS with rehabilitation resulted in demonstrable clinical improvements along with corresponding changes in movement evoked electro-encephalography (EEG) activity. High-density magneto-encephalography (MEG) characterized cortical activation changes in corresponding beta frequency range (27 Hz). MEG activation changes corresponded with reduced interhemispheric inhibition in the post-central gyri regions together with increased right superior/middle frontal activation suggesting large scale network level changes.ConclusionsThe findings provide valuable insight into the potential importance of non-invasive neuromodulation to enhance neuroplasticity mechanisms for recovery beyond the perceived limits of rehabilitation.

Identifying site- and stimulation-specific TMS-evoked EEG potentials using a quantitative cosine similarity metric.

The ability to interpret transcranial magnetic stimulation (TMS)-evoked electroencephalography (EEG) potentials (TEPs) is limited by artifacts, such as auditory evoked responses produced by discharge of the TMS coil. TEPs generated from direct cortical stimulation should vary in their topographical activity pattern according to stimulation site and differ from responses to sham stimulation. Responses that do not show these effects are likely to be artifactual. In 20 healthy volunteers, we delivered active and sham TMS to the right prefrontal, left primary motor, and left posterior parietal cortex and compared the waveform similarity of TEPs between stimulation sites and active and sham TMS using a cosine similarity-based analysis method. We identified epochs after the stimulus when the spatial pattern of TMS-evoked activation showed greater than random similarity between stimulation sites and sham vs. active TMS, indicating the presence of a dominant artifact. To do this, we binarized the derivatives of the TEPs recorded from 30 EEG channels and calculated cosine similarity between conditions at each time point with millisecond resolution. Only TEP components occurring before approximately 80 ms differed across stimulation sites and between active and sham, indicating site and condition-specific responses. We therefore conclude that, in the absence of noise masking or other measures to decrease neural artifact, TEP components before about 80 ms can be safely interpreted as stimulation location-specific responses to TMS, but components beyond this latency should be interpreted with caution due to high similarity in their topographical activity pattern.

Noradrenaline Modulates Visual Perception and Late Visually Evoked Activity

An identical sensory stimulus may or may not be incorporated into perceptual experience, depending on the behavioral and cognitive state of the organism. What determines whether a sensory stimulus will be perceived? While different behavioral and cognitive states may share a similar profile of electrophysiology, metabolism, and early sensory responses, neuromodulation is often different and therefore may constitute a key mechanism enabling perceptual awareness. Specifically, noradrenaline improves sensory responses, correlates with orienting toward behaviorally relevant stimuli, and ismarkedly reduced during sleep, while experienceis largely "disconnected" from external events. Despite correlative evidence hinting at a relationship between noradrenaline and perception, causal evidence remains absent. Here, we pharmacologically down- and upregulated noradrenaline signaling in healthy volunteers using clonidine and reboxetine in double-blind placebo-controlled experiments, testing the effects on perceptual abilities and visually evoked electroencephalography (EEG) and fMRI responses. We found that detection sensitivity, discrimination accuracy, and subjective visibility change in accordance with noradrenaline (NE) levels, whereas decision bias (criterion) is notaffected. Similarly, noradrenaline increases theconsistency of EEG visually evoked potentials, while lower noradrenaline levels delay response components around 200ms. Furthermore, blood-oxygen-level-dependent (BOLD) fMRI activations in high-order visual cortex selectively vary along with noradrenaline signaling. Taken together, these results point to noradrenaline as a key factor causally linking visual awareness to external world events. VIDEO ABSTRACT.

Image-guided transcranial focused ultrasound stimulates human primary somatosensory cortex.

Focused ultrasound (FUS) has recently been investigated as a new mode of non-invasive brain stimulation, which offers exquisite spatial resolution and depth control. We report on the elicitation of explicit somatosensory sensations as well as accompanying evoked electroencephalographic (EEG) potentials induced by FUS stimulation of the human somatosensory cortex. As guided by individual-specific neuroimage data, FUS was transcranially delivered to the hand somatosensory cortex among healthy volunteers. The sonication elicited transient tactile sensations on the hand area contralateral to the sonicated hemisphere, with anatomical specificity of up to a finger, while EEG recordings revealed the elicitation of sonication-specific evoked potentials. Retrospective numerical simulation of the acoustic propagation through the skull showed that a threshold of acoustic intensity may exist for successful cortical stimulation. The neurological and neuroradiological assessment before and after the sonication, along with strict safety considerations through the individual-specific estimation of effective acoustic intensity in situ and thermal effects, showed promising initial safety profile; however, equal/more rigorous precautionary procedures are advised for future studies. The transient and localized stimulation of the brain using image-guided transcranial FUS may serve as a novel tool for the non-invasive assessment and modification of region-specific brain function.

