Fronto Limbic and Mem Parallel Memory Systems • Episodic Memory- Hippocampal based • Procedural and “Habit” learning system: Basal Ganglia – Reward system effects on learning-ventral striatum • Frontal lobe contributions – Retrieval systems – Organization of input • Priming – Repetition priming/sensory based traces – Frontal contributions to effortful learning/priming Memory systems • Hippocampal – New associations – Episodic - temporal signature – Case examples – Tests – Paired associate learning – Effect of retrieval cues Hippocampal System • H.M. first model of episodic memory – Bilateral medial temporal lobectomy for epilepsy surgery – Cured of epilepsy – No new episodic encoding since surgery • This memory deficit is the classic amnesia syndrome • Other good ways to get this deficit: – Repeated temporal lobe seizures (mesial temporal sclerosis – Anoxia- at birth or acquired- HC especially sensitive to anoxic damage – Herpes encephalitis (limbic encephalitis). Herpes loves the HC. Neuropsych patterns in HCbased memory impairment • Difficulty forming new associations – E.g. Unrelated paired associate learning – Face-name associations • Steep forgetting curve – Delayed recall specifically impaired – Minimal to no benefit from retrieval cues – Minimal to no benefit from recognition format • Some evidence for content specificity – left vs right, verbal vs spatial dissociation Wada testing of HC function • Anterior 2/3 HC fed by the anterior choroidal artery which comes of the ICA • During Wada testing, anesthetize 1 HC • Present new information to learn (eg 6 objects) • Wait 12 minutes (with distraction) • Test for Memory for Episode (did we show you anything?) • Test for cued recall; finally, test recogntion • ***Important assess for Episodic recall Memory without episodic recall: feeling of knowing • HC memory is episodic: remember the encoding episode (eg the objects I just showed you 10 minutes ago) • Distinguish from Explicit, but nonepisodic memory (eg, yes I have seen this before, don’t remember the exact episode: “feeling of knowing” Recollection versus Familiarity • (R) Recollection - re-experiencing the encoding event at the time of recall, true episodic memory • (K) - Know - the feeling of familiarity that you’ve seen something before, but not remembering the exact encoding event – Not implicit because it is conscious Eldridge et al 2001, 2005: Remember- Know Distinction in HC R vs. K • Eldridge et al have shown the HC is selectively involved in R, not with K. Novelty Encoding Paradigm Alternating Blocks of Novel and Repeat Pictures New Rest New Repeat Outdoor New Repeat Indoor Rest Time Series for Subregions Sustained Parahippocampal Fusiform Late Activation No Activation CA 2, 3, DG CA 1 Subiculum Entorhinal Non-episodic Memory: Habit Learning System Hippocampus Striatum Patient H.M. can learn….. • Was able to navigate around his (new) environment, eventually. • Could learn new skills: initially, motor skills; ultimately found to include cognitive skills • Eg mirror reading (see next slide) • Could perform the tower of Hanoi in the optimal number of moves; but had to be explained the directions repeatedly; no memory of having seen it before • Thus there was some unconscious, implicit learning that was conceptual in nature Imaging the striatal learning system:Learning a new skill • Mirror-reading: (Poldrack et al) • College students were taught to read mirror-reversed text for ~5 hours • Scanned before and after learning using fMRI • Activity in striatum during learning • Normal in HC lesioned patients Knowlton and Squire • Performed a probabilistic learning task in Parkinson’s patients and amnestic patients: Weather Prediction Task • In this task subjects learn an association between a stimulus (a playing card) and an outcome (rain or shine) • Relationship was probabilistic, not deterministic; 66% probability of an outcome • Subjects could not memorize the associations, and ultimately guessed • However their behavior showed a learning curve despite no explicit knowledge of learning Learning concepts without consciousness • Amnesic patients learned the associations (without awareness) • Parkinson’s patients did not • Requires hundreds of trials • Testing of explicit memory results in chance • Behavior shows learning • Considered an implicit, habit based learning system • What other skills do you learn this way? Implicit learning Basal Ganglia and learning • What else is learned implicitly? – Language learning and grammar: based on probabilistic word boundaries and repetition to learn syntactic structures – Social skills: how close to stand to people, how loud to talk, where to stand in an elevator, how much eye contact, etc Striatum is Involved in Language & Communication Grammatical > Non-Grammatical (14,6,0) Lieberman et al., 2004 J Cog Neuro • Artificial grammar learning (Lieberman et al., 2004) • Subjects given sequences of letters with probabilistic sequences • Presented novel sequences that follow the same rules • Subjects can correctly classify them as right or wrong without knowing the rules or having learned the specific examples! Implicit learning and dorsal striatum • Dorsal striatum (Ca/Pu) is implicated in implicit or “habit” learning (Knowlton and Squire) • Language acquisition and social learning are thought to rely on implicit learning mechanisms – Probabilistic learning tasks (vs. deterministic) are implicit, subconscious, and rely on dorsal striatum Implicit Learning and Reward • Probabilistic Classification Task • Reported by Knowlton and Squires- impaired in PD, intact in amnesia • Inversely related to hippocampal activity • Reward variant- social vs. monetary – Stimuli predict a given outcome (1 or 2); 50% deterministic, 50% random – Reward and Cognitive (Correct / Incorrect) feedback Adults: BG activity during probabilistic learning Source: D. Ghahremani Response to