Cortical Stimulation Research Articles

Effects of Cortical Stimulation on Feedback-Dependent Vocal Control in Non-Human Primates.

Hearing plays an important role in our ability to control voice, and perturbations in auditory feedback result in compensatory changes in vocal production. The auditory cortex (AC) has been proposed as an important mediator of this behavior, but causal evidence is lacking. We tested this in an animal model, hypothesizing that AC is necessary for vocal self-monitoring and feedback-dependent control, and that altering activity in AC during vocalization will interfere with vocal control. We implanted two marmoset monkeys (Callithrix jacchus) with bilateral AC electrode arrays. Acoustic signals were recorded from vocalizing marmosets while altering vocal feedback or electrically stimulating AC during random subsets of vocalizations. Feedback was altered by real-time frequency shifts and presented through headphones and electrical stimulation delivered to individual electrodes. We analyzed recordings to measure changes in vocal acoustics during shifted feedback and stimulation, and to determine their interaction. Results were correlated with the location and frequency tuning of stimulation sites. Consistent with previous results, we found electrical stimulation alone evoked changes in vocal production. Results were stronger in the right hemisphere, but decreased with lower currents or repeated stimulation. Simultaneous stimulation and shifted feedback significantly altered vocal control for a subset of sites, decreasing feedback compensation at some and increasing it at others. Inhibited compensation was more likely at sites closer to vocal frequencies. Results provide causal evidence that the AC is involved in feedback-dependent vocal control, and that it is sufficient and may also be necessary to drive changes in vocal production. N/A Laryngoscope, 133:1-10, 2023.

Focal clonic movements elicited by electrical cortical stimulation of primary motor cortex (P1-1.Virtual)

Focal clonic movements elicited by electrical cortical stimulation of primary motor cortex (P1-1.Virtual)

Intraoperative monitoring of cortico-cortical evoked potentials of the frontal aslant tract in a patient with oligodendroglioma

The newly identified frontal aslant tract (FAT) that connects the posterior Broca’s area to the supplementary motor area is known to be involved in speech and language functions. We successfully intraoperatively monitored FAT using cortico-cortical evoked potentials generated by single-pulse electrical cortical stimulation in a patient with oligodendroglioma.

Combination of Multimodal MRI, Neuronavigation, and Awake Craniotomy in Removing Tumors of Eloquent Areas.

The results of 30 successive awake surgical interventions performed in 2017-2019 years in patients with tumors of eloquent areas have been analyzed. The main selection criterion for this type of operations was the location of the tumor in the projection or in the immediate proximity to the cortical centers of speech and motion. To minimize the damage, patients underwent functional MRI and DTI tractography at the prehospital stage to identify cortical regions and white matter tracts involved in the motor and language functions; immediately before the operation the acquired data was loaded into the navigation StealthStation S7 (Medtronic, USA) to plan and monitor surgery stages; during the surgery, direct cortical and subcortical stimulation was performed to identify the motor and speech centers (asleep-awake-asleep technique) with neurolinguistic testing. Karnofsky performance status, assessment of the patient's neurological status, frequency of epileptic seizures before and after the operation, the extent of the tumor resection, and the data analysis after the linguistic testing were used to determine the patients' condition and surgery outcomes. Improvement of the general state after the operation has been noted in 30% of patients compared to the preoperative condition, no neurological deficit dynamics has been observed in 33% of patients. Postoperative multimodal MRI showed that total tumor removal was achieved in 37% of cases, subtotal in 40%, partial removal resection in 23% of cases. The combined approach to the brain tumor resection using multimodal MRI, neuronavigation, and awake craniotomy with motor and language areas mapping allows neurosurgeons to minimize the risk of persistent neurological deficit occurrence and provides the possibility to perform maximal resection possible preserving the patients' functional status. The presented methodology is reproducible, permitting one to expand the options of surgical treatment when lesions are localized in eloquent areas.

Frontoparietal paired associative stimulation versus single-site stimulation for generalized anxiety disorder: a pilot rTMS study.

