Mahdi Mahmoudzadeh

Neurocrine Biosciences, Inc.

During the last trimester of gestation, fetuses and preterm neonates begin to respond to sensory stimulation and to discover the structure of their environment. Yet, neuronal migration is still ongoing. This late migration notably concerns the supra-granular layers neurons, which are believed to play a critical role in encoding predictions and dete...

In nature, biological systems such as the human brain are characterized by complex and non-linear dynamics. One way of quantifying signal complexity is Multiscale Entropy (MSE), which is suitable for structures with long-range correlation at different time scales. In developmental neuroscience, MSE can be taken as an index of brain maturation, and...

Significance aims: The neurovascular mechanisms underlying the initiation of absence seizures and their dynamics are still not well understood. The objective of this study was to better noninvasively characterize the dynamics of the neuronal and vascular network at the transition from the interictal state to the ictal state of absence seizures and...

In nature, biological systems such as the human brain are characterized by complex and non-linear dynamics. One way of quantifying signal complexity is Multiscale Entropy (MSE), which is suitable for structures with long-range correlation at different time scales. In developmental neuroscience, MSE can be taken as an index of brain maturation, and...

Rhythm is a fundamental component of the auditory world, present even during the prenatal life. While there is evidence that some auditory capacities are already present before birth, whether and how the premature neural networks process auditory rhythm is yet not known. We investigated the neural response of premature neonates at 30–34 weeks gesta...

In a recent study on visual episodic memory (Desaunay, Clochon, et al., 2020), we have shown event‐related potentials (ERPs) differences associated with priming (150–300 msec), familiarity (350–470 msec), and recollection (600–700 msec), in young people with autism spectrum disorders (ASD) compared with typical development (TD). To go further into...

The frontal sharp transient (FST) consists of transient electrical activity recorded around the transitional period from the in to ex utero environment. Although its positive predictive value is assumed, nothing is known about its functionality or origin. The objectives were (i) to define its characteristics and (ii) to develop functional hypothesi...

Background Autism spectrum disorder (ASD) is associated with atypical neural activity in resting state. Most of the studies have focused on abnormalities in alpha frequency as a marker of ASD dysfunctions. However, few have explored alpha synchronization within a specific interest in resting-state networks, namely the default mode network (DMN), th...

Optically pumped magnetometers (OPMs) are new, room-temperature alternatives to superconducting quantum interference devices (SQUIDs) for measuring the brain’s magnetic fields. The most used OPM in MagnetoEncephaloGraphy (MEG) are based on alkali atoms operating in the spin-exchange relaxation-free (SERF) regime. These sensors do not require coolin...

Temporal theta activity in coalescence with slow-wave (TTA-SW) is one of the first neurobiomarkers of the neurodevelopment of perisylvian networks in the electroencephalography (EEG). Dynamic changes in the microstructure and activity within neural networks are reflected in the EEG. Slow oscillation slope can reflect synaptic strength, and cross-fr...

Background Autism spectrum disorder (ASD) is associated with atypical neural activity in resting-state. Most of the studies have focused on abnormalities in alpha-frequency, as a marker of ASD dysfunctions. However, few have explored alpha synchronization, with a specific interest in resting-state networks: the default mode network (DMN), the senso...

The neonatal transition involves physiological modifications as a consequence of the complexity of the perinatal period. Various strategies can be used to attain the same level of postnatal cerebral oxygenation, depending on the status of the infant at birth. We evaluated such strategies by recording 20 full-term newborns by near-infrared spectrosc...

Rhythm is a fundamental component of the auditory world, present even during the prenatal life. While there is evidence that some auditory capacities are already present before birth, whether and how the premature neural networks process auditory rhythm is yet not known. We investigated the neural response of premature neonates at 30-34 weeks gesta...

Diffuse optical tomography is a non-invasive and non-irradiating medical imaging technique that is particularly suitable for cerebral monitoring of newborns since it can be used at the bedside of the patient. Here, a new model for optical tomography in the neonatal brain is presented that takes into account the presence of arachnoid trabeculæ in th...

Objectives Reversal learning is widely used to analyze cognitive flexibility and characterize behavioral abnormalities associated with impulsivity and disinhibition. Recent studies using fMRI have focused on regions involved in reversal learning with negative and positive reinforcers. Although the frontal cortex has been consistently implicated in...

