Regression of all untreated lesions in multifocal low-grade meningioma following fractionated stereotactic radiotherapy-abscopal effect or spontaneous regression? : Case report and review of the literature.

PURPOSE: Abscopal effects have been reported predominantly in metastatic cancers, indicating a radiographic response in a lesion that has not been included in the radiotherapy target volume. The response is interpreted as a humoral immune response to radiotherapy-generated tumour-specific antigens. In this case study, we present the first histologically confirmed multifocal low-grade meningioma with spontaneous regression of all other lesions after conventionally fractionated stereotactic radiotherapy (RT). CASE REPORT: Two localisations, right frontal and right spheno-orbital, were resected at the time of the initial diagnosis in a 66-year-old woman. RT was performed 1 year later to a progressive occipital lesion at the cerebral falx. RESULTS: Regular magnetic resonance imaging (MRI) showed slightly decreasing tumour volume in untreated lesions 1 year after RT and continued during further follow-up. Up to > 7 years after treatment, MRI demonstrated an almost complete response of all initial lesions. Two prior reports with meningioma were published in one patient with an atypical meningioma after conventionally fractionated RT and another patient with an intracranial meningiomatosis after radiosurgery. CONCLUSION: This case study supports the concepts of treating only progressive or symptomatic meningioma lesions locally and careful regular MRI surveillance for further assessment. Potential active interventions to trigger an abscopal effect are currently not known. Further research of this beneficial effect for our patients should be supported.

Correction: Representation of abstract semantic knowledge in populations of human single neurons in the medial temporal lobe.

[This corrects the article DOI: 10.1371/journal.pbio.3000290.].

Anesthesia-induced loss of consciousness disrupts auditory responses beyond primary cortex.

Despite its ubiquitous use in medicine, and extensive knowledge of its molecular and cellular effects, how anesthesia induces loss of consciousness (LOC) and affects sensory processing remains poorly understood. Specifically, it is unclear whether anesthesia primarily disrupts thalamocortical relay or intercortical signaling. Here we recorded intracranial electroencephalogram (iEEG), local field potentials (LFPs), and single-unit activity in patients during wakefulness and light anesthesia. Propofol infusion was gradually increased while auditory stimuli were presented and patients responded to a target stimulus until they became unresponsive. We found widespread iEEG responses in association cortices during wakefulness, which were attenuated and restricted to auditory regions upon LOC. Neuronal spiking and LFP responses in primary auditory cortex (PAC) persisted after LOC, while responses in higher-order auditory regions were variable, with neuronal spiking largely attenuated. Gamma power induced by word stimuli increased after LOC while its frequency profile slowed, thus differing from local spiking activity. In summary, anesthesia-induced LOC disrupts auditory processing in association cortices while relatively sparing responses in PAC, opening new avenues for future research into mechanisms of LOC and the design of anesthetic monitoring devices.

Representation of abstract semantic knowledge in populations of human single neurons in the medial temporal lobe.

Sensory experience elicits complex activity patterns throughout the neocortex. Projections from the neocortex converge onto the medial temporal lobe (MTL), in which distributed neocortical firing patterns are distilled into sparse representations. The precise nature of these neuronal representations is still unknown. Here, we show that population activity patterns in the MTL are governed by high levels of semantic abstraction. We recorded human single-unit activity in the MTL (4,917 units, 25 patients) while subjects viewed 100 images grouped into 10 semantic categories of 10 exemplars each. High levels of semantic abstraction were indicated by representational similarity analyses (RSAs) of patterns elicited by individual stimuli. Moreover, pattern classifiers trained to decode semantic categories generalised successfully to unseen exemplars, and classifiers trained to decode exemplar identity more often confused exemplars of the same versus different categories. Semantic abstraction and generalisation may thus be key to efficiently distill the essence of an experience into sparse representations in the human MTL. Although semantic abstraction is efficient and may facilitate generalisation of knowledge to novel situations, it comes at the cost of a loss of detail and may be central to the generation of false memories.

[Surgical treatment and radiation therapy of brain metastases]. / Chirurgische Behandlung und Strahlentherapie von Hirnmetastasen.

