An update on tests used for intraoperative monitoring of cognition during awake craniotomy.

PURPOSE: Mapping higher-order cognitive functions during awake brain surgery is important for cognitive preservation which is related to postoperative quality of life. A systematic review from 2018 about neuropsychological tests used during awake craniotomy made clear that until 2017 language was most often monitored and that the other cognitive domains were underexposed (Ruis, J Clin Exp Neuropsychol 40(10):1081-1104, 218). The field of awake craniotomy and cognitive monitoring is however developing rapidly. The aim of the current review is therefore, to investigate whether there is a change in the field towards incorporation of new tests and more complete mapping of (higher-order) cognitive functions. METHODS: We replicated the systematic search of the study from 2018 in PubMed and Embase from February 2017 to November 2023, yielding 5130 potentially relevant articles. We used the artificial machine learning tool ASReview for screening and included 272 papers that gave a detailed description of the neuropsychological tests used during awake craniotomy. RESULTS: Comparable to the previous study of 2018, the majority of studies (90.4%) reported tests for assessing language functions (Ruis, J Clin Exp Neuropsychol 40(10):1081-1104, 218). Nevertheless, an increasing number of studies now also describe tests for monitoring visuospatial functions, social cognition, and executive functions. CONCLUSIONS: Language remains the most extensively tested cognitive domain. However, a broader range of tests are now implemented during awake craniotomy and there are (new developed) tests which received more attention. The rapid development in the field is reflected in the included studies in this review. Nevertheless, for some cognitive domains (e.g., executive functions and memory), there is still a need for developing tests that can be used during awake surgery.

Asleep versus awake GPi DBS surgery for Parkinson's disease: A systematic review and meta-analysis.

BACKGROUND: Patients with Parkinson's Disease (PD) who receive either asleep image-guided subthalamic nucleus deep brain stimulation (DBS) or the traditional awake technique have comparable motor outcomes. However, there are fewer studies regarding which technique should be chosen for globus pallidus internus (GPi) DBS. This systematic review and meta-analysis aims to compare the accuracy of lead placement and motor outcomes of asleep versus awake GPi DBS PD population. METHODS: We systematically searched PubMed, Embase, and Cochrane for studies comparing asleep vs. awake GPi DBS lead placement in patients with PD. Outcomes were spatial accuracy of lead placement, measured by radial error between intended and actual location, motor improvement measured using (UPDRS III), and postoperative stimulation parameters. Statistical analysis was performed with Review Manager 5.1.7. and OpenMeta [Analyst]. RESULTS: Three studies met inclusion criteria with a total of 247 patients. Asleep DBS was used to treat 192 (77.7 %) patients. Follow-up ranged from 6 to 48 months. Radial error was not statistically different between groups (MD -0.49 mm; 95 % CI -1.0 to 0.02; I2 = 86 %; p = 0.06), with a tendency for higher target accuracy with the asleep technique. There was no significant difference between groups in change on motor function, as measured by UPDRS III, from pre- to postoperative (MD 8.30 %; 95 % CI -4.78 to 21.37; I2 = 67 %, p = 0.2). There was a significant difference in postoperative stimulation voltage, with the asleep group requiring less voltage than the awake group (MD -0.27 V; 95 % CI -0.46 to - 0.08; I2 = 0 %; p = 0.006). CONCLUSION: Our meta-analysis indicates that asleep image-guided GPi DBS presents a statistical tendency suggesting superior target accuracy when compared with the awake standard technique. Differences in change in motor function were not statistically significant between groups.

Cortico-cortical evoked potentials of language tracts in minimally invasive glioma surgery guided by Penfield stimulation.

