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The Illusion of the Perfect Brain Enhancer

Emiliano Santarnecchi, Alvaro Pascual-Leone
2017 Cerebrum  
Emiliano Santarnecchi, Ph.D., is an instructor of neurology and co-director of the CME course in Transcranial Current Stimulation (tCS) at Harvard Medical School and a clinical research scientist at the  ...  Santarnecchi obtained his Ph.D. in applied neurological sciences at the University of Siena School of Medicine in Italy.  ... 
pmid:30210662 pmcid:PMC6132045 fatcat:hhgb3yfnwvdoffz3pniek4oqzm

Going Beyond the Phenotype: Human Intelligence as a Neurobiological Legacy

Emiliano Santarnecchi
2013 Anthropology  
Volume 1 • Issue 3 • 1000e111 Anthropol ISSN: 2332-0915 ANTP, an open access journal Over the last decades, neurosciences have gone through a revolution in theories and methods for understanding neural function and its connections with human cognition, experience, and interindividual differences. In this context, nowadays neuroscience has developed through the integration of other research fields like genetic, cell biology, psychology, sociology, engineering and informatics. Moreover, this
more » ... tless changing process has also lead to the birth of brand new research fields like neuro-anthropology, aimed at understanding how the human brain develops, how it is structured and how it works within the genetic and cultural limits of its biology, as well as how it interacts with cultural changes. In the context of this emerging field, my primary goal is to promote a view of human intelligence study as a precious opportunity to study its practical impact on everyday life, as well to explore its "structure" as the final product of fine-tuning process lasted thousands of years. Apart from more canonical interpretations, as the ability to cope with environmental treats, to develop efficient social strategies, to communicate, to infer relationship between elements or solve abstract-reasoning problems, human intelligence might be also intended through an evolutionary point of view, considering intellectual abilities and rationality as emerging from a "social brain", evolved on the basis of adaptive pressures. Hopefully, modern neuroimaging techniques might allow us to find more and more important clues which could allow us to understand our past by "simply" looking at the present
doi:10.4172/2332-0915.1000e111 fatcat:jx5p53zmnre7dhbj4vwutym2se

Realistic modeling of ephaptic fields in the human brain [article]

Giulio Ruffini, Ricardo Salvador, Ehsan Tadayon, Roser Sanchez-Todo, Alvaro Pascual-Leone, Emiliano Santarnecchi
2019 bioRxiv   pre-print
Santarnecchi are partially supported by Office of the Director of National 650 Intelligence (ODNI), Intelligence Advanced Research Projects Activity (IARPA), via 2014-651 13121700007.  ...  Santarnecchi is supported by the Beth Israel 658 Deaconess Medical Center (BIDMC) via the Chief Academic Officer (CAO) Award 2017, the 659 Defence Advanced Research Projects Agency (DARPA) via HR001117S0030  ... 
doi:10.1101/688101 fatcat:mrfd7ybug5cyllbhagw5vat3ei

Personalization of hybrid brain models from neuroimaging and electrophysiology data [article]

Roser Sanchez-Todo, Ricardo Salvador, Emiliano Santarnecchi, Fabrice Wendling, Gustavo Deco, Giulio Ruffini
2018 bioRxiv   pre-print
Personalization is rapidly becoming standard practice in medical diagnosis and treatment. This study is part of an ambitious program towards computational personalization of neuromodulatory interventions in neuropsychiatry. We propose to model the individual human brain as a network of neural masses embedded in a realistic physical matrix capable of representing measurable electrical brain activity. We call this a hybrid brain model (HBM) to highlight that it encodes both biophysical and
more » ... ogical characteristics of an individual brain. Although the framework is general, we provide here a pipeline for the integration of anatomical, structural and functional connectivity data obtained from magnetic resonance imaging (MRI), diffuse tensor imaging (DTI connectome) and electroencephalography (EEG). We personalize model parameters through a comparison of simulated cortical functional connectivity with functional connectivity profiles derived from cortically-mapped, subject-specific EEG. We show that individual information can be represented in model space through the proper adjustment of two parameters (global coupling strength and conduction velocity), and that the underlying structural information has a strong impact on the functional outcome of the model. These findings provide a proof of concept and open the door for further advances, including the model-driven design of non-invasive brain-stimulation protocols.
doi:10.1101/461350 fatcat:7ms3p5vcwvgqnbxtzoqtcrh3li

