@article{pmid40019646,

title = {Network effects of traumatic brain injury: from infra slow to high frequency oscillations and seizures},

author = {Brianna Marsh and Sylvain Chauvette and Mingxiong Huang and Igor Timofeev and Maxim Bazhenov},

doi = {10.1007/s10827-025-00895-5},

issn = {1573-6873},

year  = {2025},

date = {2025-06-01},

journal = {J Comput Neurosci},

volume = {53},

number = {2},

pages = {247--266},

abstract = {Traumatic brain injury (TBI) can have a multitude of effects on neural functioning. In extreme cases, TBI can lead to seizures both immediately following the injury as well as persistent epilepsy over years to a lifetime. However, mechanisms of neural dysfunctioning after TBI remain poorly understood. To address these questions, we analyzed human and animal data and we developed a biophysical network model implementing effects of ion concentration dynamics and homeostatic synaptic plasticity to test effects of TBI on the brain network dynamics. We focus on three primary phenomena that have been reported in vivo after TBI: an increase in infra slow oscillations (<0.1 Hz), increase in Delta power (1 - 4 Hz), and the emergence of broadband Gamma bursts (30 - 100 Hz). Using computational network model, we show that the infra slow oscillations can be directly attributed to extracellular potassium dynamics, while the increase in Delta power and occurrence of Gamma bursts are related to the increase in strength of synaptic weights from homeostatic synaptic scaling triggered by trauma. We also show that the buildup of Gamma bursts in the injured region can lead to seizure-like events that propagate across the entire network; seizures can then be initiated in previously healthy regions. This study brings greater understanding of the network effects of TBI and how they can lead to epileptic activity. This lays the foundation to begin investigating how injured networks can be healed and seizures prevented.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40047245,

title = {The reuniens nucleus of the thalamus facilitates hippocampo-cortical dialogue during sleep},

author = {Diellor Basha and Amirmohammad Azarmehri and Elian Proulx and Sylvain Chauvette and Maryam Ghorbani and Igor Timofeev},

doi = {10.7554/eLife.90826},

issn = {2050-084X},

year  = {2025},

date = {2025-03-01},

journal = {Elife},

volume = {12},

abstract = {Memory consolidation during sleep depends on the interregional coupling of slow waves, spindles, and sharp wave-ripples (SWRs), across the cortex, thalamus, and hippocampus. The reuniens nucleus of the thalamus, linking the medial prefrontal cortex (mPFC) and the hippocampus, may facilitate interregional coupling during sleep. To test this hypothesis, we used intracellular, extracellular unit and local field potential recordings in anesthetized and head restrained non-anesthetized cats as well as computational modelling. Electrical stimulation of the reuniens evoked both antidromic and orthodromic intracellular mPFC responses, consistent with bidirectional functional connectivity between mPFC, reuniens and hippocampus in anesthetized state. The major finding obtained from behaving animals is that at least during NREM sleep hippocampo-reuniens-mPFC form a functional loop. SWRs facilitate the triggering of thalamic spindles, which later reach neocortex. In return, transition to mPFC UP states increase the probability of hippocampal SWRs and later modulate spindle amplitude. During REM sleep hippocampal theta activity provides periodic locking of reuniens neuronal firing and strong crosscorrelation at LFP level, but the values of reuniens-mPFC crosscorrelation was relatively low and theta power at mPFC was low. The neural mass model of this network demonstrates that the strength of bidirectional hippocampo-thalamic connections determines the coupling of oscillations, suggesting a mechanistic link between synaptic weights and the propensity for interregional synchrony. Our results demonstrate the presence of functional connectivity in hippocampo-thalamo-cortical network, but the efficacy of this connectivity is modulated by behavioral state.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37226640,

title = {Sleep, oscillations, and epilepsy},

author = {Christophe Bernard and Birgit Frauscher and Jennifer Gelinas and Igor Timofeev},

