Flexible modulation of network connectivity related to cognition in Alzheimer's disease

Functional neuroimaging tools, such as fMRI methods, may elucidate the neural correlates of clinical, behavioral, and cognitive performance. Most functional imaging studies focus on regional task-related activity or resting state connectivity rather than how changes in functional connectivity across conditions and tasks are related to cognitive and behavioral performance. To investigate the promise of characterizing context-dependent connectivity-behavior relationships, this study applies the method of generalized psychophysiological interactions (gPPI) to assess the patterns of associative-memory-related fMRI hippocampal functional connectivity in Alzheimer's disease (AD) associated with performance on memory and other cognitively demanding neuropsychological tests and clinical measures. Twenty-four subjects with mild AD dementia (ages 54-82, nine females) participated in a face-name paired-associate encoding memory study. Generalized PPI analysis was used to estimate the connectivity between the hippocampus and the whole brain during encoding. The difference in hippocampal-whole brain connectivity between encoding novel and encoding repeated face-name pairs was used in multiple-regression analyses as an independent predictor for 10 behavioral, neuropsychological and clinical tests. The analysis revealed connectivity-behavior relationships that were distributed, dynamically overlapping, and task-specific within and across intrinsic networks; hippocampal-whole brain connectivity-behavior relationships were not isolated to single networks, but spanned multiple brain networks. Importantly, these spatially distributed performance patterns were unique for each measure. In general, out-of-network behavioral associations with encoding novel greater than repeated face-name pairs hippocampal-connectivity were observed in the default-mode network, while correlations with encoding repeated greater than novel face-name pairs hippocampal-connectivity were observed in the executive control network (p<0.05, cluster corrected). Psychophysiological interactions revealed significantly more extensive and robust associations between paired-associate encoding task-dependent hippocampal-whole brain connectivity and performance on memory and behavioral/clinical measures than previously revealed by standard activity-behavior analysis. Compared to resting state and task-activation methods, gPPI analyses may be more sensitive to reveal additional complementary information regarding subtle within- and between-network relations. The patterns of robust correlations between hippocampal-whole brain connectivity and behavioral measures identified here suggest that there are 'coordinated states' in the brain; that the dynamic range of these states is related to behavior and cognition; and that these states can be observed and quantified, even in individuals with mild AD.

[1]  R. Buckner,et al.  Functional-Anatomic Fractionation of the Brain's Default Network , 2010, Neuron.

[2]  Luca Passamonti,et al.  Anxiety predicts a differential neural response to attended and unattended facial signals of anger and fear , 2009, NeuroImage.

[3]  Karl J. Friston,et al.  Modeling regional and psychophysiologic interactions in fMRI: the importance of hemodynamic deconvolution , 2003, NeuroImage.

[4]  J. Schneider,et al.  National Institute on Aging–Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease , 2012, Alzheimer's & Dementia.

[5]  A D Roses,et al.  Utility of the apolipoprotein E genotype in the diagnosis of Alzheimer's disease. Alzheimer's Disease Centers Consortium on Apolipoprotein E and Alzheimer's Disease. , 1998, The New England journal of medicine.

[6]  Stephen M Smith,et al.  Correspondence of the brain's functional architecture during activation and rest , 2009, Proceedings of the National Academy of Sciences.

[7]  C. Sorg,et al.  Disconnection of frontal and parietal areas contributes to impaired attention in very early Alzheimer's disease. , 2011, Journal of Alzheimer's disease : JAD.

[8]  Russell A. Poldrack,et al.  Putting names to faces: Successful encoding of associative memories activates the anterior hippocampal formation , 2003, NeuroImage.

[9]  Hongkeun Kim,et al.  A dual-subsystem model of the brain's default network: Self-referential processing, memory retrieval processes, and autobiographical memory retrieval , 2012, NeuroImage.

[10]  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.

[11]  Karl J. Friston,et al.  Psychophysiological and Modulatory Interactions in Neuroimaging , 1997, NeuroImage.

[12]  J. Peña-Casanova Alzheimer's Disease Assessment Scale–Cognitive in Clinical Practice , 1997, International Psychogeriatrics.

[13]  Maurizio Corbetta,et al.  The human brain is intrinsically organized into dynamic, anticorrelated functional networks. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[14]  Stefan Kaiser,et al.  Neural reward processing is modulated by approach- and avoidance-related personality traits , 2010, NeuroImage.

[15]  O. Sporns,et al.  Mapping the Structural Core of Human Cerebral Cortex , 2008, PLoS biology.

[16]  Katie L. McMahon,et al.  A multivariate distance-based analytic framework for connectome-wide association studies , 2014, NeuroImage.

[17]  B. Abler,et al.  Modulation of Frontostriatal Interaction Aligns with Reduced Primary Reward Processing under Serotonergic Drugs , 2012, The Journal of Neuroscience.

[18]  R. Buckner,et al.  Evidence for the Default Network's Role in Spontaneous Cognition , 2010 .

[19]  Owen T. Carmichael,et al.  Coevolution of brain structures in amnestic mild cognitive impairment , 2013, NeuroImage.

