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Prefrontal atrophy, disrupted NREM slow waves and impaired hippocampal-dependent memory in aging.

Mander BA, Rao V, Lu B, Saletin JM, Lindquist JR, Ancoli-Israel S, Jagust W, Walker MP - Nat. Neurosci. (2013)

Bottom Line: Aging has independently been associated with regional brain atrophy, reduced slow wave activity (SWA) during non-rapid eye movement (NREM) sleep and impaired long-term retention of episodic memories.We found that age-related medial prefrontal cortex (mPFC) gray-matter atrophy was associated with reduced NREM SWA in older adults, the extent to which statistically mediated the impairment of overnight sleep-dependent memory retention.Moreover, this memory impairment was further associated with persistent hippocampal activation and reduced task-related hippocampal-prefrontal cortex functional connectivity, potentially representing impoverished hippocampal-neocortical memory transformation.

View Article: PubMed Central - PubMed

Affiliation: Sleep and Neuroimaging Laboratory, University of California, Berkeley, California, USA. bamander@berkeley.edu

ABSTRACT
Aging has independently been associated with regional brain atrophy, reduced slow wave activity (SWA) during non-rapid eye movement (NREM) sleep and impaired long-term retention of episodic memories. However, whether the interaction of these factors represents a neuropatholgical pathway associated with cognitive decline in later life remains unknown. We found that age-related medial prefrontal cortex (mPFC) gray-matter atrophy was associated with reduced NREM SWA in older adults, the extent to which statistically mediated the impairment of overnight sleep-dependent memory retention. Moreover, this memory impairment was further associated with persistent hippocampal activation and reduced task-related hippocampal-prefrontal cortex functional connectivity, potentially representing impoverished hippocampal-neocortical memory transformation. Together, these data support a model in which age-related mPFC atrophy diminishes SWA, the functional consequence of which is impaired long-term memory. Such findings suggest that sleep disruption in the elderly, mediated by structural brain changes, represents a contributing factor to age-related cognitive decline in later life.

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Related in: MedlinePlus

The sleep-dependent episodic word-pair task6,9 utilized word-nonsense word pairs to 1) maximize the novel episodic and associated hippocampal-dependent demands of the task38, and 2) minimize the semantic, and thus hippocampal-independent, demands of the task11,12,38. Words were 3–8 letters in length and drawn from a normative set of English words39. Nonsense words were 6–14 letters in length, derived from groups of common phonemes38. The word pair task began with an encoding phase composed of 120 word-nonsense word trials. (a) During each encoding trial, a word-nonsense word pair was shown for 5 s. Criterion training occurred immediately after encoding. (b) During each self-paced criterion trial, a previously studied probe word was presented with its original nonsense word associate from encoding (outlined in the grey box) and two new nonsense words not previously shown. Upon responding, the participant was given feedback for 1 s, with incorrect responses resulting in trial repetition at random intervals. (c) During recognition trials, either a previously studied probe word or a new (foil) probe word was shown for 5 s with four response options presented below. When a previously studied probe word was presented, the following response options were presented below: (1) the nonsense word originally paired with that probe word at encoding (‘Hit’), (2) a previously studied nonsense word, but one presented with a different previously studied probe word (‘Lure’), (3) a new nonsense word never seen during encoding, and (4) an option designating the shown probe word as “new”. New nonsense words were only presented once during the entire experiment, while previously studied nonsense words were presented twice during recognition testing, always in the same session, as a lure on one trial and the correct paired associate on another. When a foil probe word was presented, the four responses options consisted of three new nonsense words never presented during learning (which if chosen, would designate a ‘False alarm’), and an option designating this foil probe word as “new” (which if chosen, would designate a ‘Correct rejection’). Forty-five  events, consisting of a fixation display (1.5 s – 10 s), were interspersed throughout long delay recognition testing during fMRI acquisition, jittering trial onsets.
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Figure 1: The sleep-dependent episodic word-pair task6,9 utilized word-nonsense word pairs to 1) maximize the novel episodic and associated hippocampal-dependent demands of the task38, and 2) minimize the semantic, and thus hippocampal-independent, demands of the task11,12,38. Words were 3–8 letters in length and drawn from a normative set of English words39. Nonsense words were 6–14 letters in length, derived from groups of common phonemes38. The word pair task began with an encoding phase composed of 120 word-nonsense word trials. (a) During each encoding trial, a word-nonsense word pair was shown for 5 s. Criterion training occurred immediately after encoding. (b) During each self-paced criterion trial, a previously studied probe word was presented with its original nonsense word associate from encoding (outlined in the grey box) and two new nonsense words not previously shown. Upon responding, the participant was given feedback for 1 s, with incorrect responses resulting in trial repetition at random intervals. (c) During recognition trials, either a previously studied probe word or a new (foil) probe word was shown for 5 s with four response options presented below. When a previously studied probe word was presented, the following response options were presented below: (1) the nonsense word originally paired with that probe word at encoding (‘Hit’), (2) a previously studied nonsense word, but one presented with a different previously studied probe word (‘Lure’), (3) a new nonsense word never seen during encoding, and (4) an option designating the shown probe word as “new”. New nonsense words were only presented once during the entire experiment, while previously studied nonsense words were presented twice during recognition testing, always in the same session, as a lure on one trial and the correct paired associate on another. When a foil probe word was presented, the four responses options consisted of three new nonsense words never presented during learning (which if chosen, would designate a ‘False alarm’), and an option designating this foil probe word as “new” (which if chosen, would designate a ‘Correct rejection’). Forty-five events, consisting of a fixation display (1.5 s – 10 s), were interspersed throughout long delay recognition testing during fMRI acquisition, jittering trial onsets.

