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Purpose Optic pathway gliomas (OPG) are low-grade pilocytic astrocytomas accounting for 3-5% of pediatric intracranial tumors. Accurate and quantitative follow-up of OPG using magnetic resonance imaging (MRI) is crucial for therapeutic decision making, yet is challenging due to the complex shape and heterogeneous tissue pattern which characterizes these tumors. The aim of this study was to implement automatic methods for segmentation and classification of OPG and its components, based on MRI. Methods A total of 202 MRI scans from 29 patients with chiasmatic OPG scanned longitudinally were retrospectively collected and included in this study. Data included T2 and post-contrast T1 weighted images. The entire tumor volume and its components were manually annotated by a senior neuro-radiologist, and inter- and intra-rater variability of the entire tumor volume was assessed in a subset of scans. Automatic tumor segmentation was performed using deep-learning method with U-Net+ResNet architecture. A fivefold cross-validation scheme was used to evaluate the automatic results relative to manual segmentation. Voxel-based classification of the tumor into enhanced, non-enhanced, and cystic components was performed using fuzzy c-means clustering. Results The results of the automatic tumor segmentation were: mean dice score = 0.736 ± 0.025, precision = 0.918 ± 0.014, and recall = 0.635 ± 0.039 for the validation data, and dice score = 0.761 ± 0.011, precision = 0.794 ± 0.028, and recall = 0.742 ± 0.012 for the test data. The accuracy of the voxel-based classification of tumor components was 0.94, with precision = 0.89, 0.97, and 0.85, and recall = 1.00, 0.79, and 0.94 for the non-enhanced, enhanced, and cystic components, respectively. Conclusion This study presents methods for automatic segmentation of chiasmatic OPG tumors and classification into the different components of the tumor, based on conventional MRI. Automatic quantitative longitudinal assessment of these tumors may improve radiological monitoring, facilitate early detection of disease progression and optimize therapy management.

OBJECTIVEExperiential 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.METHODSA 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.RESULTSIn 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.CONCLUSIONSThese 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.

Resolving approach-avoidance conflicts relies on encoding motivation outcomes and learning from past experiences. Accumulating evidence points to the role of the Medial Temporal Lobe (MTL) and Medial Prefrontal Cortex (mPFC) in these processes, but their differential contributions have not been convincingly deciphered in humans. We detect 310 neurons from mPFC and MTL from patients with epilepsy undergoing intracranial recordings and participating in a goal-conflict task where rewards and punishments could be controlled or not. mPFC neurons are more selective to punishments than rewards when controlled. However, only MTL firing following punishment is linked to a lower probability for subsequent approach behavior. mPFC response to punishment precedes a similar MTL response and affects subsequent behavior via an interaction with MTL firing. We thus propose a model where approach-avoidance conflict resolution in humans depends on outcome value tagging in mPFC neurons influencing encoding of such value in MTL to affect subsequent choice., Optimizing approach-avoidance behavior calls for neural encoding of related motivation outcomes. Here, the authors show that behavioral choice under conflict relies on differential neuronal firing patterns after punishment, in which mPFC neurons decode the outcome’s value and MTL neurons follow by reducing subsequent approach.

OBJECTIVEPreoperative localization of seizure onset zones (SOZs) is an evolving field in the treatment of refractory epilepsy. Both magnetic source imaging (MSI), and the more recent EEG-correlated functional MRI (EEG-fMRI), have shown applicability in assisting surgical planning. The purpose of this study was to evaluate the capability of each method and their combination in localizing the seizure onset lobe (SL).METHODSThe study included 14 patients who underwent both MSI and EEG-fMRI before undergoing implantation of intracranial EEG (icEEG) as part of the presurgical planning of the resection of an epileptogenic zone (EZ) during the years 2012–2018. The estimated location of the SL by each method was compared with the location determined by icEEG. Identification rates of the SL were compared between the different methods.RESULTSMSI and EEG-fMRI showed similar identification rates of SL locations in relation to icEEG results (88% ± 31% and 73% ± 42%, respectively; p = 0.281). The additive use of the coverage lobes of both methods correctly identified 100% of the SL, significantly higher than EEG-fMRI alone (p = 0.039) and nonsignificantly higher than MSI (p = 0.180). False-identification rates of the additive coverage lobes were significantly higher than MSI (p = 0.026) and EEG-fMRI (p = 0.027). The intersecting lobes of both methods showed the lowest false identification rate (13% ± 6%, p = 0.01).CONCLUSIONSBoth MSI and EEG-fMRI can assist in the presurgical evaluation of patients with refractory epilepsy. The additive use of both tests confers a high identification rate in finding the SL. This combination can help in focusing implantation of icEEG electrodes targeting the SOZ.

