The face-selective response in the human occipito-temporal cortex has been extensively explored at the level of large neural populations (e.g., using functional MRI [fMRI], electroencephalography / magnetoencephalography, or intracranial local field potential), but not at the level of single or multi-units. We have recently reported a rare case of two face-selective units located in the vicinity of the Fusiform Face Area, recorded from a patient with epilepsy (Axelrod et al., 2019, Neurology). These units exhibited a robust (300% and more) modulation for a variety of facial stimuli. In addition to the stimulus-evoked response, it is well established that neurons also fire spontaneously, without any task. Notably, the degree of similarity between the magnitudes of stimulus-evoked activity and spontaneous activity is still unclear. In the present study we capitalized on a rare face-selective multi-unit recording from a human subject, to compare stimulus-evoked activity elicited by static images of faces and spontaneous activity recorded during a 6-minute continuous resting-state session. We found that generally, the magnitude of the face-selective stimulus-evoked response was much greater than the magnitude of spontaneous activity. However, this difference also depended on the duration of the time-window (i.e. a period of interest) utilized to examine the response. In particular, for time-windows of 150 ms and more, there were few spontaneous responses with comparable firing rates to those found in the face-selective evoked response. However, for shorter periods of interest (e.g. 50 ms), when comparing an equal number of windows, about 10-20% of the firing rates recorded during spontaneous activity were comparable to those recorded during the face-selective stimulus-evoked response. Overall, the present results provide a unique perspective on the relationship between stimulus-evoked and spontaneous neural activity.
Periventricular nodular heterotopia (PNH) is a malformation of cortical development that frequently causes drug-resistant epilepsy. The epileptogenicity of ectopic neurons in PNH as well as their role in generating interictal and ictal activity is still a matter of debate. We report the first in vivo microelectrode recording of heterotopic neurons in humans. Highly consistent interictal patterns (IPs) were identified within the nodules: (1) Periodic Discharges PLUS Fast activity (PD+F), (2) Sporadic discharges PLUS Fast activity (SD+F), and (3) epileptic spikes (ES). Neuronal firing rates were significantly modulated during all IPs, suggesting that multiple IPs were generated by the same local neuronal populations. Furthermore, firing rates closely followed IP morphologies. Among the different IPs, the SD+F pattern was found only in the three nodules that were actively involved in seizure generation but was never observed in the nodule that did not take part in ictal discharges. On the contrary, PD+F and ES were identified in all nodules. Units that were modulated during the IPs were also found to participate in seizures, increasing their firing rate at seizure onset and maintaining an elevated rate during the seizures. Together, nodules in PNH are highly epileptogenic and show several IPs that provide promising pathognomonic signatures of PNH. Furthermore, our results show that PNH nodules may well initiate seizures.
Abstract Status epilepticus is a condition resulting either from the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms that lead to abnormally prolonged seizures and require urgent administration of antiepileptic drugs. Refractory status epilepticus requires anesthetics drugs and may lead to brain injury with molecular and cellular alterations (eg, inflammation, and neuronal and astroglial injury) that could induce neurologic sequels and further development of epilepsy. Outcome scores based on demographic, clinical, and electroencephalography (EEG) condition are available, allowing prediction of the risk of mortality, but the severity of brain injury in survivors is poorly evaluated. New biomarkers are needed to predict with higher accuracy the outcome of patients admitted with status in an intensive care unit. Here, we summarize the findings of studies from patients and animal models of status epilepticus. Specific protein markers can be detected in the cerebrospinal fluid and the blood. One of the first described markers of neuronal death is the neuron‐specific enolase. Gliosis resulting from inflammatory responses after status can be detected through the increase of S100‐beta, or some cytokines, like the High Mobility Group Box 1. Other proteins, like progranulin may reflect the neuroprotective mechanisms resulting from the brain adaptation to excitotoxicity. These new biomarkers aim to prospectively identify the severity and development of disability, and subsequent epilepsy of patients with status. We discuss the advantages and disadvantages of each biomarker, by evaluating their brain specificity, stability in the fluids, and sensitivity to external interferences, such as hemolysis. Finally, we emphasize the need for further development and validation of such biomarkers in order to better assess patients with severe status epilepticus.
Background Huntington's disease is characterized by neuronal loss throughout the disease course. V oxel‐based morphometry studies have reported reductions in gray matter concentration ( GMC ) in many brain regions in patients with Huntington. The description of the time course of gray matter loss may help to identify some evolution markers. Here, we conducted a meta‐analysis of voxel‐based morphometry studies of H untington's disease to describe the evolution of brain gray matter loss. Methods A systematic search led to the inclusion of 11 articles on Huntington's disease (297 patients and 205 controls). We extracted data from patients with preclinical Huntington, patients with clinical Huntington, and controls. Finally, anatomical likelihood estimation analyses were conducted to identify GMC changes between preclinical patients and controls, between clinical patients and controls, and between preclinical and clinical patients. Results Preclinical patients exhibited gray matter loss in the left basal ganglia and the prefrontal cortex. Clinical patients had bilateral gray matter loss in the basal ganglia, the prefrontal cortex, and the insula. The left striatum was smaller in clinical patients than in preclinical patients. Conclusions Neurodegenerative processes associated with Huntington's disease, as assessed by GMC reduction, begin in the left hemisphere and extend to the contralateral hemisphere throughout the inexorable course of the disease. Changes in gray matter, especially the volumetric side ratio of the striatum, could represent a relevant biomarker for characterizing the different progression stages of the disease.
To address the memory functioning after medial temporal lobe (MTL) surgery for refractory epilepsy and relationships with the side of the hippocampal removal, 22 patients with pharmaco-resistant epilepsy who had undergone MTL resection (10 right/12 left) at the Salpêtrière Hospital were compared with 21 matched healthy controls. We designed a specific neuropsychological binding memory test that specifically addressed hippocampal cortex functioning, and left-right material-specific lateralization. Our results showed that both left and right mesial temporal lobe removal cause a severe memory impairment, for both verbal and visual material. The removal of left medial temporal lobe causes worse memory impairment than the right removal regardless of the stimuli type (verbal or visual) questioning the theory of the hippocampal material-specific lateralization. The present study provided new evidence for the role of both hippocampus and surrounding cortices in memory-binding whatever the material type and also suggested that a left MTL removal is more deleterious for both verbal and visual episodic memory in comparison with right MTL removal.
