Intracranial Electrical Stimulation Research Articles

Posterior cingulate epilepsy: Seizure semiology and intracranial electrical stimulation using SEEG

PurposeThis study aimed to explore seizure semiology and the effects of intracerebral electrical stimulation on the human posterior cingulate cortex (PCC) using Stereoelectroencephalography (SEEG) to deepen our comprehension of posterior cingulate epilepsy (PCE). MethodsThis study examined the characteristics of seizures through video documentation, by assessing the outcomes of intracranial electrical stimulation (iES) during SEEG. We further identified the connection between the observed semiology and precise anatomical locations within the PCC subregions where seizure onset zones (SOZ) were identified. ResultsAnalysis was conducted on 59 seizures from 15 patients recorded via SEEG. Behavioural arrest emerged as the predominant manifestation across the PCC subregions. Where ictal activity extended to both the mesial and lateral temporal cortex, automatism was predominantly observed in seizures originating from the ventral PCC (vPCC). The retrosplenial cortex (RSC) is associated with complex motor behaviour, with seizure discharges spreading to the temporal lobe. Seizures originating from the PCC include axial tonic and autonomic seizures. Only one case of positive clinical seizures was documented. High frequencies of iES within the PCC induced various clinical responses, categorised as vestibular, visual, psychological, and autonomic, with vestibular reactions primarily occurring in the dorsal PCC (dPCC) and RSC, visual responses in the left RSC, and autonomic reactions in the vPCC and RSC. ConclusionThe manifestations of seizures in PCE vary according to the SOZ and the patterns of seizure propagation. The occurrence of seizures induced by iES is exceedingly rare, indicating that mapping of the PCC could pinpoint the primary sector of PCC.

Neural response properties predict perceived contents and locations elicited by intracranial electrical stimulation of human auditory cortex.

Intracranial electrical stimulation (iES) of auditory cortex can elicit sound experiences with a variety of perceived contents (hallucination or illusion) and locations (contralateral or bilateral side), independent of actual acoustic inputs. However, the neural mechanisms underlying this elicitation heterogeneity remain undiscovered. Here, we collected subjective reports following iES at 3062 intracranial sites in 28 patients (both sexes) and identified 113 auditory cortical sites with iES-elicited sound experiences. We then decomposed the sound-induced intracranial electroencephalogram (iEEG) signals recorded from all 113 sites into time-frequency features. We found that the iES-elicited perceived contents can be predicted by the early high-γ features extracted from sound-induced iEEG. In contrast, the perceived locations elicited by stimulating hallucination sites and illusion sites are determined by the late high-γ and long-lasting α features, respectively. Our study unveils the crucial neural signatures of iES-elicited sound experiences in human and presents a new strategy to hearing restoration for individuals suffering from deafness.

Effect of intracranial electrical stimulation on dynamic functional connectivity in medically refractory epilepsy.

The objective of this study was to explore the distributed network effects of intracranial electrical stimulation in patients with medically refractory epilepsy using dynamic functional connectivity (dFC) and graph indicators. The time-varying connectivity patterns of dFC (state-based metrics) as well as topological properties of static functional connectivity (sFC) and dFC (graph indicators) were assessed before and after the intracranial electrical stimulation. The sliding window method and k-means clustering were used for the analysis of dFC states, which were characterized by connectivity strength, occupancy rate, dwell time, and transition. Graph indicators for sFC and dFC were obtained using group statistical tests. DFCs were clustered into two connectivity configurations: a strongly connected state (state 1) and a sparsely connected state (state 2). After electrical stimulation, the dwell time and occupancy rate of state 1 decreased, while that of state 2 increased. Connectivity strengths of both state 1 and state 2 decreased. For graph indicators, the clustering coefficient, k-core, global efficiency, and local efficiency of patients showed a significant decrease, but the brain networks of patients exhibited higher modularity after electrical stimulation. Especially, for state 1, there was a significant decrease in functional connectivity strength after stimulation within and between the frontal lobe and temporary lobe, both of which are associated with the seizure onset. Our findings demonstrated that intracranial electrical stimulation significantly changed the time-varying connectivity patterns and graph indicators of the brain in patients with medically refractory epilepsy. Specifically, the electrical stimulation decreased functional connectivity strength in both local-level and global-level networks. This might provide a mechanism of understanding for the distributed network effects of intracranial electrical stimulation and extend the knowledge of the pathophysiological network of medically refractory epilepsy.

