Self-Regulation of Attention in Children in a Virtual Classroom Environment: A Feasibility Study.

Attention is a crucial cognitive function that enables us to selectively focus on relevant information from the surrounding world to achieve our goals. Impairments in sustained attention pose challenges, particularly in children with attention deficit hyperactivity disorder, a neurodevelopmental disorder characterized by impulsive and inattentive behavior. While psychostimulant medications are the most effective ADHD treatment, they often yield unwanted side effects, making it crucial to explore non-pharmacological treatments. We propose a groundbreaking protocol that combines electroencephalography-based neurofeedback with virtual reality (VR) as an innovative approach to address attention deficits. By integrating a virtual classroom environment, we aim to enhance the transferability of attentional control skills while simultaneously increasing motivation and interest among children. The present study demonstrates the feasibility of this approach through an initial assessment involving a small group of healthy children, showcasing its potential for future evaluation in ADHD children. Preliminary results indicate high engagement and positive feedback. Pre- and post-protocol assessments via EEG and fMRI recordings suggest changes in attentional function. Further validation is required, but this protocol is a significant advancement in neurofeedback therapy for ADHD. The integration of EEG-NFB and VR presents a novel avenue for enhancing attentional control and addressing behavioral challenges in children with ADHD.

Validation of Lead-DBS ß-Oscillation Localization with Directional Electrodes.

In deep brain stimulation (DBS) studies in patients with Parkinson's disease, the Lead-DBS toolbox allows the reconstruction of the location of ß-oscillations in the subthalamic nucleus (STN) using Vercise Cartesia directional electrodes (Boston Scientific). The objective was to compare these probabilistic locations with those of intraoperative monopolar ß-oscillations computed from local field potentials (0.5-3 kHz) recorded by using shielded single wires and an extracranial shielded reference electrode. For each electrode contact, power spectral densities of the ß-band (13-31 Hz) were compared with those of all eight electrode contacts on the directional electrodes. The DBS Intrinsic Template AtLas (DISTAL), electrophysiological, and DBS target atlases of the Lead-DBS toolbox were applied to the reconstructed electrodes from preoperative MRI and postoperative CT. Thirty-six electrodes (20 patients: 7 females, 13 males; both STN electrodes for 16 of 20 patients; one single STN electrode for 4 of 20 patients) were analyzed. Stimulation sites both dorsal and/or lateral to the sensorimotor STN were the most efficient. In 33 out of 36 electrodes, at least one contact was measured with stronger ß-oscillations, including 23 electrodes running through or touching the ventral subpart of the ß-oscillations' probabilistic volume, while 10 did not touch it but were adjacent to this volume; in 3 out of 36 electrodes, no contact was found with ß-oscillations and all 3 were distant from this volume. Monopolar local field potentials confirmed the ventral subpart of the probabilistic ß-oscillations.

Electrophysiological confrontation of Lead-DBS-based electrode localizations in patients with Parkinson's disease undergoing deep brain stimulation.

Microelectrode recordings (MERs) are often used during deep brain stimulation (DBS) surgeries to confirm the position of electrodes in patients with advanced Parkinson's disease. The present study focused on 32 patients who had undergone DBS surgery for advanced Parkinson's disease. The first objective was to confront the anatomical locations of intraoperative individual MERs as determined electrophysiologically with those determined postoperatively by image reconstructions. The second aim was to search for differences in cell characteristics among the three subthalamic nucleus (STN) subdivisions and between the STN and other identified subcortical structures. Using the DISTAL atlas implemented in the Lead-DBS image reconstruction toolbox, each MER location was determined postoperatively and attributed to specific anatomical structures (sensorimotor, associative or limbic STN; substantia nigra [SN], thalamus, nucleus reticularis polaris, zona incerta [ZI]). The STN dorsal borders determined intraoperatively from electrophysiology were then compared with the STN dorsal borders determined by the reconstructed images. Parameters of spike clusters (firing rates, amplitudes - with minimum amplitude of 60 µV -, spike durations, amplitude spectral density of ß-oscillations) were compared between structures (ANOVAs on ranks). Two hundred and thirty one MERs were analyzed (144 in 34 STNs, 7 in 4 thalami, 5 in 4 ZIs, 34 in 10 SNs, 41 others). The average difference in depth of the electrophysiological dorsal STN entry in comparison with the STN entry obtained with Lead-DBS was found to be of 0.1 mm (standard deviation: 0.8 mm). All 12 analyzed MERs recorded above the electrophysiologically-determined STN entry were confirmed to be in the thalamus or zona incerta. All MERs electrophysiologically attributed to the SN were confirmed to belong to this nucleus. However, 6/34 MERs that were electrophysiologically attributed to the ventral STN were postoperatively reattributed to the SN. Furthermore, 44 MERs of 3 trajectories, which were intraoperatively attributed to the STN, were postoperatively reattributed to the pallidum or thalamus. MER parameters seemed to differ across the STN, with higher spike amplitudes (H = 10.64, p < 0.01) and less prevalent ß-oscillations (H = 9.81, p < 0.01) in the limbic STN than in the sensorimotor and associative subdivisions. Some cells, especially in the SN, showed longer spikes with lower firing rates, in agreement with described characteristics of dopamine cells. However, these probabilistic electrophysiological signatures might become clinically less relevant with the development of image reconstruction tools, which deserve to be applied intraoperatively.

