Review Article

The consequences of sleep deprivation on cognitive

performance

Mohammad A. Khan, MD, MRCP, Hamdan Al-Jahdali,MD, MRCP.

ABSTRACT S leep deprivation (SD) can be divided in partial and

total SD. Partial SD refers to a night of reduced or
interrupted sleep, and total SD to no sleep for at least
ً‫ا‬
‫تسلسل حيو ًيا‬ ‫ إال أن النوم يعتبر‬،‫على الرغم من عدم فهمه متا ًما‬ one night during the normal sleep/wake cycle. Total SD
‫منتظما كل ليلة لضمان‬
ً ‫برنامجا دور ًيا‬
ً ‫ومنظما لألحداث التي تتبع‬
ً is frequently studied, which could be due to the easier
‫ أو‬، ‫ قلة النوم‬.‫قدرة جسم اإلنسان على األداء في أفضل حاالته‬ monitoring of brain activity as longer periods of SD
‫ ظاهرة منتشرة ميكن أن حتدث تغييرات سلبية‬، ‫احلرمان من النوم‬ cause increased impaired cognitive functioning. Studies
‫ ركزت هذه املراجعة على التفسير احليوي‬.‫في األداء اإلدراكي‬ show that consistently restricting sleep overtime is more
‫وكذلك في التأثيرات التي ميكن أن يحدثها احلرمان من النوم‬ harmful in comparison to a single night of total SD.1
When sleeping, an individual experiences 3 NREM
‫ يؤدي احلرمان من النوم الى تأثيرات سلبية على‬.‫على اإلدراك‬ (non-rapid eye movement) and one REM (rapid eye
‫الذاكرة واالنتباه واليقظة واحلكم واتخاذ القرار وكذلك القدرات‬ movement) sleep phases. REM SD appears to have a
‫ مما يؤدي إلى انخفاض الوظيفة وضعف‬، ‫املعرفية العامة في الدماغ‬ notable effect on exciting neurons, which is vital for
.‫األداء املعرفي‬ assessing possible danger as well as processing reactions
to stimuli associated with threats. The NREM sleep
Although not fully understood, sleep is accepted as a deprivation reduces the normal release of specific
vital and organized sequence of events that follows a neurotransmitters, which can affect the ability of the
regular cyclic program each night to ensure the human receptors to refresh and restore sensitivity.2 Without
body can perform at its optimum. A lack of sleep, or these stages of sleep, the result is reduced cognition.
sleep deprivation (SD), is a widespread phenomenon
Two processes that affect the amount of sleep
that can induce adverse changes in cognitive
performance. This review focused on the biological
obtained are the circadian and homeostatic processes.
explanation as well as the research investigating the The circadian process theory proposes a regulating
numerous effects that SD can have on cognition. A internal circadian clock, which causes the onset and
reduction in sleep does not occur independently of offset of sleep incidents. This facilitates the control
the effects on memory, attention, alertness, judgment, wake and sleep cycles as well as the secretion of different
decision-making, and overall cognitive abilities in the hormones. The homeostatic process depends on the
brain, resulting in decreased function and impaired wakeful and sleep periods, and the sleep requirements
cognitive performance. increase with inadequate sleeping hours. As SD
increases, the homeostatic functions of the brain become
Neurosciences 2023; Vol. 28 (2): 91-99 increasingly impaired. The brain attempts to counter
doi: 10.17712/nsj.2023.2.20220108
this by secreting hormones in a wave-like manner to
College of Medicine (Khan, Al-Jahdali), King Saud bin Abdulaziz prompt wakefulness or sleep.3 The interaction of the 2
University for Health Sciences, from King Abdullah International processes regulates the sleep/wake cycle.
Medical Research Center (Khan, Al-Jahdali), and from Department of The SD effects on judgement and decision- making.
Medicine, Pulmonary Division, Ministry of National Guard‑Health
Affairs (Khan, Al-Jahdali), Riyadh, Kingdom of Saudi Arabia. Individuals with SD loose the functional connectivity
between the amygdala and the medial prefrontal
Address correspondence and reprint request to: Dr. Hamdan AL-
Jahdali, Department of Medicine, Pulmonary Division, Ministry of
National Guard‑Health Affairs, Riyadh, Kingdom of Saudi Arabia
E-mail: Jahdalih@gmail.com
ORCID ID: https://orcid.org/0000-0001-6950-1290
Disclosure. The authors declare no conflicting interests,
support or funding from any drug company.