OBJECTIVE: We investigated the feasibility of recording cortico-cortical evoked potentials (CCEPs) in patients with low- and high-grade glioma. We compared CCEPs during awake and asleep surgery, as well as those stimulated from the functional Broca area and recorded from the functional Wernicke area (BtW), and vice versa (WtB). We also analyzed CCEP properties according to tumor location, histopathology, and aphasia. METHODS: We included 20 patients who underwent minimally invasive surgery in an asleep-awake-asleep setting. Strip electrode placement was guided by classical Penfield stimulation of positive language sites and fiber tracking of the arcuate fascicle. CCEPs were elicited with alternating monophasic single pulses of 1.1 Hz frequency and recorded as averaged signals. Intraoperatively, there was no post-processing of the signal. RESULTS: Ninety-seven CCEPs from 19 patients were analyzed. There was no significant difference in CCEP properties when comparing awake versus asleep, nor BtW versus WtB. CCEP amplitude and latency were affected by tumor location and histopathology. CCEP features after tumor resection correlated with short- and long-term postoperative aphasia. CONCLUSION: CCEP recordings are feasible during minimally invasive surgery. CCEPs might be surrogate markers for altered connectivity of the language tracts. SIGNIFICANCE: This study may guide the incorporation of CCEPs into intraoperative neurophysiological monitoring.

Functions and mechanisms of adenosine and its receptors in sleep regulation.

Sleep is a natural and recurring state of life. Long-term insomnia can lead to physical and mental fatigue, inattention, memory loss, anxiety, depression and other symptoms, imposing immense public health and economic burden worldwide. The sleep and awakening regulation system is composed of many nerve nuclei and neurotransmitters in the brain, and it forms a neural network that interacts and restricts each other to regulate the occurrence and maintenance of sleep-wake. Adenosine (AD) is a neurotransmitter in the central nervous system and a driver of sleep. Meanwhile, the functions and mechanisms underlying sleep-promoting effects of adenosine and its receptors are still not entirely clear. However, in recent years, the increasing evidence indicated that adenosine can promote sleep through inhibiting arousal system and activating sleep-promoting system. At the same time, astrocyte-derived adenosine in modulating sleep homeostasis and sleep loss-induced related cognitive and memory deficits plays an important role. This review, therefore, summarizes the current research on the functions and possible mechanisms of adenosine and its receptors in the regulation of sleep and homeostatic control of sleep. Understanding these aspects will provide us better ideas on clinical problems such as insomnia, hypersomnia and other sleep disorders.

Hippocampal barques and their manifestation as 14&6 Hz positive spikes during sleep.

OBJECTIVE: This study investigates variations in hippocampal barque occurrence during sleep and compares findings to respective variations of their scalp manifestation as 14&6/sec positive spikes. METHODS: From 11 epilepsy patients, 12 non-epileptogenic hippocampi with barques were identified for this study. Using the first seizure-free whole-night sleep stereo-encephalography (sEEG) recording, we performed sleep staging and measured the occurrence of barques and 14&6/sec positive spikes variants. RESULTS: Hippocampal barques (total count: 9,183; mean count per record: 765.2 ± 251.2) occurred predominantly during non-rapid eye movement (NREM) II sleep (total: 5,744; mean: 478.6 ± 176.1; 62.2 ± 6.0%) and slow-wave sleep (SWS) (total: 2,950; mean: 245.83 ± 92.9; 32.0 ± 6.2%), with rare to occasional occurrence in NREM I (total: 85; mean: 7.0 ± 2.8; 0.9 ± 0.4%), rapid eye movement (REM) (total: 153; mean: 12.75 ± 4.0; 1.7 ± 0.6) and wakefulness (total: 251; mean: 20.9 ± 6.3; 2.9 ± 0.9%). Barque rate increased during SWS (mean: 2.7 ± 1.0 per min) compared to NREM II (2.2 ± 1.0 per min) and other states (wakefulness: 0.1 ± 0.0 per min; NREM I: 0.3 ± 0.1 per min; REM: 0.1 ± 0.0 per min). The 14&6/sec positive spikes variant (total count: 2,406; mean: 343.7 ± 106.7) was present in NREM II (total: 2,059; mean: 249.1 ± 100.2, 84.9 ± 3.6%) and SWS (total: 347; mean: 49.5 ± 12.8, 15.0 ± 3.6%) stages, and absent from the rest of sleep and wakefulness. While all 14&6/sec positive spikes correlated with barques, only 44.7 ± 6.1% of barques manifested as 14&6/sec positive spikes. CONCLUSIONS: Hippocampal barques are predominant in NREM II and SWS, and tend to increase their presence during SWS. Their scalp manifestation as 14&6/sec positive spikes is confounded by wakefulness, REM and NREM I stages, and "masked" by the co-occurrence of NREM II and SWS slow waves, and overlapping reactive micro-arousal elements. SIGNIFICANCE: Our study highlighted the overnight profile of hippocampal barques, in relation to the respective profile of their scalp manifestation, the 14&6/sec positive spikes variant.

