Memory and Self : Theoretical Approaches and Implications for Cancer Patients Francis Eustache and Bénédicte Giffard Inserm‐EPHE‐Université de Caen Basse Normandie, Unité de Recherche U1077, Caen, France Memory and Self : Theoretical Approaches and Implications for Cancer Patients • What is Memory? What is Self? And what are the links between both? • The central concept of Autobiographical Memory (AM) – Examples with Amnesic syndromes and Alzheimer’s Disease • AM functioning in Depression and PTSD • Implications and first results in Cancer patients Patient H.M. (Scoville & Milner, Corkin) Patient K.C. (Tulving) Sergeï Korsakoff What is Memory? I spent my holidays in Italy last summer «ToI dial remember a number» Rome is the capital of Italy « I know » Perceptive priming Tulving’s SPI model (1995) To go cycling MEMORY SYSTEM CONSCIOUSNESS Autonoetic Noetic Anoetic Tulving (1985) Eustache & Desgranges, MNESIS model (2008) What is Self? The concept of self results from two complementary aspects: - a set of personal complex and multidimentional mental representations about ourselves - the flow of self-consciousness which is associated SELF Structural dimension Functional dimension Self Representations Self‐ consciousness Klein & Lax, 2010 Structural dimension Self Representations Semantic self‐representations = Conceptual self Abstract traits knowledge about oneself I’m an honest person Semantic AM General knowledge of personal significance Episodic self‐representations Episodic AM Specific personal information closely related to unique self‐ experienced events My name is Francis I’m a sensitive person, because yesterday the movie made me cry Temporal perspective Past self Present self Futur, possible self Fonctional dimension Self‐ consciousness ‐ Mobilized in various cognitive activities (e.g., self‐ evaluation, self‐projection into time) ‐ Accompanies subjective and phenomenological experiences sense of continuity and coherence Bidirectional relationship between Memory and Self Memory both shapes, and is shaped by Self MEMORY SELF Memory should be conceived ‘‘not as an ability to revive accurately impressions once obtained, but as the integration of impressions into the whole personality and their revival according to the needs of the whole personality.’’ Rapaport (1952/1961). Emotions and memory. New York: Science Editions The central concept of Autobiographical Memory Autobiographical memory is the memory for information and experiences of one’s personal life that gives a sense of identity and self‐continuity. Extended over time At the core of one’s identity Autobiographical memory Episodic component I precisely remember the day I broke my arm Specific events • Situated in a precise spatiotemporal context • Retrieved with phenomenological details • Autonoetic consciousness Semantic component I know the name of my school mates General events • On one’s life • Repeated or extended over time • Independent of a spatiotemporal context • Noetic consciousness Autobiographical memory constructive framework (adapted from Conway, 2005) Generative retrieval mode Direct retrieval mode Event‐specific knowledge Episodic memories Generic events Semantic knowledge Life time periods Working memory “Working self” Conceptual self attitudes, values, aims, beliefs, desires… The working self moderates between the demands of coherence and correspondence in the formation of memories and in their construction. Memories CORRESPONDENCE COHERENCE memory should correspond to experience memory should be consistent with ones current goals and self‐image The most crucial components of the AM retrieval network FOR: feeling‐of‐rightness (correspondence/coherence) Cabeza & St Jacques, 2007 Amnesic hippocampal patients HM controls •Insight into his memory problems, ability to reflect on them •Understood the concept of time and that the life is a continuum Patient K.C. Tulving et al., 1988; Tulving, 2001 Retrograde amnesia Anterograde amnesia Episodic component Semantic component - + Unable to relive personal events with “warmth and intimacy” Lacks autonoetic consciousness and the ability to project himself into the past or future • Semantic AM largely intact • Retains accurate abstracted trait self‐knowledge about his identity • • → Dissociation between episodic and semantic self‐representation → We do not need episodic AM to maintain a self‐identity, but self‐ representations are less rich and more fossilized Alzheimer’s disease William Utermohlen (1933‐2007). Self Portraits. Patient PH • Hehman et al., 2005 : 83 years‐old, severe stage AD (MMS=7) • self‐knowledge not updated • Temporally graded breakdown in semantic memory function Autobiographical memory in AD Controls 16 AD 14 12 10 8 6 4 2 0 0-17 yrs 18-30 yrs > 30 yrs last 5 yrs last 12 months Piolino et al., Brain (2003) AM functioning in Depression • Mood‐congruent memory effect – spontaneously recall more negative than positive memories • Overgeneral memories – Tendency to recall repeated events rather than specific events – In response to the cue