The aim of this work is to outline the principles of interdisciplinary treatment of brain metastases. Interdisciplinary treatment is determined by the clinical situation, anatomical conditions and tumor entity and has the goal of reducing toxicity. Magnetic resonance imaging, computed tomography (CT) and positron emission tomography-CT are used to diagnose brain metastases. Neurosurgery is used for accessible, symptomatic metastases. For localized metastases, including multiple metastases, that are surgically inaccessible, radiosurgery is used. If possible, partial brain irradiation is preferred to whole-brain irradiation. Protection of the hippocampus during whole-brain radiotherapy reduces therapy toxicity. In emergency situations, steroids provide effective support and a neurosurgical intervention may be life-saving. The options for systemic drug therapy are increasing.

The impact of MRI steady-state sequences as an additional assessment modality in vestibular schwannoma patients after LINAC stereotactic radiotherapy or radiosurgery.

PURPOSE: Data concerning the clinical usefulness of steady-state sequences (SSS) for vestibular schwannomas (VS) after linear accelerator (LINAC) stereotactic radiosurgery (SRS) or stereotactic radiotherapy (SRT) are scarce. The aim of the study was to investigate whether SSS provide an additional useful follow-up (FU) tool to the established thin-layered T1 sequences with contrast enhancement. METHODS: Pre- and post-treatment SSS were identified in 45 consecutive VS patients (2012-2016) with a standardized FU protocol including SSS at 2-3 months and 6 months/yearly in our prospective database and were retrospectively re-evaluated. The SSS were used throughout for the segmentation of the cochlea and partly of the trigeminal nerve in the treatment planning. Data analysis included signal conversion in SSS and possible correlation with neuro-otological outcome and volumetric assessment after a certain time interval. RESULTS: The series included 42 SRS and 3 SRT patients (31 female/14 male; mean age 59.3 years, range: 25-81 years). An SSS signal conversion was observed in 20 tumors (44.4%) within a mean time of 11 months (range: 7-15 months). Mean FU time was 26 months (median of 4 FU visits) and demonstrated tumor volume shrinkage in 29 cases (64.4%) correlating with FU time (p = 0.07). The incidence rate of combined shrinkage and signal conversion (48.3%) compared to those without signal conversion (51.7%) did not differ significantly (p = 0.49). In case of an early signal conversion at the first FU, a weak statistical significance (p = 0.05) for a higher shrinkage rate of VS with signal conversion was found. Side effects in cases with signal conversion (9/20, 45%) were more frequently than without signal conversion (6/25, 24%) without reaching statistical significance (p = 0.13). CONCLUSION: Our data confirmed the usefulness of SSS for anatomical segmentation of VS in LINAC-SRS/SRT treatment planning and add data supporting their potential as an adjunctive FU option in VS patients.

Extended Long-Term Effects of Cervical Vagal Nerve Stimulation on Headache Intensity/Frequency and Affective/Cognitive Headache Perception in Drug Resistant Complex-Partial Seizure Patients.

OBJECTIVES: Invasive vagal nerve stimulation (iVNS) is an established treatment option for drug-resistant focal seizures and has been assumed to diminish frequent co-incidental daily headache/migraine. However, long-term effects on cognitive/affective head pain perception, headache intensity/frequency are lacking. We therefore investigated potential iVNS-induced effects in patients with drug-resistant focal seizure and daily headache/migraine. MATERIALS AND METHODS: A clinical database was used to select 325 patients with drug-resistant epilepsy treated by either iVNS plus best medical treatment (BMT) or BMT alone, compared to a healthy control group (HC). We assessed headache intensity (VAS), headache frequency, affective/cognitive pain perception (PASS; FSVA), migraine disability scores (MIDAS), sleep architecture (PSQI), depressive symptoms (BDI), and body weight (BMI). RESULTS: Nineteen patients with daily headache/migraine composed the clinical groups (10 iVNS and 9 BMT; iVNS mean age 49 years, range 36-61 years; BMT mean age 45 years, range 23-63 years; equally distributed gender). Cervical iVNS was applied from 5-13 years (mean 8 years) with following stimulation patterns: 1.3 mA (0.5-2 mA), 20 Hz, 250 µsec, 30 sec on/1.9 min off (0.5-5 min). The iVNS group had significantly lower VAS scores (iVNS 5.4; BMT 7.8; p = 0.03) and PASS cognitive/anxiety subscores (iVNS 21; BMT 16; p = 0.02) compared to BMT and HC. Global PASS (p = 0.07), FSVA, PSQI, BDI, and BMI scores did not differ significantly between groups. CONCLUSIONS: iVNS appears to have positive modulatory long-term effects on headache and affective/cognitive head pain perception in patients with drug-resistant focal epilepsy, thus deserving further attention.