Electrophysiological Evidence for Ventral Stream Deficits in Schizophrenia Patients

Schizophrenic patients suffer from many deficits including visual, attentional, and cognitive ones. Visual deficits are of particular interest because they are at the fore-end of information processing and can provide clear examples of interactions between sensory, perceptual, and higher cognitive functions. Visual deficits in schizophrenic patients are often attributed to impairments in the dorsal (where) rather than the ventral (what) stream of visual processing. We used a visual-masking paradigm in which patients and matched controls discriminated small vernier offsets. We analyzed the evoked electroencephalography (EEG) responses and applied distributed electrical source imaging techniques to estimate activity differences between conditions and groups throughout the brain. Compared with controls, patients showed strongly reduced discrimination accuracy, confirming previous work. The behavioral deficits corresponded to pronounced decreases in the evoked EEG response at around 200 ms after stimulus onset. At this latency, patients showed decreased activity for targets in left parietal cortex (dorsal stream), but the decrease was most pronounced in lateral occipital cortex (in the ventral stream). These deficiencies occurred at latencies that reflect object processing and fine shape discriminations. We relate the reduced ventral stream activity to deficient top-down processing of target stimuli and provide a framework for relating the commonly observed dorsal stream deficiencies with the currently observed ventral stream deficiencies.

Navigated TMS combined with EEG in mild cognitive impairment and Alzheimer's disease: A pilot study

Our aim was to assess the potential of navigated transcranial magnetic stimulation (TMS)-evoked electroencephalographic (EEG) responses in studying neuronal reactivity and cortical connectivity in Alzheimer's disease (AD) and in mild cognitive impairment (MCI). We studied 14 right-handed subjects: five patients with AD, five patients with MCI and four healthy controls. Fifty TMS-pulses at an intensity of 110% of individually determined motor threshold were delivered to the hand area of primary motor cortex (M1) with navigated brain stimulation (NBS). Spreading of primary NBS-evoked neuronal activity was monitored with a compatible 60-channel EEG, and analyzed in time, frequency and spatial-domains. We found significantly reduced TMS-evoked P30 (time-locked response 30ms after the magnetic stimulation) in the AD subjects. This reduction was seen in the temporo-parietal area ipsilateral to stimulation side as well as in the contralateral fronto-central cortex corresponding to the sensorimotor network, which is anatomically interconnected with the stimulated M1. In addition, there was a significant decrease in the N100 amplitude in the MCI subjects when compared with the control subjects. Thus, the combination of NBS and EEG revealed prominent changes in functional cortical connectivity and reactivity in the AD subjects. This pilot study suggests that the method may provide a novel tool for examining the degree and progression of dementia.

Modelling event-related responses in the brain

The aim of this work was to investigate the mechanisms that shape evoked electroencephalographic (EEG) and magneto-encephalographic (MEG) responses. We used a neuronally plausible model to characterise the dependency of response components on the models parameters. This generative model was a neural mass model of hierarchically arranged areas using three kinds of inter-area connections (forward, backward and lateral). We investigated how responses, at each level of a cortical hierarchy, depended on the strength of connections or coupling. Our strategy was to systematically add connections and examine the responses of each successive architecture. We did this in the context of deterministic responses and then with stochastic spontaneous activity. Our aim was to show, in a simple way, how event-related dynamics depend on extrinsic connectivity. To emphasise the importance of nonlinear interactions, we tried to disambiguate the components of event-related potentials (ERPs) or event-related fields (ERFs) that can be explained by a linear superposition of trial-specific responses and those engendered nonlinearly (e.g., by phase-resetting). Our key conclusions were; (i) when forward connections, mediating bottom-up or extrinsic inputs, are sufficiently strong, nonlinear mechanisms cause a saturation of excitatory interneuron responses. This endows the system with an inherent stability that precludes nondissipative population dynamics. (ii) The duration of evoked transients increases with the hierarchical depth or level of processing. (iii) When backward connections are added, evoked transients become more protracted, exhibiting damped oscillations. These are formally identical to late or endogenous components seen empirically. This suggests that late components are mediated by reentrant dynamics within cortical hierarchies. (iv) Bilateral connections produce similar effects to backward connections but can also mediate zero-lag phase-locking among areas. (v) Finally, with spontaneous activity, ERPs/ERFs can arise from two distinct mechanisms: For low levels of (stimulus related and ongoing) activity, the systems response conforms to a quasi-linear superposition of separable responses to the fixed and stochastic inputs. This is consistent with classical assumptions that motivate trial averaging to suppress spontaneous activity and disclose the ERP/ERF. However, when activity is sufficiently high, there are nonlinear interactions between the fixed and stochastic inputs. This interaction is expressed as a phase-resetting and represents a qualitatively different explanation for the ERP/ERF.