word party: « I never enjoy parties » rather than « I went to a terrible party last Friday » • Intrusive memories and related avoidance – Spontaneous, painful and enduring memories, often related to stressful events – Avoidance is positively correlated with overgenerality • Mood congruent effect : may be explained by the current (depressed) self • Overgenerality (generative retrieval) : – affect regulation hypothesis : reduced specificity represents a cognitive strategy to protect the self against stressful memories (voluntary process)? – Related to executive dysfunction + current (depressed) self? • Intrusive memories (automatic retrieval) : lack of executive control during Generative retrieval mode direct retrieval accidental access at the event‐specific level Event‐specific knowledge Generic events Life time period Working memory “Working self” Conceptual self attitudes, values… • Mood congruent effect : may be explained by the current (depressed) self • Overgenerality (generative retrieval) : – affect regulation hypothesis : reduced specificity represents a cognitive strategy to protect the self against stressful memories (voluntary process)? – Related to executive dysfunction + current (depressed) self? • Intrusive memories (automatic retrieval) : lack of executive control during Generative retrieval mode direct retrieval accidental access at the event‐specific level Event‐specific knowledge Generic events Life time period Working memory “Working self” Conceptual self attitudes, values… • Mood congruent effect : may be explained by the current (depressed) self • Overgenerality (generative retrieval) : – affect regulation hypothesis : reduced specificity represents a cognitive strategy to protect the self against stressful memories (voluntary process)? – Related to executive dysfunction + current (depressed) self? • Intrusive memories (automatic retrieval) : lack of executive control during direct retrieval irrepressible access at the event‐specific level Direct retrieval mode Event‐specific knowledge Generic events Life time period Working memory “Working self” Conceptual self attitudes, values… Differences in hemodynamic activity during AM recall in depressed (MDD) subjects vs. controls (Young et al., 2012, Psychol Med) Memory dysfunction in PTSD • Persistent re‐experience of the traumatic event (includes intrusive memories, flashbacks, nightmares…) • Persistent avoidance of stimuli associated with the trauma • Both memory intensification for the core traumatic event and memory impairment for the context surrounding the trauma: may be due to peritraumatic dissociation (disrupts processes of elaboration and consolidation) trauma memories are disorganized and poorly integrated with other autobiographical memories and views of oneself • Overgeneral non‐traumatic memories Some symptoms are common between PTSD and Depression, but… • PTSD is a more dissociative disorder than depression intrusions: → For depressed patients: the event is experienced as belonging to the past → For PTSD: the sense that the event is actually reoccurring in the present: trauma memories are disorganized and poorly integrated with other autobiographical memories and views of oneself • Posttraumatic distress, unlike depression, is not reliably associated with marked deficits in executive control overgenerality: – For PTSD: levels of memory specificity might be more associated with affect regulation than with executive control, – For depressed patients, reduced executive control capacity may play a greater role PTSD VOLUMETRIC ABNORMALITIES Anterior cingulate cortex Corpus callosum Hippocampal volume on MRI Hippocampus FUNCTIONAL ABNORMALITIES Hypoactivation Rostral anterior cingulate cortex Medial prefrontal cortex mPF dysfunction during exposure to traumatic slides and sounds Hippocampus Hyperactivation Amygdala From Bremner, 2007 Amygdala activation during acquisition of fear learning Bremner’s theory (2007) + ACC hypoactivation (-) involves Amygdala hyperactivation(+) hyperactivation(+) Bremner’s theory (2007) - Hippocampus atrophy + ACC hypoactivation (-) involves Amygdala hyperactivation(+) hyperactivation(+) Hippocampus atrophy Layton & Krikorian, 2002 Implications and first results Implications and first results in Cancer patients Cancer, PTSD and Depression • DSM‐IV: PTSD may be precipitated by life‐threatening illness, such as being diagnosed with cancer • Prevalence rate of cancer‐related PTSD (Kangas et al., 2002): 3‐22% (4%‐6% in most Breast Cancer studies) • Yet many survivors report one or more PTSD symptoms (intrusion and hyperarousal symptoms) • Prevalence rates of depression: 20‐27% (Lee et al., 2007) • Expression of psychological effect, of cytokine deregulation… • Relationship between depression and ASD/PTSD following trauma, including cancer, frequently observed (Mundy et al., 2000) Intrusive memories of specific negative events (Brewin et al. 1998): one of the common symptoms Distinctive features of Cancer‐related PTSD and Depression • Major depressive episodes after cancer