Rhythm processing involves building expectations according to the hierarchical temporal structure of auditory events. Although rhythm processing has been addressed in the context of predictive coding, the properties of the oscillatory response in different cortical areas are still not clear. We explored the oscillatory properties of the neural resp...

Background: Reversal learning is widely used to analyze cognitive flexibility and characterize behavioral abnormalities associated with impulsivity and disinhibition. Recent studies using fMRI have focused on regions involved in reversal learning with negative and positive reinforcers. Although the frontal cortex has been consistently implicated in...

Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment for idiopathic Parkinson’s disease. Despite recent progress, the mechanisms responsible for the technique’s effectiveness have yet to be fully elucidated. The purpose of the present study was to gain new insights into the interactions between STN-DBS and cortical network...

Interictal spikes (IISs) may result from a disturbance of the intimate functional balance between various neuronal (synaptic and non-synaptic), vascular, and metabolic compartments. To better characterize the complex interactions within these compartments at different scales we developed a simultaneous multimodal-multiscale approach and measure the...

Rhythm processing involves building expectations according to the hierarchical temporal structure of auditory events. Although rhythm processing has been addressed in the context of predictive coding, the properties of the oscillatory response in different cortical areas is still not clear. We explored the oscillatory properties of the neural respo...

Electroencephalography is the only clinically available technique that can address the premature neonate normal and pathological functional development week after week. The changes in the electroencephalogram (EEG) result from gradual structural and functional modifications that arise during the last trimester of pregnancy. Here, we review the stru...

Behavioral data on episodic recollection in autism spectrum disorders (ASD) point limited relational memory functioning. However, the involvement of successive memory processes in the profile of episodic memory in ASD needs more study. Here, we used event‐related potentials (ERP) to investigate the time course of episodic recollection with an assoc...

Functional responses recorded during the last trimester of gestation reveal that human sensory activity begins before birth, allowing the brain to process the external environment. Along with the maturation of the brain, new cognitive skills emerge in the human infant’s brain. The development of non-invasive techniques provides the opportunity to s...

Objective: Characterization of the spatial and temporal dynamics of interictal epileptic discharges (IED) using time-frequency analysis (TFA) and electrical-source localization (ESL). Methods: TFA was performed on IED (spikes, spike waves, and polyspike waves) recorded by high-density-EEG (HD-EEG) in 19 refractory focal epileptic children. Temporal...

Temporal theta slow‐wave activity (TTA‐SW) in premature infants is a specific neurobiomarker of the early neurodevelopment of perisylvian networks observed as early as 24 weeks of gestational age (wGA). It is present at the turning point between non‐sensory driven spontaneous networks and cortical network functioning. Despite its clinical importanc...

The neonatal brain is an extremely dynamic organization undergoing essential development in terms of connectivity and function. Several functional imaging investigations of the developing brain have found neurovascular coupling (NVC) patterns that contrast with those observed in adults. These discrepancies are partly due to that NVC is still develo...

MEDELOPT® - Systèmes diagnostiques de l’activité cérébrale issus des recherches hospitalo-universitaires amiénoises Mieux comprendre l’épilepsie, ou les Accidents Vasculaires Cérébraux est l’ambition de Medelopt®, premier casque d’imagerie cérébrale ambulatoire créé, au bout de 15 années de recherche en neurodéveloppement, au sein du Service d’Exp...

Epilepsy with Centrotemporal Spikes (ECTS) is the most common form of self-limited focal epilepsy. The pathophysiological mechanisms by which ECTS induces neuropsychological impairment in 15–30% of affected children remain unclear. The objective of this study is to review the current state of knowledge concerning the brain structural and functional...

Abstract Sensory development of the human brain begins prenatally, allowing cortical auditory responses to be recorded at an early age in preterm infants. Despite several studies focusing on the temporal characteristics of preterm infants’ cortical responses, few have been conducted on frequency analysis of these responses. In this study, we perfor...

Background Epilepsy with Centrotemporal Spikes (ECTS) is the most common form of self-limited focal epilepsy. The pathophysiological mechanisms by which ECTS induces neuropsychological impairment in 30% of affected children remain unclear. Objectives The objective is to review the current state of knowledge concerning the brain structural and func...

Background Temporal theta slow-wave activity (TTA-SW) in premature infants is a specific signature of the early development of temporal networks, as it is observed at the turning point between nonsensory driven spontaneous local processing and cortical network functioning. Previous studies have demonstrated that preterms from 28 weeks of gestationa...

