Cortico-cortical Evoked Potential Responses Research Articles

An anatomo-functional study of the interactivity between the paracentral lobule and the primary motor cortex.

The purpose of this study was to understand the anatomical and functional connections between the paracentral lobule (PCL) and the primary motor cortex (M1) of the human brain. This retrospective study included 16 patients who underwent resection of lesions located near M1. Nine patients had lesions in the dominant hemisphere. Tractography was performed to visualize the connectivity between two regions of interest (ROIs)-the convexity and the interhemispheric fissure-that were shown by functional MRI to be activated during a finger tapping task. The number, mean length, and fractional anisotropy (FA) of the fibers between the ROIs were estimated. During surgery, subdural electrodes were placed on the brain surface, including the ROIs, using a navigation system. Cortico-cortical evoked potentials (CCEPs) were evoked by applying electrical stimuli to the hand region of M1 using electrodes placed on the convexity and were measured with electrodes placed on the interhemispheric fissure. To verify CCEP bidirectionality, electrical stimuli were applied to electrodes on the interhemispheric fissure that showed CCEP responses. Correlations of CCEP amplitudes and latencies with the number, mean length, and mean FA value obtained from tractography were determined. The correlations between these parameters and perioperative motor functions were also analyzed. Fibers of 14 patients were visualized by diffusion tensor imaging (DTI). Unidirectional CCEPs between the PCL and M1 were measurable in all 16 patients, and bidirectional CCEPs between them were measurable in 14 patients. There was no significant difference between the two directions in the maximum CCEP amplitude or latency (amplitude, p = 0.391; latency, p = 0.583). Neither the amplitude nor latency showed any apparent correlation with the number, mean length, or mean FA value of the fibers obtained from tractography. Pre- and postoperative motor function of the hands was not significantly correlated with CCEP amplitude or latency. The number and mean FA value of fibers obtained by DTI, as well as the maximum CCEP amplitude, varied between patients. This study demonstrated an anatomical connection and a bidirectional functional connection between the PCL, including the supplementary motor area, and M1 of the human brain. The observed variability between patients suggests possible motor function plasticity. These findings may serve as a foundation for further studies.

Utilizing Excitatory and Inhibitory Activity Derived from Interictal Intracranial Electroencephalography as Potential Biomarkers for Epileptogenicity.

Epileptogenic zones (EZs), where epileptic seizures cease after resection, are localized by assessing the seizure-onset zone using ictal electroencephalography (EEG). Owing to the difficulty in capturing unpredictable seizures, biomarkers capable of identifying EZs from interictal EEG are anticipated. Recent studies using intracranial EEG have identified several potential candidate biomarkers for epileptogenicity. High-frequency oscillation (HFO) was initially expected to be a robust biomarker of abnormal excitatory activity in the ictogenic region. However, HFO-guided resection failed to improve seizure prognosis. Meanwhile, the regularity of low-gamma oscillations (30-80 Hz) indicates inhibitory interneurons' hypersynchronization, which could be used to localize the EZ. Besides resting-state EEG assessments, evoked potentials elicited by single-pulse electrical stimulation, such as corticocortical evoked potentials (CCEP), became valuable tools for assessing epileptogenic regions. CCEP responses recorded in the cortex remote from the stimulation site indicate functional connectivity, revealing increased internal connectivity within the ictogenic region and elevated inhibitory input from the non-involved regions to the ictogenic region. Conversely, large responses close to the stimulation site reflect local excitability, manifesting as an increased N1 amplitude and overriding HFO. Further research is required to establish whether these novel electrophysiological methods, either individually or in combination, can function as robust biomarkers of epileptogenicity and hold promise for improving seizure prognosis.