Background:At present, the use of repetitive transcranial magnetic stimulation (rTMS) for generalized anxiety disorder (GAD) is limited to single-site interventions. We investigated whether dual-site frontoparietal stimulation delivered using cortical–cortical paired associative stimulation (ccPAS) had stronger clinical efficacy than single-site stimulation in patients with GAD.Methods:We randomized 50 patients with GAD to 1 Hz rTMS (10 sessions) using 1 of the following protocols: single-site stimulation over the right dorsolateral prefrontal cortex (dlPFC; 1500 pulses per session); single-site stimulation over the right posterior parietal cortex (PPC; 1500 pulses per session); repetitive dual-site ccPAS (rds-ccPAS) over the right dlPFC and right PPC with 1500 pulses per session (rd-ccPAS-1500); or rds-ccPAS over the right dlPFC and right PPC with 750 pulses per session (rd-ccPAS-750). Both rds-ccPAS treatments used a between-site interval of 100 ms.Results:Clinical scores for anxiety, depression and insomnia were reduced in all 4 groups after treatment. We found greater improvements in anxiety symptoms in the rds-ccPAS-1500 group compared to the rds-ccPAS-750 and single-site groups. We found greater improvements in depression symptoms and insomnia in the rds-PAS-1500 group compared to the single-site groups. The rds-ccPAS-1500 group also showed significant or trend-level improvements in anxiety symptoms and insomnia at 10-day and 1-month followup. More patients responded to treatment with rds-ccPAS-1500 than with single-site stimulation. The between-group differences in response rates persisted to the 3-month follow-up. Treatment using rds-ccPAS with a between-site interval of 100 ms induced a more significant improvement than the between-site interval of 50 ms we evaluated in a previous study.Limitations:These results need to be replicated in a larger sample using sham control and equal-pulse single-site stimulation.Conclusion:Frontoparietal rds-ccPAS may be a better treatment option for GAD.

Comparison of Thresholds between Bipolar and Monopolar Electrical Cortical Stimulation.

Electrical cortical stimulation is widely performed and is the gold standard for functional mapping in intractable epilepsy patients; however, a standard protocol has not yet been established. With respect to stimulation methods, two techniques can be applied: monopolar and bipolar stimulation. We compared the threshold to induce clinical symptoms between these two stimulation techniques. Twenty patients with intractable epilepsy who underwent electrical cortical stimulation for functional mapping were retrospectively investigated. We evaluated the stimulation intensity thresholds required to induce motor, sensory, and language symptoms. A total of 114 electrodes in 20 patients were used to investigate motor, sensory, and language symptoms. The thresholds required to induce motor (median value, bipolar: 4 mA, monopolar: 5 mA, p < 0.05) and language symptoms (bipolar: 8 mA, monopolar: 10 mA, p < 0.0005) were significantly higher for monopolar stimulation than those for bipolar stimulation. However, for sensory symptoms, no significant differences were found in the required thresholds between monopolar and bipolar stimulation (bipolar: 4 mA, monopolar: 4 mA, p = 0.474). Bipolar cortical stimulation required lower intensities to produce clinical motor and language symptoms and thus would be safe and suitable for screening of the eloquent area in functional mapping.

Up to What Extent Does Dravet Syndrome Benefit From Neurostimulation Techniques?