Background Ruminative responding involves repetitive and passive thinking about one's negative affect. This tendency interferes with initiation of goal-directed rewarding strategies, which could alleviate depressive states. Such reward-directed response selection has been shown to be mediated by ventral striatum/nucleus accumbens (VS/NAcc) function. However, to date, no study has examined whether trait rumination relates to VS/NAcc functionality. Here, we tested whether rumination moderates VS/NAcc function both in response to reward and during a ruminative state. Methods Trait rumination was considered dimensionally using Rumination Response Scale (RRS) scores. Our sample (N = 80) consisted of individuals from a community sample and from patients diagnosed with major depressive disorder, providing a broad range of RRS scores. Participants underwent fMRI to assess two modes of VS/NAcc functionality: 1) in response to reward, and 2) during resting-state, as a proxy for ruminative state. We then tested for associations between RRS scores and VS/NAcc functional profiles, statistically controlling for overall depressive symptom severity. Results RRS scores correlated positively with VS/NAcc response to reward. Furthermore, we noted that higher RRS scores were associated with increased ruminative-dependent resting-state functional connectivity of the VS/NAcc with the left orbitofrontal cortex. Conclusions These findings suggest that ruminative tendencies manifest in VS/NAcc reward- and rumination-related functions, providing support for a theoretical-clinical perspective of rumination as a habitual impairment in selection of rewarding, adaptive coping strategies.

Objectives Electroencephalography-correlated functional magnetic resonance imaging (EEG-fMRI) allows imaging of brain-wide epileptic networks, and demonstrates that focal interictal epileptic activity is sometimes accompanied by bilateral functional activations. The corpus callosum (CC) facilitates bilateral spread of epileptic activity and at times targeted surgically for drug-resistant epilepsy (DRE). We hypothesized that focal epileptic networks are more unilateral in patients lacking intact CC. Methods We included focal DRE patients who underwent pre-surgical EEG-fMRI and had CC agenesis (group A, n = 5), patients who previously underwent anterior callosotomy as treatment for drop attacks and continued having seizures (group B, n = 6), and control group of patients with focal epilepsy and intact CC (group C, n = 9). Blood-oxygenation-level-dependent (BOLD) signal maps were generated for interictal epileptic discharges. To quantify bi-hemispheric distribution of epileptic networks, laterality indices were compared between groups. Anatomical and diffusion-weighted imaging demonstrated white matter pathways. Results 96% of studies demonstrated bilateral activations. Laterality indices were similar in groups A and C, whereas group B demonstrated a more bilateral network than group C (p = 0.028). Diffusion-weighted and anatomical imaging showed aberrant white matter pathways and larger anterior commissure in groups A and B. 68% of studies showed maximal activation cluster concordant with the presumed epileptic focus, 28% showed non-maximal activation at presumed focus. Significance Focal epileptic activity is associated with bilateral functional activations despite lack of intact CC, and is associated with stronger contralateral activation in patients after anterior callosotomy compared to controls. These findings disprove our initial hypothesis, and combined with white matter structural imaging, may indicate that the CC is not a sole route of propagation of epileptic activity, which might spread via anterior commissure. Our study demonstrates the utility of EEG-fMRI in assessing epileptic networks and potentially aiding in tailoring surgical treatments in DRE patients with callosal anomalies, and in callosal surgeries.

Objective: Although simultaneous recording of EEG and MRI has gained increasing popularity in recent years, the extent of its clinical use remains limited by various technical challenges. Motion interference is one of the major challenges in EEG-fMRI. Here we present an approach which reduces its impact with the aid of an MR compatible dual-array EEG (daEEG) in which the EEG itself is used both as a brain signal recorder and a motion sensor. Methods: We implemented two arrays of EEG electrodes organized into two sets of nearly orthogonally intersecting wire bundles. The EEG was recorded using referential amplifiers inside a 3 T MR-scanner. Virtual bipolar measurements were taken both along bundles (creating a small wire loop and therefore minimizing artifact) and across bundles (creating a large wire loop and therefore maximizing artifact). Independent component analysis (ICA) was applied. The resulting ICA components were classified into brain signal and noise using three criteria: 1) degree of two-dimensional spatial correlation between ICA coefficients along bundles and across bundles; 2) amplitude along bundles vs. across bundles; 3) correlation with ECG. The components which passed the criteria set were transformed back to the channel space. Motion artifact suppression and the ability to detect interictal epileptic spikes following daEEG and Optimal Basis Set (OBS) procedures were compared in 10 patients with epilepsy. Results: The SNR achieved by daEEG was 11.05 +/- 3.10 and by OBS was 8.25 +/- 1.01 (p