Molecular classification of diffuse cerebral WHO grade II/III gliomas using genome- and transcriptome-wide profiling improves stratification of prognostically distinct patient groups.

Cerebral gliomas of World Health Organization (WHO) grade II and III represent a major challenge in terms of histological classification and clinical management. Here, we asked whether large-scale genomic and transcriptomic profiling improves the definition of prognostically distinct entities. We performed microarray-based genome- and transcriptome-wide analyses of primary tumor samples from a prospective German Glioma Network cohort of 137 patients with cerebral gliomas, including 61 WHO grade II and 76 WHO grade III tumors. Integrative bioinformatic analyses were employed to define molecular subgroups, which were then related to histology, molecular biomarkers, including isocitrate dehydrogenase 1 or 2 (IDH1/2) mutation, 1p/19q co-deletion and telomerase reverse transcriptase (TERT) promoter mutations, and patient outcome. Genomic profiling identified five distinct glioma groups, including three IDH1/2 mutant and two IDH1/2 wild-type groups. Expression profiling revealed evidence for eight transcriptionally different groups (five IDH1/2 mutant, three IDH1/2 wild type), which were only partially linked to the genomic groups. Correlation of DNA-based molecular stratification with clinical outcome allowed to define three major prognostic groups with characteristic genomic aberrations. The best prognosis was found in patients with IDH1/2 mutant and 1p/19q co-deleted tumors. Patients with IDH1/2 wild-type gliomas and glioblastoma-like genomic alterations, including gain on chromosome arm 7q (+7q), loss on chromosome arm 10q (-10q), TERT promoter mutation and oncogene amplification, displayed the worst outcome. Intermediate survival was seen in patients with IDH1/2 mutant, but 1p/19q intact, mostly astrocytic gliomas, and in patients with IDH1/2 wild-type gliomas lacking the +7q/-10q genotype and TERT promoter mutation. This molecular subgrouping stratified patients into prognostically distinct groups better than histological classification. Addition of gene expression data to this genomic classifier did not further improve prognostic stratification. In summary, DNA-based molecular profiling of WHO grade II and III gliomas distinguishes biologically distinct tumor groups and provides prognostically relevant information beyond histological classification as well as IDH1/2 mutation and 1p/19q co-deletion status.

Treatment of acromegaly patients with risk-adapted single or fractionated stereotactic high-precision radiotherapy: High local control and low toxicity in a pooled series.

PURPOSE: The purpose of this work was to evaluate a prospectively initiated two-center protocol of risk-adapted stereotactic radiosurgery (SRS) or stereotactic radiotherapy (SRT) in patients with acromegaly. PATIENTS AND METHODS: In total 35 patients (16 men/19 women, mean age 54 years) were prospectively included in a treatment protocol of SRS [planning target volume (PTV < 4 ccm, > 2 mm to optic pathways = low risk] or SRT (PTV ≥ 4 ccm, ≤ 2 mm to optic pathways = high risk). The mean tumor volume was 3.71 ccm (range: 0.11-22.10 ccm). Based on the protocol guidelines, 21 patients were treated with SRS and 12 patients with SRT, 2 patients received both consecutively. RESULTS: The median follow-up (FU) reached 8 years with a 5-year overall survival (OS) of 87.3% [confidence interval (CI): 70.8-95.6%] and 5-year local control rate of 97.1% (CI: 83.4-99.8%). Almost 80% (28/35) presented tumor shrinkage during FU. Endocrinological cure was achieved in 23% and IGF-1 normalization with reduced medication was achieved in 40% of all patients. An endocrinological response was generally achieved within the first 3 years, but endocrinological cure can require more than 8 years. A new adrenocorticotropic hypopituitarism occurred in 13 patients (46.4%). A new visual field disorder and a new oculomotor palsy occurred in 1 patient, respectively. Patients with occurrence of visual/neurological impairments had a longer FU (p = 0.049). CONCLUSION: Our SRS/SRT protocol proved to be safe and successful in terms of tumor control and protection of the visual system. The timing and rate of endocrine improvements are difficult to predict. One has to accept an unavoidable rate of additional adrenocorticotropic hypopituitarism in the long term.