BackgroundDravet syndrome (DS) is a refractory developmental and epileptic encephalopathy (EE) with a variety of comorbidities, including cognitive impairment, autism-like behavior, speech dysfunction, and ataxia, which can seriously affect the quality of life of patients and impose a great burden on society and their families. Currently, the pharmacological therapy is patient dependent and may work or not. Neuromodulation techniques, including vagus nerve stimulation (VNS), deep brain stimulation (DBS), transcranial magnetic stimulation (TMS), responsive neurostimulation (RNS), and chronic subthreshold cortical stimulation (CSCS), have become common adjuvant therapies for neurological diseases, but their efficacy in the treatment of DS is unknown.MethodsWe searched Web of Science, PubMed, and SpringerLink for all published cases related to the neuromodulation techniques of DS until January 15, 2022. The systematic review was supplemented with relevant articles from the references. The results reported by each study were summarized narratively.ResultsThe Web of science, PubMed and SpringerLink search yielded 258 items. A total of 16 studies published between 2016 and 2021 met the final inclusion criteria. Overall, 16 articles (109 cases) were included in this study, among which fifteen (107 patients) were involved VNS, and one (2 patients) was involved DBS. After VNS implantation, seizures were reduced to ≥50% in 60 cases (56%), seizure free were found in 8 cases (7.5%). Only two DS patients received DBS treatment, and the initial outcomes of DBS implantation were unsatisfactory. The seizures significantly improved over time for both DBS patients after the addition of antiepileptic drugs.ConclusionMore than half of the DS patients benefited from VNS, and VNS may be effective in the treatment of DS. However, it is important to note that VNS does not guarantee improvement of seizures, and there is a risk of infection and subsequent device failure. Although DBS is a safe and effective strategy for the treatment of refractory epilepsy, the role of DBS in DS needs further study, as the sample size was small. Thus far, there is no strong evidence for the role of DBS in DS.

A descriptive study of eye and head movements in versive seizures

BackgroundVersive seizures, consisting of forced, involuntary, sustained and unnatural turning of eyes and head toward one side, lateralize to the hemisphere contralateral to the direction of the eye and head turn. The characteristics of eye and head movements in version have been rarely and incompletely studied in spontaneous epileptic seizures as opposed to direct cortical stimulation studies. MethodsWe performed a single center retrospective analysis of a cohort of 28 patients with 43 seizures, who had been admitted to the adult epilepsy monitoring unit at University Hospitals Cleveland Medical Center between January 2009 and August 2020. We only included patients with clear, high-resolution seizure videos and interpretable EEG. ResultsThe eye movements were conjugate and contralateral to the hemisphere of seizure onset in 100% of the focal-onset seizures. The eye movements were saccadic in 89.3% with a predominant vector in oblique upward direction in 86.8% of the seizures. Head deviation was present in 100% of the seizures and the eyes and head deviated in the same direction in 97.6% of the seizures. In addition to deviation along the horizontal meridian, there was a vertical component to the head deviation as well, as evidenced by movement of the chin upward along the vertical axis in 93% of the seizures, thus indicating strong activation of the sternocleidomastoid muscle ipsilateral to the hemisphere of seizure onset. Concomitant facial motor activity ipsilateral to the direction of version was seen in 93% of the seizures. The most common pattern was a clonic superimposed on tonic facial contraction. DiscussionVersion remains a reliable and highly lateralizing sign. The majority of the eye movements during version occur in a saccadic fashion rather than one smooth movement, mostly in an oblique upward direction. Head deviation is very closely associated with eye deviation, thus indicating a common symptomatogenic zone for both, which is most likely the frontal eye field. A high concurrence of ipsilateral facial motor activity with version is likely because of close proximity of the frontal eye field to the face area in the primary motor cortex.

Transcranial magnetic stimulation in neurosurgery

Transcranial magnetic stimulation (TMS) is a relatively new diagnostic and therapeutic method. Its widespread introduction into neurosurgical practice began in 2009. The method is used for non-invasive detection of eloquent brain areas. The combination with tractography facilitates the projection of pathways. The review summarizes the main results of TMS in the planning of neurosurgical interventions. We described the principle of method, analyzed its benefi ts and shortcomings, compared it with direct cortical stimulation which is a “gold standart” in detection of eloquent brain centers.