Distinct connectivity patterns in human medial parietal cortices: Evidence from standardized connectivity map using cortico-cortical evoked potential

The medial parietal cortices are components of the default mode network (DMN), which are active in the resting state. The medial parietal cortices include the precuneus and the dorsal posterior cingulate cortex (dPCC). Few studies have mentioned differences in the connectivity in the medial parietal cortices, and these differences have not yet been precisely elucidated. Electrophysiological connectivity is essential for understanding cortical function or functional differences. Since little is known about electrophysiological connections from the medial parietal cortices in humans, we evaluated distinct connectivity patterns in the medial parietal cortices by constructing a standardized connectivity map using cortico-cortical evoked potential (CCEP). This study included nine patients with partial epilepsy or a brain tumor who underwent chronic intracranial electrode placement covering the medial parietal cortices. Single-pulse electrical stimuli were delivered to the medial parietal cortices (38 pairs of electrodes). Responses were standardized using the z-score of the baseline activity, and a response density map was constructed in the Montreal Neurological Institutes (MNI) space. The precuneus tended to connect with the inferior parietal lobule (IPL), the occipital cortex, superior parietal lobule (SPL), and the dorsal premotor area (PMd) (the four most active regions, in descending order), while the dPCC tended to connect to the middle cingulate cortex, SPL, precuneus, and IPL. The connectivity pattern differs significantly between the precuneus and dPCC stimulation (p<0.05). Regarding each part of the medial parietal cortices, the distributions of parts of CCEP responses resembled those of the functional connectivity database. Based on how the dPCC was connected to the medial frontal area, SPL, and IPL, its connectivity pattern could not be explained by DMN alone, but suggested a mixture of DMN and the frontoparietal cognitive network. These findings improve our understanding of the connectivity profile within the medial parietal cortices. The electrophysiological connectivity is the basis of propagation of electrical activities in patients with epilepsy. In addition, it helps us to better understand the epileptic network arising from the medial parietal cortices.

Effects of propofol on cortico-cortical evoked potentials in the dorsal language white matter pathway

ObjectiveIn order to evaluate the clinical utility even under general anesthesia, the present study aimed to clarify the effect of anesthesia on the cortico–cortical evoked potentials (CCEPs). MethodsWe analyzed 14 patients’ data in monitoring the integrity of the dorsal language pathway by using CCEPs both under general anesthesia with propofol and remifentanil and awake condition, with the main aim of clarifying the effect of anesthesia on the distribution and waveform of CCEPs. ResultsThe distribution of larger CCEP response sites, including the locus of the maximum CCEP response site, was marginally affected by anesthesia. With regard to similarity of waveforms, the mean waveform correlation coefficient indicated a strong agreement. CCEP N1 amplitude increased by an average of 25.8% from general anesthesia to waking, except three patients. CCEP N1 latencies had no correlation in changes between the two conditions. ConclusionsWe demonstrated that the distribution of larger CCEP responses was marginally affected by anesthesia and that the CCEP N1 amplitude had tendency to increase from general anesthesia to the awake condition. SignificanceThe CCEP method provides the efficiency of intraoperative monitoring for dorsal language white matter pathway even under general anesthesia.

Recording cortico-cortical evoked potentials of the human arcuate fasciculus under general anaesthesia

ObjectiveWe examined the feasibility of using cortico-cortical evoked potentials (CCEPs) to monitor the major cortical white matter tract involved in language, the arcuate fasciculus (AF), during surgery under general anaesthesia. MethodsWe prospectively recruited nine patients undergoing surgery for lesions in the left peri-sylvian cortex, for whom awake surgery was not indicated. High angular resolution diffusion imaging (HARDI) tractography was used to localise frontal and temporal AF terminations, which guided intraoperative cortical strip placement. ResultsCCEPs were successfully evoked in 5/9 patients, showing a positive potential (P1) at 12 ms and a negative component (N1) at 21 ms when stimulating from the frontal lobe and recording in the temporal lobe. CCEP responses peaked in the posterior middle temporal gyrus. No CCEPs were evoked when stimulating temporal sites and recording from frontal contacts. ConclusionFor the first time, we show that CCEPs can be evoked from the peri-sylvian cortices also in adult patients who are not candidates for awake procedures. Our results are akin to those described in the awake setting and suggest the recorded activity is conveyed by the arcuate fasciculus. SignificanceThis intraoperative approach may have promising implications in reducing deficits in patients that require surgery in language areas under general anesthesia.

