Spatial distribution and hemispheric asymmetry of electrically evoked experiential phenomena in the human brain

Michal M. Andelman-Gur Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel;

Search for other papers by Michal M. Andelman-Gur in
Current site
Google Scholar
PubMed
Close
,
Tomer Gazit Sagol Brain Institute,

Search for other papers by Tomer Gazit in
Current site
Google Scholar
PubMed
Close
 PhD
,
Fani Andelman Functional Neurosurgery Unit,

Search for other papers by Fani Andelman in
Current site
Google Scholar
PubMed
Close
 PhD
,
Svetlana Kipervasser Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel;
Epilepsy and EEG Unit, and

Search for other papers by Svetlana Kipervasser in
Current site
Google Scholar
PubMed
Close
 MD
,
Uri Kramer Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel;
Pediatric Epilepsy Unit, Tel Aviv Medical Center, Tel Aviv, Israel; and

Search for other papers by Uri Kramer in
Current site
Google Scholar
PubMed
Close
 MD
,
Miri Y. Neufeld Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel;
Epilepsy and EEG Unit, and

Search for other papers by Miri Y. Neufeld in
Current site
Google Scholar
PubMed
Close
 MD
,
Itzhak Fried Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel;
Functional Neurosurgery Unit,
Department of Neurosurgery, University of California, Los Angeles, California

Search for other papers by Itzhak Fried in
Current site
Google Scholar
PubMed
Close
 MD, PhD
, and
Firas Fahoum Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel;
Epilepsy and EEG Unit, and

Search for other papers by Firas Fahoum in
Current site
Google Scholar
PubMed
Close
 MD, MSc
Full access

OBJECTIVE

Experiential phenomena (EP), such as illusions and complex hallucinations, are vivid experiences created in one’s mind. They can occur spontaneously as epileptic auras or can be elicited by electrical brain stimulation (EBS) in patients undergoing presurgical evaluation for drug-resistant epilepsy. Previous work suggests that EP arise from activation of different nodes within interconnected neural networks mainly in the temporal lobes. Yet, the anatomical extent of these neural networks has not been described and the question of lateralization of EP has not been fully addressed. To this end, an extended number of brain regions in which electrical stimulation elicited EP were studied to test whether there is a lateralization propensity to EP phenomena.

METHODS

A total of 19 drug-resistant focal epilepsy patients who underwent EBS as part of invasive presurgical evaluation and who experienced EP during the stimulation were included. Spatial dispersion of visual and auditory illusions and complex hallucinations in each hemisphere was determined by calculation of Euclidean distances between electrodes and their centroid in common space, based on (x, y, z) Cartesian coordinates of electrode locations.

RESULTS

In total, 5857 stimulation epochs were analyzed; 917 stimulations elicited responses, out of which 130 elicited EP. Complex visual hallucinations were found to be widely dispersed in the right hemisphere, while they were tightly clustered in the occipital lobe of the left hemisphere. Visual illusions were elicited mostly in the occipital lobes bilaterally. Auditory illusions and hallucinations were evoked symmetrically in the temporal lobes.

CONCLUSIONS

These findings suggest that complex visual hallucinations arise from wider spread in the right compared to the left hemisphere, possibly mirroring the asymmetry in the white matter organization of the two hemispheres. These results offer some insights into lateralized differences in functional organization and connectivity that may be important for functional mapping and planning of surgical resections in patients with epilepsy.

ABBREVIATIONS

DTI = diffusion tensor imaging; EBS = electrical brain stimulation; ED = Euclidean distance; EP = experiential phenomena; fMRI = functional MRI; IFG = inferior frontal gyrus; MNI = Montreal Neurological Institute; TLVMC = Tel Aviv Medical Center.

OBJECTIVE

Experiential phenomena (EP), such as illusions and complex hallucinations, are vivid experiences created in one’s mind. They can occur spontaneously as epileptic auras or can be elicited by electrical brain stimulation (EBS) in patients undergoing presurgical evaluation for drug-resistant epilepsy. Previous work suggests that EP arise from activation of different nodes within interconnected neural networks mainly in the temporal lobes. Yet, the anatomical extent of these neural networks has not been described and the question of lateralization of EP has not been fully addressed. To this end, an extended number of brain regions in which electrical stimulation elicited EP were studied to test whether there is a lateralization propensity to EP phenomena.

METHODS

A total of 19 drug-resistant focal epilepsy patients who underwent EBS as part of invasive presurgical evaluation and who experienced EP during the stimulation were included. Spatial dispersion of visual and auditory illusions and complex hallucinations in each hemisphere was determined by calculation of Euclidean distances between electrodes and their centroid in common space, based on (x, y, z) Cartesian coordinates of electrode locations.

RESULTS

In total, 5857 stimulation epochs were analyzed; 917 stimulations elicited responses, out of which 130 elicited EP. Complex visual hallucinations were found to be widely dispersed in the right hemisphere, while they were tightly clustered in the occipital lobe of the left hemisphere. Visual illusions were elicited mostly in the occipital lobes bilaterally. Auditory illusions and hallucinations were evoked symmetrically in the temporal lobes.

CONCLUSIONS

These findings suggest that complex visual hallucinations arise from wider spread in the right compared to the left hemisphere, possibly mirroring the asymmetry in the white matter organization of the two hemispheres. These results offer some insights into lateralized differences in functional organization and connectivity that may be important for functional mapping and planning of surgical resections in patients with epilepsy.

In Brief

Studying the precise anatomical regions in which electrical brain stimulation evoked experiential phenomena, the authors found that complex visual hallucinations could be elicited over widespread cortical regions spanning all lobes of the right hemisphere but only rarely over the left occipital lobe. These results offer some insights into lateralized differences in functional connectivity that may be used for presurgical functional mapping of the designated surgical area in patients with epilepsy.