Effective treatment of refractory complex facial pain with motor cortex stimulation by spinal paddle electrodes using multimodal imaging

BackgroundComplex facial pain is a debilitating condition with varying etiologies that overall responds poorly to both medical and traditional surgical management. Cortical stimulation is a unique therapeutic intervention which can be effective for some types of complex facial pain syndromes (CFPS). However, the novel use of preoperative functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) coupled with intraoperative stimulation mapping and phase reversal to improve the accuracy for placement of spinal paddle electrodes in motor cortex stimulation, to our knowledge, has not been reported in the literature.Case presentationHere, we present a unique case of a 56-year-old male who developed left-sided complex facial pain syndrome after a stroke refractory to medical management and peripheral nerve stimulation. He previously underwent microvascular decompression (MVD) with limited control of his left-sided facial pain. In order to treat this, the patient underwent motor cortex stimulation. The motor strip of the face and tongue was identified preoperatively with functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI). Intraoperatively, phase reversal was used to identify corticospinal tracts and stimulus mapping confirmed the location before the epidural placement of two spinal paddle electrodes. Postoperatively, the patient reported significant reduction in pain levels, burning dysesthesias, and intensity and frequency of symptoms. This trend continued, and the patient experienced equivalent levels of relief at 6 months.ConclusionsThis is a rare case report of successful motor cortex stimulation with the novel preoperative use of fMRI and DTI, coupled with intraoperative functional mapping, to successfully guide the placement of spinal paddle electrodes for the treatment of CFPS.

Cortical dynamics underlying speech planning in rapid conversational turn-taking

During conversation, silent gaps between speakers are typically 200ms or less—suggesting that speech planning often occurs while speakers listen to their partners’ turns. Though the psycholinguistic mechanisms of planning during turn-taking are well-studied, its neural underpinnings are largely unknown. Using intracranial electrocorticography in neurosurgical patient-volunteers, we delineated planning-related activity from dynamics underlying sensorimotor processes using an interactive question–answer paradigm (adapted from Bögels et al., 2015) and found that planning activity is largely restricted to a left hemisphere network centered on caudal inferior and middle frontal gyri. In a separate task, participants performed both speech and non-speech actions, and we found that this planning network is most active while planning spoken output. We then examined neural activity during unconstrained conversation and found that the identified planning circuit is active prior to participant turn onset and while participants listen to the turns of conversational partners. Finally, in preliminary direct cortical stimulation experiments, we found that perturbation of this planning network results in significantly longer reaction times and lexical errors but not gross articulatory disruptions. In conclusion, using controlled interactive language tasks, we uncovered a speech-selective cortical planning circuit that is active during natural conversation and required to execute rapid turn-taking.

Might pain be experienced in the brainstem rather than in the cerebral cortex?

It is nearly axiomatic that pain, among other examples of conscious experience, is an outcome of still-uncertain forms of neural processing that occur in the cerebral cortex, and specifically within thalamo-cortical networks. This belief rests largely on the dramatic relative expansion of the cortex in the course of primate evolution, in humans in particular, and on the fact that direct activation of sensory representations in the cortex evokes a corresponding conscious percept. Here we assemble evidence, drawn from a number of sources, suggesting that pain experience is unlike the other senses and may not, in fact, be an expression of cortical processing. These include the virtual inability to evoke pain by cortical stimulation, the rarity of painful auras in epileptic patients and outcomes of cortical lesions. And yet, pain perception is clearly a function of a conscious brain. Indeed, it is perhaps the most archetypical example of conscious experience. This draws us to conclude that conscious experience, at least as realized in the pain system, is seated subcortically, perhaps even in the “primitive” brainstem. Our conjecture is that the massive expansion of the cortex over the course of evolution was not driven by the adaptive value of implementing consciousness. Rather, the cortex evolved because of the adaptive value of providing an already existing subcortical generator of consciousness with a feed of critical information that requires the computationally intensive capability of the cerebral cortex.

Current Status of Neuromodulation-Induced Cortical Prehabilitation and Considerations for Treatment Pathways in Lower-Grade Glioma Surgery.