Topological properties and connectivity patterns in brain networks of patients with refractory epilepsy combined with intracranial electrical stimulation

Topological properties and connectivity patterns in brain networks of patients with refractory epilepsy combined with intracranial electrical stimulation

Subjective states induced by intracranial electrical stimulation matches the cytoarchitectonic organization of the human insula

Functions of the human insula have been explored extensively with neuroimaging methods and intracranial electrical stimulation studies that have highlighted a functional segregation across its subregions. A recently developed cytoarchitectonic map of the human insula has also segregated this brain region into various areas. Our knowledge of the functional organization of this brain region at the level of these fine-parceled microstructural areas remains only partially understood. We address this gap of knowledge by applying a multimodal approach linking direct electrical stimulation and task-evoked intracranial EEG recordings with microstructural subdivisions of the human insular cortex. In 17 neurosurgical patients with 142 implanted electrodes, stimulation of 40 % of the sites induced a reportable change in the conscious experience of the subjects in visceral/autonomic, anxiety, taste/olfactory, pain/temperature as well as somatosensory domains. These subjective responses showed a topographical allocation to microstructural areas defined by probabilistic cytoarchitectonic parcellation maps of the human insula. We found the pain and thermal responses to be located in areas lg2/ld2, while non-painful/non-thermal somatosensory responses corresponded to area ld3 and visceroceptive responses to area Id6. Lastly, the stimulation of area Id7 in the dorsal anterior insula, failed to induce reportable changes to subjective experience even though intracranial EEG recordings from this region captured significant time-locked high-frequency activity (HFA). Our results provide a multimodal map of functional subdivisions within the human insular cortex at the individual brain basis and characterize their anatomical association with fine-grained cytoarchitectonic parcellations of this brain structure.

Signatures of Electrical Stimulation Driven Network Interactions in the Human Limbic System.

Stimulation-evoked signals are starting to be used as biomarkers to indicate the state and health of brain networks. The human limbic network, often targeted for brain stimulation therapy, is involved in emotion and memory processing. Previous anatomic, neurophysiological, and functional studies suggest distinct subsystems within the limbic network (Rolls, 2015). Studies using intracranial electrical stimulation, however, have emphasized the similarities of the evoked waveforms across the limbic network. We test whether these subsystems have distinct stimulation-driven signatures. In eight patients (four male, four female) with drug-resistant epilepsy, we stimulated the limbic system with single-pulse electrical stimulation. Reliable corticocortical evoked potentials (CCEPs) were measured between hippocampus and the posterior cingulate cortex (PCC) and between the amygdala and the anterior cingulate cortex (ACC). However, the CCEP waveform in the PCC after hippocampal stimulation showed a unique and reliable morphology, which we term the "limbic Hippocampus-Anterior nucleus of the thalamus-Posterior cingulate, HAP-wave." This limbic HAP-wave was visually distinct and separately decoded from the CCEP waveform in ACC after amygdala stimulation. Diffusion MRI data show that the measured end points in the PCC overlap with the end points of the parolfactory cingulum bundle rather than the parahippocampal cingulum, suggesting that the limbic HAP-wave may travel through fornix, mammillary bodies, and the anterior nucleus of the thalamus (ANT). This was further confirmed by stimulating the ANT, which evoked the same limbic HAP-wave but with an earlier latency. Limbic subsystems have unique stimulation-evoked signatures that may be used in the future to help network pathology diagnosis.SIGNIFICANCE STATEMENT The limbic system is often compromised in diverse clinical conditions, such as epilepsy or Alzheimer's disease, and characterizing its typical circuit responses may provide diagnostic insight. Stimulation-evoked waveforms have been used in the motor system to diagnose circuit pathology. We translate this framework to limbic subsystems using human intracranial stereo EEG (sEEG) recordings that measure deeper brain areas. Our sEEG recordings describe a stimulation-evoked waveform characteristic to the memory and spatial subsystem of the limbic network that we term the "limbic HAP-wave." The limbic HAP-wave follows anatomic white matter pathways from hippocampus to thalamus to the posterior cingulum and shows promise as a distinct biomarker of signaling in the human brain memory and spatial limbic network.