Experiential phenomena (EP) are subjective experiences that are not part of objective reality and are often related to events in one’s personal history.14 Illusions and complex hallucinations are the most common types of EP. Illusions are defined as perceptual distortions of real sensory stimuli, such as hearing echoes, whereas complex hallucinations are complex percepts that the patient perceives in the environment, such as hearing speech or seeing faces, objects, or scenes, in the absence of real stimuli.8,10,30 In comparison, simple hallucinations are nonformed percepts, such as seeing phosphenes, colors, or geometrical shapes or hearing tinnitus,36 and are not considered EP.15 Other types of EP include mnemonic-related experiences, such as déjà vu and flashbacks,9 and “out-of-body” experiences (OBEs), in which the person experiences the world from a point outside his or her own body.4,5 Occasionally, EP may encompass affective changes such as fear, happiness, mirth, or guilt.8,12,14

EP can arise spontaneously as epileptic auras, as first described by Hughlings-Jackson19 and more recently by Fried et al.,10,11 or be elicited during electrical brain stimulation (EBS). Penfield29 was the first to report the occurrence of EP during electrical stimulation of the temporal lobes during awake epilepsy surgery. Later reports documented EP during electrical brain stimulation (EBS) in epilepsy patients undergoing invasive presurgical evaluation.1,27,31,34 Studying EP elicited by direct brain stimulation allows us to better understand the neural basis underlying these complex human experiences.

The anatomical and neurophysiological basis of EP generation has been a matter of debate. Initially, EP were thought to arise from stimulating the mesial temporal structures.2,15,17,29 More recent reports suggest that EP are generated through the modulation of activity within a distributed and interconnected set of anatomical structures comprising a functional neural network.6,7,21,26,37 According to this latter view, similar EP can be evoked by stimulating different nodes within the same functional network.9,34 Despite this advancement in our understanding of how EP may be generated, the anatomical extent of these neural networks has not been clearly described and the question of lateralization of EP has not been fully addressed. We thus aimed to study lateralization effects of electrically elicited EP over an extended number of brain regions bilaterally.

In this retrospective work, we studied widespread cortical regions in which EBS generated an EP in the two hemispheres, focusing on visual and auditory illusions and complex hallucinations. We hypothesized that visual EP have a rightward hemispheric lateralization and that more complex auditory and visual phenomena arise from more spatially dispersed brain regions than simpler EP. We also present a case study of a patient in whom complex visual hallucinations were evoked by independently stimulating his right frontal and occipital lobes, which suggests a wide dispersion of complex visual responses and an asymmetrical organization of functional connectivity.

Methods

Patients

Between the years 2001 and 2015, 62 patients older than 12 years with intractable focal epilepsy underwent invasive video-EEG monitoring with intracranial electrodes at Tel Aviv Medical Center (TLVMC). All surgeries were performed by a single neurosurgeon (I.F.) and all EBS were conducted by the same neuropsychologist (F.A.). All patients had previously undergone a comprehensive noninvasive preoperative assessment, including scalp video-EEG monitoring, structural and functional brain imaging, and neuropsychological assessment. In selected cases where the noninvasive workup was insufficient, invasive video-EEG monitoring including EBS was conducted in order to localize and better delineate the patients’ epileptogenic regions.

Patients with incomplete documentation or patients who experienced technical problems during EBS (5 patients) were excluded from this study. Among the 57 remaining patients, 24 demonstrated EP. Of these, 5 patients did not have available postimplantation imaging and were thus also excluded, resulting in 19 patients who were included in this study. The demographic and clinical data of the 19 patients are presented in Table 1. All patients were informed about the clinical aims of the EBS and provided signed informed consent regarding the potential use of their clinical data for research purposes. The study was approved by the ethics committee at TLVMC.

TABLE 1.

Demographic and clinical characteristics of patients

Patient CharacteristicsValue
Total no. of patients19
Sex
 Males9
 Females10
Age at intracranial EEG study in yrs, mean (SD)29.79 (10.9)
Duration of epilepsy in yrs, mean (SD)12.0 (7.12)
Manual dominance
 Right14
 Left5
Language dominance, by fMRI or EBS
 Left14
 Right1
 Bilateral3
 Unknown1
Lateralization of epileptic focus
 Right10
 Left7
 Bilateral2
Lateralization of brain lesion
 Right5
 Left1
 Bilateral2
 Nonlesional11
Lateralization of electrode implantation
 Right7
 Left6
 Bilateral6
Type of aura
 EP3
 Non-EP8
 None8

Values are numbers of patients unless otherwise indicated.

Intracranial Electrode Implantation and Recordings

Up to December 2012, subdural electrodes were used for invasive studies at TLVMC. Since January 2013, either subdural or depth electrodes have been used. Subdural electrodes (AD-Tech) contain 8 to 64 platinum contacts with an exposed surface of 2.3 mm2 and an intercontact distance of 10 mm. Depth electrodes (AD-Tech) contain 8 platinum contacts with an exposed surface of 1.3 mm2 and an intercontact distance of 5 mm.

A total of 1165 subdural contacts and 134 depth electrode contacts were used in the 19 patients. The number and anatomical sites of electrode implantation were based solely on the patient’s clinical needs, with the purpose of localizing and delineating the epileptogenic regions and related functional sites.1,33,35 The electrodes were implanted in 7 patients in the right hemisphere, in 6 patients in the left hemisphere, and in 6 patients bilaterally. The overall number of contacts was 754 in the right hemisphere and 545 in the left hemisphere. Intracranial EEG was recorded using a Nicolet video-EEG monitoring system (Natus).

Localization of Intracranial Electrodes

The exact contact locations were determined by coregistration of postimplantation 3D CT images to the preimplantation T1-weighted brain MRI. Then, the coregistered volumes were normalized following the Montreal Neurological Institute (MNI) brain atlas using the SPM12 statistical parametric mapping software tool (http://www.fil.ion.ucl.ac.uk/spm/), and the exact MNI coordinates of each contact were manually extracted.

Electrical Stimulation Procedure

EBS was conducted by a multidisciplinary team that included a neurologist, a neuropsychologist, and an EEG technician. During the stimulation session, patients were asked to perform a variety of cognitive tasks, such as object naming, reading, and speaking. Motor and sensory functions were examined as well. The tasks were chosen according to the relevant clinical question for each patient, and all patients were instructed to report any change they felt in their perception of the external environment or of their bodily sensations. Patients were not aware of the timing of the stimulation or the location of the stimulated contacts.

EBS was performed using an Ojemann cortical stimulator (Integra Neurosciences) until 2010, after which a Nicolet cortical stimulator (Natus) was used. The stimulation was delivered using an alternating bipolar current between all adjacent contacts with biphasic waves, 300-μsec wave width, 50-Hz frequency, and 5-second duration. The current amplitude ranged between 1 and 10 mA for the subdural electrodes and between 1 and 4 mA for the depth electrodes.

