Parkinson's Disease: Coping Strategies, Cognitive Restructuring and Deep Brain Stimulation.

OBJECTIVE: Less is known concerning the evolution of coping strategies before and after deep brain stimulation (DBS) in Parkinson's disease (PD) patients. METHODS: In a randomized controlled trial, coping was measured with the neurological version of the CHIP (Coping with Health Injuries and Problem) and the BriefCOPE in PD patients before ( T1: DBS - 2 months) and after (T2: + 3 months, T3: + 6 months) DBS. Patients (N = 50, age 59 ± 5.7 years, disease duration 9.54 ± 3.7 years) were randomised in 3 groups: CRTG (preoperative psychological preparation with cognitive restructuring), PIG (preoperative non structured interviews), and CG (no psychological preparation). RESULTS: Coping strategies are modulated by the time of evaluation. Some strategies are significantly more used preoperatively than postoperatively, as strategies about the research for information (CHIP: F = 16.14; P = .000; η2 = .095; BriefCOPE F = 5.71; P = .005; η2 = .066), emotional regulation (F = 3.29; P = .042; η2 = .029), and well-being searching (F = 4.59; P = .013; η2 = .043). Some other strategies appear more used post than preoperatively, as palliative coping (F = 5.57; P = .005; η2 = .064), humour (F = 3.35; P = .041; η2 = .0.35), and use of substance (F = 4.43; P = .015; η2 = .070). No other specific time, group or time per group interaction effect was found. CONCLUSION: Coping strategies are crucial for PD patients to adapt to the evolution of their parkinsonian state. Their consideration should be more systematic in the neurosurgical process, particularly when neurological symptoms would remain after DBS. More insights are needed concerning the evolution of coping strategies through DBS and the impact of a preoperative psychotherapy over them in preoperative PD patients.

Stability of face recognition abilities after left or right anterior temporal lobectomy.

Patients with anterior temporal lobe (ATL) resection due to mesial temporal lobe epilepsy (MTLE) have difficulties at identifying familiar faces and explicitly remembering newly learned faces but their ability to individuate unfamiliar faces remains largely unknown. Moreover, the extent to which their difficulties with familiar face identity recognition and learning is truly due to the ATL resection remains unknown. Here, we report a study of 24 MTLE patients and matched healthy controls tested with an extensive set of seven face and visual object recognition tasks (including three tasks evaluating unfamiliar face individuation) before and about 6 months after unilateral (nine left, 15 right) ATL resection. We found that ATL resection has little or no effect on the patients' preserved pre-surgical ability to perform unfamiliar face individuation, both at the group and individual levels. More surprisingly, ATL resection also has little effect on the patients' performance at recognizing and naming famous faces as well as at learning new faces. A substantial proportion of right MTLE patients (33%) even improved their response times on several tasks, which may indicate a functional release of visuo-spatial processing after resection in the right ATL. Altogether this study shows that face recognition abilities are mainly unaffected by ATL resection in MTLE, either because the critical regions for face recognition are spared or because performance at some tasks is already lower than normal preoperatively. Overall, these findings urge caution when interpreting the causal effect of brain lesions on face recognition ability in patients with ATL resection due to MTLE. They also illustrate the complexity of predicting cognitive outcomes after epilepsy surgery because of the influence of many different intertwined factors.

Intracerebral electrical stimulation of the face-selective right lateral fusiform gyrus transiently impairs face identity recognition.

Neuroimaging and intracranial electrophysiological studies have consistently shown the largest and most consistent face-selective neural activity in the middle portion of the human right lateral fusiform gyrus ('fusiform face area(s)', FFA). Yet, direct evidence for the critical role of this region in face identity recognition (FIR) is still lacking. Here we report the first evidence of transient behavioral impairment of FIR during focal electrical stimulation of the right FFA. Upon stimulation of an electrode contact within this region, subject CJ, who shows typical FIR ability outside of stimulation, was transiently unable to point to pictures of famous faces among strangers and to match pictures of famous or unfamiliar faces presented simultaneously for their identity. Her performance at comparable tasks with other visual materials (written names, pictures of buildings) remained unaffected by stimulation at the same location. During right FFA stimulation, CJ consistently reported that simultaneously presented faces appeared as being the same identity, with little or no distortion of the spatial face configuration. Independent electrophysiological recordings showed the largest neural face-selective and face identity activity at the critical electrode contacts. Altogether, this extensive multimodal case report supports the causal role of the right FFA in FIR.

