Laughter and smile are typical expressions of mirth and fundamental means of social communication. Despite their general interest, the current knowledge about the brain regions involved in the ...production of these expressions is still very limited, and the principal insights come from electrical stimulation (ES) studies in patients, in which, nevertheless, laughter or smile have been elicited very rarely. Previous studies showed that laughter is evoked by the stimulation of nodes of an emotional network encompassing the anterior cingulate, the superior frontal and basal temporal cortex. A common feature of these stimulation studies is that the facial expression was always accompanied by motor awareness and often by mirth, in line with the affective functions attributed to these regions. Little is known, in contrast, on the neural basis of the voluntary motor control of this expression. The objective of this study was to investigate the effect of ES of the frontal operculum (FO), which is considered a crucial node for the linkage of the voluntary motor system for emotional expression and limbic emotional network. We report the case of ES applied to the frontal operculum (FO) in four patients with drug-resistant focal epilepsy undergoing stereo-electroencephalographic (SEEG) implantation of intracerebral electrodes. In all patients, ES applied to the FO produced laughter or smile. Interestingly, in one patient, the production of a smiling expression was also clearly accompanied by the lack of motor awareness. Since the lack of motor awareness has been previously observed only after the stimulation of the voluntary motor network, we speculate that FO is involved in the voluntary control of facial expressions, and is placed at the interface with the emotional network, gating limbic information to the motor system.
•ES applied to the FO produced laughter or smile in four patients.•In one patient the production of smiling was accompanied by the lack of motor awareness.•ES effects were elicited from both hemispheres.•FO plays as interface between voluntary and emotional networks.
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’.
Here we show how anatomical and functional data recorded from patients undergoing stereo-EEG can be used to decompose the cortical processing following nerve stimulation in different stages ...characterized by specific topography and time course. Tibial, median and trigeminal nerves were stimulated in 96 patients, and the increase in gamma power was evaluated over 11878 cortical sites. All three nerve datasets exhibited similar clusters of time courses: phasic, delayed/prolonged and tonic, which differed in topography, temporal organization and degree of spatial overlap. Strong phasic responses of the three nerves followed the classical somatotopic organization of SI, with no overlap in either time or space. Delayed responses presented overlaps between pairs of body parts in both time and space, and were confined to the dorsal motor cortices. Finally, tonic responses occurred in the perisylvian region including posterior insular cortex and were evoked by the stimulation of all three nerves, lacking any spatial and temporal specificity. These data indicate that the somatosensory processing following nerve stimulation is a multi-stage hierarchical process common to all three nerves, with the different stages likely subserving different functions. While phasic responses represent the neural basis of tactile perception, multi-nerve tonic responses may represent the neural signature of processes sustaining the capacity to become aware of tactile stimuli.
•StereoEEG shows different time courses in responses to peripheral nerve stimulations.•Strong phasic responses likely reflect thalamic input into primary somatosensory cortex.•Delayed responses subserve sensorimotor synergies in motor and premotor cortex.•Tonic multi-nerve responses in perisylvian region may be markers of tactile awareness.
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.
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.
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.
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.
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.
•CCEPs recorded with hd-EEG and SEEG are correlated.•hd-EEG recording is highly sensitive to changes in stimulation parameters.•Hd-EEG responses to SPES are characterized by site-specific mean frequencies.•hd-EEG responses to SPES are larger than typical sensory evoked potentials.•An open dataset of simultaneous hd-EEG and SEEG during SPES is provided.
This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be ...found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.
A description of the spatiotemporal dynamics of human cortical activity during cognitive tasks is a fundamental goal of neuroscience. In the present study, we employed stereo-EEG in order to assess ...the neural activity during tool-action observation. We recorded from 49 epileptic patients (5502 leads) implanted with intracerebral electrodes, while they observed tool and hand actions. We deconstructed actions into 3 events-video onset, action onset, and tool-object contact-and assessed how different brain regions respond to these events. Video onset, with actions not yet visible, recruited only visual areas. Aligning the responses at action onset, yielded activity in the parietal-frontal manipulation circuit and, selectively for tool actions, in the left anterior supramarginal gyrus (aSMG). Finally, by aligning to the tool-object contact that signals the achievement of the main goal of the observed action, activations were found in SII and dorsal premotor cortex. In conclusion, our data show that during tool-action observation, in addition to the general action observation network there is a selective activation of aSMG, which exhibits internally different patterns of responsiveness. In addition, neural responses selective for the contact between the tool and the object were also observed.