OBJECTIVE Providing a reliable assessment of language lateralization is an important task to be performed prior to neurosurgery in patients with epilepsy. Over the last decade, functional MRI (fMRI) has emerged as a useful noninvasive tool for language lateralization, supplementing or replacing traditional invasive methods. In standard practice, fMRI-based language lateralization is assessed qualitatively by visual inspection of fMRI maps at a specific chosen activation threshold. The purpose of this study was to develop and evaluate a new computational technique for providing the probability of each patient to be left, right, or bilateral dominant in language processing. METHODS In 76 patients with epilepsy, a language lateralization index was calculated using the verb-generation fMRI task over a wide range of activation thresholds (from a permissive threshold, analyzing all brain regions, to a harsh threshold, analyzing only the strongest activations). The data were classified using a probabilistic logistic regression method. RESULTS Concordant results between fMRI and Wada lateralization were observed in 89% of patients. Bilateral and right-dominant groups showed similar fMRI lateralization patterns differentiating them from the left-dominant group but still allowing classification in 82% of patients. CONCLUSIONS These findings present the utility of a semi-supervised probabilistic learning approach for presurgical language-dominance mapping, which may be extended to other cognitive domains such as memory and attention.

EEG-fMRI allows the localization of the hemodynamic correlates of neural activity and has been shown to be useful as a diagnostic tool in pre-surgical evaluation of refractory epilepsy. However, EEG recordings may be highly contaminated by artifacts induced by movements inside the magnetic field thus rendering the scan difficult for interpretation. Existing methods for motion correction require additional equipment or hardware modification. We introduce a simple method for motion artifact detection, the conductive gel bridge sensor (CGBS), easily applicable using the standard setup. We report examples of CGBS use in two patients with epilepsy and demonstrate the method's ability to successfully differentiate between epochs of brain activity and those of movement.

Life requires monitoring and adjusting behavior in the face of conflicts. The conflict monitoring theory implicates the anterior cingulate cortex (ACC) in these processes; its ventral aspect (vACC) specializes in emotional conflict. To elucidate the underpinning neural mechanism, we recorded vACC extracellular activity from 12 patients with mood disorders or epilepsy who performed the face-emotional Stroop task. Behaviorally, both conflict detection and adaptation to conflict were evident. The firing rate of neurons in the vACC represented current conflict, i.e., current-congruency. The late onset of the effect is compatible with a role in monitoring. Additionally, early responses of some neurons represented the immediate history of conflicts, i.e., previous-trial-congruency. Finally, in some neurons the response to the current-trial was modulated by previous-trial-congruency, laying the ground for adjusting-to-conflicts. Our results uncover a single neuron level mechanism in the vACC that encodes and integrates past and present emotional conflicts, allowing humans to accommodate their responses accordingly.

Prior research on the interaction between emotion and episodic memory established that negatively charged events are better remembered compared to neutral events (i.e. enhanced remembrance), as well as that a priori neutral cues that were present in the environment during a negative event can attain aversive meaning by themselves (i.e. acquired negativity). Improved understanding the neural mechanisms that mediate enhanced remembrance of negative episodes and acquired negativity of related neutral cues may carry substantial clinical relevance, particularly in the context of posttraumatic pathophysiology. In order to address this point forty-nine healthy participants completed a novel fMRI task that involve the presentation of neutral pictures before and after a series of short neutral and aversive video-clips from which the neutral pictures were originally extracted, and a subsequent presentation of these pictures as cues for clip recall [termed, Picture-Clip-Picture-Recall (PCPR) task]. Behavioral results indicate that aversive clips were indeed better remembered compared to neutral clips (i.e. enhanced remembrance of negative episode) and that a priori neutral pictures that appeared in aversive clips were rated more negatively after relative to before the exposure to the aversive clips (i.e. acquired negativity of related neutral cues). Whole-brain fMRI analysis revealed that increased amygdala activation in response to pictures when presented as cues for clip recall predicted successful clip remembrance, particularly remembrance of aversive clips. This amygdala activation was also correlated with the magnitude of acquired negativity of the cues following their appearance in aversive clips. Taken together our findings implicate the PCPR as a novel, naturalistic, framework for investigating the neural interface of emotional episodic memory, while highlighting the role of the amygdala in enhanced remembrance of negative episodes and acquired negativity of related neutral cues. Clinical implications are discussed.

