Gabriella Panuccio

• MD, PhD
• Principal Investigator at Istituto Italiano di Tecnologia

Epilepsy is a prevalent neurological disorder that affects approximately 1% of the global population. Approximately 30-40% of patients respond poorly to antiepileptic medications, leading to a significant negative impact on their quality of life. Closed-loop deep brain stimulation (DBS) is a promising treatment for individuals who do not respond to...

Neurological disorders are a substantial global health burden, affecting millions of people worldwide. A key challenge in developing effective treatments and preventive measures is the realization of low-power wearable systems with early detection capabilities. Traditional strategies rely on machine learning algorithms, but their computational dema...

Objective. The compromise of the hippocampal loop is a hallmark of mesial temporal lobe epilepsy (MTLE), the most frequent epileptic syndrome in the adult population and the most often refractory to medical therapy. Hippocampal sclerosis is found in >50% of drug-refractory MTLE patients and primarily involves the CA1, consequently disrupting the hi...

In this paper we present a memristor-inspired computational method for obtaining a type of running spectrogram or fingerprint of epileptiform activity generated by rodent hippocampal spheroids. It can be used to compute on the fly and with low computational cost an alert-level signal for epileptiform events onset. Here, we describe the computationa...

Objective. Therapeutic intervention in neurological disorders still relies heavily on pharmacological solutions, while the treatment of patients with drug resistance remains an unresolved issue. This is particularly true for patients with epilepsy, 30% of whom are refractory to medications. Implantable devices for chronic recording and electrical m...

Hippocampal dysfunction is the hallmark of mesial temporal lobe epilepsy (MTLE), the most common epileptic syndrome in adults and the most often refractory to medical therapy. Deep brain stimulation (DBS) may ameliorate drug-refractory MTLE, but it still cannot guarantee a seizure-free life. One major drawback is that the stimulation policy is info...

Objective. The compromise of the hippocampal loop is a hallmark of mesial temporal lobe epilepsy (MTLE); particularly, the hippocampal output to the parahippocampal cortex is disrupted by damage of the CA1. While closed-loop deep brain stimulation (DBS) is the latest frontier to improve drug-refractory MTLE, current approaches do not restore the hi...

Three-dimensional (3D) neural cell cultures inherently lend themselves to high-throughput network electrophysiology studies addressing brain function in health and disease in a more realistic architectural complexity than two-dimensional neural networks. Epilepsy is the emblem of brain network disorders, as it reflects aberrant circuit reorganizati...

Therapeutic intervention in neurological disorders still relies heavily on pharmacological solutions, while the treatment of patients with drug resistance remains an open challenge. This is particularly true for patients with epilepsy, 30% of whom are refractory to medications. Implantable devices for chronic recording and electrical modulation of...

Modern computation based on the von Neumann architecture is today a mature cutting-edge science. In the Von Neumann architecture, processing and memory units are implemented as separate blocks interchanging data intensively and continuously. This data transfer is responsible for a large part of the power consumption. The next generation computer te...

Mesial temporal lobe epilepsy (MTLE) is the most common partial complex epilepsy in adults and the most unresponsive to medications. Electrical deep brain stimulation (DBS) of the hippocampus has proved effective in controlling seizures in epileptic rodents and in drug-refractory MTLE patients. However, current DBS paradigms implement arbitrary fix...

Brain organoids are in vitro three-dimensional (3D) self-organized neural structures, which can enable disease modelling and drug screening. However, their use for standardized large-scale drug screening studies is limited by their high batch-to-batch variability, long differentiation time (10-20 weeks), and high production costs. This is particula...

Recent research provides examples of neuromorphic systems applied to process biological signals or to interface biological tissues. Usually, in such contexts, the neuromorphic system is used for automatic anomaly detection. The automation of the long-term monitoring of biological signals holds promise for lightening the burden placed on clinicians....

Identifying causal relationships is a challenging yet crucial problem in many fields of science like epidemiology, climatology, ecology, genomics, economics and neuroscience, to mention only a few. Recent studies have demonstrated that ordinal partition transition networks (OPTNs) allow inferring the coupling direction between two dynamical systems...

Brain-on-Chip (BoC) biotechnology is emerging as a promising tool for biomedical and pharmaceutical research applied to the neurosciences. At the convergence between lab-on-chip and cell biology, BoC couples in vitro three-dimensional brain-like systems to an engineered microfluidics platform designed to provide an in vivo-like extrinsic microenvir...

Epilepsy is one of the most invalidating neurological conditions, affecting 1\(\%\) of the global population. The main diagnostic tool for epilepsy is electroencephalography (EEG), used to detect local field potentials and discern pathological brain patterns, i.e., ictal activity (the EEG correlate of a clinical seizure) and interictal activity (th...

Identifying causal relationships is a challenging yet a crucial problem in many fields of science like epidemiology, climatology, ecology, genomics, economics and neuroscience, to mention only a few. Recent studies have demonstrated that ordinal partition transition networks (OPTNs) allow to infer the coupling direction between two dynamical system...

Emerging evidence highlights the several roles that meninges play in relevant brain functions as they are a protective membrane for the brain, produce and release several trophic factors important for neural cell migration and survival, control cerebrospinal fluid dynamics, and embrace numerous immune interactions affecting neural parenchymal funct...

Background: In recent years, biomedical devices have proven to be able to target also different neurological disorders. Given the rapid ageing of the population and the increase of invalidating diseases affecting the central nervous system, there is a growing demand for biomedical devices of immediate clinical use. However, to reach useful therape...

Temporal lobe epilepsy (TLE) is the most common partial complex epileptic syndrome and the least responsive to medications. Deep brain stimulation (DBS) is a promising approach when pharmacological treatment fails or neurosurgery is not recommended. Acute brain slices coupled to microelectrode arrays (MEAs) represent a valuable tool to study neuron...