Risk-adapted single or fractionated stereotactic high-precision radiotherapy in a pooled series of nonfunctioning pituitary adenomas: high local control and low toxicity.

PURPOSE: The purpose of this work was to evaluate a prospectively initiated two-center protocol of risk-adapted single-fraction (SRS) or fractionated radiotherapy (SRT) in patients with nonsecretory pituitary adenomas (NSA). PATIENTS AND METHODS: A total of 73 NSA patients (39 men/34 women) with a median age of 62 years were prospectively included in a treatment protocol of SRS [planning target volume (PTV) < 4 ccm, > 2 mm to optic pathways = low risk] or SRT (PTV ≥ 4 ccm, ≤ 2 mm to optic pathways = high risk) in two Novalis® centers. Mean tumor volume was 7.02 ccm (range 0.58-57.29 ccm). Based on the protocol guidelines, 5 patients were treated with SRS and 68 patients with SRT. RESULTS: Median follow-up (FU) reached 5 years with 5-year overall survival (OS) of 90.4 % (CI 80.2-95 %) and 5-year local control and progression-free survival rates of 100 % (CI 93.3-100 %) and 90.4 % (CI 80.2-95 %), respectively. A post-SRS/SRT new visual disorder occurred in 2 patients (2.7 %), a new oculomotor nerve palsy in one pre-irradiated patient, in 3 patients (4.1 %) a pre-existing visual disorder improved. New complete hypopituitarism occurred in 4 patients (13.8 %) and in 3 patients (25 %) with pre-existing partial hypopituitarism. Pituitary function in 26 % of patients retained normal. Patients with tumor shrinkage (65.75 %) had a significantly longer FU (p = 0.0093). Multivariate analysis confirmed correlation of new hypopituitarism with duration of FU (p = 0.008) and correlation of new hypopituitarism and tumor volume (p = 0.023). No significant influence factors for occurrence of visual disorders were found. CONCLUSION: Our SRS/SRT protocol proved to be safe and successful in terms of tumor control and protection of the visual system, especially for large tumors located close to optic pathways.

Pain Relief-Related Structural Brain Alterations in Trigeminal Neuralgia Induced by Noninvasive Stereotactic Radiosurgery: A Pilot Study.

PURPOSE: Trigeminal neuralgia (TN) is a chronic pain disorder defined by unilateral shock-like pain in at least one division of the trigeminal nerve. Although several studies have investigated structural brain plasticity in patients with TN, treatment-induced alterations remain largely uninvestigated. METHODS AND MATERIALS: Combining T1-weighted magnetic resonance imaging with voxel-based morphometry and multiple-regression analyses, we assessed gray matter maps of patients with TN to investigate changes in gray matter volume (GMV) before and 6 months after stereotactic radiosurgery (SRS). RESULTS: Comparison of pre- and post-SRS GMV of 25 patients with TN (16 women; mean age 67 years) did not yield any significant clusters, suggesting that the effect of SRS intervention itself on gray matter structure may be negligible. Regarding SRS-induced pain relief, we found a significant GMV increase in the left superior frontal gyrus associated with greater degree of pain relief (P = .024) and a trend toward an increase in GMV in the left dorsolateral prefrontal cortex (P = .097). CONCLUSIONS: In this pilot study, we observed significant increases in GMV in the left superior frontal gyrus with SRS-induced improvements in pain and a trend toward an increase in GMV in the dorsolateral prefrontal cortex. Future studies are indicated to validate these findings and determine whether SRS-induced decrease in distracting pain events and subsequent increases in GMV result in improved functionality, decreased dependence on "top-down" control, and improved cognitive/executive balance with amelioration of pain events.

FLAIR-only progression in bevacizumab-treated relapsing glioblastoma does not predict short survival.

