Approcci di intervento delle neuroscienze cliniche e della neuropsichiatria alle new e old addictions

Workshop Internazionale

Nuove metodiche di intervento in ambito neuropsichiatrico e neuroscientifico

Maria Cotelli IRCCS Fatebenefratelli - Brescia

Brescia, 8 Aprile 2017

Yücel et al 2017

Neuroscienze sociali e addiction

Experimental neuropsychology and social neuroscience approaches provide the opportunity to better describe and understand the interplay between social functioning and the development of addiction. .

Ochsner and Lieberman, 2001

Le neuroscienze sociali rappresentano un ambito di ricerca multidisciplinare che integra dati provenienti da tre differenti livelli di analisi: - Sociale - Cognitivo - Neurale

Adolphs, 1999

Cognizione sociale

È l’insieme delle capacità che

permettono ad un individuo di costruire rappresentazioni

mentali delle relazioni esistenti tra se stesso e gli altri e di

utilizzare queste informazioni per muoversi efficacemente nel

proprio mondo sociale

The social brain

Neuroscience tools

Neurofeedback

Neurostimulation and neuromodulation

Virtual reality

Social cognition/rTMS e tDCS

Tecniche non invasive di

stimolazione hanno confermato la presenza di un sistema neurale distribuito sottostante ai compiti

di cognizione sociale

Plasticità cerebrale Historical background

Egyptian tomb dating 2 500 BC, showing small boat with a man who has hooked a Nile catfish and is going to experience a painful shock

Plasticità cerebrale Historical background

In 43-48 a.c. Scribonio Largo (1529) observed that placing a live torpedo fish - delivering a strong direct electric current – over the scalp of a patient with headache elicited a sudden, transient stupor with pain relief.

Priori, 2003

Plasticità cerebrale

Piccolino, 1998

Historical background

Luigi Galvani

The prepared frog and the electric machine, 1791

Draft of Voltas’s letter to Banks, announcing the invention of the battery 1799-1800

Alessandro Volta

Plasticità cerebrale Historical background

Giovanni Aldini

Galvani’s nephew, Giovanni Aldini, in 1804 reported the successful treatment of patients suffering from melancholia by applying galvanic currents over the head.

Parent, 2004; Priori, 2003

Introduzione Repetitive Transcranial Magnetic Stimulation

rTMS

Transcranial magnetic stimulation (TMS) has provided over two decades of data in focal, non-invasive brain

stimulation based on the principles of electromagnetic induction.

TMS is a neurostimulation and neuromodulation technique

In general, “high-frequency stimulation” refers to frequencies above ≥5Hz and is considered to produce an excitatory effect, whereas “low frequency stimulation” refers to frequencies below ≤1Hz causing inhibition of cortical excitability.

rTMS: Meccanismi di azione

Chen et al., 1997; Fregni and Pascual-Leone, 2007

Plasticità cerebrale Polarity-dependent excitability-modulation during tDCS

m-cS

kS

prm

m

pom

oc

Electrode positions:

m = motor cortex; prm = premotor

cortex; pom = post-motor cortex; oc

= occipital ; cS = contralateral

forehead; cm = kontralateral motor

cortex

cm

0.5

0.75

1.0

1.25

1.5

ME

P-A

mplit

ude w

ith

/without

tDC

S

*

*anodal

stimulation

cathodal

stimulation

Weak tDCS (1÷ 2mA) with a homogenous current field modulate brain excitability via

membrana polarization

tDCS is a neuromodulation technique

Nitsche & Paulus, 2000

Plasticità cerebrale transcranial Direct Current Stimulation (tDCS)

5 minutes of Anodal or Cathodal tDCS (1mA) modify MEPs amplitude

Nitsche and Paulus, 2000; 2001; Wassermann and Grafman, 2005

• Very inexpensive and portable • Sham Stimulation: comparable

perceptual feelings • Spatial resolution of stimulation:

tDCS has poor spatial resolution • tDCS is ideal for online protocols • Believed to be exceptionally safe • Does not induce action potentials in

axons • Believed to modulate the firing rate

of active neurons • Depending on polarity, tDCS can

induce cortical excitability reduction or enhancement that can persists for hours or days

• Relatively expensive • Sham Stimulation: Sham coil • Spatial resolution of TMS stimulation

depends of coils size and configuration • Moderate side effects (e.g. mild

speech arrest) • TMS is less ideal to be used during a

training/task • Safe, but there are reports of inducing

seizures when high amplitude and frequency are combined

• TMS induces a current that can elicit action potentials in neurons;

• Depending on frequency, sustained TMS can induce excitability reduction or enhancements that can persist for hours or days.

