1. Abraha m Peled MD Abraham Peled © All rights resaved Oct 2015

2. To cure mental disorders the Psychiatrist of the future will need to discover the causes of mental disorders Abraham Peled © All rights resaved Oct 2015

3. 1) Reformulate mental disorders as brain - disorders 2) Validate the brain disorders 3) Develop cure intervention / device Abraham Peled © All rights resaved Oct 2015

4. Psychiatric diagnosis is descriptive it is based on signs ( the patient looks sad ) and symptoms ( the patient complains of depression ) Abraham Peled © All rights resaved Oct 2015

5. I feel depresse d I look depresse d Abraham Peled © All rights resaved Oct 2015

6. While most clinicians agree that mental disorders are brain disorders, psychiatric diagnosis is not Brain - related Abraham Peled © All rights resaved Oct 2015

7. The term “ brain ” is not included in psychiatric taxonomy Brainitis Brainosis Connectomics Connectopathies Abraham Peled © All rights resaved Oct 2015

8. Without knowing exactly what is wrong with the brains of our patients we will never be able to cure ( fix ) them Abraham Peled © All rights resaved Oct 2015

9. In recent years we have learned a lot about the brain Abraham Peled © All rights resaved Oct 2015

10. For example we know that the brain is organized as a network Abraham Peled © All rights resaved Oct 2015

11. We also know that the brain is organized as a Small World network with Clusters and Hubs Clusters Hubs Abraham Peled © All rights resaved Oct 2015

12. We know that Small World brain organization is optimal for modal - specific specialization and multimodal integration Unimodal Transmodal multimodal Abraham Peled © All rights resaved Oct 2015

13. We also know that Small World brain organization supports Hierarchy with higher - level processing High - Level Low - Level H i e r a r c h yH i e r a r c h y Abraham Peled © All rights resaved Oct 2015

14. We know that such Small World brain organization is optimal for coherent integrated conscious experience Visual Auditory Conscious integration Abraham Peled © All rights resaved Oct 2015

15. The brain is Plastic. Neurons continually create ( Synaptogenesis ) and lose ( Atrophy ) connections Synaptogenesis Atrophy Abraham Peled © All rights resaved Oct 2015

16. The Plastic Brain interacts with the Environment Environment Action sensation Abraham Peled © All rights resaved Oct 2015

17. The Plastic Brain learns ( Hebb ) from the environment, memories Environment Action sensation memories Abraham Peled © All rights resaved Oct 2015

18. The Plastic Brain uses memories to create an Internal - Representation of the environment an internal model of the world Environment Action sensation Internal Representations model Abraham Peled © All rights resaved Oct 2015

19. When ‘ Adaptive ’ the internal model matches the environment, difference ( free energy ) between environment and internal representation is reduced Environment Action sensation Internal Representations model Adapt Match Free Ener gy Redu ced Abraham Peled © All rights resaved Oct 2015

20. Once created the internal model determines how we view the world and react to it, Experience - Dependent - Plasticity updates continually our internal model of the world Abraham Peled © All rights resaved Oct 2015

21. Experience - Dependent - Plasticity updates continually our internal model of the world The internal model determines how we view the psychosocial world and react to it, this is our personality style Abraham Peled © All rights resaved Oct 2015

22. Each of the organizational dynamics described so far can be disturbed in the brain of our patients Abraham Peled © All rights resaved Oct 2015

23. Network Organization Can be disturbed Abraham Peled © All rights resaved Oct 2015

24. Plasticity and Adaptability Can be disturbed Abraham Peled © All rights resaved Oct 2015

25. Internal Representations Can be disturbed Abraham Peled © All rights resaved Oct 2015

26. Multiple disturbances typically occur together to various extents Network organization Plasticity and Adaptability Internal Representations Can be disturbed Abraham Peled © All rights resaved Oct 2015

27. Each type of disturbance generates ( causes ) a different set of phenomenology ( suffering ) Network organization Plasticity and Adaptability Internal Representations Can be disturbed Abraham Peled © All rights resaved Oct 2015

28. Network organization Disturbed consciousn ess Psychosis and schizophre nia Disturbanc e to network organizati on generates disturbed consciousn ess Psychosis and schizophre nia Abraham Peled © All rights resaved Oct 2015

29. Plasticity and Adaptability Mood and Anxiety disorders Disturb ances to plastic ity and adaptab ility causes Mood and Anxiety disorde rs Abraham Peled © All rights resaved Oct 2015

30. Internal Representations Personal ity Disorder s Disturbanc es to the Internal - Representa tions cause the different Personalit y Disorders Abraham Peled © All rights resaved Oct 2015

31. Network organization Plasticity and Adaptability Internal Representations Disturbed consciousn ess Psychosis and schizophre nia Mood and Anxiety disorders Personal ity Disorder s All together we begin to see the correlation between brain disturbances and phenomenology Abraham Peled © All rights resaved Oct 2015

