Rejuvenating silicon probes for acute neurophysiology.

Neurophysiological recording with a new probe often yields better signal quality than with a used probe. Why does the signal quality degrade after only a few experiments? Here, we considered silicon probes in which the contacts are densely packed, and each contact is coated with a conductive polymer that increases its surface area. We tested 12 Cambridge Neurotech silicon probes during 61 recording sessions from the brain of 3 marmosets. Out of the box, each probe arrived with an electrodeposited polymer coating on 64 gold contacts, and an impedance of around 50k Ohms. With repeated use, the impedance increased and there was a corresponding decrease in the number of well-isolated neurons. Imaging of the probes suggested that the reduction in signal quality was due to a gradual loss of the polymer coating. To rejuvenate the probes, we first stripped the contacts, completely removing their polymer coating, and then recoated them in a solution of 10 mM EDOT monomer with 11 mM PSS using a current density of about 3mA/cm2 for 30 seconds. This recoating process not only returned probe impedance to around 50k Ohms, but it also yielded significantly improved signal quality during neurophysiological recordings. Thus, insertion into the brain promoted loss of the polymer that coated the contacts of the silicon probes. This led to degradation of signal quality, but recoating rejuvenated the probes.

The olivary input to the cerebellum dissociates sensory events from movement plans.

Neurons in the inferior olive are thought to anatomically organize the Purkinje cells (P-cells) of the cerebellum into computational modules, but what is computed by each module? Here, we designed a saccade task in marmosets that dissociated sensory events from motor events and then recorded the complex and simple spikes of hundreds of P-cells. We found that when a visual target was presented at a random location, the olive reported the direction of that sensory event to one group of P-cells, but not to a second group. However, just before movement onset, it reported the direction of the planned movement to both groups, even if that movement was not toward the target. At the end of the movement if the subject experienced an error but chose to withhold the corrective movement, only the first group received information about the sensory prediction error. We organized the P-cells based on the information content of their olivary input and found that in the group that received sensory information, the simple spikes were suppressed during fixation, then produced a burst before saccade onset in a direction consistent with assisting the movement. In the second group, the simple spikes were not suppressed during fixation but burst near saccade deceleration in a direction consistent with stopping the movement. Thus, the olive differentiated the P-cells based on whether they would receive sensory or motor information, and this defined their contributions to control of movements as well as holding still.

Effort cost of harvest affects decisions and movement vigor of marmosets during foraging.

Our decisions are guided by how we perceive the value of an option, but this evaluation also affects how we move to acquire that option. Why should economic variables such as reward and effort alter the vigor of our movements? In theory, both the option that we choose and the vigor with which we move contribute to a measure of fitness in which the objective is to maximize rewards minus efforts, divided by time. To explore this idea, we engaged marmosets in a foraging task in which on each trial they decided whether to work by making saccades to visual targets, thus accumulating food, or to harvest by licking what they had earned. We varied the effort cost of harvest by moving the food tube with respect to the mouth. Theory predicted that the subjects should respond to the increased effort costs by choosing to work longer, stockpiling food before commencing harvest, but reduce their movement vigor to conserve energy. Indeed, in response to an increased effort cost of harvest, marmosets extended their work duration, but slowed their movements. These changes in decisions and movements coincided with changes in pupil size. As the effort cost of harvest declined, work duration decreased, the pupils dilated, and the vigor of licks and saccades increased. Thus, when acquisition of reward became effortful, the pupils constricted, the decisions exhibited delayed gratification, and the movements displayed reduced vigor.

Complex spikes perturb movements and reveal the sensorimotor map of Purkinje cells.

Computations that are performed by the cerebellar cortex are transmitted via simple spikes of Purkinje cells (P-cells) to downstream structures, but because P-cells are many synapses away from muscles, we do not know the relationship between modulation of simple spikes and control of behavior. Here, we recorded the spiking activities of hundreds of P-cells in the oculomotor vermis of marmosets during saccadic eye movements and found that following the presentation of a visual stimulus, the olivary input to a P-cell coarsely described the direction and amplitude of the visual stimulus as well as the upcoming movement. Occasionally, the complex spike occurred just before saccade onset, suppressing the P-cell's simple spikes and disrupting its output during that saccade. Remarkably, this brief suppression of simple spikes altered the saccade's trajectory by pulling the eyes toward the part of the visual space that was preferentially encoded by the olivary input to that P-cell. Thus, there is an alignment between the sensory space encoded by the complex spikes and the behavior conveyed by the simple spikes: a reduction in simple spikes is a signal to bias the ongoing movement toward the part of the sensory space preferentially encoded by the olivary input to that P-cell.

