[Chronology of Justo Gonzalo's research on brain dynamics]. / Cronología de la investigación sobre la dinámica cerebral de Justo Gonzalo.

INTRODUCTION: The Spanish neuroscientist Justo Gonzalo y Rodriguez-Leal (1910-1986) investigated the functional organisation of the cerebral cortex over more than four decades. His findings led him to formulate a neurophysiological theory based on the laws of nervous excitability, which he called brain dynamics. This paper presents in chronological order how the main ideas on which it is based arose. DEVELOPMENT: In 1939, Gonzalo observed the phenomena of dynamic action: asynchrony or disaggregation, facilitation and cerebral repercussion. This was followed by two principles: the cerebral effect of lesions according to their magnitude and position (1941), and spiral development of the sensory field (1947). At the same time, he characterised what he called the central syndrome of the cerebral cortex. In the 1950s he developed the concepts of the cortical gradient, similarity and allometry. In contrast to modular conceptions of the cerebral cortex, in which one region is responsible for one function, Gonzalo argued that 'cortical gradients provide the location of systems, while similarity and allometry reveal their functional mechanism.' CONCLUSIONS: The theory of brain dynamics was established in two stages. The first (between 1938 and 1950) had an important clinical foundation, involving the observation of new phenomena and the formulation of new concepts. The second (between 1950 and 1960) included the introduction of more far-reaching concepts, such as the functional cortical gradient, and allometry laws based on a change of scale. Today, various authors believe that the concept of the gradient is crucial for understanding how the brain is organised.

TITLE: Cronología de la investigación sobre la dinámica cerebral de Justo Gonzalo.Introducción. El neurocientífico español Justo Gonzalo y Rodríguez-Leal (1910-1986) investiga la organización funcional de la corteza cerebral durante más de cuatro décadas. Sus hallazgos le llevan a formular una teoría neurofisiológica basada en las leyes de la excitabilidad nerviosa, que denomina dinámica cerebral. En el presente trabajo se expone de forma cronológica cómo surgen las principales ideas sobre las que se articula.Desarrollo. En 1939 Gonzalo observa los denominados fenómenos de acción dinámica: desfasamiento, facilitación y repercusión cerebral. Le siguen dos principios: efecto cerebral de la lesión según la magnitud y posición (1941), y organización sensorial, según un desarrollo espiral (1947). Paralelamente, caracteriza lo que llama el síndrome central de la corteza cerebral. En la década de los cincuenta desarrolla los conceptos de gradiente cortical, similitud y alometría. En contraposición a las concepciones modulares de la corteza cerebral, en las que una región es responsable de una función, Gonzalo expresa que 'los gradientes corticales dan la localización de los sistemas mientras la similitud y alometría revelan su trama funcional'. Conclusiones. La teoría de dinámica cerebral se articula en dos etapas. La primera (de 1938 a 1950) se caracteriza por una importante base clínica con observación de nuevos fenómenos y formulación de nuevos conceptos. La segunda (de 1950 a 1960) incluye la introducción de conceptos de mayor alcance, como el gradiente funcional cortical, y leyes de alometría que se basan en un cambio de escala. Actualmente, varios autores consideran que el concepto de gradiente es clave para entender la organización cerebral.

Serial Nerve Conduction Studies in Guillain-Barré Syndrome: Its Usefulness and Precise Timing.

PURPOSE: Nerve conduction study (NCS) is essential for subclassifying Guillain-Barré syndrome (GBS). It is well known that the GBS subclassification can change through serial NCSs. However, the usefulness of serial NCSs is debatable, especially in patients with early stage GBS. METHODS: Follow-up NCS data within 3 weeks (early followed NCS, EFN) and within 3 to 10 weeks (late-followed NCS, LFN) were collected from 60 patients with GBS who underwent their first NCS (FN) within 10 days after symptom onset. Each NCS was classified into five subtypes (normal, demyelinating, axonal, inexcitable, and equivocal), according to Hadden's and Rajabally's criteria. We analyzed the frequency of significant changes in classification (SCCs) comprising electrodiagnostic aggravation and subtype shifts between demyelinating and axonal types according to follow-up timing. RESULTS: Between FN and EFN, 33.3% of patients with Hadden's criteria and 18.3% with Rajabally's criteria showed SCCs. Between FN and LFN, 23.3% of patients with Hadden's criteria and 21.7% with Rajabally's criteria showed SCCs, of which 71.4% (Hadden's criteria) and 46.2% (Rajabally's criteria) already showed SCCs from the EFN. The conditions of delayed SCCs between EFN and LFN were very early FN, mild symptoms at the FN, or persistent electrophysiological deterioration 3 weeks after symptom onset. CONCLUSIONS: A substantial proportion of patients with GBS showed significant changes in neurophysiological classification at the early stage. Serial NCS may be helpful for precise neurophysiological classification. This study suggests that follow-up NCSs should be performed within 3 weeks of symptom onset in patients with GBS in whom FN was performed within 10 days of symptom onset.