Sustained polyphasic sleep restriction abolishes human growth hormone release.

STUDY OBJECTIVES: Voluntary sleep restriction is a common phenomenon in industrialized societies aiming to increase time spent awake and thus productivity. We explored how restricting sleep to a radically polyphasic schedule affects neural, cognitive, and endocrine characteristics. METHODS: Ten young healthy participants were restricted to one 20-minute nap opportunity at the end of every 4 hours (i.e. six sleep episodes per 24 hours) without any extended core sleep window, which resulted in a cumulative sleep amount of just 2 hours per day (i.e. ~20 minutes per bout). RESULTS: All but one participant terminated this schedule during the first month. The remaining participant (a 25-year-old male) succeeded in adhering to a polyphasic schedule for five out of the eight planned weeks. Cognitive and psychiatric measures showed modest changes during polyphasic as compared to monophasic sleep, while in-blood cortisol or melatonin release patterns and amounts were apparently unaltered. In contrast, growth hormone release was almost entirely abolished (>95% decrease), with the residual release showing a considerably changed polyphasic secretional pattern. CONCLUSIONS: Even though the study was initiated by volunteers with exceptional intrinsic motivation and commitment, none of them could tolerate the intended 8 weeks of the polyphasic schedule. Considering the decreased vigilance, abolished growth hormone release, and neurophysiological sleep changes observed, it is doubtful that radically polyphasic sleep schedules can subserve the different functions of sleep to a sufficient degree.

A modular system for the synchronized multimodal data acquisition during Awake Surgery: towards the emergence of a dedicated clinical database.

Awake Surgery (AS) is considered the best treatment for brain tumors located in or near eloquent areas. During this intervention, Direct Electrical Stimulations (DES) are delivered by the surgeon on the patient's brain in order to obtain an accurate brain mapping of the patient. The patient is asked to perform various tasks (e.g. counting, object naming, emotion recognition) through neuropsychological tests during these stimulations. These DES may cause a reversible lesion inducing deficits on the patient which can be observed during these tasks by the medical staff. The resection is then performed or not according to the patient's response. The intraoperative deficits can take several forms and can be difficult to analyze and identify. The development of new solutions allowing the automatic detection of these deficits could be therefore essential. However, still today, no structured and organized AS dedicated database is available that could be used to train and test these algorithms. We propose a modular system allowing the synchronized multimodal acquisition of various information including physiological measurements, DES signals and parameters, and task-related data to create such database.Clinical relevance- Acquiring synchronized multimodal data during AS will allow the creation of a dedicated database that could then be used to reveal new correlations between DES and the patient's response, and to develop and test new algorithms for the automatic detection of deficits.

Awake craniotomy during pregnancy: A systematic review of the published literature.

Neurosurgical pathologies in pregnancy pose significant complications for the patient and fetus, and physiological stressors during anesthesia and surgery may lead to maternal and fetal complications. Awake craniotomy (AC) can preserve neurological functions while reducing exposure to anesthetic medications. We reviewed the literature investigating AC during pregnancy. PubMed, Scopus, and Web of Science databases were searched from the inception to February 7th, 2023, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Studies in English investigating AC in pregnant patients were included in the final analysis. Nine studies composed of nine pregnant patients and ten fetuses (one twin-gestating patient) were included. Glioma was the most common pathology reported in six (66.7%) patients. The frontal lobe was the most involved region (4 cases, 44.4%), followed by the frontoparietal region (2 cases, 22.2%). The awake-awake-awake approach was the most common protocol in seven (77.8%) studies. The shortest operation time was two hours, whereas the longest one was eight hours and 29 min. The mean gestational age at diagnosis was 13.6 ± 6.5 (2-22) and 19.6 ± 6.9 (9-30) weeks at craniotomy. Seven (77.8%) studies employed intraoperative fetal heart rate monitoring. None of the AC procedures was converted to general anesthesia. Ten healthy babies were delivered from patients who underwent AC. In experienced hands, AC for resection of cranial lesions of eloquent areas in pregnant patients is safe and feasible and does not alter the pregnancy outcome.