An Evolutionary Game Theory Model of Spontaneous Brain Functioning

Dario Madeo, Agostino Talarico, Alvaro Pascual-Leone, Chiara Mocenni, Emiliano Santarnecchi
2017 Scientific Reports  
doi:10.1038/s41598-017-15865-w pmid:29167478 pmcid:PMC5700053 fatcat:flpvn2ck7ndatmsxmspaqjzqou

Emotional Context Shapes the Serial Position Curve

Fabio Giovannelli, Iglis Innocenti, Emiliano Santarnecchi, Elisa Tatti, Stefano F. Cappa, Simone Rossi
2022 Brain Sciences  
Emotional contexts affect memory processes. However, the impact of contextual priming as a function of the emotional valence on the recall of neutral information is not fully understood. The aim of the present study was to evaluate how a conditioning of emotional context during encoding may influence the subsequent memory of otherwise neutral materials in a well-established phenomenon as the serial position effect. Participants performed a free recall task for neutral words in three conditions:
more » ... (i) word list alone; (ii) word list coupled with positive or neutral images; and (iii) word list coupled with negative or neutral images. Images were presented before each word stimulus. In three different experiments, the emotional context during the word list presentation was manipulated separately for primacy and recency clusters, and for the middle words ('middlecy'). Emotional context affects free recall of neutral stimuli, changing the serial position curve effect across conditions. Namely, emotional images presented in the primacy and recency clusters worsen accuracy, whereas their occurrence in the 'middlecy' cluster reduces the oblivion. The present findings show that the typical pattern related to the serial position curve for neutral information can be shaped by the conditioning of emotional context. Findings have implications in medical-legal contexts in the case of the recollection of events with high emotional content.
doi:10.3390/brainsci12050581 pmid:35624967 pmcid:PMC9139710 fatcat:2jalrslfyve3tdyamzaijywndy

Therapeutic Noninvasive Brain Stimulation in Alzheimer's Disease

Irene Gonsalvez, Roey Baror, Peter Fried, Emiliano Santarnecchi, Alvaro Pascual-Leone
2016 Current Alzheimer Research  
Poreisz et al. concluded after the analysis of 567 hancement in healthy individuals (Lapenta 2014, Dubljevic 2014, Santarnecchi et al 2013).  ... 
doi:10.2174/1567205013666160930113907 pmid:27697061 fatcat:fmjn622ia5fd5e4alef75avl7a

Bridge Over Troubled Water: Commenting on Kovacs and Conway's Process Overlap Theory

Roberto Colom, Adam Chuderski, Emiliano Santarnecchi
2016 Psychological Inquiry  
Figure 2 . 2 Meta-analysis results for fluid intelligence and executive processes (adapted and modified from Santarnecchi et al., 2016).  ...  We close this section reporting the findings of a recent metaanalysis by Santarnecchi et al. (2016) including fluid intelligence, inhibition, switching/flexibility, and updating ( Figure 2 ).  ... 
doi:10.1080/1047840x.2016.1181513 fatcat:ooi2dbcygzegdog3pbmynht33e

Prospects for transcranial temporal interference stimulation in humans: a computational study [article]