Previous studies showed that performing a bipolar stimulation between two electrodes implies that the functional response is located from within a few mm to 1-cm proximity to the electrode pair.25,32 EP accompanied by an epileptic after-discharge (sustained epileptiform electrographic activity) were not included in our analysis, as they were considered to possibly result from the spread of epileptic activity.

Data Collection and Analysis

EP evoked by EBS were analyzed by two independent researchers (M.M.A.G. and F.A.) using videotaped recordings and detailed written descriptions of patients’ responses. The elicited responses were classified into EP and non-EP subcategories as presented in Table 2. Similar to other studies,15 simple nonformed visual and auditory hallucinations (phosphenes, simple tones, etc.) were considered non-EP responses and were included as a control group to complex visual EP responses. All of the responses that were analyzed in the study were produced de novo by EBS and were not a result of an epileptic aura.

TABLE 2.

Classification of elicited responses: experiential and nonexperiential responses

SubcategoryNo. of Responses
EP130
 Visual illusions27
 Complex visual hallucinations24
 Auditory illusions22
 Complex auditory hallucinations17
 Gustatory hallucinations1
 Emotional12
 Mnemonic
 Levitation10
 Out-of-body experience3
 Forced thinking4
 Changes in will/urge10
Non-EP787
 Somatosensory sensations135
 Simple visual hallucinations59
 Simple auditory hallucinations6
 Verbal260
 Motor268
 Autonomic14
 Vestibular2
 Other12
 Multimodality31

In order to determine the spatial dispersion of EP responses in each hemisphere, Euclidean distances (EDs) from the centroid in MNI space were calculated, based on (x, y, z) Cartesian coordinates associated with visual and auditory illusions and hallucinations. First, the mean coordinate (centroid) for each of the 4 EP categories (visual illusions, complex visual hallucinations, auditory illusions, and complex auditory hallucinations) in each hemisphere was computed. Subsequently, we evaluated the distribution of distances (between each stimulation location and centroid) for each event category in each hemisphere16 (see Fig. 1). Spatial dispersion and statistical analysis were performed for EP to compare the distribution of ED between the different EP in the same hemisphere and between the same EP across both hemispheres. The same procedure was conducted for simple hallucinations. Details on the gyri of the stimulation and MNI coordinates are provided in Supplementary Table 1.

FIG. 1.
FIG. 1.

Illustration of ED calculation. The ED between any point (x, y, z) and the mean coordinate (double-pointed black arrows) is determined by the equation: . The EP coordinates are plotted as white circles, while the mean Cartesian coordinate is plotted as a black solid circle.

Statistical Analysis

Response locations of EBS were collected for each EP clinical category by hemisphere, as well as by lobe and gyrus, and are provided in Supplementary Table 1. A mixed-model statistical analysis was performed with ED as the dependent variable, in order to compare the spatial distribution of the different EP between the hemispheres. The mixed-model analysis considers each subject as a high-level subject for statistical purposes, and the data from each subject’s stimulations is considered as intercorrelated repeated measurements within the same subject. This statistical method analyzes unbalanced data sets (varying numbers of measurements per subject) and removes the biased estimates in cases when one subject has a higher number of measurements than the others.38 A two-tailed proportion test was performed to compare the proportion of each EP category with the total number of EP in each hemisphere. A chi-square test was performed to compare the distribution of simple EP between the hemispheres. Values were considered significant at p < 0.05.

Results

A total of 8384 EBS stimulation epochs were analyzed. Of these, 1477 stimulations were excluded since they included repetitions of the same stimulation intensity between the same electrode pairs. In addition, 1050 stimulations were excluded as they elicited after-discharges, bringing down the total number to 5857 stimulations. In total, 917 of 5857 stimulations elicited clinical response of any kind, of which 130 responses were EP (Table 2). The EP appeared during the stimulation only and stopped when the stimulation ended. Examples of our patients’ responses are given in Table 3. On grounds of clinical needs, depth electrodes were implanted in only 3 patients. Due to their relatively small number, a comparison between depth and subdural electrodes was not performed.

TABLE 3.

Examples of the main EP subcategories

Type of EPLocationExample
Visual illusionLt inferior occipital gyrusSaw the letters getting out of the paper and “dancing” in circles
Visual hallucinationRt temporal poleSaw a “scene from a movie,” in which two men are sitting in a pub, drinking beer and talking to each other
Auditory illusionLt middle temporal gyrusHeard his own voice disrupted, “like sounds from DVD”
Auditory hallucinationLt supramarginal gyrusHeard someone talking in a low voice, without anyone speaking in the room
Emotional responsesRt inferior frontal gyrusFelt indifferent, reported she didn’t care about the pictures that were presented
LevitationRt superior temporal gyrusFelt she was floating in the air
Out of body experienceRt inferior temporal gyrusFelt she is getting out of her body
Forced thinkingRt superior temporal gyrusFelt her head is filling with pictures and her head is getting inflated
Change in willLt superior frontal gyrusFelt a strong resistance to performing the task, said that despite his conscious will to continue with the task something blocks him

Visual Illusions

A total of 27 responses of visual illusions were collected, with 14 of 27 (52%) responses in the right hemisphere and 13 of 27 (48%) responses in the left hemisphere. No significant difference in spatial spread was observed between the 2 hemispheres (right ED average = 38.7 ± 13.5 mm, left ED average = 25.5 ± 11.7 mm; Fig. 2, light blue dots). Visual illusions were most frequently elicited in the right (7/27, 26%) and left (9/27, 33%) occipital lobes, and in the right parietal lobe (5/27, 19%), as can be seen in Fig. 3A.

FIG. 2.
FIG. 2.

EP locations from the lateral view. Lateral view of the two hemispheres with colored dots representing the areas that elicited visual illusions (light blue), complex visual hallucinations (dark blue), auditory illusions (purple), and complex auditory hallucinations (orange). Comparing the spatial dispersion of the left and right hemispheres (left and right parts, respectively) demonstrates the symmetric representation of the auditory responses compared to the complex visual hallucinations, which were distributed across the right hemisphere and clustered in the left hemisphere. Note that in the left hemisphere, 3 of the complex visual hallucinations are located medially so they do not appear in the lateral view. This figure was generated using 3D Slicer (http://www.slicer.org). Figure is available in color online only.

FIG. 3.
FIG. 3.