Human brain mapping using co-registered fUS, fMRI and ESM during awake brain surgeries: A proof-of-concept study.

Accurate, depth-resolved functional imaging is key in both understanding and treatment of the human brain. A new sonography-based imaging technique named functional Ultrasound (fUS) uniquely combines high sensitivity with submillimeter-subsecond spatiotemporal resolution available in large fields-of-view. In this proof-of-concept study we show that: (A) fUS reveals the same eloquent regions as found by fMRI while concomitantly visualizing in-vivo microvascular morphology underlying these functional hemodynamics and (B) fUS-based functional maps are confirmed by Electrocortical Stimulation Mapping (ESM), the current gold-standard in awake neurosurgical practice. This unique cross-modality experiment was performed using motor, visual and language-related functional tasks in patients undergoing awake brain tumor resection. The current work serves as an important milestone towards further maturity of fUS as well as a novel avenue to increase our understanding of hemodynamics-based functional brain imaging.

A novel cognitive neurosurgery approach for supramaximal resection of non-dominant precuneal gliomas: a case report.

Despite mounting evidence pointing to the contrary, classical neurosurgery presumes many cerebral regions are non-eloquent, and therefore, their excision is possible and safe. This is the case of the precuneus and posterior cingulate, two interacting hubs engaged during various cognitive functions, including reflective self-awareness; visuospatial and sensorimotor processing; and processing social cues. This inseparable duo ensures the cortico-subcortical connectivity that underlies these processes. An adult presenting a right precuneal low-grade glioma invading the posterior cingulum underwent awake craniotomy with direct electrical stimulation (DES). A supramaximal resection was achieved after locating the superior longitudinal fasciculus II. During surgery, we found sites of positive stimulation for line bisection and mentalizing tests that enabled the identification of surgical corridors and boundaries for lesion resection. When post-processing the intraoperative recordings, we further identified areas that positively responded to DES during the trail-making and mentalizing tests. In addition, a clear worsening of the patient's self-assessment ability was observed throughout the surgery. An awake cognitive neurosurgery approach allowed supramaximal resection by reaching the cortico-subcortical functional limits. The mapping of complex functions such as social cognition and self-awareness is key to preserving patients' postoperative cognitive health by maximizing the ability to resect the lesion and surrounding areas.

Comparison of direct cortical stimulation and transcranial magnetic stimulation in brain tumor surgery: systematic review and meta analyses.

INTRODUCTION: Brain malignancy and, at the same time central nervous system malignancy are two of the most difficult problems in the oncology field of practice. Brain tumors located near or within eloquent areas may represent another challenge toward neurosurgeon treatment. As such, electrical stimulation, either directly or through other methods, may prove necessary as proper mapping of the eloquent area thus may create a proper resection guide. Minimal resection will hopefully preserve patient neurological function and ensure patient quality of life. METHODS: This research is a systematic review and meta-analysis that aim to compare outcomes, primarily adverse event analysis, between direct cortical stimulation and transcortical magnetic stimulation. RESULTS: Fourteen studies were identified between 2010 and the 2023 interval. While this number is sufficient, most studies were not randomized and were not accompanied by blinding. Meta-analysis was then applied as a hypothesis test, which showed that TMS were not inferior compared to DCS in terms of motoric and lingual outcome which were marked subjectively by diamond location and objectively through a p-value above 0.05. CONCLUSION: TMS is a noninvasive imaging method for the evaluation of eloquent brain areas that is not inferior compared to the invasive gold-standard imaging method (DCS). However its role as adjuvant to DCS and alternative only when awake surgery is not available must be emphasized.