32. Disturbed Network organization Disturbed Plasticity and Adaptability Disturbed Internal Representations Disturbed consciousn ess Psychosis and schizophre nia Mood and Anxiety disorders Persona lity Disorde rs Thus we can begin and “ Translate ” phenomenology into brain disorders Abraham Peled © All rights resaved Oct 2015

33. Network organization 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 Plasticity and Adaptability Internal Representations The translation of Phenomenology to brain disturbances can be elaborated to form a comprehensive brain - related psychiatric diagnosis Abraham Peled © All rights resaved Oct 2015

34. Network organization 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 Plasticity and Adaptability Internal Representations For Example : Disturb ance to hierarc hy Disturb ance to connect ivity Disturbance to plasticity - related optimizatio n dynamics Disturb ed basic configu ration Abraham Peled © All rights resaved Oct 2015

35. Network organization 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 Plasticity and Adaptability Internal Representations Thus can be translated to : Delusi ons Halluc inatio ns Avolit ion Psycho sis Negati ve signs Mani a Depres sion Anxiet y Phobia Person ality disord er Abraham Peled © All rights resaved Oct 2015

36. Cs Ci Hbu Htd O D CF CF(b) DMN Delusion s Hallucin ations Avoliti on Psychos is Negativ e signs Mania Depre ssion Anxie ty Phobi a Persona lity disorde r Clinical Brain Profiling Phenomen ology Transl ation This is how we create, “ Clinical Brain Profiling ” a brain - related psychiatric diagnosis, translating phenomenology into a profile of brain disturbances Abraham Peled © All rights resaved Oct 2015

37. Clinical Brain Profiling Brain - related etiopathologica l Testa ble Personalized Abraham Peled © All rights resaved Oct 2015

38. Cs Ci Hbu Htd O D CF CF(b) DMN Clinical brain Profiling diagnostic translation is available at : http :// neuroanaly sis. org. il / ?page_ id =114 All you need to do is enter the signs and symptoms of your patient Clinical Brain Profiling Abraham Peled © All rights resaved Oct 2015

39. Cs Ci Hbu Htd O D CF CF(b) DMN Clinical Brain Profiling Abraham Peled © All rights resaved Oct 2015 To read more see PUBMED

40. To Validate Clinical Brain Profiling ( CBP ) a battery of various signal – processing methods should be put in place Pixels, Sensors Correlation analysis ( non - linear ) Graph analysis ( small - world ) SPM, DCM Entropy measures Abraham Peled © All rights resaved Oct 2015

41. Brain organization can be monitored continually using EEG wireless wearables Pixels, Sensors Correlation analysis ( non - linear ) Graph analysis ( small - world ) SPM, DCM Entropy measures Abraham Peled © All rights resaved Oct 2015

42. The Mental Status Examination can be evaluated (“ sensed ” ) using wearable, and monitoring of Cyber - activity Behavior Speech Face expressio ns Thought Cognition Abraham Peled © All rights resaved Oct 2015

43. Sensing Mental Status Examination can be synchronized with EEG monitoring Behavior Speech Face expressio ns Thought Cognition Abraham Peled © All rights resaved Oct 2015

44. Coupling ongoing phenomenolog y changes synchronized with ongoing monitoring of brain organization will generate large data that will point to the correlations between mental disorders and brain disturbance – Machine - Learning will probably work here Abraham Peled © All rights resaved Oct 2015

45. It is predicted that Machine - learning alone cannot complete the discovery process and that a theory - driven approach similar to CBP will be required Pixels, Sensors Prediction Evidence CBP Compare VALIDATE Abraham Peled © All rights resaved Oct 2015

46. Any therapeutic intervention to eliminate CBP disturbances will need a feed - back Loop mechanism one that continually guides and estimates corrections, “ Brain - Pacing mechanism ” Monitor CBP disturbance Correct CBP disturbance Monitored guided correction Correction Estimation Abraham Peled © All rights resaved Oct 2015

47. Such operation will probably require a Head Mounted Platform a hat for the therapy period / sessi on. A platform to support the sensory - guided interventio n. An interventio n engine relevant to activate remote non - invasive mediation to correct CBP disturbance s Monitor CBP disturbance Correct CBP disturbance Monitored guided correction Correction Estimation Camera Microphone Wireless transmitter Motion sensing Dry EEG electrodes Intervention Engine Abraham Peled © All rights resaved Oct 2015

48. Eventually the entire Head Mounted Platform and it ’ s operation, will have to be shrunk to the size of a Sticker and the brain intervention miniaturized to injectable ( or sniffed ) neuronal - related nanoparticles ( the CBP algorithm remains )

49. Abraham Peled © All rights resaved Oct 2015 The intervention at the brain level will need to be both neurological and CBP - relevant, for example here is a predicted intervention to the interneurons of layer 5 of the Prefrontal cortex for its Hub network - controlling effect for whole – brain organization

50. Abraham Peled MD Abraham Peled © All rights resaved Oct 2015 Good luck to us in the journey for curing mental disorders END