Deep brain stimulation in multiple sclerosis-associated tremor. A large, retrospective, longitudinal open label study, with long-term follow-up.

BACKGROUND: Tremor affects up to 25%-58% in multiple sclerosis (MS) population. Deep-brain stimulation (DBS) of the ventral-intermediate nucleus (VIM) of the thalamus is considered as a potential option following medical treatments. Long term DBS efficacy is not well known in these patients with a poor outcome mostly related to disease progression. OBJECTIVE: To report a large and retrospective study of thalamic DBS in MS tremor. METHODS: We conducted a large and retrospective study of patients with MS disabling and pharmacologically resistant upper limb tremor, who underwent thalamic DBS procedure from January 1992 to January 2015 in University Hospital of Henri Mondor, France. Demographic data, clinical assessment and activity daily living were collected. A three-month and twelve-month post-operative assessment with clinical and functional rating scales have been achieved, as well as long term follow-up for most patients. RESULTS: One hundred and four patients underwent DBS procedure. There were 71 female (68%) and 33 male (32%). At three-month post-operative assessment, 64% patients were improved clinically and functionally. Among these, 93% of patients kept a good efficacy at one-year post-operative assessment. Mean duration of follow-up for these patients was 6 years. CONCLUSION: We described a long-term sustained clinical and functional improvement in this large and retrospective report of thalamic DBS. This neuromodulation approach could be a therapeutic option for all severe upper extremity refractory tremor in MS patients.

Single neuron responses underlying face recognition in the human midfusiform face-selective cortex.

Faces are critical for social interactions and their recognition constitutes one of the most important and challenging functions of the human brain. While neurons responding selectively to faces have been recorded for decades in the monkey brain, face-selective neural activations have been reported with neuroimaging primarily in the human midfusiform gyrus. Yet, the cellular mechanisms producing selective responses to faces in this hominoid neuroanatomical structure remain unknown. Here we report single neuron recordings performed in 5 human subjects (1 male, 4 females) implanted with intracerebral microelectrodes in the face-selective midfusiform gyrus, while they viewed pictures of familiar and unknown faces and places. We observed similar responses to faces and places at the single cell level, but a significantly higher number of neurons responding to faces, thus offering a mechanistic account for the face-selective activations observed in this region. Although individual neurons did not respond preferentially to familiar faces, a population level analysis could consistently determine whether or not the faces (but not the places) were familiar, only about 50 ms after the initial recognition of the stimuli as faces. These results provide insights into the neural mechanisms of face processing in the human brain.

Age-related decrease in functional mobility score when performing a locomotor task in an immersive environment.

In recent years, immersive virtual reality technology has emerged in the field of health. Its use could allow the assessment of the motor behavior of individuals in adaptable and reproducible immersive environments, simulating real situations. This study aimed to assess the effect of an immersive scenario on functional mobility during a simple locomotor task according to age. Sixty young adults and 60 older volunteers, who were autonomous and without cognitive and neurological impairment participated. A locomotor task based on the "Timed Up and Go" task was performed in real and virtual conditions. A functional mobility score was calculated by combining the time and the number of steps used and compared between young and older people. Results showed that correlations between time and the number of steps were the same in VR and real conditions, but the locomotor performance decreased significantly in VR for both populations. Additionally, older people exhibited a more reduced locomotor performance in a virtual environment than young adults, thereby their functional mobility score decreased more to complete the task, reflecting the adoption of a more secure locomotion strategy often related to the fear of falling, with an increase in time and number of steps to support balance. The major difference between reality and VR is the visual immersion with an HMD, and visual information is more important in the sensory integration of older people. Therefore, the reduction in visual field and lack of visual exproprioceptive information about the body segments in the virtual environment could explain these results. Finally, the effect of immersion in a virtual scenario on mobility exists for both populations but is accentuated by the aging process and is therefore age dependent.

Illness perceptions in pre-operative Parkinson's disease patients.

