Impaired spatial and non-spatial configural learning in patients with hippocampal pathology

The hippocampus has been proposed to play a critical role in memory through its unique ability to bind together the disparate elements of an experience. This hypothesis has been widely examined in rodents using a class of tasks known as “configural” or “non-linear”, where outcomes are determined by specific combinations of elements, rather than any single element alone. On the basis of equivocal evidence that hippocampal lesions impair performance on non-spatial configural tasks, it has been proposed that the hippocampus may only be critical for spatial configural learning. Surprisingly few studies in humans have examined the role of the hippocampus in solving configural problems. In particular, no previous study has directly assessed the human hippocampal contribution to non-spatial and spatial configural learning, the focus of the current study. Our results show that patients with primary damage to the hippocampus bilaterally were similarly impaired at configural learning within both spatial and non-spatial domains. Our data also provide evidence that residual configural learning can occur in the presence of significant hippocampal dysfunction. Moreover, evidence obtained from a post-experimental debriefing session suggested that patients acquired declarative knowledge of the underlying task contingencies that corresponded to the best-fit strategy identified by our strategy analysis. In summary, our findings support the notion that the hippocampus plays an important role in both spatial and non-spatial configural learning, and provide insights into the role of the medial temporal lobe (MTL) more generally in incremental reinforcement-driven learning.

[1]  Andrew P. Yonelinas,et al.  Sparing of the familiarity component of recognition memory in a patient with hippocampal pathology , 2005, Neuropsychologia.

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

[3]  R. Sutherland,et al.  The hippocampal formation is necessary for rats to learn and remember configural discriminations , 1989, Behavioural Brain Research.

[4]  J. O’Keefe,et al.  Human hippocampus and viewpoint dependence in spatial memory , 2002, Hippocampus.

[5]  H. Yin,et al.  The role of the basal ganglia in habit formation , 2006, Nature Reviews Neuroscience.

[6]  M. Mishkin,et al.  Developmental amnesia associated with early hypoxic-ischaemic injury. , 2000, Brain : a journal of neurology.

[7]  R. Passingham The hippocampus as a cognitive map J. O'Keefe & L. Nadel, Oxford University Press, Oxford (1978). 570 pp., £25.00 , 1979, Neuroscience.

[8]  M. Mishkin,et al.  The effects of bilateral hippocampal damage on fMRI regional activations and interactions during memory retrieval. , 2001, Brain : a journal of neurology.

[9]  John P Aggleton,et al.  The importance of the rat hippocampus for learning the structure of visual arrays , 2006, The European journal of neuroscience.

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

[11]  Daphna Shohamy,et al.  Strategies in probabilistic categorization: results from a new way of analyzing performance. , 2006, Learning & memory.

[12]  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.

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

[14]  D. Hassabis,et al.  Patients with hippocampal amnesia cannot imagine new experiences , 2007, Proceedings of the National Academy of Sciences.

[15]  R. O’Reilly,et al.  Hippocampal and neocortical contributions to memory: advances in the complementary learning systems framework , 2002, Trends in Cognitive Sciences.

[16]  J W Rudy,et al.  Rats with damage to the hippocampal-formation are impaired on the transverse-patterning problem but not on elemental discriminations. , 1995, Behavioral neuroscience.

[17]  H. Eichenbaum Hippocampus Cognitive Processes and Neural Representations that Underlie Declarative Memory , 2004, Neuron.

[18]  M. Mishkin,et al.  Differential effects of early hippocampal pathology on episodic and semantic memory. , 1997, Science.

[19]  L. Nadel,et al.  The Hippocampus as a Cognitive Map , 1978 .

[20]  James L. McClelland,et al.  Why there are complementary learning systems in the hippocampus and neocortex: insights from the successes and failures of connectionist models of learning and memory. , 1995, Psychological review.

[21]  Mortimer Mishkin,et al.  Preserved Recognition in a Case of Developmental Amnesia: Implications for the Acaquisition of Semantic Memory? , 2001, Journal of Cognitive Neuroscience.

[22]  J. Pearce,et al.  Neural systems underlying episodic memory: insights from animal research. , 2001, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[23]  J W Rudy,et al.  Damage to the hippocampal formation in rats selectively impairs the ability to learn cue relationships. , 1989, Behavioral and neural biology.

[24]  L. Squire,et al.  Robust habit learning in the absence of awareness and independent of the medial temporal lobe , 2005, Nature.

[25]  R. Clark,et al.  The medial temporal lobe. , 2004, Annual review of neuroscience.

[26]  R. O’Reilly,et al.  Conjunctive representations in learning and memory: principles of cortical and hippocampal function. , 2001, Psychological review.

[27]  E. Maguire,et al.  The Human Hippocampus and Spatial and Episodic Memory , 2002, Neuron.

[28]  R. Sutherland,et al.  Configural association theory and the hippocampal formation: An appraisal and reconfiguration , 1995, Hippocampus.

[29]  Larry R Squire,et al.  Declarative Memory, Awareness, and Transitive Inference , 2005, The Journal of Neuroscience.

[30]  Potassium channel antibody-associated encephalopathy: a potentially immunotherapy-responsive form of limbic encephalitis. , 2004, Brain : a journal of neurology.

[31]  Jennifer D Ryan,et al.  A comparison and evaluation of the predictions of relational and conjunctive accounts of hippocampal function , 2006, Hippocampus.

[32]  L R Squire,et al.  Impaired transverse patterning in human amnesia is a special case of impaired memory for two-choice discrimination tasks. , 1999, Behavioral neuroscience.

[33]  N Burgess,et al.  Memory for events and their spatial context: models and experiments. , 2001, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[34]  Course and outcome of acute limbic encephalitis with negative voltage-gated potassium channel antibodies , 2006, Journal of Neurology, Neurosurgery & Psychiatry.

[35]  Timothy C. Rickard,et al.  Losing Their Configural Mind: Amnesic Patients Fail on Transverse Patterning , 1998, Journal of Cognitive Neuroscience.

[36]  J. Hodges Memory, Amnesia and the Hippocampal System , 1995 .

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

[38]  Simon Gerhand,et al.  Preserved Semantic Learning in an Amnesic Patient , 2002, Cortex.

[39]  Neil Burgess,et al.  The hippocampal role in spatial memory and the familiarity--recollection distinction: a case study. , 2004, Neuropsychology.

[40]  M. McKERNAN,et al.  Hippocampal lesions do not impair negative patterning: a challenge to configural association theory. , 1993, Behavioral neuroscience.

[41]  W. Scoville,et al.  LOSS OF RECENT MEMORY AFTER BILATERAL HIPPOCAMPAL LESIONS , 1957, Journal of neurology, neurosurgery, and psychiatry.

[42]  M Gallagher,et al.  Hippocampal lesions enhance configural learning by reducing proactive interference , 1998, Hippocampus.

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