One hundred years of excellence: the top one hundred authors of the Journal of Comparative Physiology A.

The Journal of Comparative Physiology A is the premier peer-reviewed scientific journal in comparative physiology, in particular sensory physiology, neurophysiology, and neuroethology. Founded in 1924 by Karl von Frisch and Alfred Kühn, it celebrates its 100th anniversary in 2024. During these 100 years, many of the landmark achievements in these disciplines were published in this journal. To commemorate these accomplishments, we have compiled a list of the Top 100 Authors over these 100 years, representing approximately 1% of all its authors. To select these individuals, three performance criteria were applied: number of publications, total number of citations attracted by these articles, and mean citation rate of the papers published by each author. The resulting list of the Top 100 Authors provides a fascinating insight into the history of the disciplines covered by the Journal of Comparative Physiology A and into the academic careers of many of their leading representatives.

So many toadfish, so little timea).

The oyster toadfish, Opsanus tau, has been a valuable biomedical model for a wide diversity of studies. However, its vocalization ability arguably has attracted the most attention, with numerous studies focusing on its ecology, behavior, and neurophysiology in regard to its sound production and reception. This paper reviews 30 years of research in my laboratory using this model to understand how aquatic animals detect, integrate, and respond to external environment cues. The dual vestibular and auditory role of the utricle is examined, and its ability to integrate multimodal input is discussed. Several suggestions for future research are provided, including in situ auditory recording, interjecting natural relevant ambient soundscapes into laboratory sound studies, adding transparency to the field of acoustic deterrents, and calls for fish bioacoustics teaching modules to be incorporated in K-12 curricula to excite and diversify the next generation of scientists.

Atypical alpha band microstates produced during eyes-closed resting state EEG in autism.

Electroencephalogram (EEG) microstates, which represent quasi-stable patterns of scalp topography, are a promising tool that has the temporal resolution to study atypical spatial and temporal networks in autism spectrum disorder (ASD). While current literature suggests microstates are atypical in ASD, their clinical utility, i.e., relationship with the core behavioural characteristics of ASD, is not fully understood. The aim of this study was to examine microstate parameters in ASD, and examine the relationship between these parameters and core behavioural characteristics in ASD. We compared duration, occurrence, coverage, global explained variance percentage, global field power and spatial correlation of EEG microstates between autistic and neurotypical (NT) adults. Modified k-means cluster analysis was used on eyes-closed, resting state EEG from 30 ASD (10 females, 28.97 ± 9.34 years) and 30 age-equated NT (13 females, 29.33 ± 8.88 years) adults. Five optimal microstates, A to E, were selected to best represent the data. Five microstate maps explaining 80.44% of the NT and 78.44% of the ASD data were found. The ASD group was found to have atypical parameters of microstate A, C, D, and E. Of note, all parameters of microstate C in the ASD group were found to be significantly less than NT. While parameters of microstate D, and E were also found to significantly correlate with subscales of the Ritvo Autism Asperger Diagnostic Scale - Revised (RAADS-R), these findings did not survive a Bonferroni Correction. These findings, in combination with previous findings, highlight the potential clinical utility of EEG microstates and indicate their potential value as a neurophysiologic marker that can be further studied.

Sleepiness should be reinvestigated through the lens of clinical neurophysiology: A mixed expertal and big-data Natural Language Processing approach.