[20]  J. Morris,et al.  Loss of Intranetwork and Internetwork Resting State Functional Connections with Alzheimer's Disease Progression , 2012, The Journal of Neuroscience.

[21]  Christopher H. Chatham,et al.  Corticostriatal Output Gating during Selection from Working Memory , 2014, Neuron.

[22]  R. Sperling,et al.  Relationship of fMRI activation to clinical trial memory measures in Alzheimer disease , 2007, Neurology.

[23]  Bharat B. Biswal,et al.  Competition between functional brain networks mediates behavioral variability , 2008, NeuroImage.

[24]  Keith Bush,et al.  A comparison of statistical methods for detecting context-modulated functional connectivity in fMRI , 2014, NeuroImage.

[25]  J. Morris The Clinical Dementia Rating (CDR) , 1993, Neurology.

[26]  M. Folstein,et al.  The Mini-Mental State Examination. , 1983, Archives of general psychiatry.

[27]  Maxime Guye,et al.  Basal functional connectivity within the anterior temporal network is associated with performance on declarative memory tasks , 2011, NeuroImage.

[28]  Talma Hendler,et al.  Cry for her or cry with her: context-dependent dissociation of two modes of cinematic empathy reflected in network cohesion dynamics. , 2014, Social cognitive and affective neuroscience.

[29]  R. Sperling,et al.  Test-retest reliability of memory task functional magnetic resonance imaging in Alzheimer disease clinical trials. , 2011, Archives of neurology.

[30]  B. Miller,et al.  Neurodegenerative Diseases Target Large-Scale Human Brain Networks , 2009, Neuron.

[31]  J. Molinuevo,et al.  Applying the new research diagnostic criteria: MRI findings and neuropsychological correlations of prodromal AD , 2012, International journal of geriatric psychiatry.

[32]  Timothy E. J. Behrens,et al.  Tools of the trade: psychophysiological interactions and functional connectivity. , 2012, Social cognitive and affective neuroscience.

[33]  Cleofé Peña-Gómez,et al.  Brain connectivity during resting state and subsequent working memory task predicts behavioural performance , 2012, Cortex.

[34]  Kelly O'Keefe,et al.  Reliability of functional magnetic resonance imaging associative encoding memory paradigms in non‐demented elderly adults , 2011, Human brain mapping.

[35]  D. Paré,et al.  Contrasting Activity Profile of Two Distributed Cortical Networks as a Function of Attentional Demands , 2009, The Journal of Neuroscience.

[36]  Adam Gazzaley,et al.  Measuring functional connectivity during distinct stages of a cognitive task , 2004, NeuroImage.

[37]  Elizabeth A. Kensinger,et al.  There are age-related changes in neural connectivity during the encoding of positive, but not negative, information , 2010, Cortex.

[38]  J. Kelso,et al.  Cortical coordination dynamics and cognition , 2001, Trends in Cognitive Sciences.

[39]  Maija Pihlajamäki,et al.  Functional MRI Assessment of Task-Induced Deactivation of the Default Mode Network in Alzheimer’s Disease and At-Risk Older Individuals , 2009, Behavioural neurology.

[40]  R. Lipton,et al.  Memory impairment on free and cued selective reminding predicts dementia , 2000, Neurology.

[41]  Katherine E. Prater,et al.  Functional connectivity tracks clinical deterioration in Alzheimer's disease , 2012, Neurobiology of Aging.

[42]  Karl J. Friston,et al.  Dynamic causal modelling , 2003, NeuroImage.

[43]  B. T. Thomas Yeo,et al.  The Organization of Local and Distant Functional Connectivity in the Human Brain , 2010, PLoS Comput. Biol..

[44]  Koene R. A. Van Dijk,et al.  The parahippocampal gyrus links the default‐mode cortical network with the medial temporal lobe memory system , 2014, Human brain mapping.

[45]  Justin L. Vincent,et al.  Intrinsic functional architecture in the anaesthetized monkey brain , 2007, Nature.

[46]  S. Black,et al.  Evidence from Functional Neuroimaging of a Compensatory Prefrontal Network in Alzheimer's Disease , 2003, The Journal of Neuroscience.

[47]  Stephen M. Smith,et al.  Investigations into resting-state connectivity using independent component analysis , 2005, Philosophical Transactions of the Royal Society B: Biological Sciences.

[48]  Sterling C. Johnson,et al.  A generalized form of context-dependent psychophysiological interactions (gPPI): A comparison to standard approaches , 2012, NeuroImage.

[49]  Douglas Greve,et al.  Functional MRI detection of pharmacologically induced memory impairment , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[50]  William J. Jagust,et al.  Lifespan brain activity, β-amyloid, and Alzheimer's disease , 2011, Trends in Cognitive Sciences.

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

[52]  M. Albert,et al.  fMRI studies of associative encoding in young and elderly controls and mild Alzheimer’s disease , 2003, Journal of neurology, neurosurgery, and psychiatry.

