Sabato Santaniello

University of Connecticut | UConn · Department of Biomedical Engineering

We present an efficient computational approach to optimizing coil placement for lobule-specific targeting and estimating the activation thresholds of cerebellar PCs. We show through computational simulations that phase-locked cerebellar TMS may be more effective for tremor suppression than rTMS.

Successful stimulation therapies of the central nervous system for chronic neurological disorders have been based so far on electric pulses that have equal amplitude and are delivered at constant intervals. Recent advancements, however, have shown that irregular and time-varying sequences of pulses can be equally effective in treating chronic disea...

We present an automated method for COVID-19 screening based on reconstructed phase profiles of red blood cells (RBCs) and a highly comparative time-series analysis (HCTSA). Video digital holographic data -was obtained using a compact, field-portable shearing microscope to capture the temporal fluctuations and spatio-temporal dynamics of live RBCs....

Transcranial direct current stimulation (tDCS) of the cerebellum has rapidly raised interest but the effects of tDCS on cerebellar neurons remain unclear. Assessing the cellular response to tDCS is challenging because of the uneven, highly stratified cytoarchitecture of the cerebellum, within which cellular morphologies, physiological properties, a...

Aberrant neural oscillations hallmark the pathophysiology of numerous neurological and psychiatric disorders. Here, we first report a method to accurately track the phase of neural oscillations in real-time by a Hilbert transform that avoids the characteristic Gibbs distortion at the end of the signal, aka endpoint-corrected Hilbert transform (ecHT...

Early neonatal epileptic encephalopathy represents a group of epilepsies often characterized by refractory seizures, regression in cognitive development, and typically poor prognosis. Dysfunction of KCNQ2 and KCNQ3 channels has emerged as a major cause of neonatal epilepsy. However, our understanding of the cellular mechanisms that may both explain...

Aberrant neural oscillations hallmark numerous brain disorders. Here, we first report a method to track the phase of neural oscillations in real-time via endpoint-corrected Hilbert transform (ecHT) that mitigates the characteristic Gibbs distortion. We then used ecHT to show that the aberrant neural oscillation that hallmarks essential tremor (ET)...

Aberrant neural oscillations hallmark numerous brain disorders. Here, we first report a method to track the phase of neural oscillations in real-time via endpoint-corrected Hilbert transform (ecHT) that mitigates the characteristic Gibbs distortion. We then used ecHT to show that the aberrant neural oscillation that hallmarks essential tremor (ET)...

Brain extracellular matrix (ECM) is often overlooked in vitro brain tissue models, despite its instructive roles during development. Using developmental stage-sourced brain ECM in reproducible 3D bioengineered culture systems, we demonstrate enhanced functional differentiation of human induced neural stem cells (hiNSCs) into healthy neurons and ast...

Gamma network oscillations in the brain are fast rhythmic network oscillations in the gamma frequency range (∼30-100 Hz), playing key roles in the hippocampus for learning, memory, and spatial processing. There is evidence indicating that GABAergic interneurons, including parvalbumin-expressing basket cells (PVBCs), contribute to cortical gamma osc...

Brain extracellular matrix (ECM) is often overlooked in vitro brain tissue models, despite its instructive roles during development. Using developmental stage-sourced brain ECM in reproducible 3D bioengineered culture systems, we demonstrate enhanced functional differentiation of human induced neural stem cells (hiNSCs) into healthy neurons and ast...

Significance We investigated the mechanisms of tremor generation in essential tremor (ET). Using computational modeling we show that tremor-related activity can originate from the olivocerebellar loop in response to a dysfunction and compensatory up-regulation of GABA receptors in the dentate nucleus of cerebellum. The emerging tremor-related activ...

Globus pallidus internus (GPi) neurons in the basal ganglia are traditionally thought to play a significant role in the promotion and suppression of movement via a change in firing rates. Here, we hypothesize that a primary mechanism of movement control by GPi neurons is through specific modulations in their oscillatory patterns. We analyzed neuron...

Synchronous network activity plays a crucial role in complex brain functions. Stimulating the nervous system with applied electric field (EF) is a common tool for probing network responses. We used a gold wire-embedded silk protein film-based interface culture to investigate the effects of applied EFs on random cortical networks of in vitro culture...