Rewards Every occurrence of a reward (any type) vs. no-reward Reward response in VS 0.25 TD ASD Magnitude (mean %) 0.2 0.15 0.1 0.05 0 Social Monetary Effect of rewards on implicit learning Total Performance 100.00 90.00 80.00 Percent Correct 70.00 60.00 ASD Money Total TD Money Total 50.00 ASD Social Total TD Social Total 40.00 30.00 20.00 10.00 0.00 1 2 Time 3 Dorsal Striatum deficits in ASD during implicit learning R L Typical children > ASD children Variation in VS activity in typical children predicts social reciprocity R Word Segmentation & Language Learning • Identifying word boundaries is one of the earliest steps in language learning (Kuhl 2002) • Infant studies suggest heavy reliance on statistical learning for word segmentation (Saffran et al., 1996; Aslin et al., 1998) • Prosodic cues (e.g., stress) aid speech parsing (Johnson & Juscyzk, 2001; Thiessen & Saffran, 2003) • Adapt well-established paradigm from infant literature Implicit Language Learning Study Unstressed Language Stressed Language Random Syllables Transitional Probabilities Only Transitional Probabilities + Prosodic Cues No Transitional Probabilities No Prosodic Cues nimoluvorifaliduramanuto… do la go ro bi ku da bu pa tu ti pi pabikugolatudaropitibudo… pabiku daropi golatu tibudo po ba vu gi no fu ko ga fi mu ka vi kagipovuganomubakafufibako… li lu to fa du ma ri ra mo nu vo ni novuka pofimu vikoga bafugi lidura vorifa manuto nimolu Implicit Language Learning Paradigm Unstressed Language Stressed Language 144s 30s 144s Random Syllables 30s TIME (seconds) 144s Comparisons with Baseline (Rest) in typical adults Random Syllables RH LH RH LH RH LH Unstressed Language Stressed Language McNealy et al., 2006 Language learning compared to Rest: indexed by signal increases over exposure U S R TD > ASD Children Stressed TD kids show significantly greater signal increases in striatum than ASD Unstressed Random RH LH Implicit Learning and Reward • Rewards augment implicit learning • Probabilistic Classification Task • Reward variant– Stimuli predict a given outcome (1 or 2) either 17% 50% or 83% – Reward and Cognitive (Correct / Incorrect) feedback • Reward type varied: Monetary Rewards or Social Rewards – Equal number of reward and cognitive feedback trials Source: D. Ghahremani Frontal contributions to memory • Attention to incoming information • Organization of incoming information – Pre-organized – Semantic categorization • Working memory capacity • Organized memory retrieval (Brodmanns area 10 found to be involved in controlled retrieval) Frontal lobe memory deficits • Information size effects (supraspan) – LM story 2 second rep; • Interference (proactive) – Eg: CVLT 5,7,10,9,8 • • • • Benefit from cues Reduced spontaneous categorization Confabulation Prospective memory impairment Some examples to discuss • Patient 1: – CVLT: 4,7,12,15,9 2 I, 4 P – List B: 4 – SF: 7 cued 9 – LF: 9 cued 12 – Recognition 15/16 3 FP • What does this pattern suggest? • What would WMS LM look like? Example 2 • • • • • • CVLT 8,10,12,13,14 B8 Sdfree 8 cued 8 Ldfree 4 cued 5 Recognition 10/16 0 FP What else would you be likely to see? What would WMS LM look like? Emotion effects on memory • Flashbulb memory: where were you on 9/11? • Most can remember exquisite details of highly emotionally charged events • Close contact between amygdala and HC facilitate strong emotional memories • Interestingly, these memories are modifiable- details are altered with retelling, easily tampered with • People retain their emotional traces, which includes a strong conviction of the accuracy of their memory for emotional events • This is exactly why eyewitness testimony is so poor. Neuroanatomy of psychiatric conditions • Eg schizophrenic auditory hallucinations: strong activity in TTG and A2 during hallucinations • Many studies of psychiatric disorders have used emotional faces as stimuli Facial Emotions: Experimental Paradigm “Match” “Label” Match Expressions: Perception only; implicit emotional processing Label Expressions: Explicit cognitive analysis Control Match Affect- normal adults -seeing negative face expressions activates Face and Fear brain c amygdala face area Hariri et al., 1999 Label Affect -interpreting negative face expressions activates Face center … down regulates the amygdala amygdala Hariri et al., 1999 Cortical Influence During “Label” -this frontal lobe region regulates and controls Fear brain center Hariri et al., 1999 FFA Response 2.5 % signal change 2 1.5 1 0.5 0 -0.5 -1 3 28 53 78 103 128 153 178 Time (sec) 203 228 253 278 Bipolar Disorder- Manic State: Altshuler et al 2005 fMRI in Mania (Altshuler et al 2005) fMRI of Panic Imagery (Bystritsky et al 2001) Emotional Face Processing in OCD (S. Rausch) Disgust and Threat Responses in OCD (Shapiro 2002) Disgust Threat Control OCD Mirror Neurons and Autism • A dysfunctional mirror neuron system (MNS) in autism? (Williams et al 2001) • Mirror neurons: class of neurons first discovered in ventral premotor cortex (area F5) of the macaque (Gallese et al 1996; Rizzolatti et al 1996); Pars opercularis (BA 44), inferior frontal gyrus, is human homologue. • Neurons fire during both the performance and observation of motor behavior; respond to intention: only fire for meaningful actions Mirror Neuron function in autism: Imitating and Observing emotions Angry Fearful Happy Sad Neutral I. II. faces Watch faces Imitate expressions + 2s + 2 Separate Functional Runs “Just look at the expression on each face” “Imitate the expression you see on each face ” 2s + 2s Activity During Imitation Motor areas TD Imitate Mirror neuron area Visual areas R L 6 5 4 t ASD Imitate 3 2 1 R L 0 Imitate: TD > ASD p<.05, corrected at cluster level R L Imitation: TD > Autism Anterior Insula z: -12 z: 8 Connection from mirror centers to emotion centers L R Amygdala: fear centers Negative faces L R Ventral striatum: Reward Centers (happy faces)