EP locations by lobes. Bar graphs showing asymmetrical locations of visual illusions (A), complex visual hallucinations (B), and symmetrical locations of auditory responses (C).

Complex Visual Hallucinations

A total of 24 complex visual hallucinations were observed, predominantly in the right hemisphere (19/24, 79%) versus the left hemisphere (5/24, 21%) (proportion test, z = 2.83, p = 0.005). The spatial dispersion of complex visual hallucinations, as reflected by ED distribution from the examined electrodes to their centroid, was significantly wider in the right hemisphere (59.2 ± 10.8 mm) compared with the left hemisphere (26.8 ± 4.4 mm) (mixed-model analysis, t = 4.1, p = 0.004), as presented in Fig. 4 and Fig. 2 (dark blue dots).

FIG. 4.
FIG. 4.

ED distribution of complex visual hallucinations. Bar graph showing a separate distribution of EDs of complex visual hallucinations (VH) between the hemispheres, with an average ED of 59.2 ± 10.8 mm in the right hemisphere and 26.8 ± 3.4 mm in the left hemisphere (p = 0.004).

In addition, we describe the distribution of complex visual hallucinations by lobes, which complements the quantitative ED method. As shown in Fig. 3B, complex visual hallucinations were elicited over widespread regions across all lobes of the right hemisphere, with 8 of 24 responses (33%) occurring in the occipital, 7 of 24 (29%) in the frontal, 2 of 24 (8%) in the temporal, and 2 of 24 (8%) in the parietal lobes, respectively. By contrast, in the left hemisphere, visual hallucinations were clustered exclusively in the occipital lobe (5/24, 21%, Fig. 3B).

Even though complex visual hallucinations were obtained from 10 patients, we note these responses were elicited from frontal regions in only 1 patient. Moreover, of these 10 patients, 4 had a left epileptic focus and 6 patients had a right epileptic focus. The side of the epileptic focus, therefore, is not likely to be responsible for the rightward asymmetry that was found.

Simple Visual Hallucinations

Simple nonformed hallucinations, such as seeing colors or geometrical shapes, are not defined as EP.36 They were included in this study in order to compare their spatial dispersion vis-à-vis complex visual hallucinations. A total of 59 simple visual hallucinations were collected and analyzed. These responses were significantly more common in the right (46/59, 78%) than in the left hemisphere (13/59, 22%) (chi-square test, χ2 = 10.6, p = 0.001), mostly occurring in the occipital lobes (for exact locations see Supplementary Table 2).

In the right hemisphere, the areas where simple visual hallucinations were elicited by EBS were located more closely together than the areas where complex visual hallucinations were elicited (ED average = 44.4 ± 16.3 mm and 59.2 ± 10.8 mm, respectively; mixed model analysis, t = 3.1, p = 0.003). By contrast, in the left hemisphere there was no such difference. Moreover, there were no significant differences between the hemispheres in dispersion of the sites where simple visual hallucinations and visual illusions were elicited.

Auditory Illusions and Hallucinations

Auditory illusions and complex hallucinations (39 responses) had similar anatomical dispersion and are therefore presented together. Auditory responses were observed in both hemispheres, 17 responses (44%) in the right and 22 responses (56%) in the left hemisphere. Auditory responses were mostly observed in the right (17/39, 44%) and left (18/39, 46%) temporal lobes, as can be seen in Figs. 2 and 3C. Auditory illusions (right ED average = 15.7 ± 8.0 mm, left ED average = 13.2 ± 6.2 mm) and complex auditory hallucinations (right ED average = 8.4 ± 5.2 mm, left ED average = 12.0 ± 5.8 mm) were tightly concentrated in both temporal lobes (Fig. 2, purple and orange dots).

The majority of auditory illusions (13/22, 59%) and complex hallucinations (10/17, 59%) were elicited from the superior temporal gyri bilaterally (Fig. 2 and Supplementary Table 1). Complex auditory hallucinations for the most part included voices without specific verbal contents, except 1 patient who reported hearing a sentence, “I see darkness.”

Multimodality Responses

One multimodality complex hallucination (visual and auditory) was observed when stimulating the right superior temporal gyrus. The patient described hearing a voice inside her and seeing someone who was speaking. Interestingly, this patient was the only one with right-hemisphere language dominance in our study.

Case Study

One of the patients in this study had unique dispersion of complex visual hallucinations. In this 17-year-old left-handed male student, epilepsy onset was at the age of 1.6 years, with pharmacologically resistant daily seizures preceded by a vertiginous aura. Surface video-EEG monitoring showed right parieto-temporal seizure onset, his MRI demonstrated questionable right medial temporo-occipital focal cortical dysplasia, neuropsychological assessment demonstrated bifrontal dysfunction, and functional MRI (fMRI) showed left-hemisphere language dominance. His antiepileptic medications at the time of hospitalization were phenytoin, clobazam, and lacosamide. The patient was implanted with a 64-contact fronto-temporal subdural grid, 16-contact anterior frontal grid, and three 8-contact strips covering the basal temporal, basal temporo-occipital, and basal occipital regions of his right hemisphere (Fig. 5). His spontaneous seizures during the invasive video-EEG monitoring indicated right medial occipital seizure onset, and the patient subsequently underwent resection, with 5-year seizure freedom postoperatively. Pathology was compatible with focal cortical dysplasia type Ia.

FIG. 5.
FIG. 5.

Functional and anatomical connectivity between EP regions of the representative case study patient. Functional and anatomical connectivity between the EP-eliciting frontal and occipital contacts using resting-state fMRI and DII tractography of the patient. Left: Lateral view of the right hemisphere, where the gray dots represent the reconstructed locations of the stimulated subdural contacts. The short white stripe represents the stimulated frontal contacts that elicited complex visual hallucinations. The blue areas represent the brain regions that are functionally connected to the stimulated frontal brain area (seed-based functional connectivity). Note that the frontal regions in which electrical stimulations elicited complex visual hallucinations are functionally connected with the occipital regions. The white matter bundle (pink) demonstrates the probabilistic tractography showing the white matter connectivity of the stimulated frontal and the occipital areas. Right: Axial view showing the white matter connectivity (green) and fMRI connectivity (t-scores, from pink to red) originating from the activated inferior frontal region, both of them reaching the occipital lobe. Figure is available in color online only.