State-specific modulation of mood using intracranial electrical stimulation of the orbitofrontal cortex

BackgroundOrbitofrontal cortex (OFC) is a promising target for intracranial electrical stimulation (iES) aimed at improving mood states. However, knowledge gaps remain regarding the underlying neural mechanisms of iES effects, such as the effect of the OFC target in comparison with other emotional network targets, the impact of brain state at the time of stimulation, and the neural response induced by iES at both local and network scales. ObjectiveOur study aims to address the neural mechanisms underlying the effects of iES in improving mood states. MethodsWe conducted a study in 24 epilepsy patients who received iES through implanted electrodes in the emotional network and compared the effects of iES on multiple targets in the emotional network. ResultsWe found that only iES applied to the orbitofrontal cortex (OFC) led to mood improvement and changes in neural activity. We also observed that iES to the OFC suppressed the delta-theta power when the brain was in a low mood state. Moreover, the iES to the OFC decreased delta-theta power and increased gamma power at local regions within the emotional network, and enhanced the information flow through the frequency domain among regions within the emotional network. ConclusionsThese findings provide insight into the neural correlates of iES-induced mood improvement and support the potential of iES as a therapeutic intervention for mood disorders.

Intracranial electrical stimulation of corticolimbic sites modulates arousal in humans

BackgroundHumans routinely shift their sleepiness and wakefulness levels in response to emotional factors. The diversity of emotional factors that modulates sleep-wake levels suggests that the ascending arousal network may be intimately linked with networks that mediate mood. Indeed, while animal studies have identified select limbic structures that play a role in sleep-wake regulation, the breadth of corticolimbic structures that directly modulates arousal in humans remains unknown. ObjectiveWe investigated whether select regional activation of the corticolimbic network through direct electrical stimulation can modulate sleep-wake levels in humans, as measured by subjective experience and behavior. MethodsWe performed intensive inpatient stimulation mapping in two human participants with treatment resistant depression, who underwent intracranial implantation with multi-site, bilateral depth electrodes. Stimulation responses of sleep-wake levels were measured by subjective surveys (i.e. Stanford Sleepiness Scale and visual-analog scale of energy) and a behavioral arousal score. Biomarker analyses of sleep-wake levels were performed by assessing spectral power features of resting-state electrophysiology. ResultsOur findings demonstrated three regions whereby direct stimulation modulated arousal, including the orbitofrontal cortex (OFC), subgenual cingulate (SGC), and, most robustly, ventral capsule (VC). Modulation of sleep-wake levels was frequency-specific: 100Hz OFC, SGC, and VC stimulation promoted wakefulness, whereas 1Hz OFC stimulation increased sleepiness. Sleep-wake levels were correlated with gamma activity across broad brain regions. ConclusionsOur findings provide evidence for the overlapping circuitry between arousal and mood regulation in humans. Furthermore, our findings open the door to new treatment targets and the consideration of therapeutic neurostimulation for sleep-wake disorders.

Canonical Response Parameterization: Quantifying the structure of responses to single-pulse intracranial electrical brain stimulation.

Single-pulse electrical stimulation in the nervous system, often called cortico-cortical evoked potential (CCEP) measurement, is an important technique to understand how brain regions interact with one another. Voltages are measured from implanted electrodes in one brain area while stimulating another with brief current impulses separated by several seconds. Historically, researchers have tried to understand the significance of evoked voltage polyphasic deflections by visual inspection, but no general-purpose tool has emerged to understand their shapes or describe them mathematically. We describe and illustrate a new technique to parameterize brain stimulation data, where voltage response traces are projected into one another using a semi-normalized dot product. The length of timepoints from stimulation included in the dot product is varied to obtain a temporal profile of structural significance, and the peak of the profile uniquely identifies the duration of the response. Using linear kernel PCA, a canonical response shape is obtained over this duration, and then single-trial traces are parameterized as a projection of this canonical shape with a residual term. Such parameterization allows for dissimilar trace shapes from different brain areas to be directly compared by quantifying cross-projection magnitudes, response duration, canonical shape projection amplitudes, signal-to-noise ratios, explained variance, and statistical significance. Artifactual trials are automatically identified by outliers in sub-distributions of cross-projection magnitude, and rejected. This technique, which we call "Canonical Response Parameterization" (CRP) dramatically simplifies the study of CCEP shapes, and may also be applied in a wide range of other settings involving event-triggered data.