The FAST graph: A novel framework for the anatomically-guided visualization and analysis of cortico-cortical evoked potentials

BackgroundIntracerebral electroencephalography (iEEG) using stereoelectroencephalography (SEEG) methodology for epilepsy surgery gives rise to complex data sets. The neurophysiological data obtained during the in-patient period includes categorization of the evoked potentials resulting from direct electrical cortical stimulation such as cortico-cortical evoked potentials (CCEPs). These potentials are recorded by hundreds of contacts, making these waveforms difficult to quickly interpret over such high-density arrays that are organized in three dimensional fashion. New MethodThe challenge in analyzing CCEPs data arises not just from the density of the array, but also from the stimulation of a number of different intracerebral sites. A systematic methodology for visualization and analysis of these evoked data is lacking. We describe the process of incorporating anatomical information into the visualizations, which are then compared to more traditional plotting techniques to highlight the usefulness of the new framework. ResultsWe describe here an innovative framework for sorting, registering, labeling, ordering, and quantifying the functional CCEPs data, using the anatomical labelling of the brain, to provide an informative visualization and summary statistics which we call the “FAST graph” (Functional-Anatomical STacked area graphs). The FAST graph analysis is used to depict the significant CCEPs responses in patient with focal epilepsy. ConclusionsThe novel plotting approach shown here allows us to visualize high-density stimulation data in a single summary plot for subsequent detailed analyses. Improving the visual presentation of complex data sets aides in enhancing the clinical utility of the data.

Connectivity of the human insula: A cortico-cortical evoked potential (CCEP) study

ObjectiveThe human insula is increasingly being implicated as a multimodal functional network hub involved in a large variety of complex functions. Due to its inconspicuous location and highly vascular anatomy, it has historically been difficult to study. Cortico-cortical evoked potentials (CCEPs), utilize low frequency stimulation to map cerebral networks. They were used to study connections of the human insula. MethodsCCEP data was acquired from each sub-region of the dominant and non-dominant insula in 30 patients who underwent stereo-EEG. Connectivity strength to the various cortical regions was obtained via a measure of root mean square (RMS), calculated from each gyrus of the insula and ranked into weighted means. ResultsThe results of all cumulative CCEP responses for each individual gyrus were represented by circro plots. Forty-nine individual CCEP pairs were stimulated across all the gyri from the right and left insula. In brief, the left insula contributed more greatly to language areas. Sensory function, pain, saliency processing and vestibular function were more heavily implicated from the right insula. Connections to the primary auditory cortex arose from both insula regions. Both posterior insula regions showed significant contralateral connectivity. Ipsilateral mesial temporal connections were seen from both insula regions. In visual function, we further report the novel finding of a direct connection between the right posterior insula and left visual cortex. SignificanceThe insula is a major multi-modal network hub with the cerebral cortex having major roles in language, sensation, auditory, visual, limbic and vestibular functions as well as saliency processing. In temporal lobe epilepsy surgery failure, the insula may be implicated as an extra temporal cause, due to the strong mesial temporal connectivity findings.

Localization of Epileptogenic Zone Based on Cortico-Cortical Evoked Potential (CCEP): A Feature Extraction and Graph Theory Approach.

