The web of laughter: frontal and limbic projections of the anterior cingulate cortex revealed by cortico-cortical evoked potential from sites eliciting laughter

According to an evolutionist approach, laughter is a multifaceted behaviour affecting social, emotional, motor and speech functions. Albeit previous studies have suggested that high-frequency electrical stimulation (HF-ES) of the pregenual anterior cingulate cortex ( pACC) may induce bursts of laughter—suggesting a crucial contribution of this region to the cortical con- trol of this behaviour—the complex nature of laughter implies that outward connections from the pACC may reach and affect a complex network of fron- tal and limbic regions. Here, we studied the effective connectivity of the pACC by analysing the cortico-cortical evoked potentials elicited by single-pulse electrical stimulation of pACC sites whose HF-ES elicited laugh- ter in 12 patients. Once these regions were identified, we studied their clinical response to HF-ES, to reveal the specific functional target of pACC representation of laughter. Results reveal that the neural representation of laughter in the pACC interacts with several frontal and limbic regions, including cingulate, orbitofrontal, medial prefrontal and anterior insular regions—involved in interoception, emotion, social reward and motor be- haviour. These results offer neuroscientific support to the evolutionist approach to laughter, providing a possible mechanistic explanation of the interplay between this behaviour and emotion regulation, speech production and social interactions. This article is part of the theme issue ‘Cracking the laugh code: laughter through the lens of biology, psychology, and neuroscience’

A case of clinical worsening after stereo-electroencephalographic-guided radiofrequency thermocoagulation in a patient with polymicrogyria

: Radiofrequency thermocoagulation (RF-TC) is a wide-used procedure for drug-resistant epilepsy. The technique is considered safe with an overall risk of 1.1% of permanent complications, mainly focal neurological deficits. We report the case of a patient with drug-resistant epilepsy who complained of immediate seizure worsening and an unexpected event seven months following RF-TC. A 35-year-old male with drug-resistant epilepsy from the age of 18 years underwent stereoelectroencephalography (SEEG) implantation for a right peri-silvian polymicrogyria. He was excluded from surgery due to extent of the epileptogenic zone and the risk of visual field deficits. RF-TC was attempted to ablate the most epileptogenic zone identified by SEEG. After RF-TC, the patient reported an increase in seizure severity/frequency and experienced episodes of postictal psychosis. Off-label cannabidiol treatment led to improved seizure control and resolution of postictal psychosis. Patients with polymicrogyria (PwP) may present with a disruption of normal anatomy and the co-existence between epileptogenic zone and eloquent cortex within the malformation. RF-TC should be considered in PwP when they are excluded from surgery for prognostic and palliative purposes. However, given the complex interplay between pathological and electrophysiological networks in these patients, the remote possibility of clinical exacerbation after RF-TC should also be taken into account

A new tool for touch-free patient registration for robot-assisted intracranial surgery: Application accuracy from a phantom study and a retrospective surgical series

OBJECTIVE The purpose of this study was to compare the accuracy of Neurolocate frameless registration system and frame-based registration for robotic stereoelectroencephalography (SEEG). METHODS The authors performed a 40-trajectory phantom laboratory study and a 127-trajectory retrospective analysis of a surgical series. The laboratory study was aimed at testing the noninferiority of the Neurolocate system. The analysis of the surgical series compared Neurolocate-based SEEG implantations with a frame-based historical control group. RESULTS The mean localization errors (LE) ± standard deviations (SD) for Neurolocate-based and frame-based trajectories were 0.67 ± 0.29 mm and 0.76 ± 0.34 mm, respectively, in the phantom study (p = 0.35). The median entry point LE was 0.59 mm (interquartile range [IQR] 0.25-0.88 mm) for Neurolocate-registration-based trajectories and 0.78 mm (IQR 0.49-1.08 mm) for frame-registration-based trajectories (p = 0.00002) in the clinical study. The median target point LE was 1.49 mm (IQR 1.06-2.4 mm) for Neurolocate-registration-based trajectories and 1.77 mm (IQR 1.25-2.5 mm) for frameregistration- based trajectories in the clinical study. All the surgical procedures were successful and uneventful. CONCLUSIONS The results of the phantom study demonstrate the noninferiority of Neurolocate frameless registration. The results of the retrospective surgical series analysis suggest that Neurolocate-based procedures can be more accurate than the frame-based ones. The safety profile of Neurolocate-based registration should be similar to that of frame-based registration. The Neurolocate system is comfortable, noninvasive, easy to use, and potentially faster than other registration devices

Event-related causality in Stereo-EEG discriminates syntactic processing of noun phrases and verb phrases

Objective: Syntax involves complex neurobiological mechanisms, which are difficult to disentangle for multiple reasons. Approach: Using a protocol able to separate syntactic information from sound information we investigated the neural causal connections evoked by the processing of homophonous phrases, i.e. with the same acoustic information but with different syntactic content. These could be either verb phrases (VP) or noun phrases (NP). We used event-related causality (ERC) from stereo-electroencephalographic (SEEG) recordings in 10 epileptic patients in multiple cortical and subcortical areas, including language areas and their homologous in the non-dominant hemisphere. The recordings were made while the subjects were listening to the homophonous phrases. Main results: We identified the different networks involved in the processing of these syntactic operations (faster in the dominant hemisphere) showing that VPs engage a wider cortical and subcortical network. We also present a proof-of-concept for the decoding of the syntactic category of a perceived phrase based on causality measures. Significance: Our findings help unravel the neural correlates of syntactic elaboration and show how a decoding based on multiple cortical and subcortical areas could contribute to the development of speech prostheses for speech impairment mitigation.

