Distinct Hippocampal and Basal Ganglia Contributions to Probabilistic Learning and Reversal

The hippocampus and the basal ganglia are thought to play fundamental and distinct roles in learning and memory, supporting two dissociable memory systems. Interestingly, however, the hippocampus and the basal ganglia have each, separately, been implicated as necessary for reversal learning—the ability to adaptively change a response when previously learned stimulus–outcome contingencies are reversed. Here, we compared the contribution of the hippocampus and the basal ganglia to distinct aspects of learning and reversal. Amnesic subjects with selective hippocampal damage, Parkinson subjects with disrupted basal ganglia function, and healthy controls were tested on a novel probabilistic learning and reversal paradigm. In this task, reversal can be achieved in two ways: Subjects can reverse a previously learned response, or they can select a new cue during the reversal phase, effectively “opting out” of the reversal. We found that both patient groups were intact at initial learning, but differed in their ability to reverse. Amnesic subjects failed to reverse, and continued to use the same cue and response learned before the reversal. Parkinson subjects, by contrast, opted out of the reversal by learning a new cue–outcome association. These results suggest that both the hippocampus and the basal ganglia support reversal learning, but in different ways. The basal ganglia are necessary for learning a new response when a previously learned response is no longer rewarding. The failure of the amnesic subjects to reverse their response or to learn a new cue is consistent with a more general role for the hippocampus in configural learning, and suggests it may also support the ability to respond to changes in cue–outcome contingencies.

[1]  S. Inati,et al.  An fMRI study of reward-related probability learning , 2005, NeuroImage.

[2]  Shawn W. Ell,et al.  Category learning deficits in Parkinson's disease. , 2003, Neuropsychology.

[3]  T. Robbins,et al.  Enhanced or impaired cognitive function in Parkinson's disease as a function of dopaminergic medication and task demands. , 2001, Cerebral cortex.

[4]  T. Robbins,et al.  Dopaminergic basis for deficits in working memory but not attentional set-shifting in Parkinson's disease , 2005, Neuropsychologia.

[5]  S M Zola,et al.  Paradoxical facilitation of object reversal learning after transection of the fornix in monkeys. , 1973, Neuropsychologia.

[6]  M. Gluck,et al.  The role of dopamine in cognitive sequence learning: evidence from Parkinson’s disease , 2005, Behavioural Brain Research.

[7]  M. Gluck,et al.  Basal ganglia and dopamine contributions to probabilistic category learning , 2008, Neuroscience & Biobehavioral Reviews.

[8]  W Todd Maddox,et al.  Information-integration category learning in patients with striatal dysfunction. , 2005, Neuropsychology.

[9]  W. Schultz Multiple reward signals in the brain , 2000, Nature Reviews Neuroscience.

[10]  L. Squire The organization and neural substrates of human memory. , 1987, International journal of neurology.

[11]  M. Gluck,et al.  Interactive memory systems in the human brain , 2001, Nature.

[12]  Peter Dayan,et al.  A Neural Substrate of Prediction and Reward , 1997, Science.

[13]  M. Gluck,et al.  Dissociating Hippocampal versus Basal Ganglia Contributions to Learning and Transfer , 2003, Journal of Cognitive Neuroscience.

[14]  L. Squire,et al.  A Neostriatal Habit Learning System in Humans , 1996, Science.

[15]  H. Eichenbaum,et al.  Memory, amnesia, and the hippocampal system , 1993 .

[16]  Michael J. Frank,et al.  By Carrot or by Stick: Cognitive Reinforcement Learning in Parkinsonism , 2004, Science.

[17]  Catherine E. Myers,et al.  Conditional spatial discrimination in humans with hypoxic brain injury , 2000, Psychobiology.

[18]  M. Gluck,et al.  Impaired probabilistic category learning in hypoxic subjects with hippocampal damage , 2004, Neuropsychologia.

[19]  J F Disterhoft,et al.  Spared discrimination and impaired reversal eyeblink conditioning in patients with temporal lobe amnesia. , 2001, Behavioral neuroscience.