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 Sleep deprivation ... Khan & Al-Jahdali

cortex (mPFC), a region known for exhibiting strong during SD. Movement in this area is also significantly
inhibitory projections to the amygdala.4 In addition, a reduced following SD.8 In contrast, a study claimed that
higher connective relationship occurs in the autonomic short-term SD does not selectively affect prefrontal
areas of the locus coeruleus and the amygdala (Figure 1). functioning. However, all the tests carried out in this
With a lack of sleep, an increased amygdala study were derived from a neuropsychological battery
hyperlimbic reaction occurs, resulting in stimuli with test created for clinical purposes, mostly to examine
negative emotional connotations.5 This varying level of brain damage. The tests could have a ceiling effect, not
amygdala activity is linked to a loss of mPFC functional influenced by short-term SD, and the participants were
connectivity when sleep deprived, suggesting a decrease all university students.9
in prefrontal lobe inhibition signals. SD results in Space Shuttle Challenger Accident acknowledged
missing a corrective brain reset reactivity due to the the role of poor judgment and human error related
dysfunctional integrity of the mPFC-amygdala circuit, to early hour shift work and sleep loss, stating that
causing inappropriate behavioral responses, such as the decision to launch should have been based on
making rational decisions and social judgements.6 A engineering judgments (V, Washington, D.C, 1986).
study examining moral judgement in individuals with Despite these comments, consideration should be given
SD reported that SD causes longer response latencies, to other factors which may have influenced proceedings
suggesting a higher level of difficulty to decide a suitable related to successful exchange communication and
course of action, as SD impairs the ability to integrate information.
cognition and emotion to pass moral judgment.7 The SD effects on memory. Sleep deprivation appears
However, the study used a debatable single to disrupt memory consolidation in the hippocampus
assessment procedure of moral judgment, which can through long-term potentiation (LTP). The NMDA
limit the generalizability of the results. receptor is required for the consolidation phase of
The EEG scans propose a noticeable function for the memory, as it allows memory to advance from an
medial prefrontal cortex in the development of ethical unstable to a more permanent form, which is disrupted
judgments and decision-making. Unique and significant in SD.10 Gais et al11 found that the NDMA receptors
changes were found in the mPFC in short- term SD allow the expression of LTP through an increased Ca2+
participants, with a further demonstration of how the influx. SD can impair the full activation of the glutamate
mPFC attempts to compensate for cognitive failing receptor by altering the surface and receptor sub-unit

Figure 1 - Comparison of the connections between the mPFC and amygdala, as well as the amygdala and the locus coeruleus, during normal sleep vs SD.
SD - Sleep deprivation, mPFC - medial prefrontal cortex

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 Sleep deprivation ... Khan & Al-Jahdali

Figure 2 - An overview of signaling pathways in the hippocampus following sleep deprivation. The dashed arrows demonstrate a reduction of a signaling
pathway. (A) Altered glutamatergic signaling. disrupted cAMP signaling. (C) Down regulated mTOR signaling. Figure adapted from Prince
and Abel14

composition expression, with a reduced Ca2+ influx. SD strengthening. Phosphodiesterase 4A (PDE4A) is an