doi = {10.1111/epi.17664},

issn = {1528-1167},

year  = {2023},

date = {2023-12-01},

journal = {Epilepsia},

volume = {64 Suppl 3},

number = {Suppl 3},

pages = {S3--S12},

abstract = {Sleep and wake are defined through physiological and behavioral criteria and can be typically separated into non-rapid eye movement (NREM) sleep stages N1, N2, and N3, rapid eye movement (REM) sleep, and wake. Sleep and wake states are not homogenous in time. Their properties vary during the night and day cycle. Given that brain activity changes as a function of NREM, REM, and wake during the night and day cycle, are seizures more likely to occur during NREM, REM, or wake at a specific time? More generally, what is the relationship between sleep-wake cycles and epilepsy? We will review specific examples from clinical data and results from experimental models, focusing on the diversity and heterogeneity of these relationships. We will use a top-down approach, starting with the general architecture of sleep, followed by oscillatory activities, and ending with ionic correlates selected for illustrative purposes, with respect to seizures and interictal spikes. The picture that emerges is that of complexity; sleep disruption and pathological epileptic activities emerge from reorganized circuits. That different circuit alterations can occur across patients and models may explain why sleep alterations and the timing of seizures during the sleep-wake cycle are patient-specific.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37735129,

title = {Derailment of Sleep Homeostatic Plasticity Affects the Most Plastic Brain Systems and Carries the Risk of Epilepsy},

author = {Peter Halász and Igor Timofeev and Anna Szűcs},

doi = {10.31083/j.jin2205111},

issn = {0219-6352},

year  = {2023},

date = {2023-08-01},

journal = {J Integr Neurosci},

volume = {22},

number = {5},

pages = {111},

abstract = {Although a critical link between non-rapid eye movement (NREM) sleep and epilepsy has long been suspected, the interconnecting mechanisms have remained obscure. However, recent advances in sleep research have provided some clues. Sleep homeostatic plasticity is now recognized as an engine of the synaptic economy and a feature of the brain's ability to adapt to changing demands. This allows epilepsy to be understood as a cost of brain plasticity. On the one hand, plasticity is a force for development, but on the other it opens the possibility of epileptic derailment. Here, we provide a summary of the phenomena that link sleep and epilepsy. The concept of "system epilepsy", or epilepsy as a network disease, is introduced as a general approach to understanding the major epilepsy syndromes, i.e., epilepsies building upon functional brain networks. We discuss how epileptogenesis results in certain major epilepsies following the derailment of NREM sleep homeostatic plasticity. Post-traumatic epilepsy is presented as a general model for this kind of epileptogenesis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37237017,

title = {Respiration organizes gamma synchrony in the prefronto-thalamic network},

author = {Diellor Basha and Sylvain Chauvette and Maxim Sheroziya and Igor Timofeev},

doi = {10.1038/s41598-023-35516-7},

issn = {2045-2322},

year  = {2023},

date = {2023-05-01},

journal = {Sci Rep},

volume = {13},

number = {1},

pages = {8529},

abstract = {Multiple cognitive operations are associated with the emergence of gamma oscillations in the medial prefrontal cortex (mPFC) although little is known about the mechanisms that control this rhythm. Using local field potential recordings from cats, we show that periodic bursts of gamma recur with 1 Hz regularity in the wake mPFC and are locked to the exhalation phase of the respiratory cycle. Respiration organizes long-range coherence in the gamma band between the mPFC and the nucleus reuniens the thalamus (Reu), linking the prefrontal cortex and the hippocampus. In vivo intracellular recordings of the mouse thalamus reveal that respiration timing is propagated by synaptic activity in Reu and likely underlies the emergence of gamma bursts in the prefrontal cortex. Our findings highlight breathing as an important substrate for long-range neuronal synchronization across the prefrontal circuit, a key network for cognitive operations.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35576961,

title = {Brain states in freely behaving marmosets},

author = {Olga Bukhtiyarova and Sylvain Chauvette and Josée Seigneur and Igor Timofeev},

