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Frazzini, V.

Publications and source records attributed to Frazzini, V..

5 recordsLinked to original sources

A learning-evoked slow-oscillatory architecture paces population activity for offline reactivation across the human medial temporal lobe

Memory processing requires the coordinated engagement of neuronal populations across distributed brain networks and across time. How such coordination is organized in the human medial temporal lobe (MTL) remains unclear. Here, we show that MTL population activity is dynamically structured by a transient slow-oscillatory architecture that emerges during online learning to promote offline consolidation and later recall. Using intracranial recordings that combine single-neuron spiking activity and local field potentials in human participants, we find that mnemonic engagement evokes on-demand slow-oscillatory bursts in the hippocampus. These hippocampal bursts synchronize gamma-band patterns across MTL regions, defining discrete coordination events that pace cross-regional coactivity motifs during learning. These learning-time population motifs are then selectively reactivated during hippocampal ripples in post-learning rest, and the strength of their reactivation predicts subsequent recall accuracy. Together, these findings identify a multi-scale coordination mechanism that links distributed population activity across learning, consolidation, and recall in humans.

neuroscience↗

Representational dynamics during extinction of fear memories in the human brain

Extinction learning - the suppression of a previously acquired fear response - is critical for adaptive behavior and core for understanding the etiology and treatment of anxiety disorders. Electrophysiological studies in rodents have revealed critical roles of theta (4-12Hz) oscillations in amygdala and hippocampus during both fear learning and extinction, and engram research has shown that extinction relies on the formation of novel, highly context-dependent memory traces that suppress the initial fear memories. Whether similar processes occur in humans and how they relate to previously described neural mechanisms of episodic memory formation and retrieval remains unknown. Intracranial EEG (iEEG) recordings in epilepsy patients provide direct access to the deep brain structures of the fear and extinction network, while representational similarity analysis (RSA) allows characterizing the memory traces of specific cues and contexts. Here we combined these methods to show that amygdala theta oscillations during extinction learning signal safety rather than threat and that extinction memory traces are characterized by stable and context-specific neural representations that are coordinated across the extinction network. We further demonstrate that context specificity during extinction learning predicts the reoccurrence of fear memory traces during a subsequent test period, while reoccurrence of extinction memory traces predicts safety responses. Our results reveal the neurophysiological mechanisms and representational characteristics of context-dependent extinction learning in the human brain. In addition, they show that the mutual competition of fear and extinction memory traces provides a mechanistic basis for clinically important phenomena such as fear renewal and extinction retrieval.

neuroscience↗

Sleep increases firing rate modulation during interictal epileptic activities in mesial structures

Epileptic seizures and interictal epileptiform discharges (IEDs) are strongly influenced by sleep and circadian rhythms. However, human data on the effect of sleep on neuronal behavior during interictal activity have been lacking. We analyzed EEG data from epileptic patients implanted with macro and micro electrodes targeting mesial temporal structures. Sleep staging was performed on concomitantly recorded polysomnography and video-EEG. Automated IED detection identified thousands of IEDs per patient. Both the rate and amplitude of IEDs were increased with deeper stages of NREM sleep. Single unit activity (SUA) and multi-unit activity (MUA) increased their firing during the IED spike, and strongly decreased during the subsequent slow wave. These time-locked firing rate modulations were shown to increase during deeper stages of NREM sleep. Finally, during resting behaviour, neuronal firing rate, bursting rate and firing regularity were all shown to progressively decrease with deeper stages of NREM sleep.

neuroscience↗

Micro-electrode in vivo signatures of human periventricular heterotopia

Periventricular nodular heterotopia (PNH) is a malformation of cortical development that frequently causes drug-resistant epilepsy. The epileptogenicity of ectopic neurons in PNH as well as their role in generating interictal and ictal activity is still a matter of debate. We report the first in vivo microelectrode recording of heterotopic neurons in humans. Highly consistent interictal patterns (IPs) were identified within the nodules: 1) Periodic Discharges PLUS Fast activity (PD+F), Sporadic discharges PLUS Fast activity (SD+F), and 3) epileptic spikes (ES). Neuronal firing rates were significantly modulated during all IPs, suggesting that multiple IPs were generated by the same local neuronal populations. Furthermore, firing rates closely followed IP morphologies. Among the different IPs, SD+FA pattern was found only in the three nodules that were actively involved in seizure generation, but was never observed in the nodule that did not take part in ictal discharges. On the contrary, PD+F and ES were identified in all nodules. Units that were modulated during the IPs were also found to participate in seizures, increasing their firing rate at seizure onset and maintaining an elevated rate during the seizures. Together, nodules in PNH are highly epileptogenic, and show several IPs that provide promising pathognomonic signatures of PNH. Furthermore, our results show that PNH nodules may well initiate seizures. HighlightsO_LIFirst in vivo microelectrode description of local epileptic activities in human PNH C_LIO_LIRecordings revealed multiple microscopic epileptic interictal patterns C_LIO_LIFiring rates of all detected units were significantly modulated during all interictal patterns C_LIO_LISeizures recruited the same units that are involved in interictal activity C_LI

pathology↗

The pharmacological perturbation of brain zinc impairs BDNF-related signalling and the cognitive performances of young mice

Zinc (Zn2+) is a pleiotropic modulator of the neuronal and brain activity. The disruption of intraneuronal Zn2+ levels triggers neurotoxic processes and affects neuronal functioning. In this study, we investigated how the pharmacological modulation of brain Zn2+ affects synaptic plasticity and cognition in wild-type mice. To manipulate brain Zn2+ levels, we employed the Zn2+ (and copper) chelator 5-chloro-7-iodo-8-hydroxyquinoline (clioquinol, CQ). CQ was administered for two weeks to 2.5-month-old (m.o.) mice, and effects studied on BDNF-related signalling, metalloproteinase activity as well as learning and memory performances. CQ treatment was found to negatively affect short- and long-term memory performances. The CQ-driven perturbation of brain Zn2+ was found to reduce levels of BDNF, synaptic plasticity-related proteins and dendritic spine density in vivo.\n\nOur study highlights the importance of choosing \"when\", \"where\", and \"how much\" in the modulation of brain Zn2+ levels. Our findings confirm the importance of targeting Zn2+ as a therapeutic approach against neurodegenerative conditions but, at the same time, underscore the potential drawbacks of reducing brain Zn2+ availability upon the early stages of development.

neuroscience↗