Mentions: The word-pairs task had an intentional encoding phase immediately followed by a criterion phase (see Fig. 1 & Supplemental Information), which was then followed by a short delay recognition test (10 min; 30 studied trials and 15 foil trials) and a long delay recognition test (10 hr, occurring 2 hours post-awakening within the MRI scanner; 90 studied trials and 45 foil trials) testing.


Prefrontal atrophy, disrupted NREM slow waves and impaired hippocampal-dependent memory in aging.

Mander BA, Rao V, Lu B, Saletin JM, Lindquist JR, Ancoli-Israel S, Jagust W, Walker MP - Nat. Neurosci. (2013)

The sleep-dependent episodic word-pair task6,9 utilized word-nonsense word pairs to 1) maximize the novel episodic and associated hippocampal-dependent demands of the task38, and 2) minimize the semantic, and thus hippocampal-independent, demands of the task11,12,38. Words were 3–8 letters in length and drawn from a normative set of English words39. Nonsense words were 6–14 letters in length, derived from groups of common phonemes38. The word pair task began with an encoding phase composed of 120 word-nonsense word trials. (a) During each encoding trial, a word-nonsense word pair was shown for 5 s. Criterion training occurred immediately after encoding. (b) During each self-paced criterion trial, a previously studied probe word was presented with its original nonsense word associate from encoding (outlined in the grey box) and two new nonsense words not previously shown. Upon responding, the participant was given feedback for 1 s, with incorrect responses resulting in trial repetition at random intervals. (c) During recognition trials, either a previously studied probe word or a new (foil) probe word was shown for 5 s with four response options presented below. When a previously studied probe word was presented, the following response options were presented below: (1) the nonsense word originally paired with that probe word at encoding (‘Hit’), (2) a previously studied nonsense word, but one presented with a different previously studied probe word (‘Lure’), (3) a new nonsense word never seen during encoding, and (4) an option designating the shown probe word as “new”. New nonsense words were only presented once during the entire experiment, while previously studied nonsense words were presented twice during recognition testing, always in the same session, as a lure on one trial and the correct paired associate on another. When a foil probe word was presented, the four responses options consisted of three new nonsense words never presented during learning (which if chosen, would designate a ‘False alarm’), and an option designating this foil probe word as “new” (which if chosen, would designate a ‘Correct rejection’). Forty-five  events, consisting of a fixation display (1.5 s – 10 s), were interspersed throughout long delay recognition testing during fMRI acquisition, jittering trial onsets.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4286370&req=5