ObjectiveEpilepsy is a chronic brain disease, which is prone to relapse and affects individuals of all ages worldwide, particularly the very young and elderly. Up to one-third of these patients are medically intractable and require resection surgery. However, the outcomes of epilepsy surgery rely upon the clear identification of epileptogenic zone (EZ). The combination of cortico-cortical evoked potential (CCEP) and electrocorticography (ECoG) provides an opportunity to observe the connectivity of human brain network and more comprehensive information that may help the clinicians localize the epileptogenic focus more precisely. However, there is no standard analysis method in the clinical application of CCEPs, especially for the quantitative analysis of abnormal connectivity of epileptic networks. The aim of this paper was to present an approach on the batch processing of CCEPs and provide information relating to the localization of EZ for clinical study.MethodsEight medically intractable epilepsy patients were included in this study. Each patient was implanted with subdural grid electrodes and electrical stimulations were applied directly to their cortex to induce CCEPs. After signal preprocessing, we constructed three effective brain networks at different spatial scales for each patient, regarding the amplitudes of CCEPs as the connection weights. Graph theory was then applied to analyze the brain network topology of epileptic patients, and the topological metrics of EZ and non-EZ (NEZ) were compared.ResultsThe effective connectivity network reconstructed from CCEPs was asymmetric, both the number and the amplitudes of effective CCEPs decreased with increasing distance between stimulating and recording sites. Besides, the distribution of CCEP responses was associated with the locations of EZ which tended to have higher degree centrality (DC) and nodal shortest path length (NLP) than NEZ.ConclusionOur results indicated that the brain networks of epileptics were asymmetric and mainly composed of short-distance connections. The DC and NLP were highly consistent to the distribution of the EZ, and these topological parameters have great potential to be readily applied to the clinical localization of the EZ.

The Influence of Anesthesia on Corticocortical Evoked Potential Monitoring Network Between Frontal and Temporoparietal Cortices

Previous studies have reported the usefulness of intraoperative corticocortical evoked potentials (CCEPs) for preserving language function during brain surgery. This study aimed to assess the influence of depth of anesthesia on CCEP to establish its clinical utility. Twenty patients with brain tumors or epilepsy who underwent awake craniotomy were included in this study. Before resection, the electrode plates were placed on the frontal and temporoparietal cortices, and 1-Hz alternating electrical stimuli were delivered to the pars opercularis/pars triangularis in a bipolar fashion. Electrocorticograms from the temporoparietal cortices time-locked to stimuli were averaged to obtain CCEP responses from a state of deep anesthesia until the awake state. The correlation between CCEP waveforms and bispectral index (BIS) was evaluated. CCEP amplitude increased with the increase in the BIS level. CCEP latency decreased in 5 patients and increased in 15 patients under anesthesia compared with the awake state. CCEP amplitudes decreased by 11.3% to 75.2% (median 31.3%) under anesthesia with <65 BIS level. These differences were statistically significant (P < 0.01, Wilcoxon signed-rank test). With respect to CCEP latencies, there was no significant difference between the awake and anesthetic states. CCEP amplitudes were correlated with depth of anesthesia, whereas CCEP latencies were not affected by anesthesia. The influence of anesthesia should be considered when applying this technique to intraoperative monitoring.

S128. Oscillatory responses evoked by single-pulse electrical stimulation in human cerebral cortex – A Cortico-Cortical Evoked Potential (CCEP) study

Introduction Human brain operates with oscillatory activity in different frequency bands. For example, mu rhythm is well known as an idling rhythm observed in the central area related to motor function. We observed some rhythmic pattern in the averaged waveforms in the CCEP investigation (called “oscillatory response” here), which is originally a method to trace connectivity by single electrical pulse stimulation. We report on the frequency and distribution of the oscillatory responses in CCEP. Methods Subjects are 5 intractable epilepsy patients who underwent chronic implantation of subdural electrodes for presurgical evaluation. Written informed consents were obtained from all subjects. Single-pulse stimuli (0.3 ms, 8–10 mA, alternating polarity, 30 × 2 trials) were applied through two adjacent electrodes (52.8 ± 15.3 stimulus sites per patient). CCEP was recorded from subdural electrodes (105.2 ± 31.8 electrodes per patient) placed on the lateral and medial aspect of the cerebral hemisphere. Lateral fronto-parietal area was covered in all subjects. An oscillatory response in CCEP was detected by visual inspection on the averaged waveform according to the following criteria; (1) it has at least two pairs of peak and trough spaced equally, (2) it can be overlapped with other evoked responses (typical N1/ N2 response). If more than one rhythms with different frequencies were observed in the same electrode, we counted the largest one in amplitude. Results Totally, 2362 oscillatory responses (7.9%) were detected in 29891 observations in 5 subjects, including 443 alpha-band responses (7.5–13.5 Hz), 312 beta-band responses (13.5–30 Hz) and 1505 theta-band responses (3.5–7.5 Hz). Theta rhythm was observed predominantly in the temporal lobe including the basal temporal area (the occurrence rate was 12.45%). Alpha rhythm was observed more often in the parietal lobe including the postcentral gyrus (the occurrence rate was 4.57%), while beta rhythm was often observed around precentral gyrus (the occurrence rate was 1.98%). The frequency of the resting rhythmic activity was equal to that of oscillatory CCEP response in the alpha band in the postcentral gyrus in all subjects. This alpha activity was considered as mu rhythm in all the 3 subjects who performed a hand grasping task. Conclusion Single pulse electrical stimulation evoked oscillatory CCEP responses preferentially in the temporal lobe and the perirolandic area. The correspondence of frequency between the oscillatory response and mu rhythm implies the phase resetting of the physiological oscillation by exogenous input. This unique oscillatory CCEP may help to map these functionally important cortical regions.