Electrical stimulation of the medial orbitofrontal cortex in humans elicits pleasant olfactory perceptions.

BACKGROUND: Olfactory hallucinations can be part of epileptic seizures of orbitofrontal origin. Olfactory hallucinations, however, are rare and therefore the semiology, localization and lateralization characteristics are underdetermined. In addition, many discrepancies are found in the literature regarding olfactory processing and orbitofrontal (OF) functions and olfactory function. Particularly, the questions of laterality and affective component in coding of odors in the OF cortex remain controversial. AIMS: This study explored whether cortical electrical stimulation of the OF and mesiotemporal brain can trigger olfactory hallucinations with special focus on olfactory percepts in terms of laterality and hedonics. MATERIALS AND METHODS: Eight patients with temporal lobe epilepsy participated in the study, at the time of invasive exploration of their epilepsy. The most distal contact of the OF and anterior hippocampus depth electrodes were stimulated (50 Hz, 0.2 ms biphasic pulse; maximal stimulation 4 mA). Patients were instructed to report any kind of sensation they might experience. Intracranial depth electrodes were localized (iElectrodes): subject-specific brain mask, subcortical segmentation and cortical parcellation based on the Destrieux atlas (FreeSurfer) were superposed to the coregistered T1-weighted MRI and CT images (SPM). The center of mass of each electrode-artifact cluster determined the electrode localization. The electrode labeling was done in patient space. To obtain the electrode coordinates in Montreal Neurological Institute (MNI) space, the images obtained previously in the patient space were first segmented and normalized (SPM). Then, the localization procedure (iElectrodes) was run again with these new normalized images in MNI space. RESULTS: No hallucination was evoked by stimulation, neither of the right nor the left hippocampus (8/8 patients). Pleasant olfactory hallucinations were evoked by OF stimulation in 5/8 patients in either hemisphere. Patients named the percept as the smell of lemon or coffee for example. Among those 5 patients, electrodes were localized in the cortex of the olfactory sulcus, medial orbital sulcus or medial OF gyrus. Increasing stimulation amplitude changed the olfactory percept identification in 3 out of those 5 patients. No affective judgement or change in perceived odor intensity was reported by the patients. No hallucination was evoked by the stimulation of the white matter of the medial OF brain in 3/8 patients independently of the hemisphere stimulated. CONCLUSIONS: This study demonstrated that stimulation of the cortex of the medial OF brain and not of its white matter elicits specific pleasant olfactory hallucinations independently of the hemisphere stimulated, supporting one symmetrical olfactory processing in human.

Language Monitoring in Brain Surgery Under General Anesthesia.

BACKGROUND: Awake surgeries for cerebral lesion resection have several limitations including patient fear, discomfort, or pain. This study aimed to determine whether components of language function could be measured under general anesthesia. In this study, the occurrence of mismatch negativity (MMN) was searched in evoked potentials for phonological sounds. MATERIALS AND METHODS: Five normal hearing, French native speaker, awake volunteers participated in evaluating the phonological task (4 females and 1 male). Eleven normal-hearing, French native speaker patients (6 left and 5 right hemisphere lesions) participated at the time of their tumor neurosurgery (3 females and 8 males). Repetitions of the standard syllable /pa/ with the insertion of 1 deviant /po/ were presented through earphones. The difference between averaged epochs of standards and deviants syllables determined the MMN. During surgery, total intravenous anesthesia was performed with propofol and synthetic opioid sufentanil. The bispectral index was targeted (40 to 60). RESULTS: The MMN was found in all awake volunteers and validated by an N250 component. In the patient group, the electroencephalogram analysis was not possible in 4 of 11 patients because of anesthesia being too deep, burst suppression, or a high level of noise (>40 µV). Significant N250 response was obtained in 5 of 7 (71.4%) patients under general anesthesia. The 2 other patients also showed MMN which did not reach significance. CONCLUSIONS: To our knowledge, this is the first demonstration that phonological processing can be measured during brain surgery under general anesthesia, suggesting that some language processing persists under the condition of unconsciousness. These results encourage further study of language processing under general anesthesia with the goal of making intraoperative neuromonitoring.

Intraoperative monitoring of olfactory function: a feasibility study.