The infiltrative character of supratentorial lower grade glioma makes it possible for eloquent neural pathways to remain within tumoural tissue, which renders complete surgical resection challenging. Neuromodulation-Induced Cortical Prehabilitation (NICP) is intended to reduce the likelihood of premeditated neurologic sequelae that otherwise would have resulted in extensive rehabilitation or permanent injury following surgery. This review aims to conceptualise current approaches involving Repetitive Transcranial Magnetic Stimulation (rTMS-NICP) and extraoperative Direct Cortical Stimulation (eDCS-NICP) for the purposes of inducing cortical reorganisation prior to surgery, with considerations derived from psychiatric, rehabilitative and electrophysiologic findings related to previous reports of prehabilitation. Despite the promise of reduced risk and incidence of neurologic injury in glioma surgery, the current data indicates a broad but compelling possibility of effective cortical prehabilitation relating to perisylvian cortex, though it remains an under-explored investigational tool. Preliminary findings may prove sufficient for the continued investigation of prehabilitation in small-volume lower-grade tumour or epilepsy patients. However, considering the very low number of peer-reviewed case reports, optimal stimulation parameters and duration of therapy necessary to catalyse functional reorganisation remain equivocal. The non-invasive nature and low risk profile of rTMS-NICP may permit larger sample sizes and control groups until such time that eDCS-NICP protocols can be further elucidated.

Motor Mapping with Functional Magnetic Resonance Imaging: Comparison with Electrical Cortical Stimulation.

The aim of the present study was to evaluate motor area mapping using functional magnetic resonance imaging (fMRI) compared with electrical cortical stimulation (ECS). Motor mapping with fMRI and ECS were retrospectively compared in seven patients with refractory epilepsy in which the primary motor (M1) areas were identified by fMRI and ECS mapping between 2012 and 2019. A right finger tapping task was used for fMRI motor mapping. Blood oxygen level-dependent activation was detected in the left precentral gyrus (PreCG)/postcentral gyrus (PostCG) along the “hand knob” of the central sulcus in all seven patients. Bilateral supplementary motor areas (SMAs) were also activated (n = 6), and the cerebellar hemisphere showed activation on the right side (n = 3) and bilateral side (n = 4). Furthermore, the premotor area (PM) and posterior parietal cortex (PPC) were also activated on the left side (n = 1) and bilateral sides (n = 2). The M1 and sensory area (S1) detected by ECS included fMRI-activated PreCG/PostCG areas with broader extent. This study showed that fMRI motor mapping was locationally well correlated to the activation of M1/S1 by ECS, but the spatial extent was not concordant. In addition, the involvement of SMA, PM/PPC, and the cerebellum in simple voluntary movement was also suggested. Combination analysis of fMRI and ECS motor mapping contributes to precise localization of M1/S1.

Capacity for consciousness under ketamine anaesthesia is selectively associated with activity in posteromedial cortex in rats.

It remains unclear how specific cortical regions contribute to the brain’s overall capacity for consciousness. Clarifying this could help distinguish between theories of consciousness. Here, we investigate the association between markers of regionally specific (de)activation and the brain’s overall capacity for consciousness. We recorded electroencephalographic responses to cortical electrical stimulation in six rats and computed Perturbational Complexity Index state-transition (PCIST), which has been extensively validated as an index of the capacity for consciousness in humans. We also estimated the balance between activation and inhibition of specific cortical areas with the ratio between high and low frequency power from spontaneous electroencephalographic activity at each electrode. We repeated these measurements during wakefulness, and during two levels of ketamine anaesthesia: with the minimal dose needed to induce behavioural unresponsiveness and twice this dose. We found that PCIST was only slightly reduced from wakefulness to light ketamine anaesthesia, but dropped significantly with deeper anaesthesia. The high-dose effect was selectively associated with reduced high frequency/low frequency ratio in the posteromedial cortex, which strongly correlated with PCIST. Conversely, behavioural unresponsiveness induced by light ketamine anaesthesia was associated with similar spectral changes in frontal, but not posterior cortical regions. Thus, activity in the posteromedial cortex correlates with the capacity for consciousness, as assessed by PCIST, during different depths of ketamine anaesthesia, in rats, independently of behaviour. These results are discussed in relation to different theories of consciousness.