Sumientra Rampersad, Biel Roig-Solvas, Mattew Yarossi, Praveen P Kulkarni, Emiliano Santarnecchi, Alan D Dorval, Dana H Brooks
2019 bioRxiv   pre-print
Transcranial alternating current stimulation (tACS) is a noninvasive method used to modulate activity of superficial brain regions. Deeper and more steerable stimulation could potentially be achieved using transcranial temporal interference stimulation (tTIS): two high-frequency alternating fields interact to produce a wave with an envelope frequency in the range thought to modulate neural activity. Promising initial results have been reported for experiments with mice. In this study we aim to
more » ... etter understand the electric fields produced with tTIS and examine its prospects in humans through simulations with murine and human head models. A murine head finite element model was used to simulate previously published experiments of tTIS in mice. With a total current of 0.776 mA, tTIS electric field strengths up to 383 V/m were reached in the modeled mouse brain, suggesting that suprathreshold stimulation is possible in mice. Using a detailed anisotropic human head model, tTIS was simulated with systematically varied electrode configurations and input currents to investigate where interference fields are largest and why, the spatial extent of those fields, and how both are influenced by electrode placement and current strengths. An exhaustive search with 88 electrode locations covering the entire head (146M total current patterns) was employed to optimize tTIS fields. In all analyses, we investigated maximal effects and effects along the direction of the neurons. We found that it was possible to steer the peak tTIS field by manipulating the relative strength of the two input fields. Deep brain areas received field strengths similar to conventional tACS, but with less stimulation in superficial areas. Maximum field strengths were much lower than in the murine model, too low to expect direct stimulation effects. While field strengths were slightly higher with tACS, our results suggest that tTIS produces more focal fields and allows for better steerability. Finally, we present optimal four-electrode current patterns to maximize tTIS in regions of the pallidum (0.37 V/m), hippocampus (0.25 V/m) and motor cortex (0.57 V/m). We conclude that tTIS has potential as a more controlled version of tACS.
doi:10.1101/602102 fatcat:i2lauvk7ijcmlhv7tdi3ftsg7a

Targeting brain networks with multichannel transcranial current stimulation (tCS)

Giulio Ruffini, Fabrice Wendling, Roser Sanchez-Todo, Emiliano Santarnecchi
2018 Current Opinion in Biomedical Engineering  
Santarnecchi, E., Momi, D., Sprugnoli, G., Neri, F., Pascual-Leone, A., Rossi, A., Rossi, S. (2018b).  ...  Santarnecchi, E., Khanna, A.R., Musaeus, C.S., Benwell, C.S.Y., Davila, P., Farzan, F., Matham, S., Pascual-Leone, A., Shafi, M.M., on behalf of Honeywell SHARP Team authors (2017b).  ... 
doi:10.1016/j.cobme.2018.11.001 fatcat:nhbge5jeurhsrnxyypt4lgjeua

