Uncovering the fast, directional signal flow through the human temporal pole during semantic processing.

The temporal pole (TP) plays a central role in semantic memory, yet its neural machinery is unknown. Intracerebral recordings in patients discriminating visually the gender or actions of an actor, yielded gender discrimination responses in the ventrolateral (VL) and tip (T) regions of right TP. Granger causality revealed task-specific signals travelling first forward from VL to T, under control of orbitofrontal cortex (OFC) and neighboring prefrontal cortex, and then, strongly, backwards from T to VL. Many other cortical regions provided inputs to or received outputs from both TP regions, often with longer delays, with ventral temporal afferents to VL signaling the actor's physical appearance. The TP response timing reflected more that of the connections to VL, controlled by OFC, than that of the input leads themselves. Thus, visual evidence for gender categories, collected by VL, activates category labels in T, and consequently, category features in VL, indicating a two-stage representation of semantic categories in TP.

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 control of this behaviour-the complex nature of laughter implies that outward connections from the pACC may reach and affect a complex network of frontal 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 laughter 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 behaviour. 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'.

Simultaneous stereo-EEG and high-density scalp EEG recordings to study the effects of intracerebral stimulation parameters.

BACKGROUND: Cortico-cortical evoked potentials (CCEPs) recorded by stereo-electroencephalography (SEEG) are a valuable tool to investigate brain reactivity and effective connectivity. However, invasive recordings are spatially sparse since they depend on clinical needs. This sparsity hampers systematic comparisons across-subjects, the detection of the whole-brain effects of intracortical stimulation, as well as their relationships to the EEG responses evoked by non-invasive stimuli. OBJECTIVE: To demonstrate that CCEPs recorded by high-density electroencephalography (hd-EEG) provide additional information with respect SEEG alone and to provide an open, curated dataset to allow for further exploration of their potential. METHODS: The dataset encompasses SEEG and hd-EEG recordings simultaneously acquired during Single Pulse Electrical Stimulation (SPES) in drug-resistant epileptic patients (N = 36) in whom stimulations were delivered with different physical, geometrical, and topological parameters. Differences in CCEPs were assessed by amplitude, latency, and spectral measures. RESULTS: While invasively and non-invasively recorded CCEPs were generally correlated, differences in pulse duration, angle and stimulated cortical area were better captured by hd-EEG. Further, intracranial stimulation evoked site-specific hd-EEG responses that reproduced the spectral features of EEG responses to transcranial magnetic stimulation (TMS). Notably, SPES, albeit unperceived by subjects, elicited scalp responses that were up to one order of magnitude larger than the responses typically evoked by sensory stimulation in awake humans. CONCLUSIONS: CCEPs can be simultaneously recorded with SEEG and hd-EEG and the latter provides a reliable descriptor of the effects of SPES as well as a common reference to compare the whole-brain effects of intracortical stimulation to those of non-invasive transcranial or sensory stimulations in humans.

Focal lesions induce large-scale percolation of sleep-like intracerebral activity in awake humans.

Focal cortical lesions are known to result in large-scale functional alterations involving distant areas; however, little is known about the electrophysiological mechanisms underlying these network effects. Here, we addressed this issue by analysing the short and long distance intracranial effects of controlled structural lesions in humans. The changes in Stereo-Electroencephalographic (SEEG) activity after Radiofrequency-Thermocoagulation (RFTC) recorded in 21 epileptic subjects were assessed with respect to baseline resting wakefulness and sleep activity. In addition, Cortico-Cortical Evoked Potentials (CCEPs) recorded before the lesion were employed to interpret these changes with respect to individual long-range connectivity patterns. We found that small structural ablations lead to the generation and large-scale propagation of sleep-like slow waves within the awake brain. These slow waves match those recorded in the same subjects during sleep, are prevalent in perilesional areas, but can percolate up to distances of 60 mm through specific long-range connections, as predicted by CCEPs. Given the known impact of slow waves on information processing and cortical plasticity, demonstrating their intrusion and percolation within the awake brain add key elements to our understanding of network dysfunction after cortical injuries.