Does EGFR Signaling Mediate Orexin System Activity in Sleep Initiation?

Sleep-wake cycle disorders are an important symptom of many neurological diseases, including Parkinson's disease, Alzheimer's disease, and multiple sclerosis. Circadian rhythms and sleep-wake cycles play a key role in maintaining the health of organisms. To date, these processes are still poorly understood and, therefore, need more detailed elucidation. The sleep process has been extensively studied in vertebrates, such as mammals and, to a lesser extent, in invertebrates. A complex, multi-step interaction of homeostatic processes and neurotransmitters provides the sleep-wake cycle. Many other regulatory molecules are also involved in the cycle regulation, but their functions remain largely unclear. One of these signaling systems is epidermal growth factor receptor (EGFR), which regulates the activity of neurons in the modulation of the sleep-wake cycle in vertebrates. We have evaluated the possible role of the EGFR signaling pathway in the molecular regulation of sleep. Understanding the molecular mechanisms that underlie sleep-wake regulation will provide critical insight into the fundamental regulatory functions of the brain. New findings of sleep-regulatory pathways may provide new drug targets and approaches for the treatment of sleep-related diseases.

Combined use of intraoperative MRI and awake tailored microsurgical resection to respect functional neural networks: preliminary experience.

INTRODUCTION: The combined use of intraoperative MRI and awake surgery is a tailored microsurgical resection to respect functional neural networks (mainly the language and motor ones). Intraoperative MRI has been classically considered to increase the extent of resection for gliomas, thereby reducing neurological deficits. Herein, we evaluated the combined technique of awake microsurgical resection and intraoperative MRI for primary brain tumours (gliomas, metastasis) and epilepsy (cortical dysplasia, non-lesional, cavernomas). PATIENTS AND METHODS: Eighteen patients were treated with the commonly used "asleep awake asleep" (AAA) approach at Lille University Hospital, France, from November 2016 until May 2020. The exact anatomical location was insular with various extensions, frontal, temporal or fronto-temporal in 8 (44.4%), parietal in 3 (16.7%), fronto-opercular in 4 (22.2%), Rolandic in two (11.1%), and the supplementary motor area (SMA) in one (5.6%). RESULTS: The patients had a mean age of 38.4 years (median 37.1, range 20.8-66.9). The mean surgical duration was 4.1 hours (median 4.2, range 2.6-6.4) with a mean duration of intraoperative MRI of 28.8 minutes (median 25, range 13-55). Overall, 61% (11/18) of patients underwent further resection, while 39% had no additional resection after intraoperative MRI. The mean preoperative and postoperative tumour volumes of the primary brain tumours were 34.7 cc (median 10.7, range 0.534-130.25) and 3.5 cc (median 0.5, range 0-17.4), respectively. Moreover, the proportion of the initially resected tumour volume at the time of intraoperative MRI (expressed as 100% from preoperative volume) and the final resected tumour volume were statistically significant (p= 0.01, Mann-Whitney test). The tumour remnants were commonly found posterior (5/9) or anterior (2/9) insular and in proximity with the motor strip (1/9) or language areas (e.g. Broca, 1/9). Further resection was not required in seven patients because there were no remnants (3/7), cortical stimulation approaching eloquent areas (3/7) and non-lesional epilepsy (1/7). The mean overall follow-up period was 15.8 months (median 12, range 3-36). CONCLUSION: The intraoperative MRI and awake microsurgical resection approach is feasible with extensive planning and multidisciplinary collaboration, as these methods are complementary and synergic rather than competitive to improve patient oncological outcomes and quality of life.

[Mapping the musician brain during awake craniotomy]. / Kartirovanie muzykal'nykh tsentrov golovnogo mozga vo vremya kraniotomii v soznanii.

Direct cortical stimulation during awake craniotomy with speech testing became the «gold standard¼ in brain mapping and preserving speech zones during neurosurgical procedures. However, there are many other cerebral functions, and their loss can be very critical for certain patients. For example, such a function is production and perception of music for musicians. This review presents the latest data on functional anatomy of musician brain, as well as aspects of neurosurgical treatment with awake craniotomy and music testing under brain mapping.