Nitsche et al., 2008; Priori et al., 2009; Dayan et al., 2013; Woods et al., 2016

tDCS vs TMS

tDCS Neuromodulation

TMS Neuromodulation, Neurostimulation

Knoch et al., 2008; Sellaro et al., 2016

• Very inexpensive and portable; • Sham Stimulation: comparable

perceptual feelings; • tDCS is ideal for online protocol; • Believed to be exceptionally safe; • Depending on polarity, tDCS can induce cortical excitability reduction or

enhancement that can persists for hours or days;

Great potential of tDCS for brain stimulation studies investigating social

interaction

tDCS e Social Neuroscience

tDCS clinical application on Addictions

Sauvaget et al., 2015

The rationale of expanding tDCS work to addictions is justified by its positive

effect on decision-making process (improved) and on risk- taking

(reduced)

Substance use

Disorders

Behavioural Addictions

tDCS e addiction

Rangel, Camerer & Montague (2008)

• Noninvasive brain stimulation, among which

transcranial direct current stimulation(tDCS), has opened up new perspectives in addiction treatment.

Goldstein and Volkow, 2002; Koob, Everitt and Robbins, 2008; Tang et al., 2015

Neurocircuitry of Addiction

Lefaucheur et al 2017

Addiction e tDCS

+

-

tDC

S

F4 F3

Bihemispheric stimulation of the DLPFC with the anode on right (F4) and cathode on the left (F3) hemisphere

Goldstein and Volkow, 2002; Koob, Everitt and Robbins, 2008; DiLeone et al 2009;Tang et al., 2015; Meng et al 2014

Gambling

tDCS e Gambling

.

36 young participants performed a gambling risk task while receiving: • Anodal tDCS over the

right and cathodal tDCS over the left DLPFC

• Anodal tDCS over the left and cathodal tDCS over the right DLPFC

• Sham tDCS

Fecteau et al., 2007

Fecteau et al., 2007

tDCS e Gambling

When healthy participants (young) received anodal

stimulation over the right DLPFC coupled with cathodal

tDCS over the left DLPFC, they chose more often the

safe prospects

they diminish risk-taking

Boggio et al., 2010

tDCS e Gambling

28 older adults performed a gambling risk task while receiving: • Anodal tDCS over the right

and cathodal tDCS over the left DLPFC

• Anodal tDCS over the left with cathodal tDCS over the right DLPFC

• Sham tDCS Participants receiving left anodal ⁄ right cathodal stimulation choose more often high-risk choices (contrary to previous findings in young subjects)

Benussi et al., 2017

tDCS e Gambling

Randomized double blind between subjects design • 20 PD patients anodal 2mA

over right DLPFC • 20 PD patients cathodal

2mA over right DLPFC • 20 PD patients placebo

stimulation During IOWA Gambling Task (IGT) Global IGT score: difference between advantageous and disadvantageous choices

*

Cathodal over the right DLPFC increased IGT score

Boggio et al., 2016

Target areas and main findings of tDCS studies on social neuroscience

La Teoria della Mente è la capacità di attribuire a sé e agli altri stati

mentali quali desideri, intenzioni, pensieri e credenze e di spiegare e

prevedere i comportamenti sulla base di queste inferenze.