Complex spikes perturb movements, revealing the sensorimotor map of Purkinje cells.

The cerebellar cortex performs computations that are critical for control of our actions, and then transmits that information via simple spikes of Purkinje cells (P-cells) to downstream structures. However, because P-cells are many synapses away from muscles, we do not know how their output affects behavior. Furthermore, we do not know the level of abstraction, i.e., the coordinate system of the P-cell's output. Here, we recorded spiking activities of hundreds of P-cells in the oculomotor vermis of marmosets during saccadic eye movements and found that following the presentation of a visual stimulus, the olivary input to a P-cell encoded a probabilistic signal that coarsely described both the direction and the amplitude of that stimulus. When this input was present, the resulting complex spike briefly suppressed the P-cell's simple spikes, disrupting the P-cell's output during that saccade. Remarkably, this brief suppression altered the saccade's trajectory by pulling the eyes toward the part of the visual space that was preferentially encoded by the olivary input to that P-cell. Thus, analysis of behavior in the milliseconds following a complex spike unmasked how the P-cell's output influenced behavior: the preferred location in the coordinates of the visual system as conveyed probabilistically from the inferior olive to a P-cell defined the action in the coordinates of the motor system for which that P-cell's simple spikes directed behavior.

Effort cost of harvest affects decisions and movement vigor of marmosets during foraging.

Our decisions are guided by how we perceive the value of an option, but this evaluation also affects how we move to acquire that option. Why should economic variables such as reward and effort alter the vigor of our movements? In theory, both the option that we choose and the vigor with which we move contribute to a measure of fitness in which the objective is to maximize rewards minus efforts, divided by time. To explore this idea, we engaged marmosets in a foraging task in which on each trial they decided whether to work by making saccades to visual targets, thus accumulating food, or to harvest by licking what they had earned. We varied the effort cost of harvest by moving the food tube with respect to the mouth. Theory predicted that the subjects should respond to the increased effort costs by choosing to work longer, stockpiling food before commencing harvest, but reduce their movement vigor to conserve energy. Indeed, in response to an increased effort cost of harvest, marmosets extended their work duration, but slowed their movements. These changes in decisions and movements coincided with changes in pupil size. As the effort cost of harvest declined, work duration decreased, the pupils dilated, and the vigor of licks and saccades increased. Thus, when acquisition of reward became effortful, the pupils constricted, the decisions exhibited delayed gratification, and the movements displayed reduced vigor. Significance statement: Our results suggest that as the brainstem neuromodulatory circuits that control pupil size respond to effort costs, they alter computations in the brain regions that control decisions, encouraging work and delaying gratification, and the brain regions that control movements, reducing vigor and suppressing energy expenditure. This coordinated response suggests that decisions and actions are part of a single control policy that aims to maximize a variable relevant to fitness: the capture rate.

Synchronous spiking of cerebellar Purkinje cells during control of movements.

SignificanceThe information that one region of the brain transmits to another is usually viewed through the lens of firing rates. However, if the output neurons could vary the timing of their spikes, then, through synchronization, they would spotlight information that may be critical for control of behavior. Here we report that, in the cerebellum, Purkinje cell populations that share a preference for error convey, to the nucleus, when to decelerate the movement, by reducing their firing rates and temporally synchronizing the remaining spikes.

P-sort: an open-source software for cerebellar neurophysiology.

Analysis of electrophysiological data from Purkinje cells (P-cells) of the cerebellum presents unique challenges to spike sorting. Complex spikes have waveforms that vary significantly from one event to the next, raising the problem of misidentification. Even when complex spikes are detected correctly, the simple spikes may belong to a different P-cell, raising the danger of misattribution. To address these identification and attribution problems, we wrote an open-source, semiautomated software called P-sort, and then tested it by analyzing data from P-cells recorded in three species: marmosets, macaques, and mice. Like other sorting software, P-sort relies on nonlinear dimensionality reduction to cluster spikes. However, it also uses the statistical relationship between simple and complex spikes to merge disparate clusters and split a single cluster. In comparison with expert manual curation, occasionally P-sort identified significantly more complex spikes, as well as prevented misattribution of clusters. Three existing automatic sorters performed less well, particularly for identification of complex spikes. To improve the development of analysis tools for the cerebellum, we provide labeled data for 313 recording sessions, as well as statistical characteristics of waveforms and firing patterns of P-cells in three species.NEW & NOTEWORTHY Algorithms that perform spike sorting depend on waveforms to cluster spikes. However, a cerebellar Purkinje-cell produces two types of spikes; simple and complex spikes. A complex spike coincides with the suppression of generating simple spikes. Here, we recorded neurophysiological data from three species and developed a spike analysis software named P-sort that relies on this statistical property to improve both the detection and the attribution of simple and complex spikes in the cerebellum.