Interictal high frequency oscillations (HFO) are a promising biomarker that can help define the seizure onset zone (SOZ) and predict the surgical outcome after the epilepsy surgery. The utility of HFO in planning the surgery, though, is un-clear. Reasons include the variability of the HFO across patients and brain regions and the influence of the s...

Ripples (80-250 Hz) are brief high-frequency oscillations that are often detected in intracranial EEG (iEEG) and are currently investigated as a potential biomarker to facilitate the Iocalization of the seizure onset zone (SOZ) in patients with drug-resistant epilepsy. While the rate and shape of these oscillations have been positively correlated w...

Over the last 30 years, deep brain stimulation (DBS) has been used to treat chronic neurological diseases like dystonia, obsessive–compulsive disorders, essential tremor, Parkinson’s disease, and more recently, dementias, depression, cognitive disorders, and epilepsy. Despite its wide use, DBS presents numerous challenges for both clinicians and en...

High frequency oscillations (HFOs) are potential biomarkers of epileptic areas. In patients with drug-resistant epilepsy, HFO rates tend to be higher in the seizure onset zone (SOZ) than in other brain regions and the resection of HFO-generating areas positively correlates with seizure-free surgery outcome. Nonetheless, the development of robust un...

Closed-loop modulation of deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson's disease (PD) is investigated to automatically adjust the stimulation to the patients' conditions, optimize the clinical outcomes, and reduce the energy requirements. This study proposes a closed-loop control system for real-time adaptation of the...

Deep brain stimulation (DBS) is a surgical treatment for Parkinson's disease (PD) but, despite clinical efficacy, the mechanisms of DBS still require investigation. Recent evidence suggests that the temporal pattern of the electrical pulses may be critical to the therapeutic merit of DBS and carefully-designed, non-regular patterns could ameliorate...

Neural decoders of kinematic variables have largely relied on task-dependent (TD) encoding models of the neural activity. TD decoders, though, require prior knowledge of the tasks, which may be unavailable, lack scalability as the number of tasks grows, and require a large number of trials per task to reduce the effects of neuronal variability. The...

Sepsis, a systemic inflammatory response to infection, is a major health care problem that affects millions of patients every year in the intensive care units (ICUs) worldwide. Despite the fact that ICU patients are heavily instrumented with physiological sensors, early sepsis detection remains challenging, perhaps because clinicians identify sepsi...

Nicely Nonlinear LQ-based Control is a novel three-stages technique to easily get a sub-optimal solution to the infinite horizon standard regulation problem for nonlinear systems. It approximates the plant with its second order-truncated Taylor series (stage I), operates a feedback linearization on the resulting linear-quadratic model (stage II) an...

A Linear Quadratic (LQ) optimal controller is proposed in combination with a Functional Electrical Stimulation (FES) system to regulate the quite standing for paraplegic subjects. The lower part of the body (i.e., legs, knees and ankles) is modeled through a double inverted pendulum with user-specific parameters and is driven by two pairs of muscle...

Complex reach, grasp, and object manipulation tasks require sequential, temporal coordination of movements by neurons in the brain. Detecting cognitive state transitions associated with motor tasks from sequential neural data is pivotal in rehabilitation engineering. The cognitive state detectors proposed thus far rely on task-dependent (TD) models...

Significance We investigated the therapeutic mechanisms of high-frequency stimulation (HFS) in Parkinson’s disease by developing a computational model of the cortico-basal ganglia-thalamo-cortical loop in normal and parkinsonian conditions under the effects of stimulation at several frequencies. We found that the stimulation injected in the loop el...

Significance In epilepsy, seizures elicit changes in the functional connectivity of the brain that shed insight into the seizures’ nature and onset zone. We investigated the brain connectivity of patients with partial epileptic seizures from continuous multiday recordings and found that ( i ) the connectivity defines a finite set of brain states, (...

Epilepsy is a network phenomenon characterized by atypical activity during seizure both at the level of single neurons and neural populations. The etiology of epilepsy is not completely understood but a common theme among proposed mechanisms is abnormal synchronization between neuronal populations. Recent advances in novel imaging and recording tec...

Relay cells are prevalent throughout sensory systems and receive two types of inputs: driving and modulating. The driving input contains receptive field properties that must be transmitted while the modulating input alters the specifics of transmission. Relay reliability of a relay cell is defined as the fraction of pulses in the driving input that...