Local and distant cortical responses to single pulse intracranial stimulation in the human brain are differentially modulated by specific stimulation parameters

BackgroundElectrical neuromodulation via direct electrical stimulation (DES) is an increasingly common therapy for a wide variety of neuropsychiatric diseases. Unfortunately, therapeutic efficacy is inconsistent, likely due to our limited understanding of the relationship between the massive stimulation parameter space and brain tissue responses. ObjectiveTo better understand how different parameters induce varied neural responses, we systematically examined single pulse-induced cortico-cortico evoked potentials (CCEP) as a function of stimulation amplitude, duration, brain region, and whether grey or white matter was stimulated. MethodsWe measured voltage peak amplitudes and area under the curve (AUC) of intracranially recorded stimulation responses as a function of distance from the stimulation site, pulse width, current injected, location relative to grey and white matter, and brain region stimulated (N = 52, n = 719 stimulation sites). ResultsIncreasing stimulation pulse width increased responses near the stimulation location. Increasing stimulation amplitude (current) increased both evoked amplitudes and AUC nonlinearly. Locally (<15 mm), stimulation at the boundary between grey and white matter induced larger responses. In contrast, for distant sites (>15 mm), white matter stimulation consistently produced larger responses than stimulation in or near grey matter. The stimulation location-response curves followed different trends for cingulate, lateral frontal, and lateral temporal cortical stimulation. ConclusionThese results demonstrate that a stronger local response may require stimulation in the grey-white boundary while stimulation in the white matter could be needed for network activation. Thus, stimulation parameters tailored for a specific anatomical-functional outcome may be key to advancing neuromodulatory therapy.

Cortical stimulation for chronic pain: from anecdote to evidence.

Epidural stimulation of the motor cortex (eMCS) was devised in the 1990's, and has now largely supplanted thalamic stimulation for neuropathic pain relief. Its mechanisms of action involve activation of multiple cortico-subcortical areas initiated in the thalamus, with involvement of endogenous opioids and descending inhibition toward the spinal cord. Evidence for clinical efficacy is now supported by at least seven RCTs; benefits may persist up to 10 years, and can be reasonably predicted by preoperative use of non-invasive repetitive magnetic stimulation (rTMS). rTMS first developed as a means of predicting the efficacy of epidural procedures, then as an analgesic method on its own right. Reasonable evidence from at least six well-conducted RCTs favors a significant analgesic effect of high-frequency rTMS of the motor cortex in neuropathic pain (NP), and less consistently in widespread/fibromyalgic pain. Stimulation of the dorsolateral frontal cortex (DLPFC) has not proven efficacious for pain, so far. The posterior operculo-insular cortex is a new and attractive target but evidence remains inconsistent. Transcranial direct current stimulation (tDCS) is applied upon similar targets as rTMS and eMCS; it does not elicit action potentials but modulates the neuronal resting membrane state. tDCS presents practical advantages including low cost, few safety issues, and possibility of home-based protocols; however, the limited quality of most published reports entails a low level of evidence. Patients responsive to tDCS may differ from those improved by rTMS, and in both cases repeated sessions over a long time may be required to achieve clinically significant relief. Both invasive and non-invasive procedures exert their effects through multiple distributed brain networks influencing the sensory, affective and cognitive aspects of chronic pain. Their effects are mainly exerted upon abnormally sensitized pathways, rather than on acute physiological pain. Extending the duration of long-term benefits remains a challenge, for which different strategies are discussed in this review.

Validation of Non-invasive Language Mapping Modalities for Eloquent Tumor Resection: A Pilot Study.