OBJECTIVES: In this study, we analyzed the prognostic value of different MRI progression patterns for survival in patients with recurrent malignant glioma treated with the vascular endothelial growth factor antibody bevacizumab. PATIENTS AND METHODS: Twenty-six adult patients with recurrent malignant glioma treated with bevacizumab or bevacizumab/irinotecan were retrospectively analyzed for the development of contrast-enhanced (T1-weighted MRI) and T2/FLAIR lesions. According to the progression pattern, patients were divided into 3 subgroups: (1) patients with primarily progressive contrast-enhanced lesions in the first MRI after initiation of therapy ('primary PD group'); (2) patients with stable or regressive enhanced lesions but progressive FLAIR lesions ('FLAIR-only PD group'), and (3) patients with stable or regressive contrast-enhanced T1 and FLAIR lesions ('no PD group'). RESULTS: Overall survival (OS) in the 6 patients in the FLAIR-only PD group was not significantly different from the 11 patients in the no PD group (median 311 vs. 254 days, respectively). In contrast, survival in the FLAIR-only PD group was significantly better (p = 0.025) than in the primary PD group. CONCLUSION: FLAIR-only progression is not an independent prognostic factor negatively influencing OS in recurrent glioblastoma treated with bevacizumab and should not lead to discontinuation of bevacizumab therapy.

Evaluation of a New Inverse, Globally Convex Treatment Planning System Algorithm for Gamma Knife Radiation Surgery Within a Prospective Trial: Advantages and Disadvantages in Practical Application.

Purpose: A new inverse planning software called IntuitivePlan (IP) based on a global convex optimization algorithm was adopted for the Gamma Knife radiation surgery. We investigated IP's suitability for daily clinical use and its applicability for different cerebral entities. Methods and Materials: For 230 target volumes, IP was tested in a prospective trial. The computed treatment plans were compared with conventional expert preplans, which included forward planning by the expert and local internal optimization. Based on the same dose constraints, we used the default settings for the inverse calculation of the treatment plans. Plan quality metrics such as the Paddick conformity index were compared for both planning techniques with additional subdivisions into the 3 selectable IP planning strategies and different entity groups. Results: IP calculated treatment plans of quality similar to that of preplans created by expert planners. Some plan quality metrics, especially those related to conformity and dose gradient, attained statistically significantly higher scores combined with high coverage for the inversely generated plans except for the selectivity optimizing strategy. Normal brain volume receiving 10 Gy or 12 Gy or higher (V 1 0 Gy or V 1 2 Gy ) did not show significant differences for the coverage optimizing strategies. The IP software demonstrated significantly shorter planning times versus manual planning as well as greater numbers of isocenters, often associated with longer treatment times. In terms of total time, these differences almost balanced out again. Conclusions: Our results suggest that IP is advantageous for complex tumors. We observed general clinical significance for conformity and superiority for the selectivity optimizing strategy. In addition, the high-quality calculation from IP enables novices in the profession to achieve pre-treatment plans of a quality similar to that of expert planners. IP allows for optimizing the sparing of surrounding tissue and conformity for benign tumors within a short time. Thus, IP forms a solid basis for further planning on the treatment day.

Neuronal codes for arithmetic rule processing in the human brain.

Arithmetic is a cornerstone of scientifically and technologically advanced human culture, but its neuronal mechanisms are poorly understood. Calculating with numbers requires temporary maintenance and manipulation of numerical information according to arithmetic rules. We explored the brain mechanisms involved in simple arithmetic operations by recording single-neuron activity from the medial temporal lobe of human subjects performing additions and subtractions. We found abstract and notation-independent codes for addition and subtraction in neuronal populations. The neuronal codes of arithmetic in different brain areas differed drastically. Decoders applied to time-resolved recordings demonstrate a static code in hippocampus based on persistently rule-selective neurons, in contrast to a dynamic code in parahippocampal cortex originating from neurons carrying rapidly changing rule information. The implementation of abstract arithmetic codes suggests different cognitive functions for medial temporal lobe regions in arithmetic.

Single-fraction stereotactic radiosurgery versus microsurgical resection for the treatment of vestibular schwannoma: a systematic review and meta-analysis.