Linear feedback control of spreading dynamics in stochastic nonlinear network models: epileptic seizures.

The development of models and approaches for controlling the spreading dynamics of epileptic seizures is an essential step towards new therapies for people with pharmacologically resistant epilepsy. Beyond resective neurosurgery, in which epileptogenic zones (EZs) are the target of surgery, closed-loop control based on intracranial electrical stimulation, applied at the very early stage of seizure evolution, has been the main alternative, e.g. the RNS system from NeuroPace (Mountain View, CA). In this approach the electrical stimulation is delivered to target brain areas after detection of seizure initiation in the EZ. Here, we examined, on model simulations, some of the closed-loop control aspects of the problem. Seizure dynamics and spread are typically modeled with highly nonlinear dynamics on complex brain networks. Despite the nonlinearity and complexity, currently available optimal feedback control approaches are mostly based on linear approximations. Alternative machine learning control approaches might require amounts of data beyond what is commonly available in the intended application. We thus examined how standard linear feedback control approaches perform when applied to nonlinear models of neural dynamics of seizure generation and spread. In particular, we considered patient-specific epileptor network models for seizure onset and spread. The models incorporate network connectivity derived from (diffusion MRI) white-matter tractography, have been shown to capture the qualitative dynamics of epileptic seizures and can be fit to patient data. For control, we considered simple linear quadratic Gaussian (LQG) regulators. The LQG control was based on a discrete-time state-space model derived from the linearization of the patient-specific epileptor network model around a stable fixed point in the regime of preictal dynamics. We show in simulations that LQG regulators acting on the EZ node during the initial seizure period tend to be unstable. The LQG solution for the control law in this case leads to global feedback to the EZ-node actuator. However, if the LQG solution is constrained to depend on only local feedback originating from the EZ node itself, the controller is stable. In this case, we demonstrate that localized LQG can easily terminate the seizure at the early stage and prevent spread. In the context of optimal feedback control based on linear approximations, our results point to the need for investigating in more detail feedback localization and additional relevant control targets beyond epileptogenic zones.

Responsive Neurostimulation in Drug-Resistant Pediatric Epilepsy: Findings From the Epilepsy Surgery Subgroup of the Pediatric Epilepsy Research Consortium

BackgroundResponsive neurostimulation (RNS), a closed-loop intracranial electrical stimulation system, is a palliative surgical option for patients with drug-resistant epilepsy (DRE). RNS is approved by the US Food and Drug Administration for patients aged ≥18 years with pharmacoresistant partial seizures. The published experience of RNS in children is limited. MethodsThis is a combined prospective and retrospective study of patients aged ≤18 years undergoing RNS placement. Patients were identified from the multicenter Pediatric Epilepsy Research Consortium Surgery Registry from January 2018 to December 2021, and additional data relevant to this study were retrospectively collected and analyzed. ResultsFifty-six patients received RNS during the study period. The mean age at implantation was 14.9 years; the mean duration of epilepsy, 8.1 years; and the mean number of previously trialed antiseizure medications, 4.2. Five patients (9%) previously trialed dietary therapy, and 19 patients (34%) underwent prior surgery. Most patients (70%) underwent invasive electroencephalography evaluation before RNS implantation. Complications occurred in three patients (5.3%) including malpositioned leads or transient weakness. Follow-up (mean 11.7 months) was available for 55 patients (one lost), and four were seizure-free with RNS off. Outcome analysis of stimulation efficacy was available for 51 patients: 33 patients (65%) were responders (≥50% reduction in seizure frequency), including five patients (10%) who were seizure free at follow-up. ConclusionsFor young patients with focal DRE who are not candidates for surgical resection, neuromodulation should be considered. Although RNS is off-label for patients aged <18 years, this multicenter study suggests that it is a safe and effective palliative option for children with focal DRE.