Figure 1: The sleep-dependent episodic word-pair task6,9 utilized word-nonsense word pairs to 1) maximize the novel episodic and associated hippocampal-dependent demands of the task38, and 2) minimize the semantic, and thus hippocampal-independent, demands of the task11,12,38. Words were 3–8 letters in length and drawn from a normative set of English words39. Nonsense words were 6–14 letters in length, derived from groups of common phonemes38. The word pair task began with an encoding phase composed of 120 word-nonsense word trials. (a) During each encoding trial, a word-nonsense word pair was shown for 5 s. Criterion training occurred immediately after encoding. (b) During each self-paced criterion trial, a previously studied probe word was presented with its original nonsense word associate from encoding (outlined in the grey box) and two new nonsense words not previously shown. Upon responding, the participant was given feedback for 1 s, with incorrect responses resulting in trial repetition at random intervals. (c) During recognition trials, either a previously studied probe word or a new (foil) probe word was shown for 5 s with four response options presented below. When a previously studied probe word was presented, the following response options were presented below: (1) the nonsense word originally paired with that probe word at encoding (‘Hit’), (2) a previously studied nonsense word, but one presented with a different previously studied probe word (‘Lure’), (3) a new nonsense word never seen during encoding, and (4) an option designating the shown probe word as “new”. New nonsense words were only presented once during the entire experiment, while previously studied nonsense words were presented twice during recognition testing, always in the same session, as a lure on one trial and the correct paired associate on another. When a foil probe word was presented, the four responses options consisted of three new nonsense words never presented during learning (which if chosen, would designate a ‘False alarm’), and an option designating this foil probe word as “new” (which if chosen, would designate a ‘Correct rejection’). Forty-five events, consisting of a fixation display (1.5 s – 10 s), were interspersed throughout long delay recognition testing during fMRI acquisition, jittering trial onsets.
Mentions: The word-pairs task had an intentional encoding phase immediately followed by a criterion phase (see Fig. 1 & Supplemental Information), which was then followed by a short delay recognition test (10 min; 30 studied trials and 15 foil trials) and a long delay recognition test (10 hr, occurring 2 hours post-awakening within the MRI scanner; 90 studied trials and 45 foil trials) testing.

Bottom Line: Aging has independently been associated with regional brain atrophy, reduced slow wave activity (SWA) during non-rapid eye movement (NREM) sleep and impaired long-term retention of episodic memories.We found that age-related medial prefrontal cortex (mPFC) gray-matter atrophy was associated with reduced NREM SWA in older adults, the extent to which statistically mediated the impairment of overnight sleep-dependent memory retention.Moreover, this memory impairment was further associated with persistent hippocampal activation and reduced task-related hippocampal-prefrontal cortex functional connectivity, potentially representing impoverished hippocampal-neocortical memory transformation.

View Article: PubMed Central - PubMed

Affiliation: Sleep and Neuroimaging Laboratory, University of California, Berkeley, California, USA. bamander@berkeley.edu

ABSTRACT
Aging has independently been associated with regional brain atrophy, reduced slow wave activity (SWA) during non-rapid eye movement (NREM) sleep and impaired long-term retention of episodic memories. However, whether the interaction of these factors represents a neuropatholgical pathway associated with cognitive decline in later life remains unknown. We found that age-related medial prefrontal cortex (mPFC) gray-matter atrophy was associated with reduced NREM SWA in older adults, the extent to which statistically mediated the impairment of overnight sleep-dependent memory retention. Moreover, this memory impairment was further associated with persistent hippocampal activation and reduced task-related hippocampal-prefrontal cortex functional connectivity, potentially representing impoverished hippocampal-neocortical memory transformation. Together, these data support a model in which age-related mPFC atrophy diminishes SWA, the functional consequence of which is impaired long-term memory. Such findings suggest that sleep disruption in the elderly, mediated by structural brain changes, represents a contributing factor to age-related cognitive decline in later life.

Show MeSH
Related in: MedlinePlus