BACKGROUND: Vestibular schwannomas are benign tumours for which various treatments are available. We performed a systematic review of prospective controlled trials comparing the patient-relevant benefits and harms of single-fraction stereotactic radiosurgery (sfSRS) with microsurgical resection (MR) in patients with vestibular schwannoma. METHODS: We searched for randomized controlled trials (RCTs) and non-randomized prospective controlled trials in MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and study registries (last search: 09/2021) and also screened reference lists of relevant systematic reviews. Manufacturers were asked to provide unpublished data. Eligible studies investigated at least one patient-relevant outcome. We assessed the risk of bias (high or low) at the study and outcome level. If feasible, meta-analyses were performed. We graded the results into different categories (hint, indication, or proof of greater benefit or harm). RESULTS: We identified three non-randomized prospective controlled trials of generally low quality with evaluable data on 339 patients with unilateral vestibular schwannoma. There was an indication of greater benefit of sfSRS compared with MR for facial palsy (OR 0.06, 95% CI 0.02-0.21, p < 0.001, 2 studies), hearing function (no pooled estimate available, 2 studies), and length of hospital stay (no pooled estimate available, 2 studies). We found no clinically relevant differences for mortality, vertigo, headaches, tinnitus, balance function, work disability, adverse events, and health-related quality of life. CONCLUSIONS: Our systematic review indicates that sfSRS has greater benefits than MR in patients with unilateral vestibular schwannoma. However, it is unclear whether this conclusion still holds after 2 years, as long-term studies are lacking. It is also unclear whether the effects of sfSRS are similar in patients with bilateral vestibular schwannomas. Long-term prospective studies including patients with this condition would therefore be useful. SYSTEMATIC REVIEW REGISTRATION: The full (German language) protocol and report (Commission No. N20-03) are available on the institute's website: www.iqwig.de/en/projects/n20-03.html.

Surgical treatment of choroid plexus tumors.

PURPOSE: The purpose of this study is to evaluate the results of microsurgical treatment for choroid plexus tumors (CPT) in adult patients. METHODS: From 1990 to 2008, 14 patients >18 years were treated at our institution for CPT, including seven males and seven females with a mean age of 46 years. Mean follow-up was 40 months. We reviewed the respective patients' charts, operative, and follow-up notes. Telephone interviews were performed as necessary. Neurological status was determined using the Karnofsky performance index pre- and post-operatively and at last follow-up. RESULTS: This series includes 12 plexus papillomas (CPP) and two atypical plexus papillomas (APP). Ten tumors were located in the fourth ventricle, two tumors in the cerebellopontine angle, one growth each in the third and lateral ventricle. In 12 cases, a complete tumor resection was achieved. No recurrence was observed in these cases. Two recurrent CPP were diagnosed 11 and 25 years after the initial surgery. Brain stem infiltration prevented a complete tumor removal in one case. In the other, the degree of resection after the first operation could not be ascertained. None of the patients received adjuvant chemo- or radiotherapy. In four patients (29%), a permanent ventricular-peritoneal shunt was necessary. Three patients initially presented with a Karnofsky index of 60 or below. During follow-up, three patients (21%) never improved beyond a Karnofsky index of 60. CONCLUSIONS: Surgery aiming radical excision is the key to successful treatment of CPP and APP in adults. Postoperative outcomes may be less than satisfactory in some patients.

Prognostic Factors for Functional Outcome of Patients with Optic Nerve Sheath Meningiomas Treated with Stereotactic Radiotherapy-Evaluation of Own and Meta-Analysis of Published Data.