[20]  C. Stark,et al.  Pattern Separation in the Human Hippocampal CA3 and Dentate Gyrus , 2008, Science.

[21]  M. Gluck,et al.  Context, conditioning, and hippocampal rerepresentation in animal learning. , 1994, Behavioral neuroscience.

[22]  S. Folstein,et al.  "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. , 1975, Journal of psychiatric research.

[23]  M. D’Esposito,et al.  Reversal learning in Parkinson's disease depends on medication status and outcome valence , 2006, Neuropsychologia.

[24]  S. Heckers,et al.  Hippocampal activation during transitive inference in humans , 2004, Hippocampus.

[25]  T W Robbins Refining the Taxonomy of Memory , 1996, Science.

[26]  David S. Olton,et al.  Learning sets, discrimination reversal, and hippocampal function , 1986, Behavioural Brain Research.

[27]  T. Robbins,et al.  The effects of ibotenic acid lesions of the nucleus accumbens on spatial learning and extinction in the rat , 1989, Behavioural Brain Research.

[28]  Alison R Preston,et al.  Hippocampal contribution to the novel use of relational information in declarative memory , 2004, Hippocampus.

[29]  M. D’Esposito,et al.  Working Memory Capacity Predicts Dopamine Synthesis Capacity in the Human Striatum , 2008, The Journal of Neuroscience.

[30]  T. Robbins,et al.  Defining the Neural Mechanisms of Probabilistic Reversal Learning Using Event-Related Functional Magnetic Resonance Imaging , 2002, The Journal of Neuroscience.

[31]  M. Moser,et al.  Pattern Separation in the Dentate Gyrus and CA3 of the Hippocampus , 2007, Science.

[32]  M. Gluck,et al.  l-dopa impairs learning, but spares generalization, in Parkinson's disease , 2006, Neuropsychologia.

[33]  H. Eichenbaum,et al.  From Conditioning to Conscious Recollection , 2001 .

[34]  Richard B. Ivry,et al.  Rule-Based Category Learning is Impaired in Patients with Parkinson's Disease but not in Patients with Cerebellar Disorders , 2005, Journal of Cognitive Neuroscience.

[35]  T. Robbins,et al.  Comparative effects of excitotoxic lesions of the hippocampus and septum/diagonal band on conditional visual discrimination and spatial learning , 1993, Neuropsychologia.

[36]  J. Gabrieli Cognitive neuroscience of human memory. , 1998, Annual review of psychology.

[37]  Corinna M. Cincotta,et al.  The Roles of the Caudate Nucleus in Human Classification Learning , 2005, The Journal of Neuroscience.

[38]  G. Schoenbaum,et al.  Neural Encoding in Ventral Striatum during Olfactory Discrimination Learning , 2003, Neuron.

[39]  S. Lewis,et al.  The role of learned irrelevance in attentional set-shifting impairments in Parkinson's disease. , 2006, Neuropsychology.

[40]  M. Gluck,et al.  Role of the basal ganglia in category learning: how do patients with Parkinson's disease learn? , 2004, Behavioral neuroscience.

[41]  M. Gluck,et al.  How do people solve the "weather prediction" task?: individual variability in strategies for probabilistic category learning. , 2002, Learning & memory.

[42]  M. Gluck,et al.  Cortico-striatal contributions to feedback-based learning: converging data from neuroimaging and neuropsychology. , 2004, Brain : a journal of neurology.

[43]  H. Eichenbaum,et al.  The hippocampus and memory for orderly stimulus relations. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[44]  N. Cohen From Conditioning to Conscious Recollection Memory Systems of the Brain. Oxford Psychology Series, Volume 35. , 2001 .

[45]  Russell A Poldrack,et al.  Modulation of competing memory systems by distraction. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[46]  Richard B. Ivry,et al.  Spatial and Temporal Sequence Learning in Patients with Parkinson's Disease or Cerebellar Lesions , 2003, Journal of Cognitive Neuroscience.

