1. Cross-talk between conscious and non conscious mind: Cortical mechanisms and clinical implications Rajendra D. Badgaiyan, MD Departments of Psychiatry and Radiology, Harvard Medical School Department of Psychology, Harvard University Massachusetts General Hospital, Boston

2. ‘Normal’ cognitive experience requires: intact conscious and non conscious processes balanced information sharing between the two processes To understand neural basis of cognitive impairments, we need to know neural network of conscious and non conscious processes neural network that allows two processes to share information

3. Classical concept: short term memory (STM) long term memory (LTM) Stimulus  STM  LTM (Attkinson & Shiffrin, 1968) Problems: patients with STM deficits may have normal LTM (Braddley & Hitch, 1974) amnesics with both STM and LTM deficits show normal performance in a variety of tests of memory (Milner, 1966) Current concept: (Graf & Schacter, 1985) explicit: conscious and intentional implicit: non conscious and incidental Memory: a model for the study of conscious and non conscious processes

4. Instructions: explicit: remember wordscomplete word-stems using a studied word implicit: count vowels complete word-stems using the first word that comes to mind 2. Picture recognition test: STUDY TEST pictures shown for 3 secstudied and non studied pictures flashed for 16 msec Instructions: explicit: remember picturesindicate whether the picture was studied implicit: look at the picturesindicate if you can recognize the picture 1. Word-stem completion task: STUDY TEST institutionpic pictureins facultyfac

5. Memory is a good model for the study of neural basis of conscious and non conscious cognitive processes and their interaction: it has a conscious and a non conscious component two components are dissociable in neuropsychiatric disorders schizophrenia depression parkinsonism evidence suggest that the two components interact with each other

6. Remember following words: candy sour sugarbittergood tastenice honeysoda chocolate heartcake eatfruitpie Interaction between explicit and implicit processes….

7. Louis Wain (1860-1939) The ‘King of cat art’

8. TASTE Did you see following word in the list just studied?

9. POINT Did you see following word in the list just studied?

10. SWEET Did you see following word in the list just studied?

11. So, we had three words….. TASTE POINT SWEET

12. Implicit memory (stem-completion task) conscious action  finding a word beginning with word stem nonconscious action  retrieval of a studied word conscious action/cognition non conscious processing Explicit memory (false memory) conscious action  encoding and retrieval of studied words nonconscious action  semantic organization of studied words

13. ‘altered’ non conscious processing  ‘altered’ conscious cognition false memory  delusional disorder PTSD hallucination ‘resetting’ of non conscious processing  ‘resetting’ of conscious cognition cognitive techniques (e.g., Crovitz technique in psychogenic amnesia) ? Neurophysiological/neurochemical techniques conscious cognition non conscious processing

14. conscious behavior/cognition could be altered by impairments of conscious processing nonconscious processing interaction between conscious and nonconscious processing using neuroimaging methods, we studied sites of conscious (explicit) memory sites of nonconscious (implicit) memory sites of interaction conscious behavior/cognition

15. Event-related potentials (ERP): high-density EEG recording high temporal but poor spatial resolution Positron emission tomography (PET): changes in regional cerebral blood flow (rCBF) estimated using radioactive tracer inhalation high spatial but poor temporal resolution Functional magnetic resonance imaging (fMRI): changes in rCBF estimated by measuring ratio of oxygenated/ deoxygenated blood high spatial but poor temporal resolution Neuroimaging techniques used

16. Conscious retrieval Studied pictures Activations sup/ mid frontal gyrus (BA 9/46) hippocampus Deactivations extrastriate cortex (BA 19) R

17. Badgaiyan & Posner, 1998

19. Conscious retrieval: studied words BESA algorithm a single dipole source located in the right hippocampus was responsible for 84 % of activity between 164 - 200 ms Badgaiyan & Posner, 1997

20. Processing sequence: conscious retrieval Processing sequence: conscious retrieval extrastriate cortex: 64 - 600 ms hippocampus: 164 - 200 ms prefrontal cortex: 200 - 600 ms