Behavioral training of marmosets and electrophysiological recording from the cerebellum.

The common marmoset (Callithrix jacchus) is a promising new model for study of neurophysiological basis of behavior in primates. Like other primates, it relies on saccadic eye movements to monitor and explore its environment. Previous reports have demonstrated some success in training marmosets to produce goal-directed actions in the laboratory. However, the number of trials per session has been relatively small, thus limiting the utility of marmosets as a model for behavioral and neurophysiological studies. In this article, we report the results of a series of new behavioral training and neurophysiological protocols aimed at increasing the number of trials per session while recording from the cerebellum. To improve the training efficacy, we designed a precisely calibrated food regulation regime that motivates the subjects to perform saccade tasks, resulting in ~1,000 reward-driven trials on a daily basis. We then developed a multichannel recording system that uses imaging to target a desired region of the cerebellum, allowing for simultaneous isolation of multiple Purkinje cells in the vermis. In this report, we describe 1) the design and surgical implantation of a computer tomography (CT)-guided, subject-specific head post, 2) the design of a CT- and MRI-guided alignment tool for trajectory guidance of electrodes mounted on an absolute encoder microdrive, 3) development of a protocol for behavioral training of subjects, and 4) simultaneous recordings from pairs of Purkinje cells during a saccade task.NEW & NOTEWORTHY Marmosets present the opportunity to investigate genetically based neurological disease in primates, in particular, diseases that affect social behaviors, vocal communication, and eye movements. All of these behaviors depend on the integrity of the cerebellum. We present training methods that better motivate the subjects, allowing for improved performance, and we also present electrophysiological techniques that precisely target the subject's cerebellum, allowing for simultaneous isolation of multiple Purkinje cells.

Atypical presentation of currarino syndrome: A case report.

INTRODUCTION: Currarino syndrome is a rare congenital disorder characterized by a triad of anorectal malformation, a sacral bone defect, and a presacral mass. It results of an abnormal separation of the ectoderm from the endoderm caused by HLXB9 mutation in chromosome 7q36 in 50% of cases. The disorder is mostly hereditary as it can also be sporadic with a variable expression spectrum. PRESENTATION OF CASE: The case of a previously healthy 3-month-old girl with abdominal distension, post-prandial vomiting, obstipation, and anuria of 5 days' history is presented in this article. Abdomino-pelvic magnetic resonance imaging (MRI) showed a large cystic multilobulated mass in the sacrococcygeal region with a dural communication evident of an anterior sacral meningocele. 1 year later, the child came back with constipation and was found to a have a malignant mixed germ cell tumor in the presacral area, a very rare presentation in Currarino syndrome. DISCUSSION: In a child presenting with at least one of the features of Currarino syndrome's triad, a diagnosis should be suspected. After reviewing the literature, the syndrome is usually missed and hence is under diagnosed. MRI is the best imaging modality for diagnostics and follow-up for any mass, benign or malignant, can bring life saving measures. Most masses are benign but can undergo malignant transformation even after resection. De novo malignancy is very rare and is described in our case. CONCLUSION: Physicians treating patients with spinal dysraphism should suspect a diagnosis of Currarino syndrome by follow up imaging for any new benign or malignant growth.

Digital Delivery of Meditative Movement Training Improved Health of Cigarette-Smoke-Exposed Subjects.