EBS in this patient yielded motor, sensory, and visual EP responses. Stimulation of the right superior frontal gyrus evoked an image of a male lavatory. Stimulation of the right middle frontal gyrus produced a report of seeing himself in a painted picture of a child, while stimulation of the right inferior frontal gyrus (IFG) caused him to see an eye moving. Stimulation of the inferior occipital gyrus yielded an image of a river as well as a feeling of being carried from lake to lake. These 4 different complex visual hallucinations appeared over remote brain areas spanning the right frontal and occipital lobes.

To test whether these distant anatomical regions in which electrical stimulation elicited complex visual hallucinations were anatomically and functionally connected, a resting-state fMRI and probabilistic diffusion tensor imaging (DTI) studies were performed. In the resting-state fMRI scan, the patient was instructed to lie in the scanner with eyes open and to fixate on the center of the screen (duration = 100 sec, TR = 3000 msec; for scanning parameters see Gazit et al.13). We performed a seed-based connectivity test for each of the 3 frontal EP-evoking sites and found correlated activations in the right occipital lobe corresponding to the occipital EP-evoking contact (p < 0.01, FDR corrected). DTI was acquired with bmax = 1000 sec/mm2, with 19 diffusion gradient–encoding directions and one volume without diffusion gradients (b = 0 sec/mm2). Using the FSL/FDT tool (https://fsl.fmrib.ox.ac.uk/fsl/fslwiki/), we performed probabilistic tractography to map fiber tracts originating from each of the 3 frontal stimulation locations and found that fibers origination from the IFG seed (and not the other 2 frontal seeds) reached occipital lobe areas (pink bundle in Fig. 5 left and green bundle in Fig. 5 right).

Taken together, these complementary modalities functionally and anatomically link the frontal and occipital regions where stimulation elicited complex visual hallucinations in the representative case study patient, suggesting that these white matter tracts, visualized with DTI, are involved in the production of complex hallucinations over widespread cortical regions in his right hemisphere.

Discussion

This study offers a unique opportunity to explore the neural basis of experiential phenomena (EP) elicited by electrical stimulation in widespread cortical regions. The precise localizations of a relatively large number of stimulation sites, combined with the application of Euclidean geometry tools, shed further light on the anatomical substrates that generate these highly complex human experiences.

The main finding of this study is a widespread dispersion of the complex visual phenomena in the right hemisphere. Within the right hemisphere, we found a significantly wider spread of complex visual hallucinations, which is reflected in the wider dispersion of Euclidean distances, as opposed to the left hemisphere. This finding suggests that complex visual EP are generated in more spatially dispersed anatomical regions, implying the involvement of long white matter tracts and their interconnected cortices in the formation of complex visual responses. It is therefore plausible that the white matter tracts underlying complex visual EP are asymmetrical, being more extensive and interconnected in the right hemisphere.

There is accumulating evidence supporting the lateralized differences in white matter tracts and their implications on cognitive function,3,7,21 such as the arcuate fasciculus in language,6 superior longitudinal fasciculus in visuo-spatial function,37 and inferior fronto-occipital fasciculus in semantic system.24 Using DTI and a graph theory framework, Iturria-Medina et al.20 found that the right hemisphere is significantly more interconnected than the left, permitting fast parallel information processing important for visuo-spatial function. The consistent neuroanatomical reports of asymmetrical hemispheric organization observed in the white matter tracts, seemingly more richly interconnected on the right, offer a partial explanation for the widespread distribution of complex visual responses in the right hemisphere as we have found.

The case study reported here enabled us to assess the anatomical and functional connectivity between cortical regions involved in the production of complex visual hallucinations. The patient reported complex visual hallucinations when his right frontal and, subsequently, his right occipital lobes were independently stimulated. We found that these regions are connected both functionally and anatomically. Stimulation of the superior, middle, and inferior frontal gyri elicited similar (but not identical) complex visual hallucinations, possibly due to modulation of separate fronto-occipital fiber tracts connecting different frontal loci to the posterior visual cortices. Therefore, our case study further supports the hypothesis of involvement of long white matter tracts connecting distant cortical regions in the generation of complex visual EP.

By contrast, the spatial distribution of visual illusions and simple hallucinations was narrower compared to the spatial distribution of complex visual hallucinations and was confined mostly to the occipital lobes, though they were elicited using similar average electrical currents. The difference between the spatial distribution of complex visual hallucinations and the simpler visual phenomena (visual illusions and simple hallucinations) supports the hypothesis of Elliott et al.,8 who argued that complex visual hallucinations have a more diffuse anatomical basis than simple hallucinations, possibly due to activation of cortico-limbic connections.

These observations are consistent with previous lesional, stimulation, and cognitive studies, suggesting a rightward asymmetry of visuo-spatial functions.18,23,28 A more recent study performed by Jonas et al.,22 where electrical stimulation was delivered using depth electrodes, the authors observed that the probability of evoking a visual hallucination by focal EBS was higher in the right than the left hemisphere. The authors conclude that there is greater sensitivity of the right temporo-occipital regions to evoke visual phenomena. Our findings support and extend the above-mentioned conclusions as we show that complex visual EP could arise from all lobes of the right hemisphere, including the frontal regions.

Finally, tight clustering of the auditory illusions and hallucinations in both the left and right temporal lobes appeared mostly while stimulating the superior temporal gyrus. This finding is in accord with the known localization of auditory phenomena in the superior temporal region, near Heschl’s gyrus,8,30 possibly suggesting that auditory EP rely on shorter and more localized neural networks compared to the widespread networks that underlie complex visual hallucinations.34

All in all, the results of our study suggest that complex visual phenomena are distributed over widespread brain regions of the right hemisphere, unlike simple visual and auditory phenomena. We suggest that asymmetrical and more widespread white matter connections in the nondominant hemisphere may possibly explain our observations. Our study has several limitations. First, invasive EEG studies cannot cover the entire volume of cortical gray matter, although most patients had subdural grids that offered a relatively large coverage of cortical areas. Second, there were more contacts in the right than the left hemisphere, though the symmetric distribution of evoked auditory and simple visual EP argues against a bias for our finding of a rightward predominance of complex visual hallucinations. Finally, due to the retrospective nature of the study, cortico-cortical evoked potentials were not measured. These might have added valuable information regarding the electrical coupling between distant cortical regions during the generation of EP.