Many studies have established a link between extent of resection and survival in patients with gliomas. Surgeons must optimize the oncofunctional balance by maximizing the extent of resection and minimizing postoperative neurological morbidity. Preoperative functional imaging modalities are important tools for optimizing the oncofunctional balance. Transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) are non-invasive imaging modalities that can be used for preoperative functional language mapping. Scarce data exist evaluating the accuracy of these preoperative modalities for language mapping compared with gold standard intraoperative data in the same cohort. This study compares the accuracy of fMRI and TMS for language mapping compared with intraoperative direct cortical stimulation (DCS). We also identified significant predictors of preoperative functional imaging accuracy, as well as significant predictors of functional outcomes. Evidence from this study could inform clinical judgment as well as provide neuroscientific insight. We used geometric distances to determine copositivity between preoperative data and intraoperative data. Twenty-eight patients were included who underwent both preoperative fMRI and TMS procedures, as well as an awake craniotomy and intraoperative language mapping. We found that TMS shows significantly superior correlation to intraoperative DCS compared with fMRI. TMS also showed significantly higher sensitivity and negative predictive value than specificity and positive predictive value. Poor cognitive baseline was associated with decreased TMS accuracy as well as increased risk for worsened aphasia postoperatively. TMS has emerged as a promising preoperative language mapping tool. Future work should be done to identify the proper role of each imaging modality in a comprehensive, multimodal approach to optimize the oncofunctional balance.

Isolating two sources of variability of subcortical stimulation to quantify fluctuations of corticospinal tract excitability

ObjectiveInvestigate the variability previously found with cortical stimulation and handheld transcranial magnetic stimulation (TMS) coils, criticized for its high potential of coil position fluctuations, bypassing the cortex using deep brain electrical stimulation (DBS) of the corticospinal tract with fixed electrodes where both latent variations of the coil position of TMS are eliminated and cortical excitation fluctuations should be absent. MethodsTen input–output curves were recorded from five anesthetized cats with implanted DBS electrodes targeting the corticospinal tract. Goodness of fit of regressions with a conventional single variability source as well as a dual variability source model was quantified using a Schwarz Bayesian Information approach to avoid overfitting. ResultsMotor evoked potentials (MEPs) through DBS of the corticospinal tract revealed short-term fluctuations in excitability of the targeted neuron pathway reflecting endogenous input-side variability at similar magnitude as TMS despite bypassing cortical networks. ConclusionInput-side variability, i.e., variability resulting in changing MEP amplitudes as if the stimulation strength was modulated, also emerges in electrical stimulation at a similar degree and is not primarily a result of varying stimulation, such as minor coil movements in TMS. More importantly, this variability component is present, although the cortex is bypassed. Thus, it may be of spinal origin, which can include cortical input from spinal projections. Further, the nonlinearity of the compound variability entails complex heteroscedastic non-Gaussian distributions and typically does not allow simple linear averages in statistical analysis of MEPs. As the average is dominated by outliers, it risks bias. With appropriate regression, the net effects of excitatory and inhibitory inputs to the targeted neuron pathways become noninvasively observable and quantifiable. SignificanceThe neural responses evoked by artificial stimulation in the cerebral cortex are variable. For example, MEPs in response to repeated presentations of the same stimulus can vary from no response to saturation across trials. Several sources of such variability have been suggested, and most of them may be technical in nature, but localization is missing.

Investigating the Precise Localization of the Grasping Action in the Mid-Cingulate Cortex and Future Directions.

ObjectiveTo prospectively study the cingulate cortex for the localization and role of the grasping action in humans during electrical stimulation of depth electrodes.MethodsAll the patients (n = 23) with intractable focal epilepsy and a depth electrode stereotactically placed in the cingulate cortex, as part of their pre-surgical epilepsy evaluation from 2015 to 2017, were included. Cortical stimulation was performed and examined for grasping actions. Post-implantation volumetric T1 MRIs were co-registered to determine the exact electrode position.ResultsFive patients (male: female 4:1; median age 31) exhibited contralateral grasping actions during electrical stimulation. All patients had electrodes implanted in the ventral bank of the right cingulate sulcus adjacent to the vertical anterior commissure (VAC) line. Stimulation of other electrodes in adjacent regions did not elicit grasping.ConclusionGrasping action elicited from a localized region in the mid-cingulate cortex (MCC) directly supports the concept of the cingulate cortex being crucially involved in the grasping network. This opens an opportunity to explore this region with deep brain stimulation as a motor neuromodulation target for treatment in specific movement disorders or neurorehabilitation.