812. Individuals at Risk for Depression Recruit Default-Mode Network to Process Stress-Relevant Information

Alzheimer’s disease (AD) is the most common form of dementia in old age, and is characterized by prominent impairment of episodic memory. Recent functional imaging studies in AD have demonstrated alterations in a distributed network of brain regions supporting memory function, including regions of the default mode network. Previous positron emission tomography studies of older individuals at risk for AD have revealed hypometabolism of association cortical regions similar to the metabolic abnormalities seen in AD patients. In recent functional magnetic resonance imaging (fMRI) studies of AD, corresponding brain default mode regions have also been found to demonstrate an abnormal fMRI task-induced deactivation response pattern. That is, the relative decreases in fMRI signal normally observed in the default mode regions in healthy subjects performing a cognitive task are not seen in AD patients, or may even be reversed to a paradoxical activation response. Our recent studies have revealed alterations in the pattern of deactivation also in elderly individuals at risk for AD by virtue of their APOE e4 genotype, or evidence of mild cognitive impairment (MCI). In agreement with recent reports from other groups, these studies demonstrate that the pattern of fMRI task-induced deactivation is progressively disrupted along the continuum from normal aging to MCI and to clinical AD and more impaired in e4 carriers compared to non-carriers. These findings will be discussed in the context of current literature regarding functional imaging of the default network in AD and at-risk populations.

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Recruitment of the default mode network during a demanding act of executive control

eLife ◽

10.7554/elife.06481 ◽

2015 ◽

Vol 4 ◽

Cited By ~ 66

Author(s):

Ben M Crittenden ◽

Daniel J Mitchell ◽

John Duncan

Keyword(s):

Executive Control ◽

Default Mode Network ◽

Pattern Analysis ◽

Relevant Information ◽

Multivoxel Pattern Analysis ◽

Default Mode ◽

Cognitive Context ◽

Increased Activity ◽

Reduced Activity ◽

Or Task

In the human brain, a default mode or task-negative network shows reduced activity during many cognitive tasks and is often associated with internally-directed processes, such as mind wandering and thoughts about the self. In contrast to this task-negative pattern, we show increased activity during a large and demanding switch in task set. Furthermore, we employ multivoxel pattern analysis and find that regions of interest within default mode network are encoding task-relevant information during task performance. Activity in this network may be driven by major revisions of cognitive context, whether internally or externally focused.

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Differential default mode network trajectories in asymptomatic individuals at risk for Alzheimer's disease

Alzheimer s & Dementia ◽

10.1016/j.jalz.2019.03.006 ◽

2019 ◽

Vol 15 (7) ◽

pp. 940-950 ◽

Cited By ~ 13

Author(s):

Patrizia A. Chiesa ◽

Enrica Cavedo ◽

Andrea Vergallo ◽

Simone Lista ◽

Marie-Claude Potier ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

At Risk ◽

Default Mode Network ◽

Default Mode ◽

Asymptomatic Individuals

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Fasting plasma insulin and the default mode network in women at risk for Alzheimer's disease

Neurobiology of Aging ◽

10.1016/j.neurobiolaging.2012.06.006 ◽

2013 ◽

Vol 34 (3) ◽

pp. 641-649 ◽

Cited By ~ 42

Author(s):

Heather Kenna ◽

Fumiko Hoeft ◽

Ryan Kelley ◽

Tonita Wroolie ◽

Bevin DeMuth ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

At Risk ◽

Default Mode Network ◽

Plasma Insulin ◽

Default Mode ◽

Fasting Plasma ◽

Fasting Plasma Insulin

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31.2 INCREASED DEFAULT MODE NETWORK CONNECTIVITY IN INDIVIDUALS AT HIGH FAMILIAL RISK FOR DEPRESSION

Journal of the American Academy of Child & Adolescent Psychiatry ◽

10.1016/j.jaac.2016.07.297 ◽

2016 ◽

Vol 55 (10) ◽

pp. S306

Author(s):

Jonathan Posner

Keyword(s):

Default Mode Network ◽

Familial Risk ◽

Network Connectivity ◽

Default Mode ◽

Risk For Depression

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Targeting Default Mode Network Dysfunction in Persons at Risk of Alzheimer’s Disease with Transcranial Magnetic Stimulation (NEST4AD): Rationale and Study Design

Journal of Alzheimer s Disease ◽

10.3233/jad-210659 ◽

2021 ◽

Vol 83 (4) ◽

pp. 1877-1889

Author(s):

Michela Pievani ◽

Anna Mega ◽

Giulia Quattrini ◽

Giacomo Guidali ◽

Clarissa Ferrari ◽

...

Keyword(s):

Alzheimer’S Disease ◽

At Risk ◽

Transcranial Magnetic Stimulation ◽

Functional Mri ◽

Default Mode Network ◽

Resting State ◽

Multimodal Imaging ◽

Magnetic Stimulation ◽

Default Mode ◽

E4 Allele

Background: Default mode network (DMN) dysfunction is well established in Alzheimer’s disease (AD) and documented in both preclinical stages and at-risk subjects, thus representing a potential disease target. Multi-sessions of repetitive transcranial magnetic stimulation (rTMS) seem capable of modulating DMN dynamics and memory in healthy individuals and AD patients; however, the potential of this approach in at-risk subjects has yet to be tested. Objective: This study will test the effect of rTMS on the DMN in healthy older individuals carrying the strongest genetic risk factor for AD, the Apolipoprotein E (APOE) ɛ4 allele. Methods: We will recruit 64 older participants without cognitive deficits, 32 APOE ɛ4 allele carriers and 32 non-carriers as a reference group. Participants will undergo four rTMS sessions of active (high frequency) or sham DMN stimulation. Multimodal imaging exam (including structural, resting-state, and task functional MRI, and diffusion tensor imaging), TMS with concurrent electroencephalography (TMS-EEG), and cognitive assessment will be performed at baseline and after the stimulation sessions. Results: We will assess changes in DMN connectivity with resting-state functional MRI and TMS-EEG, as well as changes in memory performance in APOE ɛ4 carriers. We will also investigate the mechanisms underlying DMN modulation through the assessment of correlations with measures of neuronal activity, excitability, and structural connectivity with multimodal imaging. Conclusion: The results of this study will inform on the physiological and cognitive outcomes of DMN stimulation in subjects at risk for AD and on the possible mechanisms. These results may outline the design of future non-pharmacological preventive interventions for AD.

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