Behaviour of the buccal crestal bone levels after immediate placement of implants subjected to immediate loading.

The aim of this study was to measure changes in buccal alveolar crestal bone levels after immediate placement and loading of dental implants with Morse taper prosthetic abutments after tooth extraction. This study followed the STROBE guidelines regarding prospective cohort studies. The sample comprised 12 patients with a mean age of 45 years, in whom a central or upper lateral incisor was indicated for extraction. Prior to extraction, computed tomography (CT) analysis was carried out to assess the presence of the buccal bone crest. CT scans were performed at 24 h and at 6 months after immediate implant placement and immediate loading. The distance from the most apical point of the implant platform to the buccal bone crest was assessed at the two time points. The buccal bone crest height was evaluated at three points in the mesio-distal direction: (1) the centre point of the alveolus, (2) 1mm mesial to the centre point, and (3) 1 mm distal to the centre point. The values obtained were subjected to statistical analysis, comparing the distances from the bone crest to the implant platform for the two time points. After 6 months there was a statistically significant, non-uniform reduction in height at the level of the crest of the buccal bone in the cervical direction. It is concluded that the buccal bone crest of the immediate implants that replaced the maxillary incisors underwent apical resorption when subjected to immediate loading.

Epileptic motor behaviors during sleep: anatomo-electro-clinical features.

BACKGROUND: Sleep-related complex motor seizures have long been considered pathognomonic features of Nocturnal Frontal Lobe Epilepsy (NFLE). In recent years, these manifestations have also been reported to have a temporal or insular origin. METHOD: We describe 40 drug-resistant epileptic patients with complex motor seizures during sleep, submitted to presurgical stereo-EEG (SEEG) evaluation and seizure-free after surgical resection of the epileptogenic zone. RESULTS: In a significant proportion (30%) of these patients, seizures arose from extra-frontal regions, including mainly the temporal lobe and the insular cortex, but also the parietal and occipital lobes. In patients with extra-frontal epilepsy, when complex motor behaviors appeared, SEEG revealed that the ictal discharge involved the cingulate and the frontal regions. Finally, at histology, Taylor's focal cortical dysplasia (TFCD) was the most common finding (90% of patients), independent of the site of seizure onset. CONCLUSION: As previously reported by other studies, this histologic substrate may be a major determinant of sleep-related seizures in drug-resistant epileptic patients.

Risk factors for postoperative depression in 150 subjects treated for drug-resistant focal epilepsy.

OBJECTIVE: The primary goal was to identify risk factors for post-surgical depression in subjects operated on for drug-resistant epilepsy. Secondary goals were to confirm the high rate of depression in subjects suffering from epilepsy (prior to surgery) and to look for first post-surgical depressive episode. METHODS: Case series study of 150 subjects surgically treated for partial epilepsy (side of surgery: 72 right, 78 left; site of surgery: 97 Unilobar Temporal, 17 Unilobar Frontal, 14 Posterior, 22 Multilobar). All subjects routinely had three psychiatric evaluations: before surgery (baseline) and at 6 and 12 months after surgery. Psychiatric diagnoses were made according to DSM-IV-TR criteria. Bivariate (Fisher exact test and Kruskal-Wallis rank sum test) and multivariate (logistic regression model fitting) analyses were performed. RESULTS: Thirty-three (22%) subjects had post-surgical depressive episodes, 31 of them in the first 6 months. Fourteen out of 33 experienced depression for the first time. Post-surgical depressive episodes are not associated with gender, outcome on seizures, side/site of surgical resection, histological diagnosis, psychiatric diagnoses other than depression. Depressive episodes before surgery and older age at surgery time are risk factors for post-surgical depression (p= 0.0001 and 0.01, respectively, at logistic regression analysis). No protective factors were identified. CONCLUSIONS: Our data show that lifetime depressive episodes and older age at surgery time are risk factors for postsurgery depression. Moreover, a prospective study could be useful in order to assess whether depression is really a consequence of surgery.