Background The early identification of preterm infants at high neurological risk is essential. EEG is the only functional tool, which allows evaluating the cerebral maturation during the neonatal period. One of the EEG neuro-biomarker is the length Burst Activity (BA) adjusted to Post-Menstrual Age (PMA). For extremely preterms, studies about the p...

Background Spontaneous endogenous generators are key elements in immature systems. Theta activity (TA) and the coalescent slow waves (SW) occur from 25wGA and address the basic mechanisms of cross frequency interdependencies in oscillations that compose brain rhythms in premature. Objectives To evaluate the interactions between the two oscillation...

Introduction Le cerveau du nouveau-né prématuré subit un processus dynamique de maturation avec la mise en place de générateurs spécifiques au cours de développement. L’activité thêta temporale est l’un des premiers neurobiomarqueurs. Le but de cette étude était de mieux caractériser les localisations des générateurs de ces activités. Méthodes Des...

Objectives EEG-HR source localization is a non-invasive method to better delineate the source of the epileptic activity and thus the schema for electrodes implantation. Such source localization method relies on solving an inverse problem. In this study we evaluate the impact of bone conductivity, different head models and filtering, different metho...

Objectives To better define the physiopathology of Interictal Epileptic Spikes (IES) and specially: (i) the mechanisms that propel neurons to hypersynchronizations, and (ii) the local and distant dynamic changes of neuronal population activities, we performed a time frequency analysis (TFA) of the surrounding activation of the IES. Methods HD EEG...

Si le taux de survie des enfants prématurés a augmenté, cette population reste à haut risque de développer des troubles neurocognitifs, notamment pour les prématurités extrêmes. L’EEG est le meilleur outil d’exploration fonctionnelle cérébrale en période néonatale, en faisant un excellent examen prédictif du devenir neurodéveloppemental. Parmi ces...

Introduction High Density electroencephalography (HD EEG) is the reference non-invasive technique to investigate the dynamics of neuronal networks in Benign Epilepsy with Centro-Temporal Spikes (BECTS). Analysis of local dynamic changes surrounding Interictal Epileptic Spikes (IES) might improve our knowledge of the mechanisms that propel neurons t...

Introduction Many questions concerning the mechanisms that drive neurons to hypersynchronize remain unsolved, but synaptic as well as non-synaptic events are likely to be involved. Here Optical Imaging (OI) of the epileptic brain by concomitant electroencephalography (FOS-ECoG/HD-EEG), allow investigating the changes in the cellular environment ass...

Infancy is the most critical period in human brain development. Studies demonstrate that subtle brain abnormalities during this state of life may greatly affect the developmental processes of the newborn infants. One of the rapidly developing methods for early characterization of abnormal brain development is functional connectivity of the brain at...

Intraventricular Hemorrhage (IVH) is the leading cause of neurological and cognitive impairment in preterm neonates with an incidence that increases with increasing prematurity. In the present study, we tested how preterm neonates with IVH react to external stimulation (i.e. speech syllables). We compared their neural responses measured by electroe...

Using multimodal-multiscale analysis of Fast Optical, ECoG and HD-EEG data, we demonstrated complex changes in the dynamics of cortical networks at synaptic and non-synaptic level surrounding the interictal epileptic spike (IES).

58th Annual Meeting of the Society-for-Psychophysiological-Research, Quebec City, CANADA, OCT 03-07, 2018

The non-invasive multimodal analysis of brain function in the premature babies makes it possible to evaluate the implementation of neural networks involved in various functions such as language. The establishment of neural networks is the result of (1) initial genetic factors that participate in the structural and functional development of networks...

Objective: Interictal epileptic spikes (IES) represent a signature of the transient synchronous and excessive discharge of a large ensemble of cortical heterogeneous neurons. Epilepsy cannot be reduced to a hypersynchronous activation of neurons whose functioning is impaired, resulting on electroencephalogram (EEG) in epileptic seizures or IES. Th...

Preterm infants (born at 24–34 weeks of gestational age) suffer from a high incidence of neurological complications. Cerebrovascular lesions (intraventricular hemorrhages, IVH, and ischemic injury) due to the immaturity of the vascular system and its inability to adapt to the extra-uterine environment are the major causes of adverse neurological ou...

The mechanisms of neuronal hypersynchronization during Interictal Epileptic Spikes (IES) remain unsolved. IES’s multimodal analysis figure out the dynamic of the neurovascular unit considering the interactions between the neuronal, vascular networks and the extra cellular space occurring around the IES. To evaluate these multiscale interactions, a...