Studying the physiology of mind with intracranial electrical stimulation

Studying the physiology of mind with intracranial electrical stimulation

Intracranial electrical brain stimulation as an approach to studying the (dis)continuum of memory experiential phenomena.

Déjà vu and involuntary autobiographical memories (IAM) can be induced by intracranial electric brain stimulation in epileptic patients, sometimes in the same individual. We suggest that there may be different types of IAM which should be taken into account and provide several ideas to test the hypothesis of a continuity between IAM and déjà vu phenomena.

Responses of Chemosensory Perception to Stimulation of the Human Brain.

Significant advances have been made in our understanding of the neural substrates of human chemosensory processing, involving the piriform cortex, insula, and orbitofrontal cortex. However, the important and challenging issues are to localize the brain regions with high anatomic precision that can causally produce chemosensory perception and further delineate the topography of different classifications of chemosensory perception. We quantitatively measured subjective responses of chemosensory perception to intracranial electrical stimulation over the brain in neurosurgical patients (n=302) with medically refractory epilepsy. The chemosensory perceptions including olfaction, gustation, and chemesthesis were elicited in 21 of 302 patients (7%). Chemosensory responses were evoked in 53 (0.2%) of 21,661 stimulated sites. The highest response rate (1.8%) was in the insula (37/2,051 stimulated sites from 15/163 patients). The chemosensory perception emerged predominantly during stimulation of the insula along the central sulcus axis. Notably, there existed a distinct pattern that the anteroventral insula predominately represented orthonasal olfaction, whereas different chemosensory modalities converged in the mid-dorsal insula. This study provided a detailed characterization of chemosensory perception across the brain, especially in the insula. These results suggest that the cortex along the banks of the central sulcus of the insula may play a role in producing the supramodal sensation of flavor. It also indicates that dysfunction of the central insula should be considered during the evaluation of chemosensory-related epileptic seizures. ANN NEUROL 2023;93:175-183.

Neural Substrates of External and Internal Visual Sensations Induced by Human Intracranial Electrical Stimulation.

Offline perceptions are self-generated sensations that do not involve physical stimulus. These perceptions can be induced by external hallucinated objects or internal imagined objects. However, how the brain dissociates these visual sensations remains unclear. We aimed to map the brain areas involved in internal and external visual sensations induced by intracranial electrical stimulation and further investigate their neural differences. In this study, we collected subjective reports of internal and external visual sensations elicited by electrical stimulation in 40 drug-refractory epilepsy during presurgical evaluation. The response rate was calculated and compared to quantify the dissociated distribution of visual responses. We found that internal and external visual sensations could be elicited when different brain areas were stimulated, although there were more overlapping brain areas. Specifically, stimulation of the hippocampus and inferior temporal cortex primarily induces internal visual sensations. In contrast, stimulation of the occipital visual cortex mainly triggers external visual sensations. Furthermore, compared to that of the dorsal visual areas, the ventral visual areas show more overlap between the two visual sensations. Our findings show that internal and external visual sensations may rely on distinct neural representations of the visual pathway. This study indicated that implantation of electrodes in ventral visual areas should be considered during the evaluation of visual sensation aura epileptic seizures.

Coagulation Bath‐Assisted 3D Printing of PEDOT:PSS with High Resolution and Strong Substrate Adhesion for Bioelectronic Devices

AbstractPoly(3,4‐ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) is a promising material because of its favorable electrical and mechanical properties, stability in ambient environments, and biocompatibility. It finds broad application in energy storage, flexible electronics, and bioelectronics. Additive manufacturing opens a plethora of new avenues to form and shape PEDOT:PSS, allowing for the rapid construction of customized geometries. However, there are difficulties in printing PEDOT:PSS while maintaining its attractive properties. A 3D printing method for PEDOT:PSS using a room‐temperature coagulation bath‐based direct ink writing technique is reported. This technique enables fabrication of PEDOT:PSS into parts that are of high resolution and high conductivity, while maintaining stable electrochemical properties. The coagulation bath can be further modified to improve the mechanical properties of the resultant printed part via a one‐step reaction. Furthermore, it is demonstrated that a simple post‐processing step allows the printed electrodes to strongly adhere to several substrates under aqueous conditions, broadening their use in bioelectronics. Employing 3D printing of PEDOT:PSS, a cortex‐wide neural interface is fabricated, and intracranial electrical stimulation and simultaneous optical monitoring of mice brain activity with wide field calcium imaging are demonstrated. This reported 3D‐printing technique eliminates the need for cumbersome experimental setups while offering desired material properties.