rats showed a reduction in tthe NMDA/AMPA ratio of enzyme responsible for the degradation of cAMP in
the hippocampal cells, following hippocampal synapse the hippocampus, causing a reduction in the protein
stimulation. Although there were no alterations in the kinsase A (PKA) activity. The SD follows with an
glutamate or channel sensitivity, it was observed that enhanced activity of the PDE4 and PDE4A5 protein.
SD changes the NMDAR surface expression after a Blocking the PDE4 signaling results in increased LTP,
crosslinking assay indicated that the NR2A and NR1 and reduces SD deficits in the hippocampus-dependent
components of the NMDA receptors remained in the memory consolidation. This rescue by PDE4 inhibition
cytoplasm after SD.12 indicates that this molecular disruption by SD produces
Figure 2A indicates how sleep deprivation alters the functional deficits in plasticity and behavior.14 A
glutamatergic signaling through modifications in AMPA study investigated whether the SD increased the PDE4
and NDMA receptor structure. This disturbance in the levels in the hippocampus of mice. It was found that
receptor function can reduce the molecular signaling the PDE4-specific cAMP breakdown increased in SD
cascades due to an attenuated calcium influx, resulting mice, however the non-PDE4 levels were unaffected.15
in fewer permanent memories being consolidated in the The increase in the PDE4A by SD disrupts cAMP
brain.13 intracellular signaling (Figure 2B).
The hippocampal activation of the Protein Kinase The SD also down-regulates the mammalian target
activity (PKA) and Cyclic adenosine monophosphate of rapamycin (mTOR) signaling, a translational
(cAMP) signaling plays a vital role in memory regulatory protein required for memory consolidation

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 Sleep deprivation ... Khan & Al-Jahdali

An increase in SD can result in a decrease in

these functions which can negatively affect memory
consolidation.19 In particular, the inhibition of the
RbAp48 protein in young mice caused hippocampus-
dependent memory impairment. FMRI studies showed
dysfunction in the hippocampal formation, with a
selective reduction in histone acetylation, leading to
memory loss.20 Although we can conclude that SD can
cause decreased protein synthesis of certain proteins
such as RbAp48, which can result in reduced memory,
this study did not observe the effects of SD in the mice
to be able to conclude whether sleep is the main cause
of reduced memory.
The temporal lobe serves the purpose of memory
encoding and language processing. A lack of sleep
can result in the incapacity of the brain to process
neural signals at optimal quantities causing incoherent
speech.21 Studies show that SD can disrupt the role
of NREM sleep in downregulating the histamine,
serotonin and norepinephrine neurotransmitters. This
means the receptors lack the capacity to “rest” and
restore sensitivity. In turn, the norepinephrine, serotonin
and histamine cannot function optimally and are not
produced at natural levels, leading to an impairment in
Figure 3 - Areas affected by SD (A) Areas of the brain affected by sleep the storage of memory and day- to-day speech.22 The
deprivation, affecting alertness, memory and attentional
performance. (B) In a SD state, there is unstable inhibition SD also results in a lack of the enzymes that repair brain
concerning task-related DMN and FPN activity, as well as cell damage caused by free radicals, again affecting
inconsistent increasing arousal influencing activity in the memory and speech.23 This can worsen for people with
thalamus. This leads to irregular signals of DMN activity and
reduced FPN activity during tasks. This can lead to weakened long term SD as their neurons start to degenerate due
attentiveness and working-memory functioning, becoming to the relentless brain activity.24 However, Cirelli et
better with greater thalamic activity and poorer with reduced al25 found opposing results with no evidence of brain
thalamic activity. Figure adapted from Krause et al54
cell degeneration after long-term SD in rats, indicating
more research is required the determine the cause of the
(Figure 2C). This implies that protein translation is
neuron degeneration.
The SD effects on attention and alertness. In the
necessary for plasticity and long-standing memory
sleep state, there is an equal inhibitory action of the
development. However, more studies are required to
task-related default mode network (DMN) activity
explore the changes in the gene transcription as well as and the front parietal network (FPN) activity. This is
protein synthesis following SD.16 supported by the increased arousal from the thalamus.
A low level of SD is sufficient to activate the This equal inhibition means there is consistent
unfolded protein response (UPR), which results in a attentional performance in the brain.26 The DMN is
reduction of protein synthesis.17 The initiation of plastic the collection of brain areas that activate and deactivate
modifications during an aroused state can increase the depending on an individual’s external tasks, while the
need for protein synthesis; however, after wake surpasses FPN are the networks and brain regions linked to
its physiological duration in SD, protein synthesis is attention (Figure 3A). In a sleep-deprived state, there
compromised. The decreased energy consumption by is an imbalanced inhibition between the task-related
the synaptic transmission in SD indicates that sleep in DMN and FPM activity, and inconsistent increasing
slow waves may signify an interval for the brain cells arousal activity that influences the thalamic activity.27
to conduct many roles, including membrane recycling, This results in an irregular disturbance of the DMN
restoring glutamate vesicles, protein translation, activity and a reduced FPN activity during external
restoring calcium in the presynaptic stores, and tasks. Suppressing the DMN is vital to allow appropriate
mitochondrial rest.18 brain networks to achieve successful behavior towards

