2. Exciting Times
Computational
Psychiatry
Digital Mental Health

3. Psychiatric diagnosis

4. I am depressed,
sad, feel helpless,
despaired,
what do I have doctor ?
Pleas tell me

5. You have depression

6. Gee – isn’t that what I just told you
Can’t you give me any added value

7. ?!?

8. I am depressed, what do I have doctor ? Pleas tell me
You have depression
Place in the body
What happend to it
It is infected
How to treat it
Antibiotics
My stomach hurts,
what do I have doctor ?
You have Appendecitis

9. ?
Urologist
Cardiologist
Gastroenterologist
Psychiatrist

10. Urologist
Cardiologist
Gastroenterologist
Psychiatrist

11. 1973

12. US UK

13. Checklist Depressed Insomnia Pessimism Anorexia Etc …..
Allen Frances MD
Michael First MD
Checklist
Depressed
Insomnia
Pessimism
Anorexia
Etc …..
Inter-rater Reliability

15. Currently No Etiology (not brain related)
No Category & Not Personalized
No Pharmacology (no med’ efficacy)
Hampered Research (no advance)
Brain Profiler © All rights resaved August 2017

16. This is what Tom Insel had to say about the DSM
Previous head of NIMH
Moller HJ et al. DSM 5 reviewed Eur Arch Psychiatry Clin Neurosci. 2015
Cuthbert BN , & Insel TR Toward the future of psychiatric diagnosis BMC Med. 2013
Collins PY1, Insel TR, Chockalingam A, Daar A, Maddox YT. Grand challenges in global mental health PLoS Med. 2013
Tomason T 2014 file:///C:/Users/Peled/Downloads/fulltext_stamped.pdf

17. Translate

18. Biological
Psychiatry

19. RDoC

20. Biological
Psychiatry
RDoC

21. RDoC

22. Biological
Psychiatry
Explanatory
Power

23. Computational
Psychiatry
Biological

24. Computational
Psychiatry
Biological

25. Computational Psychiatry Biological
Connectivity
Plasticity
DNM

26. Example for Computational psychiatry

27. - + Hallucinations Loosening Delusions restlessness Positive symptoms
 BLEULER
1920
Mental disorganization
Affect Associations Ambivalence Autism
4 A’s
Schizophrenia
Schizo - Prenus
Hallucinations
Loosening
Delusions
restlessness
Poverty thought
Perseverations
Avolition + -
Positive
symptoms
1900
KRAEPLIN
Dementia praecox
Based on prognosis
Negative
symptoms
Function
Age 18

32. Hopfield type architecture

33. Formulate brain dynamics as a physical state-space dynamic system

34. Positive
symptoms
Negative
symptoms

36. Psychological
Event
Computational
Psychiatry
Biological
Biological
Event

37. Clinical Brain Profiling

38. What do we know about brain organization
Connectivity
Plasticity
DNM
Disorders = Perturbation
Connectivity
Plasticity
DNM

39. Connectivity segregation (Cs) De- Optimization (D)
Psychosis
De- Optimization (D)
Depression
Connectivity integration (Ci)
Negative signs
Optimization (O)
Mania
Connectivity
Plasticity
Constraint frustration (CF)
Anxiety
Hierarchical bottom-up insufficiency (Hbu)
Avolition
DNM
Stimulus bound CF(b)
Phobia
Hierarchical
top-down shift (Htd)
Delusions
Hallucinations

40. Psychosis and schizophrenia disorders

41. Connectivity segregation (Cs)
Psychosis
Connectivity integration (Ci)
Negative signs
Connectivity
Plasticity
Hierarchical bottom-up insufficiency (Hbu)
Avolition
DNM
Hierarchical
top-down shift (Htd)
Delusions
Hallucinations

42. - + Hallucinations Loosening Delusions restlessness Positive symptoms
 BLEULER
1920
Mental disorganization
Affect Associations Ambivalence Autism
4 A’s
Schizophrenia
Schizo - Prenus
Hallucinations
Loosening
Delusions
restlessness
Poverty thought
Perseverations
Avolition + -
Positive
symptoms
1900
KRAEPLIN
Dementia praecox
Based on prognosis
Negative
symptoms
Function
Age 18

43. Disconnection Syndrome Psychosis
The associations of an adult ego
could be temporarily or permanently weakened,
with a similar result of random or confused
thought processes. … resulting
in psychotic states.
Theodore Meynert
( )
Disconnection Syndrome
Psychosis