The surgical resection of the epileptogenic zone (EZ) is the only effective treatment for many drug-resistant epilepsy (DRE) patients, but the pre-surgical identification of the EZ is challenging. This study investigates whether the EZ exhibits a computationally identifiable signature during seizures. In particular, we compute statistics of the bra...

Sepsis is a systemic deleterious host response to infection. It is a major healthcare problem that affects millions of patients every year in the intensive care units (ICUs) worldwide. Despite the fact that ICU patients are heavily instrumented with physiological sensors, early sepsis detection remains challenging, perhaps because clinicians identi...

Hidden state transitions are frequent events in complex biological systems like the brain. Accurately detecting these transitions from sequential measurements (e.g., EEG, MER, EMG, etc.) is pivotal in several applications at the interface between engineering and medicine, like neural prosthetics, brain-computer interface, and drug delivery, but the...

Communication between specialized regions of the brain is a dynamic process allowing for different connections to accomplish different tasks. While the content of interregional communication is complex, the pattern of connectivity (i.e., which regions communicate) may lie in a lower dimensional state-space. In epilepsy, seizures elicit changes in c...

Automatic seizure onset detection (ASOD) from intracranial EEG recordings (iEEG) in drug-resistant epilepsy has recently gained large interest. Effective ASOD can shorten the time for offline review of the iEEG recordings, help with the development of unsupervised online monitoring systems, and contribute to responsive neurostimulation. Depending o...

Striatum is a major stage of the motor loop but, despite a pivotal role in the execution of movements, it has been poorly studied thus far under Parkinsonian conditions and Deep Brain Stimulation (DBS). We propose a computational framework to analyze the spiking activity of striatal neurons under several conditions. This framework combines point pr...

Deep brain stimulation (DBS) is a highly promising therapy for Parkinson's disease (PD). However, most patients do not get full therapeutic benefit from DBS yet, due to its critical dependence on electrode location. For this reason, we believe that the investigation of a neural modeling, estimation and control framework for the STN is an interestin...

Accurately detecting hidden clinical or behavioral states from sequential measurements is an emerging topic in neuroscience and medicine, which may dramatically impact neural prosthetics, brain-computer interface and drug delivery. For example, early detection of an epileptic seizure from sequential electroencephalographic (EEG) measurements would...

Despite a pivotal role in the motor loop, dorsolateral striatum (putamen) has been poorly studied thus far under Parkinsonian conditions and Deep Brain Stimulation (DBS). We analyze the activity of the putamen in a monkey by combining single unit recordings and point process models. The animal received DBS (30-130Hz) in the subthalamic nucleus (STN...

Deep brain stimulation (DBS) is a highly promising therapy for Parkinson's disease (PD). However, most patients do not get full therapeutic benefit from DBS, due to its critical dependence on electrode location in the Subthalamic Nucleus (STN). For this reason, we believe that the development of a novel surgical tool for DBS placement, i.e., an aut...

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) directly modulates the basal ganglia (BG), but how such stimulation impacts the cortex upstream is largely unknown. There is evidence of cortical activation in 6-hydroxydopamine (OHDA)-lesioned rodents and facilitation of motor evoked potentials in Parkinson's disease (PD) patients, but...

Epilepsy affects 50 million people worldwide, and 30% remain drug-resistant. This has increased interest in responsive neurostimulation, which is assumed to be most effective when administered right at the seizure onset. We propose a novel framework for seizure onset detection that involves (i) constructing statistics from intracranial multichannel...

Epilepsy affects 50 million people worldwide, and seizures in 30% of the cases remain drug resistant. This has increased interest in responsive neurostimulation, which is most effective when administered during seizure onset. We propose a novel framework for seizure onset detection that involves (i) constructing statistics from multichannel intracr...

The early detection of epileptic seizures requires computing relevant statistics from multivariate data and defining a robust decision strategy as a function of these statistics that accurately detects the transition from the normal to the peri-ictal (problematic) state. We model the afflicted brain as a hidden Markov model (HMM) with two hidden cl...

Quickest detection is the problem of detecting a change in the probability distribution of a sequence of random observations with as little delay as possible and with low probability of false alarm. To date, algorithms for quickest detection exist mainly for cases where the random observations are independent, and linear or exponential cost functio...