Objectives Although many studies in epilepsy have examined the synaptic mechanisms constituting the basis for most of the current principles of brain activity, relatively less studies have tried to characterize changes in the cellular environment that might predispose a network to pathologic synchronization. Methods In this study, near-infrared op...

Objective Although infantile spasms can be caused by a variety of etiologies, the clinical features are stereotypical. The neuronal and vascular mechanisms that contribute to the emergence of infantile spasms are not well understood. Methods We performed a multimodal study by simultaneously recording electroencephalogram and functional Near-infrar...

Objective High Density electroencephalography is the reference non-invasive technique to investigate the dynamics of neuronal networks in Benign Epilepsy with Centro-Temporal Spikes (BECTS). Analysis of local dynamic changes surrounding Interictal Epileptic Spikes (IES) might improve our knowledge of the mechanisms that propel neurons to the hypers...

Supplementary material

Interictal spikes can be generated by blocking GABAA receptor-mediated inhibition. The nature of the hemodynamic activities associated with interictal spikes in acute models of focal epilepsy based on GABA deactivation has not been determined. We analyzed systemic changes in hemodynamic signals associated with interictal spikes generated by acute m...

Although infantile spasms can be caused by a variety of etiologies, the clinical features are stereotypical. The neuronal and vascular mechanisms that contribute to the emergence of infantile spasms are not well understood. We performed a multimodal study by simultaneously recording electroencephalogram and functional Near-infrared spectroscopy in...

The mechanisms responsible for coupling between relative cerebral blood flow (rCBF), relative cerebral blood volume (rCBV), and relative cerebral metabolic rate of oxygen (rCMRO2), an important function of the microcirculation in preterm infants, remain unclear. Identification of a causal relationship between rCBF-rCBV and rCBF-rCMRO2 in preterms m...

Speech is a complex auditory stimulus which is processed according to several time-scales. Whereas consonant discrimination is required to resolve rapid acoustic events, voice perception relies on slower cues. Humans, right from preterm ages, are particularly efficient to encode temporal cues. To compare the capacities of preterms to those observed...

Objective: High Density electroencephalography (HD EEG) is the reference non-invasive technique to investigate the dynamics of neuronal networks in Benign Epilepsy with Centro-Temporal Spikes (BECTS). Analysis of local dynamic changes surrounding Interictal Epileptic Spikes (IES) might improve our knowledge of the mechanisms that propel neurons to...

Transient change in Global Time-Frequency Representation (GTFR) in different scaling factors (800, 400, and 200%).

Impact of varying slow wave amplitude on time-frequency analysis. (A) Simulated IES dipole in the right central sulcus, Locations, orientations. (B) Simulated IES with increasing slow wave amplitudes (0, 5, 10, 15, 20 nAm). (C) The simulated scalp IES in average reference format. The solid lines indicate the signal + noise wave forms generated by t...

Objective: Interictal epileptic spikes (IESs), apart from being a key marker of epileptic neuronal networks, constitute a nice model of the widespread endogenous phenomenon of neuronal hypersynchronization. Many questions concerning the mechanisms that drive neurons to hypersynchronize remain unresolved, but synaptic as well as nonsynaptic events...

Temporal theta slow-wave activity (TTA-SW) in premature infants is a specific signature of the early development of temporal networks, as it is observed at the turning point between non-sensory driven spontaneous local processing and cortical network functioning. The role in development and the precise location of TTA-SW remain unknown. Previous st...

28th International Symposium on Cerebral Blood Flow, Metabolism and Function / 13th International Conference on Quantification of Brain Function with PET, Int Soc Cerebral Blood Flow & Metab, Berlin, GERMANY, APR 01-04, 2017

18th World Congress of Psychophysiology of the International Organization of Psychophysiology (IOP), Havana, CUBA, AUG 31-SEP 04, 2016

During the last trimester of human gestation, neurons reach their final destination and establish long- and short-distance connections. Due to the difficulties obtaining functional data at this age, the characteristics of the functional architecture at the onset of sensory thalamocortical connectivity in humans remain largely unknown. In particular...

In this study, we investigated changes in functional connectivity (FC) of the brain networks in patients with benign epilepsy with centrotemporal spikes (BECTS) compared to healthy controls using high-density EEG data collected under eyes-closed resting state condition. EEG source reconstruction was performed with exact Low Resolution Electromagnet...