Many FA who flew prior to the ban on smoking in commercial aircraft exhibit an unusual pattern of long-term pulmonary dysfunction. This randomized controlled study tested the hypothesis that digitally delivered meditative movement (MM) training improves chronic obstructive pulmonary disease (COPD)-related symptoms in flight attendants (FA) who were exposed to second-hand cigarette smoke (SHCS) while flying. Phase I of this two-phase clinical trial was a single-arm non-randomized pilot study that developed and tested methods for MM intervention; we now report on Phase II, a randomized controlled trial comparing MM to a control group of similar FA receiving health education (HE) videos. Primary outcomes were the 6-min walk test and blood levels of high sensitivity C-reactive protein (hs-CRP). Pulmonary, cardiovascular, autonomic and affective measures were also taken. There were significant improvements in the 6-min walk test, the Multidimensional Assessment of Interoceptive Awareness (MAIA) score, and the COPD Assessment Test. Non-significant trends were observed for increased dehydroepiandrosterone sulfate (DHEAS) levels, decreased anxiety scores and reduced blood hs-CRP levels, and increased peak expiratory flow (PEF). In a Survey Monkey questionnaire, 81% of participants who completed pre and post-testing expressed mild to strong positive opinions of the study contents, delivery, or impact, while 16% expressed mild negative opinions. Over the course of the year including the study, participant adoption of the MM practices showed a significant and moderately large correlation with overall health improvement; Pearson's R = 0.62, p < 0.005. These results support the hypothesized benefits of video-based MM training for this population. No adverse effects were reported. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT02612389.

Recurrent posterior reversible encephalopathy syndrome with cerebellar involvement leading to acute hydrocephalus.

Posterior reversible encephalopathy syndrome or PRES is a proposed cliniconeuroradiological entity that is characterized by headache, confusion, seizure, cortical visual disturbances or even blindness and, to a lesser extent, focal neurological signs. The etiology of this entity includes a sudden increase in blood pressure, renal failure, immunosuppressive drugs, infections, and intravenous immunoglobulin (IVIG). Classically, magnetic resonance imaging (MRI) findings show a symmetric reversible vasogenic edema in the parietooccipital lobes. PRES can involve the brainstem and cerebellum and sometimes can leave irreversible lesions but it can also recur, which is a very rare presentation. In this article, we report a case of recurrent PRES with cerebellar involvement associated with non-communicating hydrocephalus in a 2-year-old child with renal failure on peritoneal dialysis after receiving Etoposide for macrophage activation syndrome.

Spontaneous otogenic pneumocephalus due to altitude changes: A case report and review of literature.

BACKGROUND AND IMPORTANCE: Pneumocephalus secondary to trauma, infection or a tumor is a rare entity. In the absence of an underlying cause, it is considered to be spontaneous and represents around 1% of cases of pneumocephalus. CASE REPORT: In the present article, we describe the case of a male patient who presented with altered level of consciousness following his transition to an increased altitude (1000 m). CT scan demonstrated air located in the subdural, intraventricular and intraparenchymal compartments. He was found to have spontaneous otogenic pneumocephalus with an osteo-dural defect at the upper level of the petrous temporal bone resulting from a change in atmospheric pressure brought on by a change in altitude. A right subtemporal craniotomy with a right temporal duraplasty was performed. The patient had no recurrence after three years of follow-up. CONCLUSION: A fistula at the level of the temporal bone should be investigated in any patient with otologic manifestations and nonspecific neurological signs. This is the first case to describe a patient with spontaneous otogenic pneumocephalus with distribution of air in three intracranial locations. Surgery remains the treatment of choice for spontaneous otogenic pneumocephalus.

[Regional anesthesia for lumbar microdiscectomy]. / Anesthésie locorégionale pour cure microchirurgicale des hernies discales lombaires.

GOAL OF THE STUDY: Lumbar microdiscectomy surgery is already performed under spinal anesthesia (SA) in many institutions. The aim of this study is to compare the quality of analgesia and recovery after SA when compared to general anesthesia (GA) after lumbar microdiscectomy surgery. METHODS: Following light sedation, SA is performed with the patient in the left lateral decubitus position, one to two levels above the herniated disc level. Isobaric 0.5% bupivacaine 3-3.5 ml was injected intrathecally followed by wound infiltration with 15 ml of bupivacaine with 1/200 000 epinephrine prior to surgical incision. RESULTS: Despite randomization, we found significantly more females in the GA group. Pain scores at 4 and 8 h postoperatively were lower in SA group as well as total analgesic consumption during the first 24 h. Postoperative recovery including time to drinking, eating and walking were more rapid after SA when compared to GA. During the postoperative period, the incidence of urinary retention was comparable between groups but the occurrence of postoperative nausea and vomiting was significantly higher in the GA group. Moreover, the overall patient's and surgeon's satisfaction were significantly better in the SA group. CONCLUSION: SA associated to wound infiltration using bupivacaine is an interesting alternative to general anesthesia for outpatient lumbar microdiscectomy surgery.