P3-1-2. Assessment of the atypical cortico-cortical evoked potentials

Cortico-cortical evoked potential (CCEP) has been widely used to probe brain network. Typically CCEP waveform consists of two negative potentials, N1 (peak: 10–50 ms) and N2 (peak: 100–500 ms). We, however, occasionally encounter atypical responses, such as those with prolonged N1 peak latency. We attempt to classify these atypical patterns and clarify their anatomical distribution. We retrospectively reviewed CCEP responses in two patients with intractable focal epilepsy, in whom CCEPs were obtained bystimulating all the implanted subdural electrodes (IRB#443). We classified CCEP into 6 groups based upon the N1 and N2 peak latencies; IA: N1 (10–50 ms), N2 (100–500 ms), IB: N1 (10–50 ms), N2: (50–100 ms), IIA: N1 (50–100 ms), N2: (100–500 ms), IIB: N1 (50–100 ms) without definite N2, III: mirror CCEP response with positive peaks, IV: N1 (100–500 ms) without definite N2. Atypical CCEP responses (IIA, IIB, III, IV) accounted for 16.0% among all the recording. They mostly distributed in the temporal lobe. There was a tendency of preferred locations for each pattern; IIB in the lateral temporal region and frontal operculum, III in the superior temporal gyrus and mesial temporal region, IV in the temporal pole. Further case accumulation is warranted to verify the results, which helps understand the significance of CCEP for presurgical evaluation.

Frontal Fibers Connecting the Superior Frontal Gyrus to Broca Area: A Corticocortical Evoked Potential Study.

The frontal aslant tract is a deep frontal pathway connecting the superior frontal gyrus (SFG) to Broca area. This fiber is assumed to be associated with language functions, especially speech initiation and spontaneity. The aim of this study was to electrophysiologically investigate this network using corticocortical evoked potentials (CCEPs). This study enrolled 8 patients with brain tumors or medically intractable focal epilepsies who underwent frontal craniotomy over the language-dominant side. All patients underwent CCEP recordings during tumor resection or during invasive evaluation for epilepsy surgery. Alternating 1-Hz electrical stimuli were delivered to pars opercularis (pO) and pars triangularis (pT), corresponding to Broca area, and SFG via the subdural grid electrodes with intensity of 10 mA. Electrocorticograms from SFG and pO/pT time-locked to 50 stimuli were averaged in each trial to obtain CCEP responses. In all patients, stimulation of pO/pT induced CCEP responses in SFG. CCEP responses were recorded in lateral SFG in 5 patients and in supplementary motor areas in 4 patients. Reciprocality was observed in 7 patients in the stimulation of SFG. CCEP responses were significantly faster at SFG from pO/pT than at pO/pT from SFG (Wilcoxon signed rank test, P= 0.028). The present study demonstrated a corticocortical network connecting Broca areas and SFG in a reciprocal manner. Our findings might provide new insight into language and motor integration.