Surgical treatment of drug-resistant nocturnal frontal lobe epilepsy.

Of the cases with nocturnal frontal lobe epilepsy (NFLE) approximately 30% are refractory to antiepileptic medication, with several patients suffering from the effects of both ongoing seizures and disrupted sleep. From a consecutive series of 522 patients operated on for drug-resistant focal epilepsy, 21 cases (4%), whose frontal lobe seizures occurred almost exclusively (>90%) during sleep, were selected. All patients underwent a comprehensive pre-surgical evaluation, which included history, interictal EEG, scalp video-EEG monitoring, high-resolution MRI and, when indicated, invasive recording by stereo-EEG (SEEG). There were 11 males and 10 females, whose mean age at seizure onset was 6.2 years, mean age at surgery was 24.7 years and seizure frequency ranged from <20/month to >300/month. Nine patients reported excessive daytime sleepiness (EDS). Prevalent ictal clinical signs were represented by asymmetric posturing (6 cases), hyperkinetic automatisms (10 cases), combined tonic posturing and hyperkinetic automatisms (4 cases) and mimetic automatisms (1 case). All patients reported some kind of subjective manifestations. Interictal and ictal EEG provided lateralizing or localizing information in most patients. MRI was unrevealing in 10 cases and it showed a focal anatomical abnormality in one frontal lobe in 11 cases. Eighteen patients underwent a SEEG evaluation to better define the epileptogenic zone (EZ). All patients received a microsurgical resection in one frontal lobe, tailored according to pre-surgical evaluations. Two patients were operated on twice owing to poor results after the first resection. Histology demonstrated a Taylor-type focal cortical dysplasia (FCD) in 16 patients and an architectural FCD in 4. In one case no histological change was found. After a post-operative follow-up of at least 12 months (mean 42.5 months) all the 16 patients with a Taylor's FCD were in Engel's Class Ia and the other 5 patients were in Engel's Classes II or III. After 6 months post-surgery EDS had disappeared in the 9 patients who presented this complaint pre-operatively. It is concluded that patients with drug-resistant, disabling sleep-related seizures of frontal lobe origin should be considered for resective surgery, which may provide excellent results both on seizures and on epilepsy-related sleep disturbances. An accurate pre-surgical evaluation, which often requires invasive EEG recording, is mandatory to define the EZ. Further investigation is needed to explain the possible causal relationships between FCD, particularly Taylor-type, and sleep-related seizures, as observed in this cohort of NFLE patients.

Stereo-EEG in children.

BACKGROUND: Stereotactic placement of intracerebral multilead electrodes for chronic EEG recording of seizures or stereoelectroencephalography (SEEG) was introduced 50 years ago at Saint Anne Hospital in Paris, France for the presurgical evaluation of patients with drug-resistant focal epilepsy. SEEG explorations are indicated whenever the noninvasive tests fail to adequately localize the epileptogenic zone (EZ). INDICATIONS: Currently, approximately 35% of our operated-on children require a SEEG evaluation. Arrangement of electrodes is individualized according to the peculiar needs of each child, to verify a predetermined hypothesis of localization of the EZ based on pre-SEEG anatomo-electro-clinical findings. Multilead intracerebral electrodes are designed to sample cortical structures on the lateral, intermediate, and mesial aspect of the hemisphere, as well as deep-seated lesions. Stereotactic stereoscopic teleangiograms and coregistered 3-D MRI are employed to plan avascular trajectories and to accurately target the desired structures. Pre-SEEG stereotactic neuroradiology and electrode implantation are usually performed in separate procedures. Electrodes are removed once video-SEEG monitoring is completed. INTRACEREBRAL ELECTRICAL STIMULATIONS: Intracerebral electrical stimulations are used to better define the EZ and to obtain a detailed functional mapping of critical cortical and subcortical regions. MORBIDITY: Surgical morbidity of SEEG is definitely low in children. SEEG-GUIDED RESECTIVE SURGERY: In 90% of evaluated children, SEEG provides a guide for extratemporal or multilobar resections. SEEG-guided resective surgery may yield excellent results on seizures with 60% of patients in Engel's Class I.

