Remote effects of hippocampal damage on default network connectivity in the human brain

In the healthy human brain the hippocampus is known to work in concert with a variety of cortical brain regions. It has recently been linked to the default network of the brain, with the precuneus being its core hub. Here we studied the remote effects of damage to the hippocampus on functional connectivity patterns of the precuneus. From 14 epilepsy patients with selective, unilateral hippocampal sclerosis and 8 healthy control subjects, we acquired functional MRI data during performance of an object-location memory task. We assessed functional connectivity of a functionally defined region in the precuneus, which showed the typical properties of the default network: significant task-related deactivation, which was reduced in patients compared to control subjects. In control subjects, a largely symmetrical pattern of functional coherence to the precuneus emerged, including canonical default network areas such as ventral medial prefrontal cortex, inferior parietal cortex, and the hippocampi. Assessment of group differences within the default network areas revealed reduced connectivity to the precuneus in ipsilesional middle temporal gyrus and hippocampus in left hippocampal sclerosis patients compared to controls. Furthermore, left hippocampal sclerosis patients showed lower connectivity than right hippocampal sclerosis patients in left middle temporal gyrus, ventral medial prefrontal cortex, and left amygdala. We report remote effects of unilateral hippocampal damage on functional connectivity between distant brain regions associated with the default network of the human brain. These preliminary results underline the impact of circumscribed pathology on functionally connected brain regions.

[1]  A. Schulze-Bonhage,et al.  Lateralization of hippocampal activation differs between left and right temporal lobe epilepsy patients and correlates with postsurgical verbal learning decrement , 2008, Epilepsy Research.

[2]  Christian E Elger,et al.  Memory Outcome after Selective Amygdalohippocampectomy in Patients with Temporal Lobe Epilepsy: One‐year Follow‐up , 2004, Epilepsia.

[3]  Morris Moscovitch,et al.  Consequences of hippocampal damage across the autobiographical memory network in left temporal lobe epilepsy. , 2007, Brain : a journal of neurology.

[4]  S. Berkovic,et al.  Lateralization of verbal memory and unilateral hippocampal sclerosis: evidence of task-specific effects. , 1993, Journal of clinical and experimental neuropsychology.

[5]  Bradford C. Dickerson,et al.  Functional abnormalities of the medial temporal lobe memory system in mild cognitive impairment and Alzheimer's disease: Insights from functional MRI studies , 2008, Neuropsychologia.

[6]  Benjamin J. Shannon,et al.  Parietal lobe contributions to episodic memory retrieval , 2005, Trends in Cognitive Sciences.

[7]  M. Greicius,et al.  Default-Mode Activity during a Passive Sensory Task: Uncoupled from Deactivation but Impacting Activation , 2004, Journal of Cognitive Neuroscience.

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

[9]  D. Schacter,et al.  Episodic Simulation of Future Events , 2008, Annals of the New York Academy of Sciences.

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

[11]  S. Rombouts,et al.  Altered resting state networks in mild cognitive impairment and mild Alzheimer's disease: An fMRI study , 2005, Human brain mapping.

[12]  A. Sakamoto,et al.  Cognitive decline in temporal lobe epilepsy due to unilateral hippocampal sclerosis , 2007, Epilepsy & Behavior.

[13]  Friedrich G Woermann,et al.  Carbamazepine reduces memory induced activation of mesial temporal lobe structures: a pharmacological fMRI-study , 2001, BMC neurology.

[14]  M. Greicius Resting-state functional connectivity in neuropsychiatric disorders , 2008, Current opinion in neurology.

[15]  John Suckling,et al.  For personal use. Only reproduce with permission from The Lancet Publishing Group. Effect of sunlight and season on serotonin turnover in the brain , 2002 .

[16]  M. Fox,et al.  Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging , 2007, Nature Reviews Neuroscience.

[17]  J. Gotman,et al.  Generalized epileptic discharges show thalamocortical activation and suspension of the default state of the brain. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[18]  W. Paesschen,et al.  Qualitative and quantitative imaging of the hippocampus in mesial temporal lobe epilepsy with hippocampal sclerosis. , 2004, Neuroimaging clinics of North America.

[19]  A. Kleinschmidt,et al.  Linking Generalized Spike‐and‐Wave Discharges and Resting State Brain Activity by Using EEG/fMRI in a Patient with Absence Seizures , 2006, Epilepsia.