[53]  Trey Hedden Disruption of functional connectivity in clinically normal older adults harboring amyloid burden , 2010, Alzheimer's & Dementia.

[54]  Y. Liu,et al.  Resting-State Functional Connectivity Predicts Impulsivity in Economic Decision-Making , 2013, The Journal of Neuroscience.

[55]  Jonathan D. Power,et al.  Multi-task connectivity reveals flexible hubs for adaptive task control , 2013, Nature Neuroscience.

[56]  D. Price,et al.  Synapse loss in the temporal lobe in Alzheimer's disease , 1993, Annals of neurology.

[57]  Vinod Menon,et al.  Functional connectivity in the resting brain: A network analysis of the default mode hypothesis , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[58]  M. Folstein,et al.  Clinical diagnosis of Alzheimer's disease , 1984, Neurology.

[59]  B R Rosen,et al.  Encoding novel face‐name associations: A functional MRI study , 2001, Human brain mapping.

[60]  G. Glover,et al.  Dissociable Intrinsic Connectivity Networks for Salience Processing and Executive Control , 2007, The Journal of Neuroscience.

[61]  David C. Van Essen,et al.  A Population-Average, Landmark- and Surface-based (PALS) atlas of human cerebral cortex , 2005, NeuroImage.

[62]  Florin Dolcos,et al.  Neural Correlates of Opposing Effects of Emotional Distraction on Working Memory and Episodic Memory: An Event-Related fMRI Investigation , 2013, Front. Psychol..

[63]  R. Sperling,et al.  Functional MRI Studies of Associative Encoding in Normal Aging, Mild Cognitive Impairment, and Alzheimer's Disease , 2007, Annals of the New York Academy of Sciences.

[64]  Steven Mennerick,et al.  Synaptic Activity Regulates Interstitial Fluid Amyloid-β Levels In Vivo , 2005, Neuron.

[65]  E. DeYoe,et al.  Functional magnetic resonance imaging (FMRI) of the human brain , 1994, Journal of Neuroscience Methods.

[66]  David Bartrés-Faz,et al.  Distinct functional activity of the precuneus and posterior cingulate cortex during encoding in the preclinical stage of Alzheimer's disease. , 2012, Journal of Alzheimer's disease : JAD.

[67]  Scott T Grafton,et al.  Medial temporal lobe BOLD activity at rest predicts individual differences in memory ability in healthy young adults , 2008, Proceedings of the National Academy of Sciences.

[68]  Keith A. Johnson,et al.  Amyloid Deposition Is Associated with Impaired Default Network Function in Older Persons without Dementia , 2009, Neuron.

[69]  Justin L. Vincent,et al.  Spontaneous neuronal activity distinguishes human dorsal and ventral attention systems. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[70]  Karl J. Friston,et al.  Analysis of fMRI Time-Series Revisited , 1995, NeuroImage.

[71]  M. Hasselmo,et al.  Scopolamine Reduces Persistent Activity Related to Long-Term Encoding in the Parahippocampal Gyrus during Delayed Matching in Humans , 2005, The Journal of Neuroscience.

[72]  Richard S. Frackowiak,et al.  Inhibition in early Alzheimer's disease: An fMRI-based study of effective connectivity , 2011, NeuroImage.

[73]  Karine Lebreton,et al.  Is Neocortical–Hippocampal Connectivity a Better Predictor of Subsequent Recollection than Local Increases in Hippocampal Activity? New Insights on the Role of Priming , 2011, Journal of Cognitive Neuroscience.

[74]  Richard S. J. Frackowiak,et al.  Alzheimer's patients engage an alternative network during a memory task , 2005, Annals of neurology.

[75]  R. Turner,et al.  Characterizing Evoked Hemodynamics with fMRI , 1995, NeuroImage.

[76]  Meghan B. Mitchell,et al.  Tracking Cognitive Change over 24 Weeks with Longitudinal Functional Magnetic Resonance Imaging in Alzheimer’s Disease , 2012, Neurodegenerative Diseases.

[77]  Niall W. Duncan,et al.  Neuropsychiatric symptoms in Alzheimer's disease are related to functional connectivity alterations in the salience network , 2014, Human brain mapping.

[78]  Tianzi Jiang,et al.  Changes in hippocampal connectivity in the early stages of Alzheimer's disease: Evidence from resting state fMRI , 2006, NeuroImage.

[79]  M. Greicius,et al.  Default-mode network activity distinguishes Alzheimer's disease from healthy aging: Evidence from functional MRI , 2004, Proc. Natl. Acad. Sci. USA.

[80]  Jessica A. Turner,et al.  Behavioral Interpretations of Intrinsic Connectivity Networks , 2011, Journal of Cognitive Neuroscience.

[81]  Peter J Hellyer,et al.  The Control of Global Brain Dynamics: Opposing Actions of Frontoparietal Control and Default Mode Networks on Attention , 2014, The Journal of Neuroscience.

[82]  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.

[83]  Sheng Zhang,et al.  Decreased saliency processing as a neural measure of Barratt impulsivity in healthy adults , 2012, NeuroImage.