Selective down-regulation of [(125)I]Y0-alpha-conotoxin MII binding in rat mesostriatal dopamine pathway following continuous infusion of nicotine.

Prolonged exposure to nicotine, as occurs in smokers, results in up-regulation of all the neuronal nicotinic acetylcholine receptor subtypes studied so far, the only differences residing in the extent and time course of the up-regulation. alpha6beta2*-Nicotinic acetylcholine receptors are selectively enriched in the mesostriatal dopaminergic system and may play a crucial role in nicotine dependence. Here we show that chronic nicotine treatment (3mg/kg/day for two weeks, via s.c. osmotic minipumps) caused a significant decrease (36% on average) in the binding of [(125)I]Y(0)-alpha-conotoxin MII (a selective ligand for alpha6beta2*-nicotinic acetylcholine receptors in this system) to all the five regions of the rat dopaminergic pathway analyzed in this study. After one week of withdrawal, binding was still lower than control in striatal terminal regions (namely the caudate putamen and the accumbens shell and core). In somatodendritic regions (the ventral tegmental area and the substantia nigra) the decrease was significant at the end of the treatment and recovered within one day of withdrawal. This effect was not due to displacement of [(125)I]Y(0)-alpha-conotoxin MII binding by residual nicotine. In fact the binding was not changed by 565 ng/g nicotine (obtained with a single injection of nicotine), a concentration much higher than that found in the brain of rats chronically treated with nicotine (240 ng/g). In addition, consistent with previous studies reporting an up-regulation of other subtypes of nicotinic acetylcholine receptors, we found that nicotine exposure significantly increased (40% on average) the binding of [(125)I]epibatidine (a non-selective agonist at most neuronal heteromeric nicotinic acetylcholine receptors) in three up to five regions containing only alpha-conotoxin MII-insensitive [(125)I]epibatidine binding sites, namely the primary motor, somatosensory and auditory cortices. In conclusion, this work is the first to demonstrate that alpha6beta2*-nicotinic acetylcholine receptors, unique within the nicotinic acetylcholine receptor family, are down-regulated following chronic nicotine treatment in rat dopaminergic mesostriatal pathway, a finding that may shed new light in the complex mechanisms of nicotine dependence.

Intracerebral recordings of minor motor events, paroxysmal arousals and major seizures in nocturnal frontal lobe epilepsy.

The clinical features of nocturnal frontal lobe epilepsy (NFLE) consist of a spectrum of paroxysmal motor manifestations ranging from minor motor events (MMEs) to paroxysmal arousals (PAs) and major seizures. During MMEs and PAs scalp EEG generally does not show definite ictal abnormalities. We describe the clinical and electrophysiological features of three patients affected by drug-resistant NFLE studied with intracerebral electrodes during a presurgical evaluation. The stereo-EEG (SEEG) investigation revealed that MMEs can be fragments of the major seizure and occur during a brief epileptic discharge or on the following arousal. PAs, in the same subject, do not show a definite stereotypy despite the morphological and topographic similarity of the epileptic discharges, thus indicating that other variables may influence the clinical features of PAs.

Sleep-related hyperkinetic seizures: always a frontal onset?