Stimulation artifact correction method for estimation of early cortico-cortical evoked potentials

BackgroundEffective connectivity can be explored using direct electrical stimulations in patients suffering from drug-resistant focal epilepsies and investigated with intracranial electrodes. Responses to brief electrical pulses mimic the physiological propagation of signals and manifest as cortico-cortical evoked potentials (CCEP). The first CCEP component is believed to reflect direct connectivity with the stimulated region but the stimulation artifact, a sharp deflection occurring during a few milliseconds, frequently contaminates it. New methodIn order to recover the characteristics of early CCEP responses, we developed an artifact correction method based on electrical modeling of the electrode–tissue interface. The biophysically motivated artifact templates are then regressed out of the recorded data as in any classical template-matching removal artifact methods. ResultsOur approach is able to make the distinction between the physiological responses time-locked to the stimulation pulses and the non-physiological component. We tested the correction on simulated CCEP data in order to quantify its efficiency for different stimulation and recording parameters. We demonstrated the efficiency of the new correction method on simulations of single trial recordings for early responses contaminated with the stimulation artifact. The results highlight the importance of sampling frequency for an accurate analysis of CCEP. We then applied the approach to experimental data. Comparison with existing methodThe model-based template removal was compared to a correction based on the subtraction of the averaged artifact. ConclusionsThis new correction method of stimulation artifact will enable investigators to better analyze early CCEP components and infer direct effective connectivity in future CCEP studies.

Connectivity of the frontal and anterior insular network: a cortico-cortical evoked potential study.

OBJECT The frontal and insular fiber network in humans remains largely unknown. This study investigated the connectivity of the frontal and anterior insular network in humans using cortico-cortical evoked potential (CCEP). METHODS This retrospective analysis included 18 patients with medically intractable focal epilepsy who underwent stereoelectroencephalography and CCEP. Alternating 1-Hz electrical stimuli were delivered to parts of the frontal lobe and anterior insula (prefrontal cortex [PFC], ventrolateral and dorsolateral premotor area [vPM and dPM, respectively], presupplementary motor area [pre-SMA], SMA, frontal operculum, and anterior insula). A total of 40-60 stimuli were averaged in each trial to obtain CCEP responses. The distribution of CCEP was evaluated by calculating the root mean square of CCEP responses. RESULTS Stimulation of the PFC elicited prominent CCEP responses in the medial PFC and PMs over the ipsilateral hemisphere. Stimulation of the vPM and dPM induced CCEP responses in the ipsilateral frontoparietal areas. Stimulation of the pre-SMA induced CCEP responses in the ipsilateral medial and lateral frontal areas and contralateral pre-SMA, whereas stimulation of the SMA induced CCEP responses in the bilateral frontoparietal areas. Stimulation of the frontal operculum induced CCEP responses in the ipsilateral insula and temporal operculum. CCEPs were observed in the ipsilateral medial, lateral frontal, and frontotemporal operculum in the anterior insular stimulation. Stimulation of the vPM and SMA led to the network in the dominant hemisphere being more developed. CONCLUSIONS Various regions within the frontal lobe and anterior insula were linked to specific ipsilateral and contralateral regions, which may reflect distinct functional roles.

Bidirectional neural connectivity between basal temporal and posterior language areas in humans

ObjectiveThe basal temporal language area (BTL) is known to be involved in the semantic processing of language. To investigate the neural connectivity between BTL and the posterior language area (PL), we used cortico-cortical evoked potential (CCEP) technique. MethodsFour patients with intractable epilepsy who underwent presurgical evaluation with subdural electrodes were examined. All patients were right-handed and left language dominance by Wada test. We directly stimulated 20 pairs of electrodes placed on BTL in patient 1–3, putative BTL in patient 4, and PL in patient 1–4. In patient 4, all electrodes on the left temporal basal area were stimulated. ResultsWe could record 132 CCEP responses including 40 responses by the left basal temporal stimulation in patient 4. The waveforms from PL to BTL were triphasic, while those from BTL to PL were biphasic. The mean latency of the first negative peak (N1) was shorter at BTL (31.8–41.0ms; mean 35.1ms) than at PL (39.6–73.2ms; mean 52.3ms). ConclusionsWe revealed the uneven bidirectional connection between BTL and PL. SignificanceWe speculated that the two language areas are connected mainly through subcortical fibers from PL to BTL and through cortico-cortical fibers from BTL to PL, mediated by multisynaptic transmissions.

