'Psiquiatría: situación actual y perspectivas de futuro'. Este es el título del simposio internacional que organizamos el 20 de junio de 2016 en la Fundación Ramón Areces con las fundaciones Juan José López-Ibor y Lilly en homenaje al doctor Juan José López-Ibor, fallecido en enero de 2015. Durante esta jornada, expertos internacionales abordaron la profunda crisis que atraviesa la psiquiatría como disciplina científica y especialidad médica. Además, se presentó el libro con el mismo título del simposio, también en recuerdo del doctor López-Ibor.

1. 20
Recent advances in the
understanding of mental illness:
The Default Network
Jorge Alberto Costa e Silva
Professor and Chairman of Psychiatry of the Catholic University of Rio de Janeiro (PUC-RJ)
Chairman of the Dept. of Psychiatry at Santa Casa do Rio de Janeiro
Past President of the World Psychiatric Association (WPA) and Former Director of Mental Health
(WHO – Geneva).

2. A tribute to López-Ibor

3. Increasing collaborative investments in understanding the brain
Accelerating development in applications of innovative
technologies to understand brain function
New picture of how the brain works  Integration of neuronal
and circuit activity over time and space
The new landscape of neuroscience

4. • Enrich: cognitive science, neuroscience and psychology
• Heal and Protect: medicine, neuroscience, psychiatry
• Understand: cognitive science, computer science, neuroscience
• Model: computer science, engineering, mathematics.
Decade of the brain

5. Brain Research through Advancing Neurotechnologies
Over $300 M in public and private investments
Research new ways to treat, prevent, and cure brain disorders
like Alzheimer´s, schizophrenia, autism, epilepsy and traumatic
brain injury
The White House BRAIN initiative

6. The Human Brain Project
European Commission – more than €1 billion in
funding
Collaboration across 24 countries and more than
100 institutions
Develop information and communication technology
(ICT) platforms for collecting and integrating brain
research data

7. The Human Connectome Project
Aims to build a "network map" – connectome
- that will shed light on the anatomical and
functional connectivity within the health
human brain
Produce a body of data that will facilitate
research into brain disorders such as
schizophrenia, Alzheimer´s disease, etc.

8. A focus on circuits and networks
60 years of
single-neuron
recordings
30 years of
molecular
biology
20 years
of brain imaging
(fMRI)
Cognition, emotion, memory, action
are generated by circuits and
networks of billions of interconnected
neurons
How do they work?

9. Brain imaging technologies (fMRI, PET scans)
Microscopy and optics (confocal and multifocal microscopy, spectroscopy)
Genetics / genomics / proteomics / metabolomics
Computer science
New technologies are expanding
the range of the possible:

10. Functional Segregation
Different areas of the brain are
specialised for different functions
Functional Integration
Networks of interactions among
specialised areas
Background
Localizationism
Functions are localised in
anatomic cortical regions
Damage to a region results
in loss of function
Functional Segregation
Functions are carried out by
specific areas/cells in the
cortex that can be
anatomically separated
Globalism
The brain works as a whole,
extent of brain damage is
more important than its
location
Connectionism
Networks of simple
connected units
Evolution of understanding the brain

11. Background
Systems analysis in functional neuroimaging
• Analysis of how different regions in a
neuronal system interact (coupling).
• Determines how an experimental
manipulation affects coupling
between regions.
• Univariate & Multivariate analysis
• Analyses of regionally specific effects
• Identifies regions specialized for a
particular task.
• Univariate analysis
Standard SPM
Adapted from D. Gitelman, 2011
Functional Segregation
Specialized areas exist in the cortex
Functional Integration
Networks of interactions among specialized areas
Effective
connectivity
Functional
connectivity

12. Background
Types of connectivity studies
Anatomical/structural connectivity - presence of axonal connections
- example: tracing techniques, diffusion tensor imaging
Functional connectivity - statistical dependencies between regional time series
- Simple temporal correlation between activation of remote neural areas
- example: seed voxel, eigen-decomposition (PCA, SVD), independent component
analysis (ICA)
Effective connectivity causal/directed influences between neurons or populations
- Model-based; analysed through model comparison
- examples: PPIs - Psycho-Physiological Interactions
SEM - Structural Equation Modelling
DCM - Dynamic Causal Modelling
Static Models
Dynamic Model

13. Graphical representations of connectomics
(mapping of all fiber connections in the human
brain)
Circular graphs based on diffusion MRI data and
graph theory
Demonstrate the white matter connections and
cortical characteristics for single structures,
single subjects, or populations
Connectograms

14. Background
Spontaneous BOLD activity
Occurs during task and at rest
• intrinsic brain activity
Resting-state networks
• correlation between
spontaneous BOLD signals
of brain regions known to be
functionally and/or
structurally related
Neuroscientists are studying this
spontaneous BOLD signal and
its correlation between brain
regions in order to learn about
the intrinsic functional
connectivity of the brain
Biswal et al., 1995
Van Dijk et al., 2010

15. Background
Resting state networks (RSNs)
Multiple resting-state networks (RSNs) have been found
All show activity during rest and during tasks
One of the RSNs, the default mode network (DMN), shows a decrease in activity during cognitive tasks

16. a
Pattern of brain activation when at rest – not engaged in focus or activity-
oriented tasks
The default mode of thinking is independent of external stimulus
Characterized by introspection, autobiographical memories, and thinking
about the future
A “large-scale, distributed network in which neural activity in different brain
regions spontaneously rises and falls together in temporal synchrony”
The default mode network
Raichle et al., 2001. A default mode of brain function. PNAS, 98 (2). 676-82.