OBJECTIVE: To evaluate prognostic factors for a favorable outcome (improvement of the visual acuity or visual fields) after fractionated stereotactic radiotherapy (fSRT) of optic nerve sheath meningioma (ONSM). METHODS: We performed a database search for ONSM treatments during the period from April 2008 to September 2019 in the prospective database for stereotactic radiosurgery/radiotherapy (SRS/SRT) of the Robert Janker Clinic Bonn (Department of Radiotherapy) and performed a literature review and meta-analysis of published data on ONSM between 2010 and 2019. Ophthalmic status before and after treatment was evaluated and the collective was dichotomized into two groups: functional improvement (FI; improvement of either visual acuity or visual fields) and non functional improvement (NFI; with stable or deteriorating visual acuity or visual fields). The two groups were compared regarding different variables: pretreatment visual acuity, age, gender, gross tumor volume (GTV), follow up (FU) time, tumor localization, and maximal retina dose. RESULTS: Overall, 13 stereotactic radiotherapies were performed for ONSM (12 × fSRT, 1 × SRS). Mean follow up was 3 years (range: 1-5 years). The total dose was 50.4 Gy (5 × 1.8 Gy/week) in 12 patients treated with fSRT and 1 × 14 Gy in one SRS case. Mean GTV was 1.13 ccm (range: 0.44-2.20 ccm). During follow up, all tumors were stable or showed shrinkage of tumor volume (100% tumor control), no adverse events were observed, 53% of the patients achieved either better visual acuity or visual fields. Pretreatment visual acuity was significantly different between the FI and the NFI group (0.17 vs. 0.63, p = 0.03) in our series and in the meta analysis (p < 0.01). Moreover, shorter FU time and lower retinal dose were significantly linked (p < 0.05 and p < 0.01, respectively) with a better outcome in the meta-analysis but not in our patient cohort. Intracranial tumor localization, gender, and age were not significantly different between the two outcome groups. CONCLUSION: FSRT for ONSM achieves in over 50% of cases an improvement of the ophthalmic status with low morbidity and excellent tumor control in our series and the meta analysis. Patients with a favorable outcome had in all analysis a significantly higher visual acuity before treatment start. Therefore, we advocate using fSRT as early as possible before vision deterioration occurs.

Concept neurons in the human medial temporal lobe flexibly represent abstract relations between concepts.

Concept neurons in the medial temporal lobe respond to semantic features of presented stimuli. Analyzing 61 concept neurons recorded from twelve patients who underwent surgery to treat epilepsy, we show that firing patterns of concept neurons encode relations between concepts during a picture comparison task. Thirty-three of these responded to non-preferred stimuli with a delayed but well-defined onset whenever the task required a comparison to a response-eliciting concept, but not otherwise. Supporting recent theories of working memory, concept neurons increased firing whenever attention was directed towards this concept and could be reactivated after complete activity silence. Population cross-correlations of pairs of concept neurons exhibited order-dependent asymmetric peaks specifically when their response-eliciting concepts were to be compared. Our data are consistent with synaptic mechanisms that support reinstatement of concepts and their relations after activity silence, flexibly induced through task-specific sequential activation. This way arbitrary contents of experience could become interconnected in both working and long-term memory.

Headache Perception in an Epilepsy Patient with Neuromodulation by Anterior Thalamic Nuclei Deep Brain Stimulation: A Case Report.

OBJECTIVE: Headache disorders are frequently associated with epilepsy. Some neuromodulation techniques for refractory epilepsy have been reported to positively influence the associated chronic headache. However, the exact mechanism of action of vagus nerve stimulation (VNS) and anterior thalamic nuclei-deep brain stimulation (ANT-DBS) on pain perception is unclear. METHOD: We report a structured assessment of pain perception in a patient who experienced headache relief after ANT-DBS for refractory focal epilepsy and compare it with pain perception of epilepsy patients with chronic headache who were treated with and without VNS. RESULTS: The pain-associated symptoms in the ANT-DBS case were on the Pain Anxiety Symptoms Scale (PASS-40) subscore "physiological anxiety" closer to the control collective, whereas in patients with VNS, this was more likely for the PASS-40 subscores "cognitive anxiety" or "escape and avoidance." CONCLUSION: ANT-DBS and VNS may influence epilepsy-associated chronic headache in different ways.

Single-Neuron Correlates of Decision Confidence in the Human Medial Temporal Lobe.

The human medial temporal lobe (MTL) has been suggested to play a role in valuation. However, little is known about its role in binary decisions and metacognition. We performed two decision-making tasks while recording from neurons in the human MTL. During a break, subjects consumed their preferred food item to satiation and subsequently repeated both tasks. We identified both a persistent and a transient modulation of the neural activity. Two independent subpopulations of neurons showed a persistent correlation of their firing rates with either decision confidence or reaction times. Importantly, the changes in confidence and reaction time between experimental sets were accompanied by a correlated change in the neural activity, and this correlation lasted as long as it was relevant for the behavioral task. Previous studies have suggested a transient modulation of the neural activity in the human MTL correlated with subjective value. However, in our study, neither subjective value nor unsigned value could explain this transient activity better than the nutritional features of the stimuli, calling into question the role of the human MTL in valuation.