Using an extracellular medium with high potassium/low magnesium concentration with the addition of 4-AP we induced epileptiform activity in combined hippocampus/entorhinal cortex slices of the rat brain [1]. In this in vitro model of temporal lobe epilepsy, we observed the repeating sequences of interictal discharge (IID) regimes and seizure-like e...

Whether new neurons are added in the postnatal cerebral cortex is still debated. Here, we report that the meninges of perinatal mice contain a population of neurogenic progenitors formed during embryonic development that migrate to the caudal cortex and differentiate into Satb2⁺ neurons in cortical layers II–IV. The resulting neurons are electrical...

In the quest for novel neurotechnologies to defeat brain diseases, intelligent biohybrid systems have earned a privileged role among unconventional brain repair strategies. These systems are based on the functional interaction between the nervous tissue and engineered devices, the establishment of which is mediated by artificial intelligence. As no...

In the era of intelligent biohybrid neurotechnologies for brain repair, new fanciful terms are appearing in the scientific dictionary to define what has so far been unimaginable. As the emerging neurotechnologies are becoming increasingly polyhedral and sophisticated, should we talk about evolution and rank the intelligence of these devices?

Deep Brain Stimulation (DBS) is a promising tool for treating drug-resistant epileptic patients. Currently, the most common approach is fixed-frequency stimulation (periodic pacing) by means of stimulating devices that operate under open-loop control. However, a drawback of this DBS strategy is the impossibility of tailoring a personalized treatmen...

4-aminopyridine (4AP, 50μM) induces interictal- and ictal-like discharges in brain slices including parahippocampal areas such as the entorhinal cortex (EC) but the relation between these two types of epileptiform activity remains undifined. Here, by employing field potential recordings in rat EC slices during 4AP application, we found that: (i) in...

GABAergic function of the subiculum is central to the regulation of hippocampal output activity. Subicular neuronal networks are indeed under potent control by local inhibition. However, information about the properties of GABAergic currents generated by neurons of this parahippocampal area in normal tissue is still missing. Here, we describe GABA(...

Glia can influence the outcome of an epileptogenic insult by controlling the recovery of neuronal networks and functions. In particular, glia may facilitate the establishment of epilepsy by impaired removal of glutamate from synapses or by releasing inflammatory cytokines and excitatory neurotransmitters, such as interleukin-1β or, respectively, gl...

The piriform cortex (PC) is known to be epileptic-prone and it may be involved in the manifestation of limbic seizures. Herein, we have characterized some electrophysiologic and pharmacologic properties of the spontaneous epileptiform activity generated by PC networks maintained in vitro. We performed field potential recordings from the PC in coron...

Deep brain stimulation (DBS) is a promising therapeutic approach for epilepsy treatment. Recently, research has focused on the implementation of stimulation protocols that would adapt to the patients need (adaptive stimulation) and deliver electrical stimuli only when it is most useful. A formal mathematical description of the effects of electrical...

Temporal lobe epilepsy (TLE), the most common type of partial complex epilepsy, involves the hippocampus, parahippocampal regions and the temporal neocortex. The pathophysiogenesis of TLE is yet to be well established, but several lines of evidence implicate changes in GABAergic inhibition. Moreover, the subiculum, a key structure in gating hippoca...

Exposure to cholinergic agonists is a widely used paradigm to induce epileptogenesis in vivo and synchronous activity in brain slices maintained in vitro. However, the mechanisms underlying these effects remain unclear. Here, we used field potential recordings from the lateral entorhinal cortex in horizontal rat brain slices to explore whether two...

Temporal lobe epilepsy (TLE) is a chronic epileptic disorder involving the hippocampal formation. Details on the interactions between the hippocampus proper and parahippocampal networks during ictogenesis remain, however, unclear. In addition, recent findings have shown that epileptic limbic networks maintained in vitro are paradoxically less respo...

Neurosteroids are a family of compounds synthesized directly in the brain by transforming cholesterol into pregnenolone, which is then converted to compounds such as allopregnanolone and allotetrahydrodeoxycorticosterone. In view of their ability to modulate neurotransmission, neurosteroids may influence the clinical course of epileptic disorders....

This paper presents a new methodology for automatically learning an optimal neurostimulation strategy for the treatment of epilepsy. The technical challenge is to automatically modulate neurostimulation parameters, as a function of the observed EEG signal, so as to minimize the frequency and duration of seizures. The methodology leverages recent te...

Laser-evoked potentials (LEPs) are brain responses to laser radiant heat pulses and reflect the activation of Adelta nociceptors. LEPs are to date the reference standard technique for studying nociceptive pathway function in patients with neuropathic pain. To find out whether LEPs also provide a useful neurophysiological tool for assessing antinoci...

Generation of rhythmic activity by neuronal networks may represent the epiphenomenon of pathological conditions that underlie several neurological disorders such as cingulate epilepsy, a type of partial epilepsy affecting the anterior cingulate cortex (ACC), and accompanied by progressive cognitive impairment and psychiatric disturbances. We recent...

The anterior cingulate cortex (ACC)--which plays a role in pain, emotions and behavior--can generate epileptic seizures. To date, little is known on the neuronal mechanisms leading to epileptiform synchronization in this structure. Therefore, we investigated the role of excitatory and inhibitory synaptic transmission in epileptiform activity in thi...

Deep-brain electrical or transcranial magnetic stimulation may represent a therapeutic tool for controlling seizures in patients presenting with epileptic disorders resistant to antiepileptic drugs. In keeping with this clinical evidence, we have reported that repetitive electrical stimuli delivered at approximately 1 Hz in mouse hippocampus-entorh...