Parkinson's disease (PD) is a neurodegenerative disease, that combines motor and non-motor disorders, and alters patients' autonomy. Even if subthalamic nucleus deep brain stimulation (STN-DBS) induces undisputable motor improvement, a post-operative social maladjustment was described by some patients. Our aim was to describe pre-operative illness perceptions in parkinsonian patients, and to determine the possible impact of cognitive restructuration over them. We analyzed 27 parkinsonian patient's candidates to DBS. The mean age was 59 ± 5.94 years, and mean disease duration was 9.89 ± 4.15 years. The patients had two pre-operative psychological interviews (DBS-45 days, DBS-25 days) and completed the Illness Perception Questionnaire-Revised (IPQ-R) before the first interview and at DBS-1 day. The CRTG group (n = 13) had cognitive restructuration during second interview, on dysfunctional cognitions about their perception of post-DBS life which emerged from the first interview. The PIG group (n = 14) benefited of two non-structured interviews. No significant differences were found between the visits (DBS-45 days, DBS-1 day) for IPQ-R dimensions, except for the perception of "personal control" over PD which appears significantly higher for CRTG than PIG group (p = .039) at DBS-1 day, whereas the scores were quite similar at DBS-45 days. Illness perceptions seem to be stable over time and mostly influenced by disease experience of PD. However, the perception of personal control over PD seemed to be modulated through cognitive restructuration, giving patients' control back over disease. Before DBS, illness perceptions investigation and restructuration constitute an interesting point to work on, to enhance perceived benefits of neurosurgery.Trial registration: Clinical Research Program, N°IDRCB 2008-A00655-50, approved by the local ethics committee (CPP EST III, N° CPP: 08.07.03, first version date: 04/01/2008), registered on the ClinicalTrials.gov website (NCT02893449).

A Bayesian approach for simultaneous spike/LFP separation and spike sorting.

Objective.The aim of this paper is to present a novel method for simultaneous spike waveforms extraction and sorting from the raw recorded signal. The objective is twofold: on the one hand, to enhance spike sorting performance by extracting the spike waveforms of each spike and, on the other hand, to improve the analysis of the multi-scale relationships between spikes and local field potentials (LFP) by offering an accurate separation of these two components constitutive of the raw micro recordings.Approach.The method, based on a Bayesian approach, is fully automated and provides a mean spike shape for each cluster, but also an estimate for each singular spike waveform, as well as the LFP signal cleaned of spiking activity.Main results.The performance of the algorithm is evaluated on simulated and real data, for which both the clustering and spike removal aspects are analyzed. Clustering performance significantly increases when compared to state-of-the-art methods, taking benefit from the separation of the spikes from the LFP handled by our model. Our method also performs better in removing the spikes from the LFP when compared to previously proposed methodologies, especially in the high frequency bands. The method is finally applied on real data (ClinicalTrials.gov Identifier: NCT02877576) and confirm the results obtained on benchmark signals.Significance.By separating more efficiently the spikes from the LFP background, our method allows both a better spike sorting and a more accurate estimate of the LFP, facilitating further analysis such as spike-LFP relationships.

Intracerebral Correlates of Scalp EEG Ictal Discharges Based on Simultaneous Stereo-EEG Recordings.

BACKGROUND AND OBJECTIVES: It remains unknown to what extent ictal scalp EEG can accurately predict the localization of the intracerebral seizure onset in presurgical evaluation of drug-resistant epilepsies. In this study, we aimed to define homogeneous ictal scalp EEG profiles (based on their first ictal abnormality) and assess their localizing value using simultaneously recorded scalp EEG and stereo-EEG. METHODS: We retrospectively included consecutive patients with drug-resistant focal epilepsy who had simultaneous stereo-EEG and scalp EEG recordings of at least 1 seizure in the epileptology unit in Nancy, France. We analyzed 1 seizure per patient and used hierarchical cluster analysis to group similar seizure profiles on scalp EEG and then performed a descriptive analysis of their intracerebral correlates. RESULTS: We enrolled 129 patients in this study. The hierarchical cluster analysis showed 6 profiles on scalp EEG first modification. None were specific to a single intracerebral localization. The "normal EEG" and "blurred EEG" clusters (early muscle artifacts) comprised only 5 patients each and corresponded to no preferential intracerebral localization. The "temporal discharge" cluster (n = 46) was characterized by theta or delta discharges on ipsilateral anterior temporal scalp electrodes and corresponded to a preferential mesial temporal intracerebral localization. The "posterior discharge" cluster (n = 42) was characterized by posterior ipsilateral or contralateral rhythmic alpha discharges or slow waves on scalp and corresponded to a preferential temporal localization. However, this profile was the statistically most frequent scalp EEG correlate of occipital and parietal seizures. The "diffuse suppression" cluster (n = 9) was characterized by a bilateral and diffuse background activity suppression on scalp and corresponded to mesial, and particularly insulo-opercular, localization. Finally, the "frontal discharge" cluster (n = 22) was characterized by bilateral frontal rhythmic fast activity or preictal spike on scalp and corresponded to preferential ventrodorsal frontal intracerebral localizations. DISCUSSION: The hierarchical cluster analysis identified 6 seizure profiles regarding the first abnormality on scalp EEG. None of them were specific of a single intracerebral localization. Nevertheless, the strong relationships between the "temporal," "frontal," "diffuse suppression," and "posterior" profiles and intracerebral discharge localizations may contribute to hierarchize hypotheses derived from ictal scalp EEG analysis regarding intracerebral seizure onset.