doi = {10.1093/sleep/zsac106},

issn = {1550-9109},

year  = {2022},

date = {2022-08-01},

journal = {Sleep},

volume = {45},

number = {8},

abstract = {STUDY OBJECTIVES: We evaluated common marmosets as a perspective animal model to study human sleep and wake states.nnMETHODS: Using wireless neurologger recordings, we performed longitudinal multichannel local field potential (LFP) cortical, hippocampal, neck muscle, and video recordings in three freely behaving marmosets. The brain states were formally identified using self-organizing maps.nnRESULTS: Marmosets were generally awake during the day with occasional 1-2 naps, and they slept during the night. Major electrographic patterns fall in five clearly distinguished categories: wakefulness, drowsiness, light and deep NREM sleep, and REM. Marmosets typically had 14-16 sleep cycles per night, with either gradually increasing or relatively low, but stable delta power within the cycle. Overall, the delta power decreased throughout the night sleep. Marmosets demonstrated prominent high amplitude somatosensory mu-rhythm (10-15 Hz), accompanied with neocortical ripples, and alternated with occipital alpha rhythm (10-15 Hz). NREM sleep was characterized with the presence of high amplitude slow waves, sleep spindles and ripples in neocortex, and sharp-wave-ripple complexes in CA1. Light and deep stages differed in levels of delta and sigma power and muscle tone. REM sleep was defined with low muscle tone and activated LFP with predominant beta-activity and rare spindle-like or mu-like events.nnCONCLUSIONS: Multiple features of sleep-wake state distribution and electrographic patterns associated with behavioral states in marmosets closely match human states, although marmoset have shorter sleep cycles. This demonstrates that marmosets represent an excellent model to study origin of human electrographical rhythms and brain states.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34563545,

title = {Neuronal activities during palatable food consumption in the reward system of binge-like eating female rats},

author = {Richard Quansah Amissah and Diellor Basha and Olga Bukhtiyarova and Elena Timofeeva and Igor Timofeev},

doi = {10.1016/j.physbeh.2021.113604},

issn = {1873-507X},

year  = {2021},

date = {2021-12-01},

journal = {Physiol Behav},

volume = {242},

pages = {113604},

abstract = {Binge eating disorder (BED), characterized by bingeing episodes and compulsivity, is the most prevalent eating disorder; however, little is known about its neurobiological underpinnings. In humans, BED is associated with desensitization of the reward system, specifically, the medial prefrontal cortex (mPFC), nucleus accumbens (Acb), and ventral tegmental area (VTA). Additionally, BED patients feel relieved during bingeing, suggesting that bingeing helps to decrease the negative emotions they were feeling prior to the binge episode. However, the mechanisms that underlie this feeling of relief in BED patients have not been well investigated. To investigate neuronal activity before and during palatable food consumption in BED, we performed in vivo electrophysiological recordings in a binge-like eating rat model (bingeing, n = 12 and non-bingeing, n = 14) and analyzed the firing rate of neurons in the mPFC, Acb, and VTA before and during access to sucrose solution. We also investigated changes in the firing rate of neurons in these regions during and between active bingeing, which may underlie the feeling of relief in BED patients. We found that neuronal firing rates of mPFC and VTA neurons in bingeing rats were lower than those in non-bingeing rats before and during sucrose consumption. Palatable food consumption increased neuronal firing rates during and between active bingeing in bingeing rats. Our results suggest a desynchronization in the activity of reward system regions, specifically in the mPFC, in bingeing rats, which may also contribute to BED. These results are consistent with those of functional magnetic resonance imaging (fMRI) studies that reported decreased activity in the reward system in BED patients. We propose that increased neuronal activity in the mPFC, Acb, or VTA produces an antidepressant effect in rats, which may underlie the sense of relief patients express during bingeing episodes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34841296,

title = {Just a sound: A non-pharmacological treatment approach in epilepsy},

author = {Igor Timofeev},

doi = {10.1016/j.xcrm.2021.100451},

issn = {2666-3791},

year  = {2021},

date = {2021-11-01},

journal = {Cell Rep Med},

volume = {2},

number = {11},

pages = {100451},

abstract = {Benign epilepsy with centro-temporal spikes is typically not treated by antiepileptic drugs, but it leads to cognitive disfunctions. In this issue, Klinzing et al. demonstrate that closed-loop auditory stimulation delivered after paroxysmal spikes reduces the total number of paroxysmal spikes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33867113,