OBJECTIVE: Intraoperative neuromonitoring of the chemical senses (smell and taste) has never been performed. The objective of this study was to determine if olfactory-evoked potentials could be obtained intraoperatively under general anesthesia. METHODS: A standard olfactometer was used in the surgical theater with hydrogen sulfide (4 ppm, 200 msec). Olfactory-evoked potentials were recorded in 8 patients who underwent neurosurgery for resection of cerebral lesions. These patients underwent routine target-controlled propofol and sufentanil general anesthesia. Frontal, temporal, and parietal scalp subdermal electrodes were recorded ipsilaterally and contralaterally at the site of the surgery. Evoked potentials were computed if at least 70 epochs (0.5-100 Hz) satisfying the artifact rejection criterion (threshold 45 µV) could be extracted from signals of electrodes. RESULTS: Contributive recordings were obtained for 5 of 8 patients (3 patients had fewer than 70 epochs with an amplitude < 45 µV). Olfactory-evoked potentials showed N1 responses (mean 442.8 ± 40.0 msec), most readily observed in the patient who underwent midline anterior fossa neurosurgery. No component of later latencies could be recorded consistently. CONCLUSIONS: The study confirms that olfactory-evoked potentials can be measured in response to olfactory stimuli under general anesthesia. This demonstrates the feasibility of recording olfactory function intraoperatively and opens the potential for neuromonitoring of olfactory function during neurosurgery.

What Is the Best Electrophysiologic Marker of the Outcome of Subthalamic Nucleus Stimulation in Parkinson Disease?

OBJECTIVE: Deep brain stimulation of the subthalamic nucleus (STN) is advocated in patients with advanced Parkinson disease. Intraoperative microelectrode recordings (MER) and stimulation or imaging are applied to confirm electrode targeting. The study objective was to evaluate which intraoperative electrophysiologic marker, MER, stimulation, or local field potentials (LFP) was the most predictive of the clinical efficacy. METHODS: Efficacy was determined with lateralized motor scores of Movement Disorders Society-Unified Parkinson's Disease Rating Scale in 36 patients (OFF-drug/ON-stimulation 1 year after surgery vs. OFF-drug before surgery). Trajectory lengths in STN were determined from MER. Stimulation was increased up to the thresholds of first decrease, of complete suppression of rigidity, and of excitation of pyramidal motor tract. ß oscillations (11-31 Hz) were computed from LFP of the electrode macrocontact. Univariate and multivariate analyses were computed. RESULTS: Motor improvements were linked to trajectory lengths in STN (R2 = 0.17; P > 0.005). No significant relationship was found for thresholds of first decrease or suppression in rigidity or for motor tract excitation (R2 < 0.03, P > 0.05). Motor improvements were most linked to ß oscillation increases (R2 = 0.57, P < 0.005, linear regression; R2 = 0.84, P < 0.0001, post hoc sigmoid regression). ß oscillations appeared more predictive than length (ß: t = 5.4, P < 0.001; length: t = 2.70, P < 0.03). Improvements were also slightly predicted by preoperative scores (R2 = 0.13; P < 0.005). CONCLUSIONS: Motor improvements emerged as most related to ß oscillations, before trajectory length within the STN, whereas stimulation thresholds of rigidity or of motor tract excitation failed to show any relationship. The study encourages LFP measurement to confirm STN electrode location.

Low Frequency Microstimulation Is Locally Excitatory in Patients With Epilepsy.

Deep brain stimulation (DBS) could become a palliative treatment for patients with drug-resistant epilepsy for which surgery cannot be proposed. The objective of this study was to perform microstimulation to measure the effects of DBS in epilepsy locally at the level of a few neurons, with microelectrode recordings, for the first time in patients with epilepsy. Microelectrode recordings were performed before, during and after microstimulation in nine patients with refractory epilepsy. Neuronal spikes were successfully extracted from multi-unit recordings with clustering in six out of seven patients during hippocampal and in one out of two patients during cortical dysplasia microstimulation (1 Hz, charge-balanced biphasic waveform, 60 µs/ph, 25 µA). The firing rates increased in four out of the six periods of microstimulation that could be analyzed. The firing rates were found higher than before microstimulation in all eight periods with increases reaching significance in six out of eight periods. Low-frequency microstimulation was hence sufficient to induce neuronal excitation lasting beyond the stimulation period. No inhibition was observed. This report presents the first evidence that microstimulation performed in epileptic patients produced locally neuronal excitation. Hence neuronal excitation is shown here as the local mechanism of action of DBS. This local excitation is in agreement with epileptogenic effects of low-frequency hippocampal macrostimulation.

Focal versus distributed temporal cortex activity for speech sound category assignment.