High frequency Deep Brain Stimulation in the Sub-Thalamic Nucleus is a clinically recognized therapy for the treatment of motor disorders in Parkinson's Disease. Sub-thalamic Nucleus (STN) is a small lens-shaped nucleus in the brain where it is a part of the basal ganglia system and is currently thought to play a prominent role in Parkinson's Disea...

Deep brain stimulation (DBS) is an effective therapy to treat movement disorders including essential tremor, dystonia, and Parkinson's disease. Despite over a decade of clinical experience the mechanisms of DBS are still unclear, and this lack of understanding makes the selection of stimulation parameters quite challenging. The objective of this wo...

Deep brain stimulation (DBS) is a clinically recognized electrical therapy for the treatment of several neural disorders, e.g., Parkinson's disease (PD), essential tremor, and compulsive disorders. High frequency (HF) STN DBS (Deep Brain Stimulation in SubThalamic Nucleus) is currently used to reduce the motor symptoms of PD, but the actual procedu...

Striatum (STR) is the major input stage of the basal ganglia (BG). It combines information from cortex, subthalamic nucleus (STN) and external globus pallidus (GPe), and projects to the output stages of the BG, where selection between concurrent motor programs is performed. Parkinson's disease (PD) reduces the concentration of dopamine (DA, a neuro...

Deep Brain Stimulation (DBS) is an effective surgical therapy for the treatment of movement disorders in Parkinson's disease (PD) and other neurological pathologies. DBS is known to modulate the spiking activity of the neurons within the basal ganglia, but how such modulation impacts the primary sensorimotor cortex is still uncertain. In this study...

High frequency (HF) Deep Brain Stimulation (DBS) in the Sub-Thalamic Nucleus (STN) is a clinically recognized therapy for the treatment of motor disorders in Parkinson Disease (PD). The underlying mechanisms of DBS and how it impacts neighboring nuclei, however, are not yet completely understood. Electrophysiological data has been collected in PD p...

Deep Brain Stimulation (DBS) is an effective treatment for patients with Parkinsons disease, but its impact on basal ganglia nuclei is not fully understood. DBS applied to the subthalamic nucleus (STN) affects neurons in the Globus Pallidus pars interna (GPi) through direct projections, as well as indirectly through the Globus Pallidus pars externa...

Deep brain stimulation (DBS) is an effective electric therapy to treat movement disorders associated with chronical neural diseases like essential tremor, dystonia and Parkinsonpsilas disease. In spite of a long clinical experience, the cellular effects of the DBS are still partially unknown because of the lack of information about the target sites...

Deep brain stimulation (DBS) is an effective electric therapy to treat movement disorders associated with chronical neural diseases like essential tremor, dystonia and Parkinson's disease. In spite of a long clinical experience, the cellular effects of the DBS are still partially unknown because of the lack of information about the target sites. Re...

The subthalamic nucleus (STN) plays a central role in movement actuation and manifestation of movement disorders (i.e., tremor, rigidity, akynesia and postural instability) in Parkinson's disease (PD) patients. Moreover, it has been recently revealed that an opportune electrical stimulation of the STN, called deep brain stimulation (DBS), can stron...

Deep brain stimulation (DBS) is an effective electric therapy to treat movement dis-orders associated with chronical neural diseases like essential tremor, dystonia and Parkinson's disease. In spite of a long clinical experience, the cellular effects of the DBS are still partially unknown because of the lack of information about the target sites. R...

Parkinson's disease (PD) is a neuro-degenerative pathology affecting the basal ganglia, a set of small subcortical nervous system nuclei. It induces a progressive necrosis of dopaminergic (i.e., releasing dopamine, a neurotransmitter) cells and, as a consequence, produces altered information patterns along movement-related ganglia-mediated pathways...

Parkinson's disease (PD) is treated by means of Deep Brain Stimulation (DBS), a therapy based on the injection of current on a regular basis into the basal ganglia, a set of small subcortical nervous system nuclei. DBS is effective in relief of motor symptoms and leads to a notable reduction of drug dose. From an engineering viewpoint, it also rais...

The neural spiking activity of the subthalamic nucleus (STN) is devoted to modulate movement actuation and correct movement disorders (i.e. tremor at rest, rigidity, akynesia and postural instability) in Parkinson's disease (PD) patients. Moreover, it has been recently revealed that an opportune electrical stimulation, called deep brain stimulation...