Hyperkinetic seizures are considered a typical manifestation of nocturnal frontal lobe epilepsy (NFLE). Patients with temporal lobe epilepsy with mainly sleep-related seizures have been described; however they commonly lack hyperkinetic activity and seizure frequency is low. We retrospectively analysed our population of 442 consecutive patients surgically treated between January 1996 and January 2004. Among these there were 25 patients with sleep-related hyperkinetic epileptic seizures, with a frontal lobe onset in 18 cases and a temporal lobe onset in 7. Patients with sleep-related hyperkinetic seizures with temporal lobe origin had anamnestic and clinical features strikingly similar to those with a frontal onset, with agitated movements, high seizure frequency and no history of febrile convulsions. We confirm our previous findings that this kind of epileptic manifestation is not only peculiar to frontal lobe epilepsy.

Concurrent pharmacological MRI and in situ microdialysis of cocaine reveal a complex relationship between the central hemodynamic response and local dopamine concentration.

The mechanisms underlying the signal changes observed with pharmacological magnetic resonance imaging (phMRI) remain to be fully elucidated. In this study, we obtained microdialysis samples in situ at 5-min intervals during phMRI experiments using a blood pool contrast agent to correlate relative cerebral blood volume (rCBV) changes with changes in dopamine and cocaine concentrations following acute cocaine challenge (0.5 mg/kg iv) in the rat over a duration of 30 min. Three brain areas were investigated: the dorsal striatum (n = 8), the medial prefrontal cortex (mPFC; n = 5), and the primary motor cortex (n = 8). In the striatum and mPFC groups, cocaine and dopamine temporal profiles were tightly correlated, peaking during the first 5-min period postinjection, then rapidly decreasing. However, the local rCBV changes were uncorrelated and exhibited broader temporal profiles than those of cocaine and dopamine, attaining maximal response 5-10 min later. This demonstrates that direct vasoactivity of dopamine is not the dominant component of the hemodynamic response in these regions. In the motor cortex group, microdialysis revealed no local change in dopamine in any of the animals, despite large local cocaine increase and strong rCBV response, indicating that the central hemodynamic response following acute iv cocaine challenge is not driven directly by local dopamine changes in the motor cortex. The combination of phMRI and in situ microdialysis promises to be of great value in elucidating the relationship between the phMRI response to psychoactive drugs and underlying neurochemical changes.

Sleep-related hyperkinetic seizures of temporal lobe origin.

Sleep-related hyperkinetic seizures are a common feature of nocturnal frontal lobe epilepsy. Although sleep-related seizures with a temporal lobe origin have been reported, they commonly lack hyperkinetic activity. The authors describe three patients with sleep-related seizures characterized by frenetic, agitated, hyperactive movements (bimanual/bipedal activity, rocking, axial, pelvic, and hemiballistic movements), in whom stereo-EEG investigation and surgical outcome demonstrated a temporal lobe origin of the attacks.

Hallucinations and sleep-wake cycle in PD: a 24-hour continuous polysomnographic study.

Twenty-four-hour ambulatory polysomnography was performed in 20 patients with PD who were having visual hallucinations (12 men and 8 women, mean age 70 +/- 6 years). Visual hallucinations were clearly related to daytime NREM sleep or nocturnal REM sleep in 33% of the instances. The data reinforce the hypothesis that neural mechanisms implicated in generating sleep and, in particular, in dream imagery play a role in the occurrence of visual hallucinations in PD.

Sleep hygiene in adult epilepsy patients: a questionnaire-based survey.

Two hundred and seventy epilepsy patients referred to the Epilepsy Centre of the "C. Mondino" Institute of Neurology and 230 healthy subjects comparable for age, sex and education completed a sleep questionnaire of 112 multiple choice questions including those that concern sleep hygiene practice. The percentage of subjects with habitually inappropriate sleep hygiene habits was significantly higher in controls than in epilepsy patients for 7 out of the 9 sleep hygiene practices considered (P at chi square less than 0.05). No significant relationship between kind and/or severity of epilepsy and the degree of sleep hygiene practice was found. The data show that sleep hygiene practice is more adequate in epilepsy than in control subjects. It is possible that the appropriate sleep hygiene practice of epilepsy patients derives from the fact that they habitually refrain from a lot of practices which possibly aggravate both the course of epilepsy and seizure-related complications.