[20]  P Dupont,et al.  SPECT perfusion changes during complex partial seizures in patients with hippocampal sclerosis. , 2003, Brain : a journal of neurology.

[21]  Justin L. Vincent,et al.  Distinct cortical anatomy linked to subregions of the medial temporal lobe revealed by intrinsic functional connectivity. , 2008, Journal of neurophysiology.

[22]  B. Biswal,et al.  Functional connectivity in the motor cortex of resting human brain using echo‐planar mri , 1995, Magnetic resonance in medicine.

[23]  Américo Ceiki Sakamoto,et al.  Temporal pole signal abnormality on MR imaging in temporal lobe epilepsy with hippocampal sclerosis: a fluid-attenuated inversion-recovery study. , 2007, Arquivos de neuro-psiquiatria.

[24]  Biyu J. He,et al.  Breakdown of Functional Connectivity in Frontoparietal Networks Underlies Behavioral Deficits in Spatial Neglect , 2007, Neuron.

[25]  Jerome Engel,et al.  Surgical treatment of the epilepsies , 1993 .

[26]  N C Andreasen,et al.  Remembering the past: two facets of episodic memory explored with positron emission tomography. , 1995, The American journal of psychiatry.

[27]  Chris Rorden,et al.  Extrahippocampal gray matter atrophy and memory impairment in patients with medial temporal lobe epilepsy , 2007, Human brain mapping.

[28]  Karl J. Friston,et al.  Statistical parametric maps in functional imaging: A general linear approach , 1994 .

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

[30]  D. Schacter,et al.  The Brain's Default Network , 2008, Annals of the New York Academy of Sciences.

[31]  H F Durwen,et al.  [The Verbal Learning and Retention Test. A useful and differentiated tool in evaluating verbal memory performance]. , 1990, Schweizer Archiv fur Neurologie und Psychiatrie.

[32]  Peter Fransson,et al.  The precuneus/posterior cingulate cortex plays a pivotal role in the default mode network: Evidence from a partial correlation network analysis , 2008, NeuroImage.

[33]  O W Witte,et al.  Prefrontal asymmetric interictal glucose hypometabolism and cognitive impairment in patients with temporal lobe epilepsy. , 1997, Brain : a journal of neurology.

[34]  M. Fukunaga,et al.  Low frequency BOLD fluctuations during resting wakefulness and light sleep: A simultaneous EEG‐fMRI study , 2008, Human brain mapping.

[35]  D. Chialvo,et al.  Beyond Feeling: Chronic Pain Hurts the Brain, Disrupting the Default-Mode Network Dynamics , 2008, The Journal of Neuroscience.

[36]  John S. Duncan,et al.  Correlation of cognitive functions with voxel-based morphometry in patients with hippocampal sclerosis , 2008, Epilepsy & Behavior.

[37]  G. Lamberti,et al.  DCS a visual learning and memory test for neuropsychological assessment, after F. Hillers : manual , 1999 .

[38]  G L Shulman,et al.  INAUGURAL ARTICLE by a Recently Elected Academy Member:A default mode of brain function , 2001 .

[39]  R. C. Oldfield The assessment and analysis of handedness: the Edinburgh inventory. , 1971, Neuropsychologia.

[40]  A. Cavanna,et al.  The precuneus: a review of its functional anatomy and behavioural correlates. , 2006, Brain : a journal of neurology.

[41]  A. Kleinschmidt,et al.  Temporal lobe interictal epileptic discharges affect cerebral activity in “default mode” brain regions , 2006, Human brain mapping.

[42]  Andreas Schulze-Bonhage,et al.  Hippocampal functional connectivity reflects verbal episodic memory network integrity , 2007, Neuroreport.

[43]  G. Shulman,et al.  Medial prefrontal cortex and self-referential mental activity: Relation to a default mode of brain function , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[44]  J J Halford,et al.  Asymmetrical extra-hippocampal grey matter loss related to hippocampal atrophy in patients with medial temporal lobe epilepsy , 2006, Journal of Neurology, Neurosurgery & Psychiatry.

[45]  Craig J. Brozinsky,et al.  Functional connectivity with the hippocampus during successful memory formation , 2005, Hippocampus.