Historically, the field of sleep medicine has revolved around electrophysiological tools. However, the use of these tools as a neurophysiological method of investigation seems to be underrepresented today, from both international recommendations and sleep centers, in contrast to behavioral and psychometric tools. The aim of this article is to combine a data-driven approach and neurophysiological and sleep medicine expertise to confirm or refute the hypothesis that neurophysiology has declined in favor of behavioral or self-reported dimensions in sleep medicine for the investigation of sleepiness, despite the use of electrophysiological tools. Using Natural Language Processing methods, we analyzed the abstracts of the 18,370 articles indexed by PubMed containing the terms 'sleepiness' or 'sleepy' in the title, abstract, or keywords. For this purpose, we examined these abstracts using two methods: a lexical network, enabling the identification of concepts (neurophysiological or clinical) related to sleepiness in these articles and their interconnections; furthermore, we analyzed the temporal evolution of these concepts to extract historical trends. These results confirm the hypothesis that neurophysiology has declined in favor of behavioral or self-reported dimensions in sleep medicine for the investigation of sleepiness. In order to bring sleepiness measurements closer to brain functioning and to reintroduce neurophysiology into sleep medicine, we discuss two strategies: the first is reanalyzing electrophysiological signals collected during the standard sleep electrophysiological test; the second takes advantage of the current trend towards dimensional models of sleepiness to situate clinical neurophysiology at the heart of the redefinition of sleepiness.

Global Perceptions and Utilization of Clinical Neurophysiology in Movement Disorders.

BACKGROUND: Clinical neurophysiology (CNP) involves the use of neurophysiological techniques to make an accurate clinical diagnosis, to quantify the severity, and to measure the treatment response. Despite several studies showing CNP to be a useful diagnostic tool in Movement Disorders (MD), its more widespread utilization in clinical practice has been limited. OBJECTIVES: To better understand the current availability, global perceptions, and challenges for implementation of diagnostic CNP in the clinical practice of MD. METHODS: The International Parkinson and Movement Disorders Society (IPMDS) formed a Task Force on CNP. The Task Force distributed an online survey via email to all the members of the IPMDS between August 5 and 30, 2021. Descriptive statistics were used for analysis of the survey results. Some results are presented by IPMDS geographical sections namely PanAmerican (PAS), European (ES), African (AFR), Asian and Oceanian (AOS). RESULTS: Four hundred and ninety-one IPMDS members (52% males), from 196 countries, responded. The majority of responders from the AFR (65%) and PAS (63%) sections had no formal training in diagnostic CNP (40% for AOS and 37% for ES). The most commonly used techniques are electroencephalography (EEG) (72%) followed by surface EMG (71%). The majority of responders think that CNP is somewhat valuable or very valuable in the assessment of MD. All the sections identified "lack of training" as one of the biggest challenges for diagnostic CNP studies in MD. CONCLUSIONS: CNP is perceived to be a useful diagnostic tool in MD. Several challenges were identified that prevent widespread utilization of CNP in MD.

Electroencephalographic microstates as a potential neurophysiological marker differentiating bilateral from unilateral temporal lobe epilepsy.

OBJECTIVE: Electroencephalographic (EEG) microstate abnormalities have been documented in different neurological disorders. We aimed to assess whether EEG microstates are altered also in patients with temporal epilepsy (TLE) and whether they show different activations in patients with unilateral TLE (UTLE) and bilateral TLE (BTLE). METHODS: Nineteen patients with UTLE, 12 with BTLE, and 15 healthy controls were enrolled. Resting state high-density electroencephalography (128 channels) was recorded for 15 min with closed eyes. We obtained a set of stable scalp maps representing the EEG activity, named microstates, from which we acquired the following variables: global explained variance (GEV), mean duration (MD), time coverage (TC), and frequency of occurrence (FO). Two-way repeated measures analysis of variance was used to compare groups, and Spearman correlation was performed to study the maps in association with the clinical and neuropsychological data. RESULTS: Patients with BTLE and UTLE showed differences in most of the parameters (GEV, MD, TC, FO) of the four microstate maps (A-D) compared to controls. Patients with BTLE showed a significant increase in all parameters for the microstates in Map-A and a decrease in Map-D compared to UTLE and controls. We observed a correlation between Map-A, disease duration, and spatial short-term memory, whereas microstate Map-D was correlated with the global intelligence score and short-term memory performance. SIGNIFICANCE: A global alteration of the neural dynamics was observed in patients with TLE compared to controls. A different pattern of EEG microstate abnormalities was identified in BTLE compared to UTLE, which might represent a distinctive biomarker.