Levetiracetam Alters Oscillatory Connectivity in Alzheimer's Disease

Christian S. Musaeus, Mouhsin M. Shafi, Emiliano Santarnecchi, Susan T. Herman, Daniel Z. Press
2017 Journal of Alzheimer's Disease  
U n c o r r e c t e d A u t h o r P r o o f Journal of Alzheimer's Disease xx (20xx) x-xx Abstract. Seizures occur at a higher frequency in people with Alzheimer's disease (AD) but overt, clinically obvious events are infrequent. Evidence from animal models and studies in mild cognitive impairment suggest that subclinical epileptic discharges may play a role in the clinical and pathophysiological manifestations of AD. In this feasibility study, the neurophysiological and cognitive effects of
more » ... te administration of levetiracetam (LEV) are measured in patients with mild AD to test whether it could have a therapeutic benefit. AD participants were administered low dose LEV (2.5 mg/kg), higher dose LEV (7.5 mg/kg), or placebo in a double-blind, within-subject repeated measures study with EEG recorded at rest before and after administration. After administration of higher dose of LEV, we found significant decreases in coherence in the delta band (1-3.99 Hz) and increases in the low beta (13-17.99 Hz) and the high beta band (24-29.99 Hz). Furthermore, we found trends toward increased power in the frontal and central regions in the high beta band (24-29.99 Hz). However, there were no significant changes in cognitive performance after this single dose administration. The pattern of decreased coherence in the lower frequency bands and increased coherence in the higher frequency bands suggests a beneficial effect of LEV for patients with AD. Larger longitudinal studies and studies with healthy age-matched controls are needed to determine whether this represents a relative normalization of EEG patterns, whether it is unique to AD as compared to normal aging, and whether longer term administration is associated with a beneficial clinical effect. While the majority of patients do not have clini-32 cally evident seizures, subclinical epileptic activity 33 may be more prevalent, and has been hypothe-34 sized to underlie some fluctuations in cognition 35 in AD [3]. A recent study showed that 42.4% 36 of patients with AD had subclinical epileptiform 37 activity when epilepsy was assessed by overnight 38 long-term video-electroencephalography (EEG) and 39 magnetoencephalography, as compared with 10.5% 40 of controls and that patients who showed subclin-41 ical epileptic activity had faster decline in global 42 cognition [11]. If present, even subclinical epileptic 43 U n c o r r e c t e d A u t h o r P r o o f 48 related with behavioral deficits [13, 14]. In these 49 models, the acute administration of an antiepileptic 50 drug (AED), levetiracetam (LEV), blocked the spik-51 ing activity and reversed the cognitive deficits. LEV 52 decreases the frequency and limits the propagation of 53 epileptiform activity without affecting normal neu-54 ronal excitability [15, 16]. The mechanism of action 55 of LEV is not fully understood, but it binds selectively 56 to synaptic vesicle protein SV2A and likely modu-57 lates its function [17]. In AD animal models, LEV 58 showed efficacy whereas a number of other AEDs 59 with different mechanisms of action (ethosuximide, 60 gabapentin, phenytoin, pregabalin, valproic acid, and 61 vigabatrin) were ineffective [13]. 62 The neurophysiological effects of LEV have been 63 studied in epilepsy patients, where LEV has been 64 shown to decrease the power of delta and theta bands 65 and increase that of the high alpha (10-13 Hz) and 66 middle beta (19-24 Hz) band in drug-naive epilepsy 67 patients [18]. Acute dosing of LEV at a dose of 68 500 mg caused significant reduction in the frequency 69 of interictal epileptiform activity in 8/10 patients with 70 epilepsy [19]. Another study using functional mag-71 netic resonance imaging (fMRI) to determine the 72 effects of a low dose of LEV in patients with amnes-73 tic mild cognitive impairment (aMCI) has shown 74 that it reduces the aberrantly increased fMRI activ-75 ity in the dentate gyrus/CA3 to the same level as 76 healthy controls [20]. In this study, LEV improved the 77 task-related memory performance on a forced choice 78 memory task for patients with aMCI. Elderly people 79 with cognitive impairment such as AD, mixed demen-80 tia, or MCI with epilepsy tolerated LEV as well, and 81 improvements were seen in the Mini-Mental State 82 Examination (MMSE) and the Alzheimer's Disease 83 Assessment Scale-Cognitive [21]. 84 It is difficult to directly study the occurrence of 85 epileptic activity in the medial temporal lobes of 86 patients suffering from AD since medial temporal 87 lobe sources have deep localization and are not visible 88 on scalp EEG unless activity propagates to neo-89 cortex. We therefore sought to investigate whether 90 LEV could improve abnormalities on other EEG 91 parameters using quantitative EEG, which has been 92 used to show differences between healthy controls 93 and AD. Quantitative EEG has also been used to 94 assess the progression of AD and MCI using spectral 95 power [22-26] and connectivity measures like coher-96 ence [27-33]. To date, we are unaware of any 97 published study investigating the neurophysiologi-98 cal and cognitive effects of acute administration of 99 AEDs in patients suffering from AD without known 100 epilepsy. In this feasibility study, we therefore wanted 101 to test the cognitive and neurophysiological effects 102 of acutely administering two different doses of LEV 103 (2.5 mg/kg and 7.5 mg/kg) intravenously as com-104 pared to a placebo/saline administration in patients 105 with mild AD. We sought to measure whether LEV 106 leads to changes when looking at quantitative EEG 107 or cognitive scores, and whether these changes could 108 support the hypothesis that patients with AD, even in 109 the absence of clinically evident seizures, may still 110 benefit from AED therapy. 111 METHODS 112 We conducted a double-blind, within-subject 113 crossover design study in which participants with 114 mild AD received placebo, 2.5 mg/kg, and 7.5 mg/kg 115 of LEV intravenously in a random order in three ses-116 sions. The three sessions (placebo, 2.5 mg/kg LEV, 117 and 7.5 mg/kg LEV) were held at least one week apart 118 to allow for complete washout of the drug. During 119 each session, baseline EEG was recorded for 20 min 120 prior to administration of the LEV/placebo. The drug 121 was administered over a second 20-min epoch and a 122 final 20-min epoch of EEG was recorded afterward. 123 After completing the EEG, the participants under-124 went functional brain imaging with perfusion MRI 125 and resting state functional connectivity MRI (the 126
doi:10.3233/jad-160742 pmid:28527204 fatcat:4ejp7in6bba7fnmluctnc6krny