21. Implicit retrieval Picture recognition Deactivations extrastriate cortex (BA 19) Badgaiyan, 2000

22. Implicit retrieval Word stem completion Deactivations extrastriate cortex (BA 19) Schacter, Badgaiyan & Alpert, 1999

24. Auditory word stem completion task Study Test listen: words listen: word-stems (first syllable) Instruction: complete word-stems using the first word that comes to mind Auditory priming (implicit retrieval) to ascertain that the extrastriate involvement is associated with implicit retrieval and not with some aspect of visual perceptual processing

25. Auditory priming Experiment 1 Experiment 2 Deactivations extrastriate cortex (BA 19) medial prefrontal cortex (BA 9/10) Badgaiyan, Schacter & Alpert, 1999

26. Visual-to-auditory Study Test see: words listen: word stems (first syllable) Auditory-to-visual Study Test listen: words see: word stems (first 3-letters) Instruction: complete word-stems using the first word that comes to mind Cross-modality priming to understand cortical mechanism of non-perceptual priming, we examined implicit memory under cross-modality priming condition

27. Cross-modality (visual  auditory) priming Activation superior frontal gyrus (BA 9/10) Badgaiyan, Schacter & Alpert, 1999

28. Cross-modality (auditory  visual) priming Activation superior frontal gyrus (BA 9/10) Schacter, Badgaiyan & Alpert, 1999

29. extrastriate deactivation during conscious retrieval of studied items prefrontal activation during non conscious retrieval under cross modality condition suggest cross-talk….

30. Neural evidence of interaction between explicit and implicit memory Reduced activation in the extrastriate cortex (BA 19) during: implicit retrievalimplicit retrieval explicit retrieval of studied itemsexplicit retrieval of studied items Retrieval of studied pictures Conscious retrieval Non conscious retrieval

31. - 2 µV 2 µV Nonconscious retrieval 800 Baseline Nonconscious retrieval Time course of extrastriate deactivation 200

32. Time course of prefrontal and late extrastriate activity

33. Cognitive component retrieval of studied retrieval of studied items items conscious awareness of retrieval Late extrastriate deactivation and prefrontal activity associated with conscious awareness ? Cortical processing of memory Nonconscious Conscious Cortical activity extrastriate (early) extrastriate (early) extrastriate (late) prefrontal cortex

34. Processing sequence: conscious retrieval Processing sequence: conscious retrieval extrastriate cortex: 64 - 200 ms (early) extrastriate cortex: 200 - 600 ms (late) hippocampus: 164 - 200 ms prefrontal cortex: 200 - 600 ms 64-200 ms:implicit retrieval 200-600 ms: extrastriate cortex holds implicitly retrieved information re-entrant circuit sets up between extrastriate and Prefrontal cortex conscious awareness

35. Neuropsychiatric conditions associated with impaired explicit but preserved implicit memory schizophrenia (implicit ‘better than normal’) severe PTSD MPD/psychogenic amnesia (fugue state) amnesia (hippocampal lesion) post-ECT Alzheimer’s disease organic depression anesthetic recovery tests of implicit memory could be useful diagnosis aids for these conditions

36. Cognitive impairments associated with ‘altered’ signal transmission Increased activity of… extrastriate -prefrontal connectivity: hallucination hippocampal -prefrontal connectivity: loose association

37. Cognitive impairments associated with ‘altered’ signal transmission Decreased activity of … extrastriate -prefrontal connectivity: negative symptoms dementia delirium hemineglect

38. Future prospects... if the physiological nature of the communication between implicit and explicit processes is known, it can be manipulated to ‘reset’ the impaired communication which can theoretically alleviate cognitive symptoms tests of implicit memory may help objective diagnosis of conditions like, PTSD, MPD functional neuroimaging studies may help definitive diagnosis of a variety of neuropsychiatric conditions until then, psychiatric conditions will continue to have low inter rater reliability...

39. Thank you...