# Presentation: 690100

## Neuroimaging the Aging Brain: Methodological Insights from Cognitive Neuroscience

**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 Volumetrics
Diffusion Tensor Imaging (DTI)
Task Logistics

- Functional MRI (fMRI)
- MRI Volumetrics
- Diffusion Tensor Imaging (DTI)
- Task Logistics

## Overview of Methods in Cognitive NeuroscienceNeuronal activity vs. Metabolism

**Key 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

## BASELINE

- ACTIVE

## Neuronal origins of the fMRI Hemodynamic ResponseThe fMRI BOLD response is predicted by dendritic activity (LFPs)

- Neuronal origins of the fMRI Hemodynamic Response*The fMRI BOLD response is predicted by dendritic activity (LFPs)*

- Adapted from Logothetis et al. (2002)

## Thickening of vessel walls
Hypertension
Venous occlusions
Changes in capillary structure
Reduced blood flow
Reduced oxygen consumption (CMRO2)

- Thickening of vessel walls
- Hypertension
- Venous occlusions
- Changes in capillary structure
- Reduced blood flow
- Reduced oxygen consumption (CMRO2)

- Fang (1976)

## Do these Structural Changes Influence the fMRI BOLD Signal?

- Time since stimulus onset (sec)

- 0

- 12

- BOLD Signal Change

- ~1%

- Huettel et al.* (2001)*

## Do these Structural Changes Influence the fMRI BOLD Signal?Probably not... No... and Yes

- Huettel et al.* (2001)*

**BOLD Amplitude**

**BOLD Refractory Effects**

**BOLD Signal-Noise Ratio**

**Y1**

**E1**

**Y2**

**E2**

- Two 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.

- D’Esposito et al.* (1999)*

- Buckner et al.* (2000)*

**Y1**

**E1**

**Y2**

**E2**

**Y**

**E**

**E/****Y**

## How does Increased Noise affect fMRI Analyses?Simulations show clear effects on spatial extent

- Huettel et al., 2001

- SNR =  0.10

- SNR =  0.15

- SNR =  0.25

- SNR =  1.00

- SNR =  0.52 (Young)

- SNR =  0.35 (Old)

- Number of Trials Averaged

- Number of Supra-threshold Voxels

- Age-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 testing

- 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 testing

## Structural Changes in the Elderly Brain: Gray MatterDifferent brain regions exhibit different patterns of lifespan change

- Data 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 MatterMeasurement using diffusion tensor imaging (DTI)

## White Matter Maps: Diffusion Tensor MapsDiffusion tends to be less anisotropic in elderly adults

**Older**

**Younger**

## DTI: White-Matter Changes with Aging Reduced Fractional Anisotropy

- DTI: White-Matter Changes with Aging *Reduced Fractional Anisotropy*

- Key fiber tracts in the human brain

- Data from Madden et al. (2004)

- White matter integrity, assessed in central voxels,  decreases in the elderly

## DTI: White-Matter Changes with Aging Reduced Fractional Anisotropy

- Data from Madden et al. (2004)

- Different white matter tracts mediate performance in young and elderly.

## Reduced tolerance for time in scanner

- Reduced tolerance for time in scanner

- Young

- Elderly

## Reduced tolerance for time in scanner
Reduced sensory abilities

- Reduced tolerance for time in scanner
- Reduced sensory abilities

## Reduced tolerance for time in scanner
Reduced sensory abilities
Reduced performance on many tasks

- Reduced tolerance for time in scanner
- Reduced sensory abilities
- Reduced performance on many tasks

- NST = nonsingleton target ; ST = singleton target

- Excerpts from Madden et al. (2004a, 2004b, 2006)

## Reduced tolerance for time in scanner
Reduced sensory abilities
Reduced performance on many tasks
Biased sample selection

- Reduced tolerance for time in scanner
- Reduced sensory abilities
- Reduced performance on many tasks
- Biased sample selection

## The “Super Elderly”  Performance, on many scales, approximates or exceeds the young

- Excerpts 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 scanner
Reduced sensory abilities
Reduced performance on many tasks
Biased sample selection 
Different motivation for participating

- Reduced tolerance for time in scanner
- Reduced sensory abilities
- Reduced performance on many tasks
- Biased sample selection
- Different motivation for participating

- Excerpt from Hertwig & Ortmann (2001)

**?**

**?**

## II. Functional Changes

## Memory
Control processes
Emotion and affect
Reward evaluation

- Memory
- Control processes
- Emotion and affect
- Reward evaluation

- 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., 2006

- Elderly: _Attenuation_ of recollection-based activation in hippocampus.

- Elderly: _Enhancement_ of familiarity-based activation in rhinal cortex.

## Non-Selective Deficits: EmotionSimilar regions, but less extensive activation, in the elderly

- Non-Selective Deficits: Emotion*Similar regions, but less extensive activation, in the elderly*

- Wright et al., 2006

- Tessitore et al., 2005

## Compensation: MemoryElderly adults recruit additional regions to maintain performance

- Cabeza et al., 2002a

- In 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 phenomenon

- Cabeza, 2002; Cabeza et al., 2004

- The 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).

## Divided minus Central

- Madden et al., 1997

**Divided minus Central**

- Younger Adults

- Older Adults

## Compensation: Executive Control Elderly adults recruit additional, non-prefrontal regions

- Compensation: Executive Control *Elderly adults recruit additional, non-prefrontal regions*

- Madden et al., 2004

- Posano et al., 2005

- Younger adults: Prefrontal Cortex

- Elderly adults: Thalamus/BG

- Elderly adults: Parietal Cortex

## Compensation: Methodological Caveats fMRI provides information about what’s active, not what’s not active 

- Compensation: Methodological Caveats *fMRI provides information about what’s active, not what’s not active *

- Cabeza, 2002

## Selective Deficits, Compensation: Reward systems?

- Almost nothing known... hence, this meeting.

## Acknowledgments

- Faculty collaborators, discussed projects
- David Madden
- Roberto Cabeza
- Len White
- Gregory McCarthy
- External support
- NIMH (Huettel)
- NINDS (McCarthy)
- NIA (Madden, Cabeza)

**neuroeconomics.duke.edu**

- Current Laboratory Members
- Alexandru Avram
- J. Neil Bearden
- Jacqui Detwiler
- Erin Douglas
- Wilko Schultz-Mahlendorf
- Mark Sutherland
- Dharol Tankersley
- Bethany Weber

- Recommended Readings:
- Cabeza, Nyberg, & Park (2005). *Cognitive Neuroscience of Aging. *Oxford Univ. Press
- Hedden & Gabrieli (2004). *Nature Reviews Neuroscience*
- D’Esposito, Deouell, & Gazzaley (2003).* Nature Reviews Neuroscience*
- All uncredited figures from:
- Huettel, Song, & McCarthy (2004). *Functional Magnetic Resonance Imaging*