Conclusions

In our study, we found that complex visual hallucinations are elicited more frequently and over widespread cortical regions in the right hemisphere while only rarely over the left occipital lobe. This striking asymmetry suggests that evoked complex visual hallucinations may involve modulation of widespread neural networks within distant regions in the right hemisphere, mirroring the asymmetrical organization of white matter connectivity between the two hemispheres. The results of our study shed light on the neural basis of unique brain functions revealed during a preoperative invasive evaluation. This finding may increase understanding of different sensory phenomena encountered during preoperative functional mapping and may be important for surgical decisions and planning of epilepsy surgery. Future studies combining evoked potentials in a large number of patients may reveal the anatomo-functional networks that are involved in the generation of this fascinating product of the human mind.

Acknowledgments

We thank Dr. M. Artzi for her help with DTI analysis, Prof. R. Mukamel for useful comments and suggestions, and Prof. D. Steinberg for his advice on statistical analysis.

Disclosures

The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

Author Contributions

Conception and design: Andelman-Gur, Gazit, Fried, Fahoum. Acquisition of data: all authors. Analysis and interpretation of data: Andelman-Gur, Gazit, Andelman, Fahoum. Drafting the article: Andelman-Gur, Andelman, Fahoum. Critically revising the article: Andelman-Gur, Gazit, Andelman, Neufeld, Fried, Fahoum. Statistical analysis: Andelman-Gur. Administrative/technical/material support: Gazit. Study supervision: Fried, Fahoum.

Supplemental Information

Online-Only Content

Supplemental material is available with the online version of the article.

Previous Presentations

Portions of this work were presented in poster form at the annual meeting of the Israeli Neurology Society, Galilion Hotel, Israel, December 2017, and at the annual meeting of the Israeli League against Epilepsy, Herzeliya, Israel, January 2018.

References

  • 1

    Balestrini S, Francione S, Mai R, Castana L, Casaceli G, Marino D, et al.: Multimodal responses induced by cortical stimulation of the parietal lobe: a stereo-electroencephalography study. Brain 138:25962607, 2015

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2

    Bancaud J, Brunet-Bourgin F, Chauvel P, Halgren E: Anatomical origin of déjà vu and vivid ‘memories’ in human temporal lobe epilepsy. Brain 117:7190, 1994

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3

    Barrick TR, Lawes IN, Mackay CE, Clark CA: White matter pathway asymmetry underlies functional lateralization. Cereb Cortex 17:591598, 2007

  • 4

    Blanke O, Landis T, Spinelli L, Seeck M: Out-of-body experience and autoscopy of neurological origin. Brain 127:243258, 2004

  • 5

    Blanke O, Ortigue S, Landis T, Seeck M: Stimulating illusory own-body perceptions. Nature 419:269270, 2002

  • 6

    Catani M, Allin MP, Husain M, Pugliese L, Mesulam MM, Murray RM, et al.: Symmetries in human brain language pathways correlate with verbal recall. Proc Natl Acad Sci U S A 104:1716317168, 2007

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

    Duffau H: Stimulation mapping of white matter tracts to study brain functional connectivity. Nat Rev Neurol 11:255265, 2015

  • 8

    Elliott B, Joyce E, Shorvon S: Delusions, illusions and hallucinations in epilepsy: 1. Elementary phenomena. Epilepsy Res 85:162171, 2009

  • 9

    Fish DR, Gloor P, Quesney FL, Olivier A: Clinical responses to electrical brain stimulation of the temporal and frontal lobes in patients with epilepsy. Pathophysiological implications. Brain 116:397414, 1993

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Fried I: Auras and experiential responses arising in the temporal lobe. J Neuropsychiatry Clin Neurosci 9:420428, 1997

  • 11

    Fried I, Spencer DD, Spencer SS: The anatomy of epileptic auras: focal pathology and surgical outcome. J Neurosurg 83:6066, 1995

  • 12

    Fried I, Wilson CL, MacDonald KA, Behnke EJ: Electric current stimulates laughter. Nature 391:650, 1998

  • 13

    Gazit T, Andelman F, Glikmann-Johnston Y, Gonen T, Solski A, Shapira-Lichter I, et al.: Probabilistic machine learning for the evaluation of presurgical language dominance. J Neurosurg 125:481493, 2016

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14

    Gloor P: Experiential phenomena of temporal lobe epilepsy. Facts and hypotheses. Brain 113:16731694, 1990

  • 15

    Gloor P, Olivier A, Quesney LF, Andermann F, Horowitz S: The role of the limbic system in experiential phenomena of temporal lobe epilepsy. Ann Neurol 12:129144, 1982

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Gschwend O, Beroud J, Carleton A: Encoding odorant identity by spiking packets of rate-invariant neurons in awake mice. PLoS One 7:e30155, 2012

  • 17

    Halgren E, Walter RD, Cherlow DG, Crandall PH: Mental phenomena evoked by electrical stimulation of the human hippocampal formation and amygdala. Brain 101:83117, 1978

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    Hecaen H, Angelergues R: La cécité psychique. Paris: Masson, 1963

  • 19

    Hughlings-Jackson J: On a particular variety of epilepsy (“intellectual aura”), one case with symptoms of organic brain disease. Brain 11:179207, 1888

  • 20

    Iturria-Medina Y, Pérez Fernández A, Morris DM, Canales-Rodríguez EJ, Haroon HA, García Pentón L, et al.: Brain hemispheric structural efficiency and interconnectivity rightward asymmetry in human and nonhuman primates. Cereb Cortex 21:5667, 2011

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21

    Iwabuchi SJ, Häberling IS, Badzakova-Trajkov G, Patston LLM, Waldie KE, Tippett LJ, et al.: Regional differences in cerebral asymmetries of human cortical white matter. Neuropsychologia 49:35993604, 2011

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22

    Jonas J, Frismand S, Vignal JP, Colnat-Coulbois S, Koessler L, Vespignani H, et al.: Right hemispheric dominance of visual phenomena evoked by intracerebral stimulation of the human visual cortex. Hum Brain Mapp 35:33603371, 2014

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23

    Kertesz A, Dobrowolski S: Right hemisphere deficits, lesion site and location. J Clin Neuropsychol 3:283299, 1981

  • 24

    Martino J, Brogna C, Robles SG, Vergani F, Duffau H: Anatomic dissection of the inferior fronto-occipital fasciculus revisited in the lights of brain stimulation data. Cortex 46:691699, 2010