diagnosis : – reactive depression, short duration – non‐specificity of somatic symptoms (fatigue, anxiety…) • Cancer‐related PTSD: – Chronicity of threat: • Protracted nature of cancer • Multiple traumatic experiences (diagnosis, treatments, recurrence…) • future‐oriented anxiety concerning cancer recurrence and death – Internality of threat: bodily signs as persistent reminders of the trauma • Cancer associated with other factors (neurotoxic treatments, biological changes…) No significant difference in hippocampal volume between breast cancer (BC) survivors with depression vs BC without depression Inagaki et al., 2004, Am J Psychiatry Yoshikawa et al., 2006, Biol Psychiatry No significant difference in hippocampal volume between BC survivors with PTSD vs without PTSD (Hara et al., 2008, J Neuropsychiatry Clin Neurosci) Nakano et al., 2002, Am J Psychiatry • Intrusive symptoms, rather than cancer‐related PTSD, are associated with smaller hippocampal volume • comparison with healthy controls? Smaller orbitofrontal cortex (right BA11) in BC survivors with PTSD compared to survivors without PTSD and to healthy controls (Hakamata et al., 2007, Neurosci Res) BC with PTSD vs BC without PTSD (3‐15 months after BC surgery) BC with PTSD vs healthy controls (2 years after the first scan) Autobiographical Memory in Cancer Depressed vs non‐ depressed cancer patients (Brewin et al, 1998) • Intrusive memories of stressful events and related avoidance mainly in depressed patients • Overgeneral memories in response to cue‐words in depressed patients (correlation with intrusion and avoidance) Autobiographical Memory in Cancer Depressed vs non‐ depressed cancer patients (Brewin et al, 1998) • Intrusive memories of stressful ASD vs non‐ASD cancer patients (Kangas et al, 2005) In newly diagnosed cancer patients events and related avoidance (within 1 month of the diagnosis): mainly in depressed patients Overgeneral memories in response • Overgeneral memories in response to cue‐words in depressed patients (correlation with intrusion and avoidance) to cue‐words in ASD patients Overgenerality in Depression or post‐stress disorders (generative retrieval): Generative retrieval mode – Affect regulation hypothesis (to protect the self against stressful memories)? – Related to executive dysfunction + current (depressed/stressed) self? Event‐specific knowledge Generic events Life time period Working memory “Working self” Conceptual self attitudes, values… AM in Cancer patients without a stress‐related psychiatric disorder • Overgeneral memories in BC patients compared with healthy controls (Nilsson‐Ihrfelt et al, 2004; Bergouignan et al, 2011) • Smaller hippocampal volume (post.) in BC patients relative to healthy controls Bergouignan et al, 2011, PlosOne Inagaki et al., 2004; Yoshikawa et al., 2006 AM in Cancer patients without stress‐related psychiatric disorder • Overgeneral memories in BC patients compared with healthy controls (Nilsson‐Ihrfelt et al, 2004; Bergouignan et al, 2011) • Smaller hippocampal volume (post.) in BC patients relative to healthy controls Smaller post Hpc + deficits of episodic AM: Reflect the effect of : ‐Cumulative stressful events ‐Aggressive treatments Bergouignan et al, 2011, PlosOne (McDonald et al, 2010; Deprez et al 2012; de Ruiter et al 2011…) AM in BC patients before any adjuvant therapy Patients without any psychiatric symptom and self‐willed TEMPau: To retrieve specific events located in time and space, which occurred once and lasted less than 1 day (Piolino et al, 2009) CANCER DIAGNOSIS TEMPau task START OF CT Surgery PERIOD 1 (18‐30 yrs old) reminiscence bump PERIOD 2 ‘before cancer’ period 1 event 1 event State of consciousness Spatio‐temporal score noetic autonoetic Factual score Emotional score PERIOD 3 ‘cancer’ period 1 event no cancer BC patients vs Healthy controls: No overgeneral memories * * * * * * P<0.05 Active adaptation process in these patients with « fighting spirit »? Adaptation process different from that used by depressed patients In conclusion, AM in Cancer patients Lots of questions and some hypotheses: • Aggressive treatments at the origin of many cognitive impairments, notably overgeneral AM (medial temporal, prefrontal retrieval, executive functions…) • Different psychological profiles (from psychiatric disorders to « fighting spirit ») would lead to different patterns of AM ? • AM and Self In conclusion, AM in Cancer patients Lots of questions and some hypotheses: • Aggressive treatments at the origin of many cognitive impairments, notably overgeneral AM • Event‐specific (medial temporal, prefrontal retrieval, executive functions…) knowledge Different psychological profiles (from psychiatric disorders to « fighting spirit ») would lead to different patterns of AM ? Generic events • AM and Self Life time period Working memory Conceptual self “Working self” attitudes, values, aims, beliefs, desires… Inserm U1077, Caen Collaboration: Unité de recherche clinique Centre F. Baclesse (Pr Florence Joly) Many thanks to Armelle Viard and Nastassja Morel