Immediate reuse of patch-clamp pipettes after ultrasonic cleaning.

The patch-clamp technique has revolutionized neurophysiology by allowing to study single neuronal excitability, synaptic connectivity, morphology, and the transcriptomic profile. However, the throughput in recordings is limited because of the manual replacement of patch-pipettes after each attempt which are often also unsuccessful. This has been overcome by automated cleaning the tips in detergent solutions, allowing to reuse the pipette for further recordings. Here, we developed a novel method of automated cleaning by sonicating the tips within the bath solution wherein the cells are placed, reducing the risk of contaminating the bath solution or internal solution of the recording pipette by any detergent and avoiding the necessity of a separate chamber for cleaning. We showed that the patch-pipettes can be used consecutively at least ten times and that the cleaning process does not negatively impact neither the brain slices nor other patched neurons. This method, combined with automated patch-clamp, highly improves the throughput for single and especially multiple recordings.

Technical Considerations in EEG Source Imaging.

SUMMARY: EEG source imaging is an established technique for identifying the origin of interictal and ictal epileptiform discharges in patients with epilepsy, and it is an important tool in neurophysiology research. Accurate and reliable EEG source imaging requires appropriate choices of how the head, skull, and scalp are modeled, and understanding of the different approaches to modeling is important to guide these choices. Similarly, numerous different approaches to modeling the electrical sources within the brain exist, and appropriate understanding of the strengths and limitations of each are essential to obtaining accurate, reliable, and interpretable solutions. This review aims to describe the essential theoretical basis for these head and source models while also discussing the practical implications of each in clinical or research applications.

Interictal Electrical Source Imaging.

SUMMARY: Interictal electrical source imaging (ESI) determines the neuronal generators of epileptic activity in EEG occurring outside of seizures. It uses computational models to take anatomic and neuronal characteristics of the individual patient into account. The presented article provides an overview of application and clinical value of interictal ESI in patients with pharmacoresistant focal epilepsies undergoing evaluation for surgery. Neurophysiological constraints of interictal data are discussed and technical considerations are summarized. Typical indications are covered as well as issues of integration into clinical routine. Finally, an outlook on novel markers of epilepsy for interictal source analysis is presented. Interictal ESI provides diagnostic performance on par with other established methods, such as MRI, PET, or SPECT. Although its accuracy benefits from high-density recordings, it provides valuable information already when applied to EEG with only a limited number of electrodes with complete coverage. Novel oscillatory markers and the integration of frequency coupling and connectivity may further improve accuracy and efficiency.

Inserting a Neuropixels probe into awake monkey cortex: two probes, two methods.

BACKGROUND: Neuropixels probes have revolutionized neurophysiological studies in the rodent, but inserting these probes through the much thicker primate dura remains a challenge. NEW METHODS: Here we describe two methods we have developed for the insertion of two types of Neuropixels probes acutely into the awake macaque monkey cortex. For the fine rodent probe (Neuropixels 1.0, IMEC), which is unable to pierce native primate dura, we developed a dural-eyelet method to insert the probe repeatedly without breakage. For the thicker short NHP probe (Neuropixels NP1010), we developed an artificial dura system to insert the probe. RESULTS AND COMPARISON WITH EXISTING METHODS: We have now conducted successful experiments in 3 animals across 7 recording chambers with the procedures described here and have achieved recordings with similar yields over several months in each case. CONCLUSION: We hope that our hardware, surgical preparation, methods for insertion and methods for removal of broken probe parts are of value to primate physiologists everywhere.

Making sense of music: Insights from neurophysiology and connectivity analyses in naturalistic listening conditions.