Enhancing cognition using transcranial electrical stimulation

Emiliano Santarnecchi, Anna-Katharine Brem, Erica Levenbaum, Todd Thompson, Roi Cohen Kadosh, Alvaro Pascual-Leone
2015 Current Opinion in Behavioral Sciences  
Current Opinion in Behavioral Sciences 2015, 4:171-178 Cognitive enhancement using tES Santarnecchi et al. 173 Current Opinion in Behavioral Sciences 2015  ... 
doi:10.1016/j.cobeha.2015.06.003 fatcat:jgl7zfrmfbcjxg326drvk7hqaq

In-vivo phase-dependent enhancement and suppression of brain oscillations by transcranial alternating current stimulation (tACS) [article]

David Haslacher, Asmita Narang, Alessia Cavallo, Khaled Nasr, Emiliano Santarnecchi, Surjo Soekadar
2022 bioRxiv   pre-print
Transcranial alternating current stimulation (tACS) can influence human perception and behavior, with recent evidence also suggesting its potential impact in clinical settings, but the underlying mechanisms are poorly understood. Behavioral and indirect physiological evidence indicates that phase-dependent constructive and destructive interference between the tACS electric field and ongoing brain oscillations may play an important role, but direct in-vivo validation was infeasible because
more » ... ation artifacts impeded such assessment. Using stimulation artifact source separation (SASS), a real-time compatible artifact suppression approach, we overcame this limitation and provide direct evidence for millisecond-by-millisecond phase-dependent enhancement and suppression of ongoing brain oscillations during amplitude-modulated tACS (AM-tACS) across 29 healthy human volunteers. We found that AM-tACS enhanced and suppressed targeted brain oscillations by 11.7 +/- 5.14% and 10.1 +/- 4.07% respectively. Millisecond-precise modulation of oscillations predicted modulation of behavior (r = 0.65, p < 0.001). These results not only provide direct evidence for constructive and destructive interference as a key mechanism of AM-tACS but suggest superiority of phase-locked (closed-loop) AM-tACS over conventional (open-loop) AM-tACS to purposefully enhance or suppress brain oscillations.
doi:10.1101/2022.02.28.482226 fatcat:fmm53r5epvfdlirn5ailyenzrm

Dissecting the parieto-frontal correlates of fluid intelligence: A comprehensive ALE meta-analysis study

Emiliano Santarnecchi, Alexandra Emmendorfer, Alvaro Pascual-Leone
2017 Intelligence  
doi:10.1016/j.intell.2017.04.008 fatcat:rihsh5nlvzafniyor5bqwfsxvy

Newly Discovered Neuron-to-Glioma Communication: New Noninvasive Therapeutic Opportunities on the Horizon?

Giulia Sprugnoli, Alexandra J Golby, Emiliano Santarnecchi
2021 Neuro-Oncology Advances  
The newly discovered functional integration of glioma cells into brain networks in mouse models provides groundbreaking insight into their aggressiveness and resistance to treatments, also suggesting novel potential therapeutic avenues and targets. In the context of such neuron-to-glioma communication, noninvasive brain modulation techniques that have been traditionally applied to focally modulate neuronal function in neurological and psychiatric diseases (e.g. increase/decrease cortical
more » ... ility and plasticity) should now be tested in patients with brain tumors to suppress glioma's activity and its pathological crosstalk with healthy brain tissue.
doi:10.1093/noajnl/vdab018 pmid:33738449 pmcid:PMC7954106 fatcat:re4yr4vrsveqjlgmhyf34cmdjy
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