44. Disconnection Syndrome
Aberrant frontal and temporal complex network structure in schizophrenia: a graph theoretical analysis.
J Neurosci Nov 24;30(47):
van den Heuvel MP, Mandl RC, Stam CJ, Kahn RS, Hulshoff Pol HE our findings suggest that schizophrenia patients have a less strongly globally integrated structural brain network with a reduced central role for key frontal hubs, resulting in a limited structural capacity to integrate information across brain regions
Yu Q, Sui J, Rachakonda S, He H, Pearlson G, Calhoun VD. Altered small-world brain networks in temporal lobe in patients with schizophrenia performing an auditory oddball task. Front Syst Neurosci Feb 8;5:7.
Pettersson-Yeo W, Allen P, Benetti S, McGuire P, Mechelli A. Dysconnectivity in schizophrenia: Where are we now? Neurosci Biobehav Rev Apr;35(5): Review
Guye M, Bettus G, Bartolomei F, Cozzone PJ. Theoretical analysis of structural and functional connectivity MRI in normal and pathological brain networks. MAGMA Dec;23(5-6): Epub 2010 Mar 27.Graph
Bassett DS, Bullmore E, Verchinski BA, Mattay VS, Weinberger DR, Meyer-Lindenberg A. Hierarchical organization of human cortical networks in health and schizophrenia. J Neurosci Sep 10;28(37):
Bodnar M, Harvey PO, Malla AK, Joober R, Lepage M. The parahippocampal gyrus as a neural marker of early remission in first-episode psychosis: a voxel-based morphometry study. Clin Schizophr Relat Psychoses Jan;4(4):
Jones MW. Errant ensembles: dysfunctional neuronal network dynamics in schizophrenia. Biochem Soc Trans Apr;38(2): Review
Psychosis
Disconnection Syndrome

45. Negative symptoms Positive symptoms Giulio Tononi Order Randomness
Complexity
Neural
Complexity
Disconnection
dynamics
Over-connection
dynamics
Negative
symptoms
Positive
symptoms 45

47. Negative
symptoms
Positive
symptoms

48. Avolition
Negative
symptoms
Positive
symptoms
Delusions
Joaquin Fuster

49. Bernard Baars Marcel Mesulam Stanislav Dehene Giulio Tononi
Hallucinations
Giulio Tononi

50. Clinical Brain Profiling (CBP)Cs Ci
Htd
Hbu D O CF
CF(b)
DMN
Clinical Brain Profiling (CBP)
Connectivity segregation (Cs)
Psychosis
Connectivity integration (Ci)
Negative signs
Connectivity
Plasticity
Hierarchical bottom-up insufficiency (Hbu)
Avolition
DNM
Hierarchical
top-down shift (Htd)
Delusions
Hallucinations

51. Mood disorders

52. Connectivity segregation (Cs) De- Optimization (D)
Psychosis
De- Optimization (D)
Depression
Connectivity integration (Ci)
Negative signs
Optimization (O)
Mania
Connectivity
Plasticity
Constraint frustration (CF)
Anxiety
Hierarchical bottom-up insufficiency (Hbu)
Avolition
Stimulus bound CF(b)
Phobia
Hierarchical
top-down shift (Htd)
Delusions
Hallucinations

53. Plasticity Environment SSRI Mood Depression Anxiety Optimization
Adaptability
Free energy

54. Clinical Brain Profiling (CBP)Cs Ci
Htd
Hbu D O CF
CF(b)
DMN
Clinical Brain Profiling (CBP)
Plasticity
Optimization (O)
Mania
De- Optimization (D)
Depression
Constraint frustration (CF)
Anxiety
Stimulus bound CF(b)
Phobia

55. Personality disorders

56. Connectivity segregation (Cs) De- Optimization (D)
Psychosis
De- Optimization (D)
Depression
Connectivity integration (Ci)
Negative signs
Optimization (O)
Mania
Connectivity
Plasticity
Constraint frustration (CF)
Anxiety
Hierarchical bottom-up insufficiency (Hbu)
Avolition
DNM
Stimulus bound CF(b)
Phobia
Hierarchical
top-down shift (Htd)
Delusions
Hallucinations

