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. 2021 Apr 19;14(4):383. doi: 10.3390/ph14040383

Table 2.

Main features and key findings of studies reporting data on the effect of transcranial current stimulation and auditory stimulation techniques on NREM sleep features and memory in healthy and pathological aging.

Reference Sample Age Stimulation Parameters Key Findings on Sleep Key Findings on Memory
Transcranial current stimulation
Eggert et al., 2013 26 cognitively healthy older adults (10 M)
 Mean: 69.1 y
Range: 60–90 y		 Type: anodal sinusoidally oscillating stimulation
Period: early NREM during night sleep
Duration: 31:20 min (five intervals, each composed of 5:16 min of stimulation and 1 min free of stimulation)
Frequency: 0.75 Hz
Site: bilateral frontal (F3-F4) locations, referenced to the mastoids
  • -

    Increased time awake and reduced NREM stage 3 in the five 1-min stimulation free intervals
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    Absence of effects on memory
Westerberg et al., 2015 19 cognitively healthy older adults (3 M)
 Mean: 73.4 y
Range: 65–85 y		 Type: anodal sinusoidally oscillating stimulation
Period: afternoon nap, starting 4 min after the onset of stage 2
Duration: 30 min (five alternating 5-min “on” and 1-min “off periods)
Frequency: 0.75 Hz
Site: bilateral frontal (F7-F8) locations, referenced to the mastoids
  • -

    Increased frontal SO activity

  • -

    Reduced central fast spindle density
  • -

    Improvement of verbal recall
Landebauer et al., 2016 18 healthy older subjects (8 M) Mean: 65
Range: 57–77 y		 Type: anodal sinusoidally oscillating stimulation
Period: afternoon nap, starting 4 min after the onset of stable stage 2
Duration: five 5-min blocks of stimulation separated by 1:40 min of stimulation-free inter-block intervals
Frequency: 0.75 Hz
Site: bilateral frontal (F3-F4) locations, referenced to the mastoids
  • -

    Increased frontal SO activity

  • -

    Increased frontal and parietal fast spindle activity
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    Improvement of picture memory retention
Paßmann et al., 2016 21 healthy older adults (11 M)
 Mean: 65 y Type: anodal sinusoidally oscillating stimulation
Period: early NREM during night sleep
Duration: five 5-min blocks of stimulation separated by 1 min of stimulation-free inter-block intervals
Frequency: 0.75 Hz
Site: bilateral frontal (F3-F4) locations, referenced to the mastoids
  • -

    Increased power in SO activity and spindle frequency bands

  • -

    Reduced NREM Stage 4 sleep for the entire night and (non-significant) increase of time awake after sleep onset
  • -

    Decreased visuo-spatial performance
Landebauer et al., 2017 16 aMCI patients (9 M) Mean: 71 y
Range: 53–81 y
 Type: anodal sinusoidally oscillating stimulation
Period: afternoon nap, starting 4 min after the onset of stable stage 2
Duration: five 5-min blocks of stimulation separated by 1:40 min of stimulation-free inter-block intervals
Frequency: 0.75 Hz
Site: bilateral frontal (F3-F4) locations, referenced to the mastoids
  • -

    Increased SO and sleep spindle power

  • -

    Enhanced SO-fast spindle coupling

  • -

    Increased NREM Stage 2 sleep
  • -

    Improved visual memory performance

  • -

    Association between visual memory performance and greater SO-fast spindle coupling
Auditory stimulation
Papalambros et al., 2017 13 cognitively healthy older adults (3 M) Mean: 75.2 y
Range: 60–84 y		 Type: phase-locked acoustic stimulation; slow wave detection
Period: NREM of entire night sleep
Stimulus: Pink noise (30–50 db)
Protocol: 50 ms pulses at ~0.85 Hz (adaptive) in blocks of 5, separated by ~1.2 s, followed by ~6 s off period.Target phase:20 degree to slow-wave peak
  • -

    Increased SWA and spindle density and amplitude during the stimulation blocks
  • -

    Improvement of overnight declarative memory performance

  • -

    Overnight memory improvement associated with the enhancement of SWA
Schneider et al., 2020 17 healthy middle-aged adults (8 M)
 Mean: 55.7 y
Range: 49–63 y		 Type: auditory closed loop stimulation; slow wave detection
Period: 3.5 h from the first stable NREM sleep
Stimulus: Pink noise (mean: 54.5 dB)
Protocol: two pulses separated by and individual delay (mean 1091.47 ms), followed by a detection pause of 2.5 s
  • -

    Prolonged endogenous train od SOs

  • -

    Increased fast sleep spindles activity phase-locked to the induced SO up-states

  • -

    Compared to a group of younger cohort, the older adults showed (a) reduction of the brain responses, and (b) different temporal dynamics of the stimulation effect on SO and sleep spindles
  • -

    Impaired declarative memory retention
Papalambros et al., 2019 9 aMCI patients (4 M) Mean: 72 y
Range: 62-86 y		 Type: phase-locked acoustic stimulation; slow wave detection
Period: NREM of entire night sleep
Stimulus: Pink noise (30–50 db)
Protocol: 50 ms pulses at ~0.85 Hz (adaptive) in blocks of 5, separated by ~1.2 s, followed by ~6 s off period.Target phase: 20 degree to slow-wave peak
  • -

    Increase in SO activity and SWA during the stimulation intervals

  • -

    Increased word-pair recall in only five out of nine patients.

  • -

    Enhanced word-pair recall associated with increased SWA

Abbreviations: M, males; NREM, non-rapid eye movement; SO, slow oscillation; SWA, slow wave activity; y, years.