Subcortical language localization using sign language and awake craniotomy for dominant posterior temporal glioma resection in a hearing-impaired patient.

Intraoperative direct cortical stimulation (DCS) is the gold standard technique to maximize the extent of resection of tumors located in eloquent areas. To date, there are three cases reported of awake mapping for language centers in deaf patients who could communicate only with sign language. We present the case of DCS in a deaf patient who could communicate vocally, native to American Sign Language and English, that underwent intraoperative awake mapping. DCS showed similar disruption of expressive phonology to both pictorial and gestural stimuli, confirming that sign language follows the same pattern as oral language.

The current state of the art of primary motor mapping for tumor resection: A focused survey.

INTRODUCTION: Cortical and subcortical motor mapping has advanced the notion of maximal safe resection of intra-axial brain tumours, thereby preserving neurological functions as well as improving survival. Despite being an age-old and established neurosurgical procedure across the world, the strategy and techniques involved in motor mapping have a gamut of variation due to a lack of defined standard protocols. METHODS: We disseminated a structured survey among focused group of neurosurgeons with established practices involving brain mapping. It consisted of 40 questions, split into five sections assessing the practice description, general approach for motor mapping, preference for asleep versus awake mapping, operative techniques and approach to representative tumor cases. Practice-patterns during primary motor mapping for brain tumours were analysed from responses of 51 neurosurgeons. RESULTS: 60.8 % felt that any lesion even near (without infiltration) was suffice to define "involvement" of the cortical/subcortical motor pathways. 82.4 % felt that motor mapping was necessary for brain tumours involving motor pathways, irrespective of the tumor histology or patient age. 90.2 % opined that tumor location was the predominant factor affecting their choice between awake or asleep mapping. 31.4 % believed that all cases should be performed awake unless patient-related medical, psychological, or anaesthetic contraindications exist, whereas 45.1 % felt that all cases should be performed asleep unless language mapping is required. MRI, DTI-based tractography and intra-operative fluorescence were the most commonly employed surgical adjuncts. CONCLUSIONS: The data from this survey may serve as a preliminary foundation for a more standardized approach to patient selection and the approach to motor mapping for brain tumors.

Localization patterns of speech and language errors during awake brain surgery: a systematic review.

Awake craniotomy with direct electrical stimulation (DES) is the standard treatment for patients with eloquent area gliomas. DES detects speech and language errors, which indicate functional boundaries that must be maintained to preserve quality of life. During DES, traditional object naming or other linguistic tasks such as tasks from the Dutch Linguistic Intraoperative Protocol (DuLIP) can be used. It is not fully clear which speech and language errors occur in which brain locations. To provide an overview and to update DuLIP, a systematic review was conducted in which 102 studies were included, reporting on speech and language errors and the corresponding brain locations during awake craniotomy with DES in adult glioma patients up until 6 July 2020. The current findings provide a crude overview on language localization. Even though subcortical areas are in general less often investigated intraoperatively, still 40% out of all errors was reported at the subcortical level and almost 60% at the cortical level. Rudimentary localization patterns for different error types were observed and compared to the dual-stream model of language processing and the DuLIP model. While most patterns were similar compared to the models, additional locations were identified for articulation/motor speech, phonology, reading, and writing. Based on these patterns, we propose an updated DuLIP model. This model can be applied for a more adequate "location-to-function" language task selection to assess different linguistic functions during awake craniotomy, to possibly improve intraoperative language monitoring. This could result in a better postoperative language outcome in the future.

Recovery of Visual Field After Awake Stimulation Mapping of the Optic Pathway in Glioma Patients.

