Neuroimaging the Aging Brain: Methodological Insights from Cognitive Neuroscience
Major Themes: Methodology and Function
How do neuroimaging methods change when studying elderly adults?Are there general principles underlying functional changes in the elderly brain, and how can those principles be addressed using neuroimaging?
I. Methodological Changes
Functional MRI (fMRI)MRI VolumetricsDiffusion Tensor Imaging (DTI)Task LogisticsOverview of Methodological Changes in Neuroimaging
Overview of Methods in Cognitive NeuroscienceNeuronal activity vs. MetabolismKey idea: distinguish changes in our measure from changes in function.
Neuronal Activity: Signaling and Integration Local field potentials (LFPs) reflect the summed activity of many neurons
The fMRI Blood-Oxygenation-Level-Dependent (BOLD) ResponseIncreased neuronal activity results in increased MR (T2*) signalBASELINEACTIVE
Neuronal origins of the fMRI Hemodynamic ResponseThe fMRI BOLD response is predicted by dendritic activity (LFPs)Adapted from Logothetis et al. (2002)
Thickening of vessel wallsHypertensionVenous occlusionsChanges in capillary structureReduced blood flowReduced oxygen consumption (CMRO2)Age-Related Changes in Cerebrovascular SystemStructural changes that may have functional consequencesFang (1976)
Do these Structural Changes Influence the fMRI BOLD Signal?
Time since stimulus onset (sec)012BOLD Signal Change~1%Huettel et al. (2001)
Do these Structural Changes Influence the fMRI BOLD Signal?Probably not No and YesHuettel et al. (2001)BOLD AmplitudeBOLD Refractory EffectsBOLD Signal-Noise RatioY1E1Y2E2Two of three studies report that BOLD amplitude is similar in young (Y) and elderly (E) adults.Two studies report that the BOLD signal has similar refractory properties (i.e., to multiple events in rapid succession) in young and elderly adults.Two studies report that the BOLD signal has reduced signal-noise ratio (SNR) in elderly adults.DEsposito et al. (1999)Buckner et al. (2000)Y1E1Y2E2YEE/Y
How does Increased Noise affect fMRI Analyses?Simulations show clear effects on spatial extentHuettel et al., 2001SNR = 0.10SNR = 0.15SNR = 0.25SNR = 1.00SNR = 0.52 (Young)SNR = 0.35 (Old)Number of Trials AveragedNumber of Supra-threshold VoxelsAge-related differences in how much of the brain is activated may reflect differences in SNR, not cognition.
FMRI is a hemodynamic measure
Aging causes cardiovascular changes
BOLD response form unchanged with age
BOLD response SNR decreased with age
Problematic for between-group comparisons
Suggestion: Group by Condition testingConclusions: Aging and BOLD fMRIEffects not in principle, but for practice
Structural Changes in the Elderly Brain: Gray MatterDifferent brain regions exhibit different patterns of lifespan changeData from Raz et al. (2004); figure from Hedden & Gabrieli (2004)These effects are attributable primarily to loss of synaptic density (secondarily, to cell death).Image courtesy Gregory McCarthy
Structural Changes in the Elderly Brain: White MatterMeasurement using diffusion tensor imaging (DTI)
White Matter Maps: Diffusion Tensor MapsDiffusion tends to be less anisotropic in elderly adultsOlderYounger
DTI: White-Matter Changes with Aging Reduced Fractional AnisotropyKey fiber tracts in the human brainData from Madden et al. (2004)White matter integrity, assessed in central voxels, decreases in the elderly
DTI: White-Matter Changes with Aging Reduced Fractional AnisotropyData from Madden et al. (2004)Different white matter tracts mediate performance in young and elderly.
Reduced tolerance for time in scanner
Logistical Changes Differences in experimental proceduresYoungElderly
Reduced tolerance for time in scannerReduced sensory abilities
Logistical Changes Differences in experimental procedures
Reduced tolerance for time in scannerReduced sensory abilitiesReduced performance on many tasks
Logistical Changes Differences in experimental proceduresNST = nonsingleton target ; ST = singleton targetExcerpts from Madden et al. (2004a, 2004b, 2006)
Reduced tolerance for time in scannerReduced sensory abilitiesReduced performance on many tasksBiased sample selection
Logistical Changes Differences in experimental procedures
The Super Elderly Performance, on many scales, approximates or exceeds the youngExcerpts from Madden et al. (2004a, 2004b)Is the typical elderly adult someone who is college-educated, has no significant health problems, is taking only minimal medication, and has a vocabulary (etc.) similar to a Duke undergraduate?
Reduced tolerance for time in scannerReduced sensory abilitiesReduced performance on many tasksBiased sample selection Different motivation for participating
Logistical Changes Differences in experimental procedures for elderly subjectsExcerpt from Hertwig & Ortmann (2001)??
II. Functional Changes
MemoryControl processesEmotion and affectReward evaluationOverview of Functional Changes
Theme I: Selective and Non-selective deficits Theme II: Functional compensation?
Selective Deficits: Memory Aging has greater effects on recollection (hippocampally mediated)Cabeza et al., 2006Elderly: Attenuation of recollection-based activation in hippocampus.Elderly: Enhancement of familiarity-based activation in rhinal cortex.
Non-Selective Deficits: EmotionSimilar regions, but less extensive activation, in the elderlyWright et al., 2006Tessitore et al., 2005
Compensation: MemoryElderly adults recruit additional regions to maintain performanceCabeza et al., 2002aIn a memory retrieval task, elderly adults who perform similarly to young adults (Old-High) show increased activation in left PFC, compared to elderly adults with impaired performance.
Compensation: Memory (and other)Frontal compensation is a robust phenomenonCabeza, 2002; Cabeza et al., 2004The reductions in asymmetry are found both when hemispheric specialization is based on process (e.g., memory retrieval / encoding) and when based on stimulus domain (e.g., verbal / spatial working memory).
Compensation: Attention Increased frontal activation in elderly adults under divided attentionMadden et al., 1997Divided minus CentralYounger AdultsOlder Adults
Compensation: Executive Control Elderly adults recruit additional, non-prefrontal regionsMadden et al., 2004Posano et al., 2005Younger adults: Prefrontal CortexElderly adults: Thalamus/BGElderly adults: Parietal Cortex
Compensation: Methodological Caveats fMRI provides information about whats active, not whats not active Cabeza, 2002
Selective Deficits, Compensation: Reward systems?
Almost nothing known hence, this meeting.
AcknowledgmentsFaculty collaborators, discussed projectsDavid Madden Roberto CabezaLen WhiteGregory McCarthy
External supportNIMH (Huettel)NINDS (McCarthy)NIA (Madden, Cabeza)neuroeconomics.duke.eduCurrent Laboratory MembersAlexandru Avram J. Neil BeardenJacqui Detwiler Erin DouglasWilko Schultz-MahlendorfMark SutherlandDharol TankersleyBethany WeberRecommended Readings:Cabeza, Nyberg, & Park (2005). Cognitive Neuroscience of Aging. Oxford Univ. PressHedden & Gabrieli (2004). Nature Reviews NeuroscienceDEsposito, Deouell, & Gazzaley (2003). Nature Reviews Neuroscience
All uncredited figures from:Huettel, Song, & McCarthy (2004). Functional Magnetic Resonance Imaging