title = {Chronic Stress Induces Sex-Specific Functional and Morphological Alterations in Corticoaccumbal and Corticotegmental Pathways},

author = {Thibault P Bittar and Mari Carmen Pelaez and Jose Cesar Hernandez Silva and Francis Quessy and Andrée-Anne Lavigne and Daphnée Morency and Léa-Jeanne Blanchette and Eric Arsenault and Yoan Cherasse and Josée Seigneur and Igor Timofeev and Chantelle F Sephton and Christophe D Proulx and Benoit Labonté},

doi = {10.1016/j.biopsych.2021.02.014},

issn = {1873-2402},

year  = {2021},

date = {2021-08-01},

journal = {Biol Psychiatry},

volume = {90},

number = {3},

pages = {194--205},

abstract = {BACKGROUND: The medial prefrontal cortex (mPFC) is part of a complex circuit controlling stress responses by sending projections to different limbic structures including the nucleus accumbens (NAc) and ventral tegmental area (VTA). However, the impact of chronic stress on NAc- and VTA-projecting mPFC neurons is still unknown, and the distinct contribution of these pathways to stress responses in males and females is unclear.nnMETHODS: Behavioral stress responses were induced by 21 days of chronic variable stress in male and female C57BL/6NCrl mice. An intersectional viral approach was used to label both pathways and assess the functional, morphological, and transcriptional adaptations in NAc- and VTA-projecting mPFC neurons in stressed males and females. Using chemogenetic approaches, we modified neuronal activity of NAc-projecting mPFC neurons to decipher their contribution to stress phenotypes.nnRESULTS: Chronic variable stress induced depressive-like behaviors in males and females. NAc- and VTA-projecting mPFC neurons exhibited sex-specific functional, morphological, and transcriptional alterations. The functional changes were more severe in females in NAc-projecting mPFC neurons, while males exhibited more drastic reductions in dendritic complexity in VTA-projecting mPFC neurons after chronic variable stress. Finally, chemogenetic overactivation of the corticoaccumbal pathway triggered anxiety and behavioral despair in both sexes, while its inhibition rescued the phenotype only in females.nnCONCLUSIONS: Our results suggest that stress responses in males and females result from pathway-specific changes in the activity of transcriptional programs controlling the morphological and synaptic properties of corticoaccumbal and corticotegmental pathways in a sex-specific fashion.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34912190,

title = {Compulsive Eating in a Rat Model of Binge Eating Disorder Under Conditioned Fear and Exploration of Neural Mechanisms With  mRNA Expression},

author = {Zhi Fei Li and Sandrine Chometton and Geneviève Guèvremont and Elena Timofeeva and Igor Timofeev},

doi = {10.3389/fnins.2021.777572},

issn = {1662-4548},

year  = {2021},

date = {2021-01-01},

journal = {Front Neurosci},

volume = {15},

pages = {777572},

abstract = {Compulsive eating is the most obstinate feature of binge eating disorder. In this study, we observed the compulsive eating in our stress-induced binge-like eating rat model using a conflicting test, where sucrose and an aversively conditioned stimulus were presented at the same time. In this conflicting situation, the binge-like eating prone rats (BEPs), compared to the binge-like eating resistant rats (BERs), showed persistent high sucrose intake and inhibited fear response, respectively, indicating a deficit in palatability devaluation and stronger anxiolytic response to sucrose in the BEPs. We further analyzed the neuronal activation with  mRNA  hybridization. Surprisingly, the sucrose access under conditioned fear did not inhibit the activity of amygdala; instead, it activated the central amygdala. In the BEPs, sucrose reduced the response of the paraventricular hypothalamic nucleus (PVN), while enhancing activities in the lateral hypothalamic area (LHA) to the CS. The resistance to devaluating the palatable food in the BEPs could be a result of persistent Acb response to sucrose intake and attenuated recruitment of the medial prefrontal cortex (mPFC). We interpret this finding as that the reward system of the BEPs overcame the homeostasis system and the stress-responding system.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}