Premack e Woodruff, 1978

Brune and Brune-Cohrs. 2006

ToM è un'abilità fondamentale per la vita sociale

La teoria della mente (ToM) permette di interpretare il proprio mondo sociale con la consapevolezza che le persone agiscono sulla base dei rispettivi contenuti mentali e viene utilizzata dal soggetto ogni qualvolta si trova a cercare di attribuire un significato al comportamento proprio e altrui

Bora e Nabi, 2016; Onuoha et al., 2016; Sanvicente-Vieira et al 2017

Teoria della mente e addiction

Le abilità di ToM e di riconoscimento delle emozioni appaiono deficitarie in soggetti

con diagnosi di Abuso e/o Dipendenza da alcol

Amodio and Frith, 2006; Saxe and Powell, 2006; Carrington and Bailey, 2009

Correlati neurali della ToM

Sistema neurale distribuito sottostante il meccanismo neurocognitivo della

Teoria della Mente

Conson et al., 2015

tDCS e ToM

16 Soggetti (8 maschi e 8 femmine)

1.0 mA biemisferica tDCS per 15 minuti

Anodica Left/ catodica Right oppure Anodica R/catodica L - tDCS o sham

I partecipanti eseguono compiti

sperimentali dopo tDCS

Due task: 1. Riconoscimento emozioni 2. Abilità di adottare la prospettiva dell’altro

Conson et al., 2015

tDCS e ToM

Esclusivamente nel gruppo dei partecipanti maschi si osserva riduzione dei RT

per il riconoscimento dell’espressione facciale di paura dopo tDCS anodica destra e catodica sinistra.

Nessun effetto nelle donne

1. Riconoscimento emozioni

Conson et al., 2015

tDCS e ToM

In tutti i soggetti (maschi e

femmine) tDCS anodica destra e catodica sinistra riduce la

capacità di adottare la prospettiva dell’altro

(aumento tempi reazione e riduzione accuratezza)

2. Abilità di adottare la prospettiva dell’altro

Frontotemporal Dementia

Alzheimer’s Disease ?

ToM e differenze di genere

Theory of Mind e empathizing–systemizing theory

Baron-Cohen, 2010

According to empathizing–systemizing theory females are, on average, more disposed to an empathizing style— i.e., the drive to identify others’ mental states in order to predict their behavior and respond with an appropriate emotion. On the other hand, males are, on average, more disposed to a systematizing style, i.e., the drive to predict and to respond to the behavior of non-agentive deterministic systems by inferring the rules that govern such systems.

Nei maschi maggiore attivazione mPFC

quando si fa credere che il partner di gioco è

un uomo e non un computer partner

Krach et al 2009

Neuroimaging, ToM e differenze di genere

Krach et al., 2009

RME task

Baron-Cohen et al., 2001 Serafin and Surian, 2004

Adenzato et al., 2017

tDCS and theory of mind

EXP 1: 16 males & 16 females mPFC and placebo

EXP 2: 16 females CZ and placebo

Adenzato et al., 2017

tDCS and theory of mind

Adenzato et al., 2017

Plasticità cerebrale Highlights

• Experimental neuropsychology and social neuroscience approaches now provide the opportunity to better describe and understand the interplay between social functioning and the development of addiction.

• tES techniques are considered well tolerated (where precise established protocols are followed) and operated by influencing neuronal activity, generating gradual changes in neural networks.

• tDCS is an effective and relevant technique to be used in social neuroscience.

• Studies on non-invasive brain stimulation with weak electrical currents have shown potential benefits by the induction of changes in cortical excitability and, consequently, in neuroplasticity.

Plasticità cerebrale Highlights

• To date, findings are encouraging, but sham-controlled studies are still insufficient to allow endorsement of widespred use of these techniques, despite the great margin of safety if appropriate guidelines and precautions are followed.

• The effects of these techniques seem to depend on the parameters of the stimulation which explains the variability of the results.

• While there is an increased understanding of the mechanisms of tDCS, the mechanisms that underline other tES methods are poorly understood.

Grazie Centro di Scienza Cognitiva Dipartimento di Psicologia,

Università degli studi di Torino

Mauro Adenzato Ivan Enrici

Unità di Neuropsicologia IRCCS Centro San Giovanni di Dio

Fatebenefratelli Brescia

Rosa Manenti Michela Brambilla

Sandra Rosini

Unità di Ricerca in Neuroscienze sociali e delle emozioni Dipartimento di psicologia

Università Cattolica del Sacro Cuore

Michela Balconi Davide Crivelli Francesca Pala

Maria Elide Vanutelli

Clinica Neurologica, Università degli studi di Brescia

Alessandro Padovani

Barbara Borroni Alberto Benussi

Plasticità cerebrale

Thanks for your attention