Extracting the Invisible: Mesial Temporal Source Detection in Simultaneous EEG and SEEG Recordings.

Epileptic source detection relies mainly on visual expertise of scalp EEG signals, but it is recognised that epileptic discharges can escape to this expertise due to a deep localization of the brain sources that induce a very low, even negative, signal to noise ratio. In this methodological study, we aimed to investigate the feasibility of extracting deep mesial temporal sources that were invisible in scalp EEG signals using blind source separation (BSS) methods (infomax ICA, extended infomax ICA, and JADE) combined with a statistical measure (kurtosis). We estimated the effect of different methodological and physiological parameters that could alter or improve the extraction. Using nine well-defined mesial epileptic networks (1949 spikes) obtained from seven patients and simultaneous EEG-SEEG recordings, the first independent component extracted from the scalp EEG signals was validated in mean from 46 to 80% according to the different parameters. The three BSS methods equally performed (no significant difference) and no influence of the number of scalp electrodes used was found. At the opposite, the number and amplitude of spikes included in the averaging before the extraction modified the performance. Anyway, despite their invisibility in scalp EEG signals, this study demonstrates that deep source extraction is feasible under certain conditions and with the use of common signal analysis toolboxes. This finding confirms the crucial need to continue the signal analysis of scalp EEG recordings which contains subcortical signals that escape to expert visual analysis but could be found by signal processing.

Effects of using immersive virtual reality on time and steps during a locomotor task in young adults.

Immersive virtual reality makes possible to perceive and interact in a standardized, reproductible and digital environment, with a wide range of simulated situations possibilities. This study aimed to measure the potential effect of virtual reality on time and number of steps when performing a locomotor task, in a young adult's population. Sixty young adults (32W, 28M, mean age 21.55 ± 1.32), who had their first immersive virtual reality experience, performed a locomotor task based on "Timed Up and Go" (TUG) task in real, in virtual reality in a stopped train and in virtual reality in a moving train. Time and number of steps variables representing primary locomotion indicators were measured and compared between each condition. Results showed significant increases in time and number of steps in the two virtual reality conditions compared to real but not between the two virtual reality conditions. There was an effect of virtual reality in young adults when performing the locomotor task. It means that technological and digital characteristics of the immersive virtual reality experience led to modify motor strategies employed. Adding a plausible visual optic flow did not appear to affect motor control further when the information is negligible and not essential for performing the task.

Low and high frequency intracranial neural signals match in the human associative cortex.

In vivo intracranial recordings of neural activity offer a unique opportunity to understand human brain function. Intracranial electrophysiological (iEEG) activity related to sensory, cognitive or motor events manifests mostly in two types of signals: event-related local field potentials in lower frequency bands (<30 Hz, LF) and broadband activity in the higher end of the frequency spectrum (>30 Hz, High frequency, HF). While most current studies rely exclusively on HF, thought to be more focal and closely related to spiking activity, the relationship between HF and LF signals is unclear, especially in human associative cortex. Here, we provide a large-scale in-depth investigation of the spatial and functional relationship between these 2 signals based on intracranial recordings from 121 individual brains (8000 recording sites). We measure category-selective responses to complex ecologically salient visual stimuli - human faces - across a wide cortical territory in the ventral occipito-temporal cortex (VOTC), with a frequency-tagging method providing high signal-to-noise ratio (SNR) and the same objective quantification of signal and noise for the two frequency ranges. While LF face-selective activity has higher SNR across the VOTC, leading to a larger number of significant electrode contacts especially in the anterior temporal lobe, LF and HF display highly similar spatial, functional, and timing properties. Specifically, and contrary to a widespread assumption, our results point to nearly identical spatial distribution and local spatial extent of LF and HF activity at equal SNR. These observations go a long way towards clarifying the relationship between the two main iEEG signals and reestablish the informative value of LF iEEG to understand human brain function.

Cell to network computational model of the epileptic human hippocampus suggests specific roles of network and channel dysfunctions in the ictal and interictal oscillations.