OBJECTIVEResection of intraaxial tumors adjacent to the optic radiation (OR) may be associated with postoperative visual field (VF) deficits. Intraoperative navigation using MRI-based tractography and electrophysiological monitoring of the visual pathways may allow maximal resection while preserving visual function. In this study, the authors evaluated the value of visual pathway mapping in a series of patients undergoing awake craniotomy for tumor resection.METHODSA retrospective analysis of prospectively collected data was conducted in 18 patients who underwent an awake craniotomy for resection of intraaxial tumors involving or adjacent to the OR. Preoperative MRI-based tractography was used for intraoperative navigation, and intraoperative acquisition of 3D ultrasonography images was performed for real-time imaging and correction of brain shift. Goggles with light-emitting diodes were used as a standard visual stimulus. Direct cortical visual evoked potential (VEP) recording, subcortical recordings from the OR, and subcortical stimulation of the OR were used intraoperatively to assess visual function and proximity of the lesion to the OR. VFs were assessed pre- and postoperatively.RESULTSBaseline cortical VEP recordings were available for 14 patients (77.7%). No association was found between preoperative VF status and baseline presence of cortical VEPs (p = 0.27). Five of the 14 patients (35.7%) who underwent subcortical stimulation of the OR reported seeing phosphenes in the corresponding contralateral VF. There was a positive correlation (r = 0.899, p = 0.04) between the subcortical threshold stimulation intensity (3–11.5 mA) and the distance from the OR. Subcortical recordings from the OR demonstrated a typical VEP waveform in 10 of the 13 evaluated patients (76.9%). These waveforms were present only when recordings were obtained within 10 mm of the OR (p = 0.04). Seven patients (38.9%) had postoperative VF deterioration, and it was associated with a length of < 8 mm between the tumor and the OR (p = 0.05).CONCLUSIONSIntraoperative electrophysiological monitoring of the visual pathways is feasible but may be of limited value in preserving the functional integrity of the posterior visual pathways. Subcortical stimulation of the OR may identify the location of the OR when done in proximity to the pathways, but such proximity may be associated with increased risk of postoperative worsening of the VF deficit.

Invasive brain–computer interfaces (BCI) provide better signal quality in terms of spatial localization, frequencies and signal/noise ratio, in addition to giving access to deep brain regions that play important roles in cognitive or affective processes. Despite some anecdotal attempts, little work has explored the possibility of integrating such BCI input into more sophisticated interactive systems like those which can be developed with game engines. In this article, we integrated an amygdala depth electrode recorder with a virtual environment controlling a virtual crowd. Subjects were asked to down regulate their amygdala using the level of unrest in the virtual room as feedback on how successful they were. We report early results which suggest that users adapt very easily to this paradigm and that the timing and fluctuations of amygdala activity during self-regulation can be matched by crowd animation in the virtual room. This suggests that depth electrodes could also serve as high-performance affective interfaces, notwithstanding their strictly limited availability, justified on medical grounds only.

Direct cortical stimulation (DCS) is considered the gold-standard for functional cortical mapping during awake surgery for brain tumor resection. DCS is performed by stimulating one local cortical area at a time. We present a feasibility study using an intra-operative technique aimed at improving our ability to map brain functions which rely on activity in distributed cortical regions. Following standard DCS, Multi-Site Stimulation (MSS) was performed in 15 patients by applying simultaneous cortical stimulations at multiple locations. Language functioning was chosen as a case-cognitive domain due to its relatively well-known cortical organization. MSS, performed at sites that did not produce disruption when applied in a single stimulation point, revealed additional language dysfunction in 73% of the patients. Functional regions identified by this technique were presumed to be significant to language circuitry and were spared during surgery. No new neurological deficits were observed in any of the patients following surgery. Though the neuro-electrical effects of MSS need further investigation, this feasibility study may provide a first step towards sophistication of intra-operative cortical mapping.

Head movements during an MEG recording are commonly considered an obstacle. In this computer simulation study, we introduce an approach, the virtual MEG helmet (VMH), which employs the head movements for data quality improvement. With a VMH, a denser MEG helmet is constructed by adding new sensors corresponding to different head positions. Based on the Shannon's theory of communication, we calculated the total information as a figure of merit for comparing the actual 306-sensor Elekta Neuromag helmet to several types of the VMH. As source models, we used simulated randomly distributed source current (RDSC), simulated auditory and somatosensory evoked fields. Using the RDSC model with the simulation of 360 recorded events, the total information (bits/sample) was 989 for the most informative single head position and up to 1272 for the VMH (addition of 28.6%). Using simulated AEFs, the additional contribution of a VMH was 12.6% and using simulated SEF only 1.1%. For the distributed and bilateral sources, a VMH can provide a more informative sampling of the neuromagnetic field during the same recording time than measuring the MEG from one head position. VMH can, in some situations, improve source localization of the neuromagnetic fields related to the normal and pathological brain activity. This should be investigated further employing real MEG recordings.