Brain mapping during awake craniotomy for gliomas can help preserve neurological functions, including maintenance of central and peripheral vision. However, the consecutive changes in the visual field remain unknown. We retrospectively assessed 14 patients who underwent awake craniotomy for gliomas infiltrating into the optic radiation. Cortico-subcortical direct electrical stimulation (DES) was intraoperatively applied until transient visual symptoms were elicited and recorded. The visual fields were examined consecutively in the preoperative period and postoperative subacute and chronic periods. To evaluate the anatomo-functional validity of the recordings, all DES-elicited points were overlaid onto a three-dimensional template that included the optic radiation, using voxel-based morphometry (VBM) mapping. All patients experienced visual symptoms that were classified as phosphenes, blurred vision, or hallucinations during DES, and surgical resection was limited to within the functional boundaries. In VBM, almost all the subcortical positive mapping points overlapped with the surface of the optic radiation, and the distribution of sites that induced visual phenomena in the upper or lower visual fields could be differentiated in the anatomical space. We observed no postoperative visual deficit in four patients (29%), time-dependent improvements in five out of eight patients that presented transient quadrantanopia or partial visual defect (36% out of 57%), and permanent hemianopsia (14%) in two patients with occipital lesions. Intraoperative DES that identifies and preserves optic radiation in awake craniotomy for gliomas is a reliable and effective technique to reduce risk of permanent deficits, but has a low success rate in patients with occipital involvement.

Acute head-fixed recordings in awake mice with multiple Neuropixels probes.

Multi-electrode arrays such as Neuropixels probes enable electrophysiological recordings from large populations of single neurons with high temporal resolution. By using such probes, the activity from functionally interacting, yet distinct, brain regions can be measured simultaneously by inserting multiple probes into the same subject. However, the use of multiple probes in small animals such as mice requires the removal of a sizable fraction of the skull, while also minimizing tissue damage and keeping the brain stable during the recordings. Here, we describe a step-by-step process designed to facilitate reliable recordings from up to six Neuropixels probes simultaneously in awake, head-fixed mice. The procedure involves four stages: the implantation of a headframe and a removable glass coverslip, the precise positioning of the Neuropixels probes at targeted points on the brain surface, the placement of a perforated plastic imaging window and the insertion of the probes into the brain of an awake mouse. The approach provides access to multiple brain regions and has been successfully applied across hundreds of mice. The procedure has been optimized for dense recordings from the mouse visual system, but it can be adapted for alternative recording configurations to target multiple probes in other brain areas. The protocol is suitable for users with experience in stereotaxic surgery in mice.

NREM-REM alternation complicates transitions from napping to non-napping behavior in a three-state model of sleep-wake regulation.

The temporal structure of human sleep changes across development as it consolidates from the polyphasic sleep of infants to the single nighttime sleep episode typical in adults. Experimental studies have shown that changes in the dynamics of sleep need may mediate this developmental transition in sleep patterning, however, it is unknown how sleep architecture interacts with these changes. We employ a physiologically-based mathematical model that generates wake, rapid eye movement (REM) and non-REM (NREM) sleep states to investigate how NREM-REM alternation affects the transition in sleep patterns as the dynamics of the homeostatic sleep drive are varied. To study the mechanisms producing these transitions, we analyze the bifurcations of numerically-computed circle maps that represent key dynamics of the full sleep-wake network model by tracking the evolution of sleep onsets across different circadian (∼ 24 h) phases. The maps are non-monotonic and discontinuous, being composed of branches that correspond to sleep-wake cycles containing distinct numbers of REM bouts. As the rates of accumulation and decay of the homeostatic sleep drive are varied, we identify the bifurcations that disrupt a period-adding-like behavior of sleep patterns in the transition between biphasic and monophasic sleep. These bifurcations include border collision and saddle-node bifurcations that initiate new sleep patterns, period-doubling bifurcations leading to higher-order patterns of NREM-REM alternation, and intervals of bistability of sleep patterns with different NREM-REM alternations. Furthermore, patterns of NREM-REM alternation exhibit variable behaviors in different regimes of constant sleep-wake patterns. Overall, the sequence of sleep-wake behaviors, and underlying bifurcations, in the transition from biphasic to monophasic sleep in this three-state model is more complex than behavior observed in models of sleep-wake regulation that do not consider the dynamics of NREM-REM alternation. These results suggest that interactions between the dynamics of the homeostatic sleep drive and the dynamics of NREM-REM alternation may contribute to the wide interindividual variation observed when young children transition from napping to non-napping behavior.