According to the latest frameworks, auditory perception and memory involve the constant prediction of future sound events by the brain, based on the continuous extraction of feature regularities from the environment. The neural hierarchical mechanisms for predictive processes in perception and memory for sounds are typically studied in relation to simple acoustic features in isolated sounds or sound patterns inserted in highly certain contexts. Such studies have identified reliable prediction formation and error signals, e.g., the N100 or the mismatch negativity (MMN) evoked responses. In real life, though, individuals often face situations in which uncertainty prevails and where making sense of sounds becomes a hard challenge. In music, not only deviations from predictions are masterly set up by composers to induce emotions but sometimes the sheer uncertainty of sound scenes is exploited for aesthetic purposes, especially in compositional styles such as Western atonal classical music. In very recent magnetoencephalography (MEG) and electroencephalography (EEG) studies, experimental and technical advances in stimulation paradigms and analysis approaches have permitted the identification of prediction-error responses from highly uncertain, atonal contexts and the extraction of prediction-related responses from real, continuous music. Moreover, functional connectivity analyses revealed the emergence of cortico-hippocampal interactions during the formation of auditory memories for more predictable vs. less predictable patterns. These findings contribute to understanding the general brain mechanisms that enable us to predict even highly uncertain sound environments and to possibly make sense of and appreciate even atonal music.

A neurophysiological approach to mirror movements in amyotrophic lateral sclerosis.

OBJECTIVE: To investigate mirror activity in amyotrophic lateral sclerosis (ALS) patients, using a simple paradigm of signal quantification. METHODS: Patients were asked to perform a brief isometric maximum contraction of the abductor digiti minimi (ADM) or tibialis anterior (TA) on one side, while relaxing the contralateral side of the body. Both sides were investigated. Signals were stored and analyzed offline, for quantification of electromyographic signal. Clinical signs of upper motor neuron (UMN) dysfunction, transcranial magnetic stimulation (TMS) for the upper (UL) and lower limbs (LL), the ADM ipsilateral cortical silent period (iSP) and the Edinburgh Cognitive and Behavioral ALS Screen (ECAS) cognitive scale were also investigated. RESULTS: 42 ALS patients were included. In the 4 investigated muscles the amount of mirror activity was significantly higher than in the matched healthy group. The amount of mirror activity was similar between sides, but significantly higher in UL and LL with abnormal TMS results for ADM (p = 0.005) and TA (p = 0.002), as well as in UL with abnormal iSP values (p = 0.009). No association was found between mirror activity and clinical signs of UMN involvement. CONCLUSIONS: Mirror activity is a common phenomenon in ALS. Mirror activity intensity corresponds to the severity of UMN dysfunction, as measured by TMS, and probably derives from the abnormal transcallosal inhibition as mirrored by iSP abnormality. SIGNIFICANCE: Mirror activity is increased in ALS and is associated with abnormal transcallosal inhibition and UMN dysfunction.

Does the brain behave like a (complex) network? I. Dynamics.

Graph theory is now becoming a standard tool in system-level neuroscience. However, endowing observed brain anatomy and dynamics with a complex network structure does not entail that the brain actually works as a network. Asking whether the brain behaves as a network means asking whether network properties count. From the viewpoint of neurophysiology and, possibly, of brain physics, the most substantial issues a network structure may be instrumental in addressing relate to the influence of network properties on brain dynamics and to whether these properties ultimately explain some aspects of brain function. Here, we address the dynamical implications of complex network, examining which aspects and scales of brain activity may be understood to genuinely behave as a network. To do so, we first define the meaning of networkness, and analyse some of its implications. We then examine ways in which brain anatomy and dynamics can be endowed with a network structure and discuss possible ways in which network structure may be shown to represent a genuine organisational principle of brain activity, rather than just a convenient description of its anatomy and dynamics.

Circadian neurogenetics and its implications in neurophysiology, behavior, and chronomedicine.

The circadian rhythm affects multiple physiological processes, and disruption of the circadian system can be involved in a range of disease-related pathways. The genetic underpinnings of the circadian rhythm have been well-studied in model organisms. Significant progress has been made in understanding how clock genes affect the physiological functions of the nervous system. In addition, circadian timing is becoming a key factor in improving drug efficacy and reducing drug toxicity. The circadian biology of the target cell determines how the organ responds to the drug at a specific time of day, thus regulating pharmacodynamics. The current review brings together recent advances that have begun to unravel the molecular mechanisms of how the circadian clock affects neurophysiological and behavioral processes associated with human brain diseases. We start with a brief description of how the ubiquitous circadian rhythms are regulated at the genetic, cellular, and neural circuit levels, based on knowledge derived from extensive research on model organisms. We then summarize the latest findings from genetic studies of human brain disorders, focusing on the role of human clock gene variants in these diseases. Lastly, we discuss the impact of common dietary factors and medications on human circadian rhythms and advocate for a broader application of the concept of chronomedicine.