57. Default Mode Network
Environment

58. Default Mode Network
Environment
Hebbian Dynamics
Personality

59. Cs Ci
Htd
Hbu D O CF
CF(b)
DMN
Clinical Brain Profiling (CBP)
DNM

60. Brain Profiler

61. Brain Related Psychiatric Diagnosis
Bain Profiler © All rights resaved August 2017

62. Cs connectivity segregation
All of the various brain disturbances are mapped onto a 9 axis profile “the Clinical Brain Profile (CBP) Cs Ci
Htd
Hbu D O CF
CF(b)
DMN
Clinical Brain Profiling (CBP)
Cs connectivity segregation
Optimal brain
Disturbance
to plasticity and
Optimization
Ci connectivity
integration
Htd Hierarchal
top down shift
Hbu Hierarchal
Bottom-up
insufficiency
D De-optimization
O Hyper-
optimization
CF Constrain
Frustration
CF(b) Constrain
Bound
Default
Mode
Network
to connectivity

63. Clinical Brain Profiling
The Clinical Brain Profile (CBP) of the patient looks like this:
Millisecond range activity
Plasticity over weeks and
months
Lifetime
Developmental
Plasticity
DNM
Connectivity Cs
Connectivity segregation Ci
Connectivity integration
Hbu
Hierarchical bottom-up insufficiency
Htd
Hierarchical
top-down shift O
Optimization D
De- Optimization CF
Constraint frustration
CF(b)
Stimulus bound
DMN
Default Mode Network
Negative signs
Mania
Delusions
Hallucinations
Avolition
Psychosis
Depression
Anxiety
Phobia
Personality disorder
Clinical Brain Profiling

64. Unsupervised fuzzy clustering of CBP into two categories classifies patients based on clinical severity validating CBP sensitivity to clinically meaningful phenomenology.

65. Total N= 642 Corr = 0.56 Corr = 0.8 Corr = 0.87 Corr = 0.63
Schizophrenia N= 304
Archetype schizophrenia
positive signs
Axis Y= Percentages
Axis X :
1 = DMN Default Mode Network
2= D De-optimization
3 = O Optimization
4 = CF Constraint Frustration
5= CF Constraint Frustration bound
6 = Cs Connectivity segregation
7= Ci Connectivity integration
8= Hbu Hierarchical bottom-up
9 = Htd Hierarchical top- down
Corr = 0.56
Archetype schizophrenia
Negatives signs
Corr = 0.8
Schizoaffective N=34
Archetype Schizoaffective
Corr = 0.87
Total N= 642
Depression N=59
Archetype Depression
Corr = 0.63
Anxiety N=94
Archetype Anxiety
Corr = 0.66
Archetype Personality
disorder
Personality
Disorders N=40
Others N=111
Corr = 0.9

66. The Brain Profiler Site

67. Brain Profiler is a Computer and an App platform
Brain Profiler © All rights resaved August 2017

68. EEG Subjective Condition Objective digital Psychiatrist Assessment
Powerful
Statistics

69. COMPUTATIONAL PSYCHIATRY
Clinician
Scale pheno CBP
Unique
Patient
Symptoms CBP Cs Ci
Htd
Hbu D O CF
CF(b)
DMN
Clinical Brain Profiling (CBP)
CBP
Unique
Cyber Mob sensors
Obj’ digital CBP
Brain Imaging
VALID CBP
Unique
Personalized
Tele-medicine
Alerts & Notifications
Queuing and Management
Treatment-Response
EMR

70. Signal Processing & Validation

71. EEG Attractor signals can be informative about chaotic and periodic dynamics of disconnection and over-connection activity respectively. They can also inform about general stability of the brain systems

72. Calculating correlation matrices can inform us about brain connectivity by constructing Graphs of connectivity patterns. These can be evaluated over different and extended time-scales.

73. Graphs can help estimate Small-World optimal brain networks as well as fixed overly connected or randomly disconnected networks.
SMALL WORLD NETWORK

74. Node attacks (random versus degree-related) can measure network reliance and vulnerability to functional perturbations
Brain Profiler © All rights resaved August 2017

75. Path length = inversely related to global
efficacy of parallel information transfer
Clustering Coefficient = Measure of density of
connections between nearest neighbors
Small-worldness = high clustering small path length
comparable to random graph
Node = cortical region or neuron
Hierarchy = Hubs with many long distance connections and few local connections
Edge = statistical measure of association
Mean connection distance = Euclidean distance between centers in stereotactic space
Degree = the number of edges connecting a node
Assortativity = measures the preference of a node to connect to other nodes of similar degree
Rent exponent = topo-physical embedment in physical space of the network, scaling relationships

76. Dynamic Causal Modeling (DCM) can be specifically relevant to estimating error predictions in hierarchical systems, and matching dynamics with free energy reduction within hierarchies.
Brain Profiler © All rights resaved August 2017

77. Contact information
Brain Profiler © All rights resaved August 2017