Investigating the effect of transcranial direct electrical stimulation (tDCS) and neuro-verbal programming (NLP) on reducing women's depression, anxiety and stress

Aim: The present study was conducted with the aim of investigating the effect of transcranial direct electrical stimulation (tDCS) and neuro-verbal programming (NLP) on reducing the level of depression, anxiety and stress of women referring to comprehensive health service centers in Zahedan. Method: pre-test-post-test research design. With experimental groups (transcranial direct electrical stimulation (tDCS) and neuro-verbal programming (NLP)) and a control group. The statistical population consisted of all women with three disorders of depression, anxiety and stress who referred to mental health experts of comprehensive health service centers in Zahedan city, from which a sample of 45 people was selected by simple random sampling method, so 30 people were in the experimental groups. The first intervention was 10 sessions of direct electrical and cranial stimulation (tDCS), the second group was given 8 weeks of neuro-verbal programming (NLP), while 15 people in the control group were not given any training. After completing the Depression Anxiety Stress Scale-21 (DASS-21) questionnaire, data was collected and then analyzed using SPSS version 23 software. Results: The results of the multivariate covariance analysis showed that the mean scores of depression (F=23.47, P=0.001), anxiety (F=65.46, P=0.001) and stress (38.30) There is a significant decrease between the pre- and post-test scores of the treatment groups. Conclusion: The results of Tukey's post-hoc test showed that the mean direct intracranial electrical stimulation (TDCS) is lower than neuro-verbal programming (NLP) in reducing the level of depression, anxiety and stress.

Dissociation and Brain Rhythms: Pitfalls and Promises.

Recently, Vesuna et al. proposed a novel circuit mechanism underlying dissociative states using optogenetics and pharmacology in mice in combination with intracranial recordings and electrical stimulation in an epilepsy patient. Specifically, the authors identified a posteromedial cortical delta-rhythm that underlies states of dissociation. In the following, we would like to critically review these findings in the context of the human literature on dissociation as well as highlight the challenges in translational neuroscience to link complex behavioral phenotypes in psychiatric syndromes to circumscribed circuit mechanisms.

Waving together single pulse intracranial electrical stimulation with concurrent stereo EEG and scalp hd-EEG recording

Waving together single pulse intracranial electrical stimulation with concurrent stereo EEG and scalp hd-EEG recording

Investigating visuo-spatial neglect and visual extinction during intracranial electrical stimulations: The role of the right inferior parietal cortex

Both visuo-spatial neglect and visual extinction may occur following right-brain damage. So far, studies on brain-damaged patients have not provided definite evidence about which lesion patterns may lead to the association or dissociation of these deficits. This study was set out to address this issue using Intracranial Electrical Stimulation (IES) in a group of nine patients affected by refractory epilepsy. Cerebral regions associated with visuo-spatial neglect and visual extinction were stimulated, including the right frontal, temporal, and posterior parietal areas. During IES, patients with intracranial implantation involving at least one of these cortical regions were administered with a manual line bisection task (N = 9) to assess visuo-spatial neglect, and a computerized task (N = 8) assessing visual extinction. Results showed that parietal IES induced a rightward bias at the manual bisection task, together with a general improvement in reaction times at bilateral and unilateral visual stimuli detection at the extinction task. The occurrence of visual extinction did not vary across stimulations. By adopting a complementary approach to anatomo-clinical correlation studies, our work corroborates the notion that lesions to the right inferior parietal lobule play a pivotal role in the pathogenesis of visuo-spatial neglect. Importantly, our results also suggest that temporarily interfering with the activity of this region is not sufficient per se to generate visual extinction, which instead may involve a broader and/or different network, possibly extending beyond the cerebral regions considered here, posing important theoretical and clinical implications.