Percepts and words can be decoded from distributed neural activity measures. However, the existence of widespread representations might conflict with the more classical notions of hierarchical processing and efficient coding, which are especially relevant in speech processing. Using fMRI and magnetoencephalography during syllable identification, we show that sensory and decisional activity colocalize to a restricted part of the posterior superior temporal gyrus (pSTG). Next, using intracortical recordings, we demonstrate that early and focal neural activity in this region distinguishes correct from incorrect decisions and can be machine-decoded to classify syllables. Crucially, significant machine decoding was possible from neuronal activity sampled across different regions of the temporal and frontal lobes, despite weak or absent sensory or decision-related responses. These findings show that speech-sound categorization relies on an efficient readout of focal pSTG neural activity, while more distributed activity patterns, although classifiable by machine learning, instead reflect collateral processes of sensory perception and decision.

Continuous Intraoperative Monitoring of Temporal Lobe Epilepsy Surgery.

BACKGROUND/AIMS: The monitoring of interictal epileptiform discharge rates (IEDRs) all along anterior temporal lobe resections (ATLRs) has never been reported. Here the effect of ATLR on continuous IEDR monitoring is described. METHODS: IEDRs computed automatically during entire interventions were recorded in 34 patients (38.2%, 13/34 depth; 61.8%, 21/34 scalp electrodes only). Monitorings were invalidated when burst suppression occurred or if initial IEDRs were <5. RESULTS: Monitoring was successful for 69.2% (9/13) of the patients with depth recordings and for 4.8% (1/21) of the patients with scalp recordings. Burst suppressions precluded it in 30.8% (4/13) of the depth and in 57.1% (12/21) of the scalp recordings. Initial IEDRs were <5 for 38.1% (8/21) of the scalp recordings. Significant IEDR decreases were observed in 8/10 patients with successful monitoring. These decreases started with resection of the superior temporal gyrus. IEDRs decreased further with amygdalohippocampectomy in 3/5 patients. At the 12-month follow-up, all patients with IEDR decreases remained seizure free; both patients without did not. CONCLUSION: IEDR monitoring was possible with depth, but not with scalp electrodes. IEDR decreases started with resection of the superior temporal gyrus. A larger patient cohort is necessary to confirm the high predictive values of IEDR monitoring that could become a tool for surgery customization.

Basic instinct undressed: early spatiotemporal processing for primary sexual characteristics.

This study investigates the spatiotemporal dynamics associated with conscious and non-conscious processing of naked and dressed human bodies. To this effect, stimuli of naked men and women with visible primary sexual characteristics, as well as dressed bodies, were presented to 20 heterosexual male and female participants while acquiring high resolution EEG data. The stimuli were either consciously detectable (supraliminal presentations) or were rendered non-conscious through backward masking (subliminal presentations). The N1 event-related potential component was significantly enhanced in participants when they viewed naked compared to dressed bodies under supraliminal viewing conditions. More importantly, naked bodies of the opposite sex produced a significantly greater N1 component compared to dressed bodies during subliminal presentations, when participants were not aware of the stimulus presented. A source localization algorithm computed on the N1 showed that the response for naked bodies in the supraliminal viewing condition was stronger in body processing areas, primary visual areas and additional structures related to emotion processing. By contrast, in the subliminal viewing condition, only visual and body processing areas were found to be activated. These results suggest that naked bodies and primary sexual characteristics are processed early in time (i.e., <200 ms) and activate key brain structures even when they are not consciously detected. It appears that, similarly to what has been reported for emotional faces, sexual features benefit from automatic and rapid processing, most likely due to their high relevance for the individual and their importance for the species in terms of reproductive success.

Effects of repetitive transcranial magnetic stimulation on spike pattern and topography in patients with focal epilepsy.

Repetitive Transcranial Magnetic Stimulation (rTMS) is a non-invasive method for brain stimulation. Group-studies applying rTMS in epilepsy patients aiming to decrease epileptic spike- or seizure-frequency have led to inconsistent results. Here we studied whether therapeutic trains of rTMS have detectable effects on individual spike pattern and/or frequency in patients suffering from focal epilepsy. Five patients with focal epilepsy underwent one session of rTMS online with EEG using a 6 Hz prime/1 Hz rTMS protocol (real and sham). The EEG was recorded continuously throughout the stimulation, and the epileptic spikes recorded immediately before (baseline) and after stimulation (sham and real) were subjected to further analysis. Number of spikes, spike-strength and spike-topography were examined. In two of the five patients, real TMS led to significant changes when compared to baseline and sham (decrease in spike-count in one patient, change in topography of the after-discharge in the other patient). Spike-count and topography remained unchanged the remaining patients. Overall, our results do not indicate a consistent effect of rTMS stimulation on interictal spike discharges, but speak in favor of a rather weak and individually variable immediate effect of rTMS on focal epileptic activity. The individuation of most effective stimulation patterns will be decisive for the future role of rTMS in epilepsies and needs to be determined in larger studies.