Connections of the limbic network: A corticocortical evoked potentials study

Papez proposed a network for higher brain function, which is termed the limbic network. However, the in vivo human limbic network has not been established. We investigated the connectivity of the human limbic system using corticocortical evoked potential (CCEP). This retrospective analysis included 28 patients with medically intractable focal epilepsy who underwent stereoelectroencephalography (SEEG) and CCEP. Alternating 1 Hz electrical stimuli were delivered to parts of the limbic system [anterior and posterior hippocampus, temporal pole, parahippocampal gyrus (PHG), amygdala, anterior (ACG) and posterior cingulate gyrus (PCG), medial and lateral orbitofrontal cortex (OF)]. A total of 40–60 stimuli were averaged in each trial to obtain CCEP responses. CCEP distributions were evaluated by calculating the root mean square (RMS) of CCEP responses. Anterior hippocampal stimulation elicited prominent CCEP responses in medial and lateral temporal structures, PCG, medial OF and insula over the ipsilateral hemisphere. Posterior hippocampal stimulation induced CCEP responses in the ipsilateral medial and lateral temporal structures and PCG. The findings also revealed connections from temporal pole to the ipsilateral medial temporal structures, and connections from PHG to the ipsilateral hippocampus and PCG. The amygdala projected to broad areas including the ipsilateral medial and lateral temporal structures, medial and lateral frontal areas, the cingulate gyrus, insula and inferior parietal lobule. ACG and PCG showed connections to the ipsilateral medial fronto-parietal areas and connections to bilateral medial temporo-parieto-occipital and lateral parieto-occipital areas, respectively. Medial and lateral OF stimulation induced responses in the adjacent cortices. This study revealed that various regions within the limbic network are intimately connected in reverberating circuits and are linked to specific ipsilateral and contralateral regions, which may reflect distinct functional roles.

In vivo human hippocampal cingulate connectivity: A corticocortical evoked potentials (CCEPs) study

ObjectiveTo investigate the human limbic system using cortico-cortical evoked potential (CCEP), which reveals the brain networks. MethodsFive patients with nonlesional medically intractable focal epilepsy with ictal onset outside the limbic system were enrolled. All patients underwent stereoelectroencephalogram electrode implantation in order to delineate the epileptogenic zone. Alternating 1Hz electrical stimuli were delivered to the hippocampus and posterior cingulate gyrus. A total of sixty stimuli were averaged in each trial to obtain CCEP responses. ResultsHippocampal stimulation elicited prominent CCEP responses in the posterior cingulate gyrus. The latencies of early (N1) and late (N2) negative peak ranged 20–60ms and 102–175ms respectively. In addition, CCEP responses were observed in the posterior parahippocampal gyrus, medial superior frontal gyrus (SFG) and orbitofrontal cortex. Stimulation of posterior cingulate contacts induced CCEPs in the hippocampus with N1 and N2 latencies of 25–43ms and 90–234ms respectively in all five patients. ConclusionThis finding supports the assertion that the hippocampus is connected with the posterior cingulate gyrus, posterior parahippocampal gyrus, medial SFG and orbitofrontal cortex. The hippocampus and posterior cingulate gyrus have a bidirectional network through the cingulum. SignificanceThe present study provides new insight into the human limbic network.