The mechanisms underlying the generation of hippocampal epileptic seizures and interictal events and their interactions with the sleep-wake cycle are not yet fully understood. Indeed, medial temporal lobe epilepsy is associated with hippocampal abnormalities both at the neuronal (channelopathies, impaired potassium and chloride dynamics) and network level (neuronal and axonal loss, mossy fiber sprouting), with more frequent seizures during wakefulness compared with slow-wave sleep. In this article, starting from our previous computational modeling work of the hippocampal formation based on realistic topology and synaptic connectivity, we study the role of micro- and mesoscale pathological conditions of the epileptic hippocampus in the generation and maintenance of seizure-like theta and interictal oscillations. We show, through the simulations of hippocampal activity during slow-wave sleep and wakefulness that: (i) both mossy fiber sprouting and sclerosis account for seizure-like theta activity, (ii) but they have antagonist effects (seizure-like activity occurrence increases with sprouting but decreases with sclerosis), (iii) though impaired potassium and chloride dynamics have little influence on the generation of seizure-like activity, they do play a role on the generation of interictal patterns, and (iv) seizure-like activity and fast ripples are more likely to occur during wakefulness and interictal spikes during sleep.

Naming impairments evoked by focal cortical electrical stimulation in the ventral temporal cortex correlate with increased functional connectivity.

BACKGROUND: High-frequency cortical electrical stimulations (HF-CES) are the gold standard for presurgical functional mapping. In the dominant ventral temporal cortex (VTC) HF-CES can elicit transient naming impairment (eloquent sites), defining a basal temporal language area (BTLA). OBJECTIVE: Whether naming impairments induced by HF-CES within the VTC are related to a specific pattern of connectivity of the BTLA within the temporal lobe remains unknown. We addressed this issue by comparing the connectivity of eloquent and non-eloquent sites from the VTC using cortico-cortical evoked potentials (CCEP). METHODS: Low frequency cortical electrical stimulations (LF-CES) were used to evoke CCEP in nine individual brains explored with Stereo-Electroencephalography. We compared the connectivity of eloquent versus non eloquent sites within the VTC using Pearson's correlation matrix. RESULTS: Overall, within the VTC, eloquent sites were associated with increased functional connectivity compared to non-eloquent sites. Among the VTC structures, this pattern holds true for the inferior temporal gyrus and the parahippocampal gyrus while the fusiform gyrus specifically showed a high connectivity in both non eloquent and eloquent sites. CONCLUSIONS: Our findings suggest that the cognitive effects of focal HF-CES are related to the functional connectivity properties of the stimulated sites, and therefore to the disturbance of a wide cortical network. They further suggest that functional specialization of a cortical region emerges from its specific pattern of functional connectivity. Cortical electrical stimulation functional mapping protocols including LF coupled to HF-CES could provide valuable data characterizing both local and distant functional architecture.

The dural angioleiomyoma harbors frequent GJA4 mutation and a distinct DNA methylation profile.

The International Society for the Study of Vascular Anomalies (ISSVA) has defined four vascular lesions in the central nervous system (CNS): arteriovenous malformations, cavernous angiomas (also known as cerebral cavernous malformations), venous malformations, and telangiectasias. From a retrospective central radiological and histopathological review of 202 CNS vascular lesions, we identified three cases of unclassified vascular lesions. Interestingly, they shared the same radiological and histopathological features evoking the cavernous subtype of angioleiomyomas described in the soft tissue. We grouped them together with four additional similar cases from our clinicopathological network and performed combined molecular analyses. In addition, cases were compared with a cohort of 5 soft tissue angioleiomyomas. Three out 6 CNS lesions presented the same p.Gly41Cys GJA4 mutation recently reported in hepatic hemangiomas and cutaneous venous malformations and found in 4/5 soft tissue angioleiomyomas of our cohort with available data. Most DNA methylation profiles were not classifiable using the CNS brain tumor (version 12.5), and sarcoma (version 12.2) classifiers. However, using unsupervised t-SNE analysis and hierarchical clustering analysis, 5 of the 6 lesions grouped together and formed a distinct epigenetic group, separated from the clusters of soft tissue angioleiomyomas, other vascular tumors, inflammatory myofibroblastic tumors and meningiomas. Our extensive literature review identified several cases similar to these lesions, with a wide variety of denominations. Based on radiological and histomolecular findings, we suggest the new terminology of "dural angioleiomyomas" (DALM) to designate these lesions characterized by a distinct DNA methylation pattern and frequent GJA4 mutations.