17. a
Two reliable characteristics:
1 - Shows greater BOLD activity during quiet restfulness (e.g. the
resting state) than during active cognition.
• Internal dialogue hypothesis: the default network forms part of the
neural substrates underlying autobiographical memory and social
cognition
The default mode network
Raichle et al., 2001. A default mode of brain function. PNAS, 98 (2). 676-82.

18. a
Two reliable characteristics:
2 - Activity is suppressed when individuals engage in goal-
directed, task specific processing
• The default mode network is inherently anti-correlated with task positive networks
The default mode network
Fair & Raichle, 2007 Nature Review Neuroscience

19. The default network and mental illness
The default mode network has been hypothesized to be relevant to disorders
including:
- Alzheimer´s disease – Reduction in glucose within the areas of the default mode
network. Disruptions in the DMN begin even before individuals show signs of Alzheimer’s
disease -> possible biomarker
- Autism – The default network is disrupted. Fewer connections between the mPFC
(involved in thinking about the self and others) and the PCC (the central core of the DMN).
- Major depressive disorder (MDD) - Hyperconnectivity of the default network has
been linked to rumination in depression. Deactivation is impaired.

20. a
The network dysfunction that underlies MDD have shown aberrant
communications in the following networks
a) the frontoparietal network (FN) - top-down regulation of
attention and emotion.
b) the default mode network (DMN) – internally oriented attention
c) the dorsal attention network (DAN) - externally oriented
attention
d) the affective network (AN) and the ventral attention network
(VAN) - processing emotion or monitoring for salient events
The default mode network in MDD

21. Pauline Delaveau1*, PhD, Tiago Arruda Sanchez4, PhD, Ricardo Steffen4, MD,
PhD, Karine Deschet5, PhD, Maritza Jabourian5, PhD, Vincent Perlbarg6, PhD,
Stéphanie Dubal1, PhD, Jorge Costa e Silva7, MD, PhD, Philippe Fossati1,2,3,
MD, PhD
1. Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06, UMR
S 1127, Institut du Cerveau et de la Moelle, ICM, Social and Affective Neuroscience
(SAN) Laboratory, F-75013, Paris, France
2. AP-HP, Pitié-Salpêtrière Hospital, Department of Psychiatry, F-75013 Paris, France
3. Institut de recherche translationnelle en Neurosciences ICM-A-IHU, Paris, France
4. Santa Casa de Misericórdia do Rio de Janeiro, Department of Psychiatry, Rio de
Janeiro, Brazil
5. Institut de Recherches Internationales Servier, Suresnes, France
Default mode and task-positive networks connectivity
during the N-back task in remitted depressed patients
with or without emotional residual symptoms

22. Study the impact of emotional blunting on neural networks dynamics in remitted depressed
patients during a memory task.
26 outpatients in full remission (HAMD<7) of depression with paroxetine performed a memory
task during fMRI assessment.
Two sub-groups of patients - Non-emotionally blunted NEB=14 and emotionally Blunted
EB=12
Identify functional network maps across participants (NEDICA approach)
Within and between Task Positive Network (TPN) and Default Mode Network (DMN)
connectivity were assessed and related to variability of performance on the memory task and
rumination scores.
Goals and Methods

23. Found that a negative correlation between DMN and TPN was
significantly lower in the EB than NEB group.
This anti-correlation was differently related to variability in reaction time
in the N-Back task and rumination in both remitted depressed groups.
Clinical remission in depression is associated with biological
heterogeneity. Emotional blunting may compromise cognitive functioning
of remitted depressed patients by impacting on cooperation between
DMN and TPN and dampening cognitive resources for monitoring
rumination.
Results

24. A. Group t-maps of the DMN (warm colours) and TPN (cold
colours) B. Mean activity time courses (arbitrary units) of the
DMN (red) and TPN (blue) during the N-back task. Correlations between the functional connectivity and
the measure of intra-individual behavioural variability
(CV) during the 3-back condition in the NEB patients
(A) and EB patients (B)

25. Conclusions
The brain’s default network is a relative new concept in how we
view the brain´s organization and function
May play a major role in our understating of basic, intrinsic brain
activity and its large-scale functional organization
While other perspectives (cellular) are a crucial aspect to
integrating our understanding of the brain from the molecular
level and translating it to changes in higher hierarchical levels,
to changes in brain disorders and diseases – understanding
how it works at a systems level is important