Olfaction is a fundamental sensory modality that guides animal and human behaviour1,2. However, the underlying neural processes of human olfaction are still poorly understood at the fundamental—that is, the single-neuron—level. Here we report recordings of single-neuron activity in the piriform cortex and medial temporal lobe in awake humans performing an odour rating and identification task. We identified odour-modulated neurons within the piriform cortex, amygdala, entorhinal cortex and hippocampus. In each of these regions, neuronal firing accurately encodes odour identity. Notably, repeated odour presentations reduce response firing rates, demonstrating central repetition suppression and habituation. Different medial temporal lobe regions have distinct roles in odour processing, with amygdala neurons encoding subjective odour valence, and hippocampal neurons predicting behavioural odour identification performance. Whereas piriform neurons preferably encode chemical odour identity, hippocampal activity reflects subjective odour perception. Critically, we identify that piriform cortex neurons reliably encode odour-related images, supporting a multimodal role of the human piriform cortex. We also observe marked cross-modal coding of both odours and images, especially in the amygdala and piriform cortex. Moreover, we identify neurons that respond to semantically coherent odour and image information, demonstrating conceptual coding schemes in olfaction. Our results bridge the long-standing gap between animal models and non-invasive human studies and advance our understanding of odour processing in the human brain by identifying neuronal odour-coding principles, regional functional differences and cross-modal integration.
Focal cortical dysplasias (FCDs) are malformations of cortical development and one of the most common pathologies causing pharmacoresistant focal epilepsy. Resective neurosurgery yields high success rates, especially if the full extent of the lesion is correctly identified and completely removed. The visual assessment of magnetic resonance imaging does not pinpoint the FCD in 30%–50% of cases, and half of all patients with FCD are not amenable to epilepsy surgery, partly because the FCD could not be sufficiently localized. Computational approaches to FCD detection are an active area of research, benefitting from advancements in computer vision. Automatic FCD detection is a significant challenge and one of the first clinical grounds where the application of artificial intelligence may translate into an advance for patients' health. The emergence of new methods from the combination of health and computer sciences creates novel challenges. Imaging data need to be organized into structured, well‐annotated datasets and combined with other clinical information, such as histopathological subtypes or neuroimaging characteristics. Algorithmic output, that is, model prediction, requires a technically correct evaluation with adequate metrics that are understandable and usable for clinicians. Publication of code and data is necessary to make research accessible and reproducible. This critical review introduces the field of automatic FCD detection, explaining underlying medical and technical concepts, highlighting its challenges and current limitations, and providing a perspective for a novel research environment.
2 December 2020 in Annals of Clinical and Translational Neurology
Objective: Transsylvian selective amygdalo‐hippocampectomy (tsSAHE) represents a generally recognized surgical procedure for drug‐resistant mesial temporal lobe epilepsy (mTLE). Although postoperative seizure freedom can be achieved in about 70% of tsSAHE, there is a considerable amount of patients with persisting postoperative seizures. This might partly be explained by differing extents of resection of various tsSAHE target volumes. In this study we analyzed the resected proportions of hippocampus, amygdala as well as piriform cortex in regard of postoperative seizure outcome.Methods: Between 2012 and 2017, 82 of 103 patients with mTLE who underwent tsSAHE at the authors’ institution were included in the analysis. Resected proportions of hippocampus, amygdala and temporal piriform cortex as target structures of tsSAHE were volumetrically assessed and stratified according to favorable (International League Against Epilepsy (ILAE) class 1) and unfavorable (ILAE class 2–6) seizure outcome.Results: Patients with favorable seizure outcome revealed a significantly larger proportion of resected temporal piriform cortex volumes compared to patients with unfavorable seizure outcome (median resected proportional volumes were 51% (IQR 42–61) versus (vs.) 13 (IQR 11–18), P = 0.0001). Resected proportions of hippocampus and amygdala did not significantly differ for these groups (hippocampus: 81% (IQR 73–88) vs. 80% (IQR 74–92) (P = 0.7); amygdala: 100% (IQR 100–100) vs. 100% (IQR 100–100) (P = 0.7)).Interpretation: These results strongly suggest temporal piriform cortex to constitute a key target resection volume to achieve seizure freedom following tsSAHE.
Introduction: The postoperative seizure freedom represents an important secondary outcome measure in glioblastoma surgery. Recently, supra-total glioblastoma resection in terms of anterior temporal lobectomy (ATL) has gained growing attention with regard to superior long-term disease control for temporal-located glioblastoma compared to conventional gross-total resections (GTR). However, the impact of ATL on seizure outcome in these patients is unknown. We therefore analyzed ATL and GTR as differing extents of resection in regard of postoperative seizure control in patients with temporal glioblastoma and preoperative symptomatic seizures. Methods: Between 2012 and 2018, 33 patients with preoperative seizures underwent GTR or ATL for temporal glioblastoma at the authors’ institution. Seizure outcome was assessed postoperatively and 6 months after tumor resection according to the International League Against Epilepsy (ILAE) classification and stratified into favorable (ILAE class 1) versus unfavorable (ILAE class 2–6). Results: Overall, 23 out of 33 patients (70%) with preoperative seizures achieved favorable seizure outcome following resection of temporal located glioblastoma. For the ATL group, postoperative seizure freedom was present in 13 out of 13 patients (100%). In comparison, respective rates for the GTR group were 10 out of 20 patients (50%) (p = 0.002; OR 27; 95% CI 1.4–515.9). Conclusions: ATL in terms of a supra-total resection strategy was associated with superior favorable seizure outcome following temporal glioblastoma resection compared to GTR. Regarding above mentioned survival benefit following ATL compared to GTR, ATL as an aggressive supra-total resection regime might constitute the surgical modality of choice for temporal-located glioblastoma.
Objective: Medial temporal lobe epilepsy (MTLE) is a drug‐resistant focal epilepsy that can be caused by a broad spectrum of different inciting events, including tumors, febrile seizures, and viral infections. In human epilepsy surgical resections as well as in animal models, an involvement of the adaptive immune system was observed. We here analyzed the presence of T cells in various subgroups of MTLE. We aimed to answer the question of how much inflammation was present and whether the presence of T cells was associated with seizures or associated with hippocampal neurodegeneration.Methods: We quantified the numbers of CD3+ T cells and CD8+ cytotoxic T cells in the hippocampus of patients with gangliogliomas (GGs; intrahippocampal and extrahippocampal, with and without sclerosis), febrile seizures, and postinfectious encephalitic epilepsy and compared this with Rasmussen encephalitis, Alzheimer disease, and normal controls.Results: We could show that T cell numbers were significantly elevated in MTLE compared to healthy controls. CD3+ as well as CD8+ T cell numbers, however, varied highly among MTLE subgroups. By comparing GG patients with and without hippocampal sclerosis (HS), we were able to show that T‐cell numbers were increased in extrahippocampal GG patients with hippocampal neuronal loss and HS, whereas extrahippocampal GG cases without hippocampal neuronal loss (i.e., absence of HS) did not differ from healthy controls. Importantly, T cell numbers in MTLE correlated with the degree of neuronal loss, whereas no correlation with seizure frequency or disease duration was found. Finally, we found that in nearly all MTLE groups, T cell numbers remained elevated even years after the inciting event.Significance: We here provide a detailed histopathological investigation of the involvement of T cells in various subgroups of MTLE, which suggests that T cell influx correlates to neuronal loss rather than seizure activity.