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25

    Nathan SS, Sinha SR, Gordon B, Lesser RP, Thakor NV: Determination of current density distributions generated by electrical stimulation of the human cerebral cortex. Electroencephalogr Clin Neurophysiol 86:183192, 1993

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26

    Ocklenburg S, Friedrich P, Güntürkün O, Genç E: Intrahemispheric white matter asymmetries: the missing link between brain structure and functional lateralization? Rev Neurosci 27:465480, 2016

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27

    Ojemann GA: Cortical organization of language. J Neurosci 11:22812287, 1991

  • 28

    Ojemann GA: Intrahemispheric localization of language and visuospatial function: Evidence from stimulation mapping during craniotomies for epilepsy, in Akimoto H, Kazamatsuri H, Seino M, et al. (eds): Advances in Epileptology. 13th Epilepsy International Symposium. New York: Raven Press, 1982

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29

    Penfield W: The cerebral cortex in man. I. The cerebral cortex and consciousness. Arch Neurol Psychiatry 40:417442, 1938

  • 30

    Penfield W, Perot P: The brain’s record of auditory and visual experience: a final summary and discussion. Brain 86:595696, 1963

  • 31

    Popa I, Donos C, Barborica A, Opris I, Mălîia MD, Ene M, et al.: Intrusive thoughts elicited by direct electrical stimulation during stereo-electroencephalography. Front Neurol 7:114, 2016

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32

    Ranck JB Jr: Which elements are excited in electrical stimulation of mammalian central nervous system: a review. Brain Res 98:417440, 1975

  • 33

    Rosenow F, Lüders H: Presurgical evaluation of epilepsy. Brain 124:16831700, 2001

  • 34

    Selimbeyoglu A, Parvizi J: Electrical stimulation of the human brain: perceptual and behavioral phenomena reported in the old and new literature. Front Hum Neurosci 4:46, 2010

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 35

    Talairach J, Bancaud J: Stereotaxic approach to epilepsy: methodology of anatomo-functional stereotaxic investigations, in Krayenbühl H, Maspes PE, Sweet WH (eds): Progress in Neurological Surgery. Basel: Karger, 1973, pp 297354

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 36

    Tehovnik EJ, Slocum WM, Carvey CE, Schiller PH: Phosphene induction and the generation of saccadic eye movements by striate cortex. J Neurophysiol 93:119, 2005

  • 37

    Thiebaut de Schotten M, Dell’Acqua F, Forkel SJ, Simmons A, Vergani F, Murphy DG, et al.: A lateralized brain network for visuospatial attention. Nat Neurosci 14:12451246, 2011

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 38

    Wang Z, Goonewardene LA: The use of mixed models in the analysis of animal experiments with repeated measures data. Can J Anim Sci 84:111, 2004

  • Collapse
  • Expand

Diagram from Kondziolka et al. (pp 1–2).

  • FIG. 1.

    Illustration of ED calculation. The ED between any point (x, y, z) and the mean coordinate (double-pointed black arrows) is determined by the equation: . The EP coordinates are plotted as white circles, while the mean Cartesian coordinate is plotted as a black solid circle.

  • FIG. 2.

    EP locations from the lateral view. Lateral view of the two hemispheres with colored dots representing the areas that elicited visual illusions (light blue), complex visual hallucinations (dark blue), auditory illusions (purple), and complex auditory hallucinations (orange). Comparing the spatial dispersion of the left and right hemispheres (left and right parts, respectively) demonstrates the symmetric representation of the auditory responses compared to the complex visual hallucinations, which were distributed across the right hemisphere and clustered in the left hemisphere. Note that in the left hemisphere, 3 of the complex visual hallucinations are located medially so they do not appear in the lateral view. This figure was generated using 3D Slicer (http://www.slicer.org). Figure is available in color online only.

  • FIG. 3.

    EP locations by lobes. Bar graphs showing asymmetrical locations of visual illusions (A), complex visual hallucinations (B), and symmetrical locations of auditory responses (C).

  • FIG. 4.

    ED distribution of complex visual hallucinations. Bar graph showing a separate distribution of EDs of complex visual hallucinations (VH) between the hemispheres, with an average ED of 59.2 ± 10.8 mm in the right hemisphere and 26.8 ± 3.4 mm in the left hemisphere (p = 0.004).

  • FIG. 5.

    Functional and anatomical connectivity between EP regions of the representative case study patient. Functional and anatomical connectivity between the EP-eliciting frontal and occipital contacts using resting-state fMRI and DII tractography of the patient. Left: Lateral view of the right hemisphere, where the gray dots represent the reconstructed locations of the stimulated subdural contacts. The short white stripe represents the stimulated frontal contacts that elicited complex visual hallucinations. The blue areas represent the brain regions that are functionally connected to the stimulated frontal brain area (seed-based functional connectivity). Note that the frontal regions in which electrical stimulations elicited complex visual hallucinations are functionally connected with the occipital regions. The white matter bundle (pink) demonstrates the probabilistic tractography showing the white matter connectivity of the stimulated frontal and the occipital areas. Right: Axial view showing the white matter connectivity (green) and fMRI connectivity (t-scores, from pink to red) originating from the activated inferior frontal region, both of them reaching the occipital lobe. Figure is available in color online only.

  • 1

    Balestrini S, Francione S, Mai R, Castana L, Casaceli G, Marino D, et al.: Multimodal responses induced by cortical stimulation of the parietal lobe: a stereo-electroencephalography study. Brain 138:25962607, 2015

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2

    Bancaud J, Brunet-Bourgin F, Chauvel P, Halgren E: Anatomical origin of déjà vu and vivid ‘memories’ in human temporal lobe epilepsy. Brain 117:7190, 1994

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3

    Barrick TR, Lawes IN, Mackay CE, Clark CA: White matter pathway asymmetry underlies functional lateralization. Cereb Cortex 17:591598, 2007

  • 4

    Blanke O, Landis T, Spinelli L, Seeck M: Out-of-body experience and autoscopy of neurological origin. Brain 127:243258, 2004

  • 5

    Blanke O, Ortigue S, Landis T, Seeck M: Stimulating illusory own-body perceptions. Nature 419:269270, 2002

  • 6

    Catani M, Allin MP, Husain M, Pugliese L, Mesulam MM, Murray RM, et al.: Symmetries in human brain language pathways correlate with verbal recall. Proc Natl Acad Sci U S A 104:1716317168, 2007

