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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
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.
.
Yücel et al 2017
Le neuroscienze sociali rappresentano un ambito di ricerca
multidisciplinare che integra dati provenienti
da tre differenti livelli di analisi:
- Sociale
- Cognitivo
- Neurale
Ochsner and Lieberman, 2001
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
Adolphs, 1999
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
Historical background
Plasticità cerebrale
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
Historical background
Plasticità cerebrale
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
Historical background
Plasticità cerebrale
Luigi Galvani
Alessandro Volta
Draft of Voltas’s letter to
Banks, announcing the
invention of the battery
1799-1800
Piccolino, 1998
The prepared frog and the
electric machine, 1791
Historical background
Plasticità cerebrale
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
Repetitive Transcranial Magnetic Stimulation
Introduzione
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
rTMS: Meccanismi di azione
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.
Chen et al., 1997; Fregni and Pascual-Leone, 2007
Polarity-dependent excitability-modulation during tDCS
Plasticità cerebrale
1.5
kS
MEP-Amplitude with/without tDCS
*
prm
1.25
m
pom
*
1.0
anodal
stimulation
oc
Weak tDCS (1÷ 2mA) with a homogenous
positions:
currentElectrode
field modulate
brain excitability via
polarization
m =membrana
motor cortex;
prm = premotor
0.75
m-cS
0.5
cm
cathodal
stimulation
cortex; pom = post-motor cortex; oc
occipital;
cS = contralateral
tDCS= is
a neuromodulation
technique
forehead; cm = kontralateral motor
cortex
Nitsche & Paulus, 2000
transcranial Direct Current Stimulation (tDCS)
Plasticità cerebrale
5 minutes of Anodal or Cathodal tDCS (1mA) modify MEPs amplitude
Nitsche and Paulus, 2000; 2001; Wassermann and Grafman, 2005
tDCS vs TMS
tDCS
Neuromodulation
• 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
TMS
Neuromodulation, Neurostimulation
• 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 e Social Neuroscience
•
•
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
Knoch et al., 2008; Sellaro et al., 2016
tDCS clinical application on Addictions
Substance
use
Disorders
Behavioural
Addictions
The rationale of expanding tDCS work
to addictions is justified by its positive
effect on decision-making process
(improved) and on risk- taking
(reduced)
Sauvaget et al., 2015
tDCS e addiction
• Noninvasive brain stimulation, among which
transcranial direct current stimulation(tDCS),
has opened up new perspectives in addiction
treatment.
Rangel, Camerer & Montague (2008)
Neurocircuitry of Addiction
Goldstein and Volkow, 2002; Koob, Everitt and Robbins, 2008; Tang et al., 2015
Addiction e tDCS
Bihemispheric stimulation of the
DLPFC with the anode on right (F4) and
cathode on the left (F3) hemisphere
F4
-
tDCS
F3
+
Lefaucheur et al 2017
Gambling
Goldstein and Volkow, 2002; Koob, Everitt and Robbins, 2008; DiLeone et al 2009;Tang et al., 2015; Meng et al 2014
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
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
Fecteau et al., 2007
tDCS e Gambling
Participants receiving left anodal ⁄ right cathodal
stimulation choose more often high-risk choices
(contrary to previous findings in young subjects)
Boggio et al., 2010
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
tDCS e Gambling
*
Randomized double blind
between subjects design
•
•
•
Cathodal over the right DLPFC increased
IGT score
Benussi et al., 2017
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
Target areas and main findings of tDCS studies on social neuroscience
Boggio et al., 2016
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
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
ToM è un'abilità fondamentale per la vita sociale
Brune and Brune-Cohrs. 2006
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
Bora e Nabi, 2016; Onuoha et al., 2016; Sanvicente-Vieira et al 2017
Correlati neurali della ToM
Sistema neurale
distribuito sottostante il meccanismo neurocognitivo della
Teoria della Mente
Amodio and Frith, 2006; Saxe and Powell, 2006; Carrington and Bailey, 2009
tDCS e ToM
Due task:
1. Riconoscimento emozioni
2. Abilità di adottare la prospettiva dell’altro
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
Conson et al., 2015
tDCS e ToM
1. Riconoscimento emozioni
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
Conson et al., 2015
tDCS e ToM
2. Abilità di adottare la
prospettiva dell’altro
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)
Conson et al., 2015
ToM e differenze di genere
Frontotemporal Dementia
?
Alzheimer’s Disease
Theory of Mind e empathizing–systemizing theory
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.
Baron-Cohen, 2010
Neuroimaging, ToM e differenze di genere
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
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
Highlights
Plasticità cerebrale
• 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.
Highlights
Plasticità cerebrale
• 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
Unità di Ricerca in Neuroscienze sociali e delle emozioni
Dipartimento di psicologia
Università Cattolica del Sacro Cuore
Centro di Scienza Cognitiva
Dipartimento di Psicologia,
Università degli studi di Torino
Michela Balconi
Davide Crivelli
Francesca Pala
Maria Elide Vanutelli
Mauro Adenzato
Ivan Enrici
Clinica Neurologica,
Università degli studi di Brescia
Alessandro Padovani
Barbara Borroni
Alberto Benussi
Unità di Neuropsicologia
IRCCS Centro San Giovanni di Dio
Fatebenefratelli Brescia
Rosa Manenti
Michela Brambilla
Sandra Rosini
Plasticità cerebrale
Thanks for your attention