Cortical negative motor network in comparison with sensorimotor network: A cortico-cortical evoked potential study

The purpose of this study was to investigate the connectivity from the negative motor area and to elucidate the mechanism of negative motor phenomena. We report the results of cortico-cortical evoked potentials (CCEPs) by electrical stimulation of the primary motor area (MI), primary sensory area (SI), primary (PNMA) and supplementary negative motor area (SNMA) in eight epilepsy patients who underwent intracranial electrode placement. Alternating 1-Hz electrical stimuli were delivered to MI (six patients), SI (five), PNMA (six) and SNMA (two). CCEPs were recorded by averaging electrocorticograms time-locked to the stimuli. Stimulation of MI, SI and PNMA induced CCEP responses in the premotor area (PM), pre- and postcentral gyri, posterior parietal cortex and the temporo-parietal junction. Upon SNMA stimulation, CCEP responses were detected in the prefrontal cortex, PM, pre- and postcentral gyri, supplementary motor area (SMA) and preSMA. Compared with stimulation of SI and MI, PNMA stimulation revealed a broader distribution of CCEP responses in the frontal or parietal association cortex, indicating the importance of the fronto-parietal network associated with a higher level of motor control. We concluded that these connections are associated with motor control and that the negative motor phenomenon results from impairment of the organization of movements.

Correlations between ictal propagation and response to electrical cortical stimulation: A cortico-cortical evoked potential study

To better understand the process of ictal propagation in epilepsy by using cortico-cortical evoked potential (CCEP), which reveals the brain networks. Intracranial EEG recordings of 11 seizures from 11 patients with pharmacoresistant focal epilepsy were studied to identify the propagation sites and times. Six patients had a history of secondary generalization (Gen (+) group) and five patients did not (Gen (-) group). Thereafter repetitive 1Hz bipolar electrical stimuli were applied to the ictal onset zones and CCEPs were recorded by averaging electrocorticograms. The propagation of contiguous spread was significantly faster than non-contiguous spread (p=0.033). In four patients, CCEP amplitudes were significantly larger in the ictal propagation area than out of the propagation area. However, the distribution of CCEP responses was not necessarily consistent with the ictal propagation area as a whole. Furthermore, the ictal propagation areas out of CCEP-positive areas were significantly broader in Gen (+) group than Gen (-) group (p=0.017). The present findings suggest that contiguous spread is faster than non-contiguous spread, which can be explained by the enhancement of excitability around the ictal onset area. Furthermore, there is a group of fibers that is "closed" during the seizures and secondary generalization might be more associated with the impairment of cortical inhibition over the broad cortical area rather than direct connection.

Uneven interhemispheric connections between left and right primary sensori‐motor areas

To clarify the characteristics of interhemispheric connections, we investigated cortico-cortical evoked potentials (CCEP) in human. Fourteen patients with temporal lobe epilepsy who underwent invasive EEG monitoring with bilaterally implanted subdural electrodes were studied. Electric pulse stimuli were given in a bipolar fashion at two adjacent electrodes on and around the motor area (MA) or sensory area (SA), and CCEP responses were recorded by averaging electrocorticograms from the contralateral hemisphere. Seventy-two pairs of electrodes were stimulated, and 468 recordings were analyzed. Fifty-one of 468 recordings demonstrated CCEP responses. Of 51 responses, 16 consisted of an initial positive triphasic wave (Type 1), 27 had an initial negative biphasic wave (Type 2), and 8 showed an initial positive biphasic wave (type 3). The mean latencies of the earliest peaks were 13.1, 28.9, and 29.4 ms in Types 1, 2, and 3 responses, respectively. The responses were more frequently evoked by stimulating facial MA (f-MA) and nonfacial MA (nf-MA) than by stimulating SA or noneloquent area. In both f-MA and nf-MA stimulation, the responses were more frequently recorded at the contralateral f-MA than at the contralateral nf-MA or other areas. SA stimulation never evoked CCEP responses at the contralateral MA or SA. The amplitudes were maximal when f-MA was stimulated and responses recorded at the contralateral f-MA. These findings suggest that the interhemispheric connections are uneven. Both f-MA and nf-MA send dense interhemispheric connections to the contralateral f-MA. SA may have no or only rare direct connection with the contralateral MA or SA.