The introduction and the extended clinical use of nilotinib in the first-line treatment of chronic myeloid leukemia have been based on company-sponsored trials. Independent confirmations are ...extremely important. We report an investigator-sponsored study of nilotinib 300 mg twice daily in 130 chronic myeloid leukemia patients in early chronic phase. A deep molecular response was achieved in 46% (MR
) and 17% (MR
) of patients at 2 years; 58% of the enrolled patients achieved a MR
at least once, with a sustained MR
in 52% of them. With a median observation of 29 months (range 24-37 months), 77% of patients were still on treatment with nilotinib. The reasons for permanent discontinuation were: 3% progression, 5% failure or suboptimal response, 8% adverse events, 1% treatment-free remission, and 5% other reasons. Thirteen thrombotic arterial events were reported in 12 patients. A prospective evaluation of metabolic effects showed an increase of fasting glucose without significant variations of glycated hemoglobin, an increase of total cholesterol (both low density lipoprotein and high density lipoprotein fractions) and a decrease of triglycerides. This study confirms a high and rapid efficacy of nilotinib 300 mg twice daily and provides detailed information on the type and incidence of non-hematologic and metabolic adverse events (clinicaltrials.gov identifier: 01535391).
Summary
Introduction: Although there is broad knowledge on the effect of several preanalytical errors on laboratory hematology, there is no information on the reliability of routine hematological ...testing on hemolyzed specimens.
Methods: K2EDTA‐anticoagulated blood collected from 13 healthy volunteers was divided in three aliquots. Aliquot A did not undergo further manipulation, while the second and third aliquots (B and C, respectively) were passed 5 and 10 times through a small‐gauge needle to produce scalar amounts of hemolysis. Hematological testing was first performed on Advia 2120. The plasma was then separated by centrifugation and tested for lactate dehydrogenase and hemolysis index (HI).
Results: As compared with the nonhemolyzed aliquot, analytically and clinically significant variations were recorded in both mildly and frankly hemolyzed specimens for lactate dehydrogenase, HI, red blood cells count, hematocrit, mean corpuscular volume, mean hemoglobin content, lymphocytes, basophils, and large unstained cells. Both the platelets count and the mean platelet volume were also dramatically affected. The other parameters tested (hemoglobin, red blood cell distribution width, neutrophils, and eosinophils) did not vary significantly.
Conclusion: The results of routine hematological testing on mildly to frankly hemolyzed specimens might be unreliable.
Summary
Introduction
We aimed to identify simple but reliable indices for effective screening of spurious hemolysis in whole‐blood specimens.
Methods
Thirteen inpatient whole‐blood samples were ...divided in two aliquots. The former was left untreated, whereas the latter was mechanically hemolyzed by forced aspiration with an insulin syringe. All aliquots were tested on Siemens Advia 2120 and Sysmex XE‐2100. The hemolysis index (HI) was also assessed in centrifuged plasma.
Results
The mechanical hemolysis generated a 4–40% decrease in red blood cells (RBCs). A statistically significant decrease was observed for hematocrit (Ht) and mean corpuscular volume (MCV), whereas mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, and platelet count were increased. The values of hemoglobin (Hb) and white blood cells remained substantially unchanged. Two specific equations (Ht/Hb × √MCV and Ht/Hb × 100) were developed. Both equations displayed an area under the curve of ≥0.99 for identifying spurious hemolysis, much greater than that of both RBC ghosts and immature platelet fraction. A highly significant correlation was also observed between results of these equations and percentage reduction in RBCs or HI increase.
Conclusion
Provided that these results will be confirmed in further studies, these equations may provide a reliable means for screening spurious hemolysis in whole‐blood samples.
The collection of blood samples, an essential prerequisite of laboratory diagnostics, is the most vulnerable step in the total testing process.1"3 Blood samples diluted and/or contaminated with ...saline (i.e., 0.9% sodium chloride), drug(especially heparin, fibrinolytic and chemotherapeutic agents) or glucose-containing solutions are relatively frequent occurrences,4 representing nearly 2% of all unsuitable specimens referred for testing.5-6 Contamination from infusion fluids more often occurs when blood is drawn from cannulae or catheters, and if an inappropriate volume of blood is not discarded before drawing the blood into primary blood collection tubes.7 Although it remains an infrequent occurrence, the analysis of contaminated samples may be associated with production of unsuitable test results, which may jeopardise the clinical and therapeutic decision-making,8 and increase healthcare expenditure.9 Among the various intravenous infusion fluids, it is widely acknowledged that blood sample contamination in patients receiving intravenous glucose-containing solutions dramatically affects the concentration of this analyte in plasma or serum. ...even a concentration of blood glucose much lower than that suggested by Hernandez may trigger inappropriate clinical and therapeutic decision-making, thus jeopardising patient safety and wasting valuable healthcare resources. ...the aim of this small study is to establish to what extent contamination with a glucose-containing solution may affect the results of some selected laboratory parameters, for which the simple and dilutional effect from exogenous fluid may not completely explain the bias.
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