[47]  L. Radloff The CES-D Scale , 1977 .

[48]  H. Eichenbaum A cortical–hippocampal system for declarative memory , 2000, Nature Reviews Neuroscience.

[49]  Michael J. Frank,et al.  Dynamic Dopamine Modulation in the Basal Ganglia: A Neurocomputational Account of Cognitive Deficits in Medicated and Nonmedicated Parkinsonism , 2005, Journal of Cognitive Neuroscience.

[50]  R. Poldrack,et al.  Competition among multiple memory systems: converging evidence from animal and human brain studies , 2003, Neuropsychologia.

[51]  D. Schacter,et al.  Medial temporal lobe activations in fMRI and PET studies of episodic encoding and retrieval , 1999, Hippocampus.

[52]  A. M. Owen,et al.  Visuospatial memory deficits at different stages of Parkinson's disease , 1993, Neuropsychologia.

[53]  M. A. Gluck,et al.  Conditional discrimination and reversal in amnesia subsequent to hypoxic brain injury or anterior communicating artery aneurysm rupture , 2006, Neuropsychologia.

[54]  廣瀬雄一 Neuroscience 細胞死:最近の知見 , 2010 .

[55]  G. E. Alexander,et al.  Parallel organization of functionally segregated circuits linking basal ganglia and cortex. , 1986, Annual review of neuroscience.

[56]  A. Beck,et al.  Beck Depression Inventory–II , 2011 .

[57]  R. Poldrack,et al.  Striatal activation during acquisition of a cognitive skill. , 1999, Neuropsychology.

[58]  D. Shohamy,et al.  Integrating Memories in the Human Brain: Hippocampal-Midbrain Encoding of Overlapping Events , 2008, Neuron.

[59]  T. Robbins,et al.  Contrasting mechanisms of impaired attentional set-shifting in patients with frontal lobe damage or Parkinson's disease. , 1993, Brain : a journal of neurology.

[60]  T. Robbins,et al.  l-Dopa medication remediates cognitive inflexibility, but increases impulsivity in patients with Parkinson’s disease , 2003, Neuropsychologia.

[61]  Ravi S. Menon,et al.  Mental chronometry using latency-resolved functional MRI. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[62]  C. E. Polkey,et al.  Impaired dimensional selection but intact use of reward feedback during visual discrimination learning in Parkinson's disease , 2006, Neuropsychologia.

[63]  M. Frank,et al.  Anatomy of a decision: striato-orbitofrontal interactions in reinforcement learning, decision making, and reversal. , 2006, Psychological review.

[64]  T. Robbins,et al.  Probabilistic learning and reversal deficits in patients with Parkinson’s disease or frontal or temporal lobe lesions: possible adverse effects of dopaminergic medication , 2000, Neuropsychologia.

[65]  G. Schoenbaum,et al.  Lesions of Nucleus Accumbens Disrupt Learning about Aversive Outcomes , 2003, The Journal of Neuroscience.

[66]  D. Amaral,et al.  Functional Neuroanatomy of the Medial Temporal Lobe Memory System , 2004, Cortex.

[67]  M. Gluck,et al.  Probabilistic classification learning in amnesia. , 1994, Learning & memory.

[68]  P. Goldman-Rakic,et al.  Dual pathways connecting the dorsolateral prefrontal cortex with the hippocampal formation and parahippocampal cortex in the rhesus monkey , 1984, Neuroscience.

[69]  Mark A. Gluck,et al.  A Neurocomputational Model of Dopamine and Prefrontal–Striatal Interactions during Multicue Category Learning by Parkinson Patients , 2011, Journal of Cognitive Neuroscience.

[70]  E. Bigler,et al.  Hippocampal volume in normal aging and traumatic brain injury. , 1997, AJNR. American journal of neuroradiology.

[71]  W. B. Orr,et al.  Hippocampectomy selectively disrupts discrimination reversal conditioning of the rabbit nictitating membrane response , 1983, Behavioural Brain Research.