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

    Duffau H: Stimulation mapping of white matter tracts to study brain functional connectivity. Nat Rev Neurol 11:255265, 2015

  • 8

    Elliott B, Joyce E, Shorvon S: Delusions, illusions and hallucinations in epilepsy: 1. Elementary phenomena. Epilepsy Res 85:162171, 2009

  • 9

    Fish DR, Gloor P, Quesney FL, Olivier A: Clinical responses to electrical brain stimulation of the temporal and frontal lobes in patients with epilepsy. Pathophysiological implications. Brain 116:397414, 1993

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Fried I: Auras and experiential responses arising in the temporal lobe. J Neuropsychiatry Clin Neurosci 9:420428, 1997

  • 11

    Fried I, Spencer DD, Spencer SS: The anatomy of epileptic auras: focal pathology and surgical outcome. J Neurosurg 83:6066, 1995

  • 12

    Fried I, Wilson CL, MacDonald KA, Behnke EJ: Electric current stimulates laughter. Nature 391:650, 1998

  • 13

    Gazit T, Andelman F, Glikmann-Johnston Y, Gonen T, Solski A, Shapira-Lichter I, et al.: Probabilistic machine learning for the evaluation of presurgical language dominance. J Neurosurg 125:481493, 2016

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14

    Gloor P: Experiential phenomena of temporal lobe epilepsy. Facts and hypotheses. Brain 113:16731694, 1990

  • 15

    Gloor P, Olivier A, Quesney LF, Andermann F, Horowitz S: The role of the limbic system in experiential phenomena of temporal lobe epilepsy. Ann Neurol 12:129144, 1982

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Gschwend O, Beroud J, Carleton A: Encoding odorant identity by spiking packets of rate-invariant neurons in awake mice. PLoS One 7:e30155, 2012

  • 17

    Halgren E, Walter RD, Cherlow DG, Crandall PH: Mental phenomena evoked by electrical stimulation of the human hippocampal formation and amygdala. Brain 101:83117, 1978

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    Hecaen H, Angelergues R: La cécité psychique. Paris: Masson, 1963

  • 19

    Hughlings-Jackson J: On a particular variety of epilepsy (“intellectual aura”), one case with symptoms of organic brain disease. Brain 11:179207, 1888

  • 20

    Iturria-Medina Y, Pérez Fernández A, Morris DM, Canales-Rodríguez EJ, Haroon HA, García Pentón L, et al.: Brain hemispheric structural efficiency and interconnectivity rightward asymmetry in human and nonhuman primates. Cereb Cortex 21:5667, 2011

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21

    Iwabuchi SJ, Häberling IS, Badzakova-Trajkov G, Patston LLM, Waldie KE, Tippett LJ, et al.: Regional differences in cerebral asymmetries of human cortical white matter. Neuropsychologia 49:35993604, 2011

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22

    Jonas J, Frismand S, Vignal JP, Colnat-Coulbois S, Koessler L, Vespignani H, et al.: Right hemispheric dominance of visual phenomena evoked by intracerebral stimulation of the human visual cortex. Hum Brain Mapp 35:33603371, 2014

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23

    Kertesz A, Dobrowolski S: Right hemisphere deficits, lesion site and location. J Clin Neuropsychol 3:283299, 1981

  • 24

    Martino J, Brogna C, Robles SG, Vergani F, Duffau H: Anatomic dissection of the inferior fronto-occipital fasciculus revisited in the lights of brain stimulation data. Cortex 46:691699, 2010

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25

    Nathan SS, Sinha SR, Gordon B, Lesser RP, Thakor NV: Determination of current density distributions generated by electrical stimulation of the human cerebral cortex. Electroencephalogr Clin Neurophysiol 86:183192, 1993

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26

    Ocklenburg S, Friedrich P, Güntürkün O, Genç E: Intrahemispheric white matter asymmetries: the missing link between brain structure and functional lateralization? Rev Neurosci 27:465480, 2016

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27

    Ojemann GA: Cortical organization of language. J Neurosci 11:22812287, 1991

  • 28

    Ojemann GA: Intrahemispheric localization of language and visuospatial function: Evidence from stimulation mapping during craniotomies for epilepsy, in Akimoto H, Kazamatsuri H, Seino M, et al. (eds): Advances in Epileptology. 13th Epilepsy International Symposium. New York: Raven Press, 1982

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29

    Penfield W: The cerebral cortex in man. I. The cerebral cortex and consciousness. Arch Neurol Psychiatry 40:417442, 1938

  • 30

    Penfield W, Perot P: The brain’s record of auditory and visual experience: a final summary and discussion. Brain 86:595696, 1963

  • 31

    Popa I, Donos C, Barborica A, Opris I, Mălîia MD, Ene M, et al.: Intrusive thoughts elicited by direct electrical stimulation during stereo-electroencephalography. Front Neurol 7:114, 2016

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32

    Ranck JB Jr: Which elements are excited in electrical stimulation of mammalian central nervous system: a review. Brain Res 98:417440, 1975

  • 33

    Rosenow F, Lüders H: Presurgical evaluation of epilepsy. Brain 124:16831700, 2001

  • 34

    Selimbeyoglu A, Parvizi J: Electrical stimulation of the human brain: perceptual and behavioral phenomena reported in the old and new literature. Front Hum Neurosci 4:46, 2010

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 35

    Talairach J, Bancaud J: Stereotaxic approach to epilepsy: methodology of anatomo-functional stereotaxic investigations, in Krayenbühl H, Maspes PE, Sweet WH (eds): Progress in Neurological Surgery. Basel: Karger, 1973, pp 297354

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 36

    Tehovnik EJ, Slocum WM, Carvey CE, Schiller PH: Phosphene induction and the generation of saccadic eye movements by striate cortex. J Neurophysiol 93:119, 2005

  • 37

    Thiebaut de Schotten M, Dell’Acqua F, Forkel SJ, Simmons A, Vergani F, Murphy DG, et al.: A lateralized brain network for visuospatial attention. Nat Neurosci 14:12451246, 2011

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 38

    Wang Z, Goonewardene LA: The use of mixed models in the analysis of animal experiments with repeated measures data. Can J Anim Sci 84:111, 2004

Metrics

All Time Past Year Past 30 Days
Abstract Views 1233 115 0
Full Text Views 495 336 31
PDF Downloads 251 93 13
EPUB Downloads 0 0 0