Intracerebral electrical stimulation of the right anterior fusiform gyrus impairs human face identity recognition.

Brain regions located between the right fusiform face area (FFA) in the middle fusiform gyrus and the temporal pole may play a critical role in human face identity recognition but their investigation is limited by a large signal drop-out in functional magnetic resonance imaging (fMRI). Here we report an original case who is suddenly unable to recognize the identity of faces when electrically stimulated on a focal location inside this intermediate region of the right anterior fusiform gyrus. The reliable transient identity recognition deficit occurs without any change of percept, even during nonverbal face tasks (i.e., pointing out the famous face picture among three options; matching pictures of unfamiliar or familiar faces for their identities), and without difficulty at recognizing visual objects or famous written names. The effective contact is associated with the largest frequency-tagged electrophysiological signals of face-selectivity and of familiar and unfamiliar face identity recognition. This extensive multimodal investigation points to the right anterior fusiform gyrus as a critical hub of the human cortical face network, between posterior ventral occipito-temporal face-selective regions directly connected to low-level visual cortex, the medial temporal lobe involved in generic memory encoding, and ventral anterior temporal lobe regions holding semantic associations to people's identity.

Does the Management of Visual and Audible Motion Information during an Immersive Virtual Reality Timed Up and Go Test Impact Locomotor Performance in the Elderly?

BACKGROUND/AIMS: Falling among the elderly is a major public health issue, especially with the advancing age of the baby boomers. The fall risk assessment tests for many lack a context that would bring them closer to everyday life. Thus, immersive virtual reality, which makes it possible to simulate everyday situations, could make it possible to strengthen the quality of the assessment of the risk of falls. However, it is necessary to understand how the use of a virtual reality device influences the motor control of elderly participants. If vestibular physiotherapists use VR to virtualize their tools, what impact would a visual simulation of movement have on motor control in a locomotor task, if this simulation were plausible? METHODS: Sixty-two elders (70.8 ± 6.7 years old) completed a Timed Up and Go task under 3 conditions: real, virtual reality, and virtual reality with visual and sound movement information. The virtual reality task takes place in a train either stationary at a station or in uniform linear motion. The time and number of steps were recorded using video, and comparisons between conditions were made using Friedman's test. RESULTS: The results show a significant increase in the time and number of steps in "virtual reality" condition compared to the "real" condition. They do not show significant differences between the 2 virtual conditions. CONCLUSION: The use of a running virtual train to provide plausible movement is particularly distinguished from vestibular physiotherapy applications with first a fixed visual support partially obscuring the optical flow. This visual aid coupled with the attention dedicated to the task inhibits the effect of the moving environment on locomotion. However, the visual optical flow will potentially have an effect in people with fear of falling. Virtual reality shows great potential for the simulation of realistic environments for the assessment of the risk of falls and opens up avenues for the development of tests.

Transcranial Electrical Stimulation generates electric fields in deep human brain structures.

BACKGROUND: Transcranial electrical stimulation (TES) efficiency is related to the electric field (EF) magnitude delivered on the target. Very few studies (n = 4) have estimated the in-vivo intracerebral electric fields in humans. They have relied mainly on electrocorticographic recordings, which require a craniotomy impacting EF distribution, and did not investigate deep brain structures. OBJECTIVE: To measure the electric field in deep brain structures during TES in humans in-vivo. Additionally, to investigate the effects of TES frequencies, intensities, and montages on the intracerebral EF. METHODS: Simultaneous bipolar transcranial alternating current stimulation and intracerebral recordings (SEEG) were performed in 8 drug-resistant epileptic patients. TES was applied using small high-definition (HD) electrodes. Seven frequencies, two intensities and 15 montages were applied on one, six and one patients, respectively. RESULTS: At 1 mA intensity, we found mean EF magnitudes of 0.21, 0.17 and 0.07 V·m-1 in the amygdala, hippocampus, and cingulate gyrus, respectively. An average of 0.14 ± 0.07 V·m-1 was measured in these deep brain structures. Mean EF magnitudes in these structures at 1Hz were 11% higher than at 300Hz (+0.03 V·m-1). The EF was correlated with the TES intensities. The TES montages that yielded the maximum EF in the amygdalae were T7-T8 and in the cingulate gyri were C3-FT10 and T7-C4. CONCLUSION: TES at low intensities and with small HD electrodes can generate an EF in deep brain structures, irrespective of stimulation frequency. EF magnitude is correlated to the stimulation intensity and depends upon the stimulation montage.