Association Between Semiology and Anatomo-Functional Localization in Patients With Cingulate Epilepsy: A Cohort Study

Background and objectives: Cingulate epilepsy (CE) is a rare and challenging type of focal epilepsy, due to the polymorphic semiology of the seizures, mimicking other types of epilepsy, and the limited utility of scalp-EEG. Methods: We selected consecutive drug-resistant subjects with CE who were seizure-free after surgery, with seizure onset zone (SOZ) confirmed in the CC (cingulate cortex) by histology and/or SEEG. We analysed subjective and objective ictal manifestations using video recordings and correlated semeiology with anatomical CC subregions (anterior, anterior middle, posterior middle and posterior) localization of SOZ. Results: We analysed 122 seizures in 57 patients. Seizures were globally characterized by complex behaviors, typically natural seeming and often accompanied by emotional components.All objective ictal variables considered (pronation of the body or getting up from a lying/sitting position, tonic/dystonic posturing, hand movements, asymmetry, vocalizations, fluidity and repetitiveness of motor manifestations, awareness and emotional and autonomic components) were differently distributed among CC subregions (p<.05) Along the rostro-caudal axis fluidity and repetitiveness of movement, vocalizations, body pronation and emotional components decrease anterior-posteriorly, while tonic/dystonic postures, signs of lateralization and awareness increase.Vestibular and asymmetric somatosensory, somatosensory and epigastric and enteroceptive/autonomic symptoms were distributed differently among CC subregions (p<.05). Along the rostro-caudal axis vestibular, somatosensory and somatosensory asymmetric symptoms increase anterior-posterior. Discussion: CE is characterized by a spectrum of semeiological manifestations with a topographic distribution. CE semiology could indicate which cingulate sector is mainly involved

Magnetic susceptibility as a 1-year predictor of outcome in familial cerebral cavernous malformations: a pilot study

Objectives: To test whether quantitative susceptibility mapping (QSM) of cerebral cavernous malformations (CCMs) assessed at baseline may predict the presence or absence of haemorrhagic signs at 1-year follow-up. Methods: Familial CCM patients were enrolled in the longitudinal multicentre study Treat-CCM. The 3-T MRI scan allowed performing a semi-automatic segmentation of CCMs and computing the maximum susceptibility in each segmented CCM (QSMmax) at baseline. CCMs were classified as haemorrhagic and non-haemorrhagic at baseline and then subclassified according to the 1-year (t1) evolution. Between-group differences were tested, and the diagnostic accuracy of QSMmax in predicting the presence or absence of haemorrhagic signs in CCMs was calculated with ROC analyses. Results: Thirty-three patients were included in the analysis, and a total of 1126 CCMs were segmented. QSMmax was higher in haemorrhagic CCMs than in non-haemorrhagic CCMs (p < 0.001). In haemorrhagic CCMs at baseline, the accuracy of QSMmax in differentiating CCMs that were still haemorrhagic from CCMs that recovered from haemorrhage at t1 calculated as area under the curve (AUC) was 0.78 with sensitivity 62.69%, specificity 82.35%, positive predictive value (PPV) 93.3% and negative predictive value (NPV) 35.9% (QSMmax cut-off ≥ 1462.95 ppb). In non-haemorrhagic CCMs at baseline, AUC was 0.91 in differentiating CCMs that bled at t1 from stable CCMs with sensitivity 100%, specificity 81.9%, PPV 5.1%, and NPV 100% (QSMmax cut-off ≥ 776.29 ppb). Conclusions: The QSMmax in CCMs at baseline showed high accuracy in predicting the presence or absence of haemorrhagic signs at 1-year follow-up. Further effort is required to test the role of QSM in follow-up assessment and therapeutic trials in multicentre CCM studies. Key points: • QSM in semi-automatically segmented CCM was feasible. • The maximum magnetic susceptibility in a single CCM at baseline may predict the presence or absence of haemorrhagic signs at 1-year follow-up. • Multicentric studies are needed to enforce the role of QSM in predicting the CCMs' haemorrhagic evolution in patients affected by familial and sporadic forms

Focal Cortical Dysplasia IIIa in Hippocampal Sclerosis-Associated Epilepsy: Anatomo-Electro-Clinical Profile and Surgical Results From a Multicentric Retrospective Study

Abstract Background: Hippocampal sclerosis (HS) may be associated with focal cortical dysplasia IIIa (FCD IIIa) in patients undergoing surgery for temporal lobe epilepsy (TLE). Objective: To investigate whether the anatomo-electro-clinical profile and surgical outcome in patients with HS-related TLE are affected by coexisting FCD IIIa. Methods: A total of 220 patients, operated in 5 centers, with at least 24 mo follow-up (FU), were retrospectively studied. Preliminary univariate and subsequent multivariate analyses were performed to investigate possible associations between several potential presurgical, surgical, and postsurgical predictors and different variables (Engel's class I and Engel's class Ia, co-occurrence of FCD IIIa). Results: At last available postoperative control (FU: range 24-95 mo, median 47 mo), 182 (82.7%) patients were classified as Engel's class I and 142 (64.5%) as Engel's class Ia. At multivariate analysis, extension of neocortical resection and postoperative electroencephalogram were significantly associated with Engel's class I, whereas length of FU had a significant impact on class Ia in the whole cohort and in isolated HS (iHS) patients, but not in the FCD IIIa group. No differences emerged in the anatomo-electro-clinical profile and surgical results between patients with FCD IIIa and with iHS. Conclusion: Coexistence of FCD IIIa did not confer a distinct anatomo-electro-clinical profile to patients with HS-related epilepsy. Postoperative seizure outcome was similar in FCD IIIa and iHS cases. These findings indicate limited clinical relevance of FCD IIIa in HS-related epilepsy and might be useful for refining future FCD classifications. Further studies are needed to clarify the correlation of class Ia outcome with the duration of FU