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 Sleep deprivation ... Khan & Al-Jahdali

Figure 4 - The synaptic homeostasis hypothesis. Throughout wakefulness, cortical synapses potentiate relative to activity, giving a net rise in synaptic
power and a reduction is signal/noise ratio. This synaptic potentiation is linked with an escalation in slow-wave activity (SWA) in NREM sleep,
where synaptic renormalization and downscaling occurs, with an increase in signal/noise ratio. This mechanism can permit additional synaptic
plasticity to happen the resulting day alongside avoiding the metabolic downsides linked with excitability and extreme potentiation through
wakefulness. Figure adapted from Rantamäki and Kohtala.37

tasks and goals, and without its suppression, an in the thalamus and the prefrontal cortex, which are
individual is unable to maintain attention to specific both associated with attention and alertness.
tasks. Once FPN activity and DMN action are altered, This could be explained by the significant decrease
attention and concentration tasks will be unpredictable in the relative regional glucose observed predominantly
(Figure 3B). After sleep is obtained, the arousal input in the thalamus and prefrontal and posterior parietal
from the thalamus will stabilize and allow the equal cortices, indicating that alertness and attention is
activity of the DMN and FPN to be re-established.28 indirectly impacted by increased fatigue due to sleep
According to a study conducted on objective loss.31 However, in contrast, Kuhn et al32 found an increase
attention, SD resulted in slower and imprecise picture in the glucose levels in SD individuals, indicating that
sorting in addition to a lower memory detection for further research may be required to confirm the effect
the pictures. Activation in the parahippocampal place of the glucose levels on attention and alertness in SD
area (PPA) and the fronto-parietal cortex in response to individuals. In a SD state, there is unstable inhibition
task-related activity was reduced in SD. This reduction of task-related DMN and FPN activity, as well as an
in effective integration and functional connectivity of inconsistent increasing arousal influencing activity in
the sub parts of a task affects the ability to perform a the thalamus. This causes irregular signals of DMN
task successfully.29 Visual tasks given to participants activity and reduced FPN activity during tasks. This
showed that the difficulty of the tasks was related to can cause a loss of attentiveness and working-memory
parietal cortex activation, and inactivation of the insular functioning, improving with greater thalamic activity
cortices, visual cortices, and the cingulate gyrus. This and less with reduced thalamic activity.
pattern of activation and deactivation was considerably The EEG displays in rats indicate that SD results
lower in the SD participants than the group with in more cortical neurons showing periods of silence,
complete sleep. These combined factors can cause identical to the OFF periods linked with the slow
impairment in the attentional networks essential for oscillations of sleep.33 These OFF periods during wake
accurate attention performance and can lead to higher may result from the heightened neural bistability as a
vulnerability to risks and accidents in routine life.30 The result of the increased inclination to hyperpolarization.
PET scans indicated decreased brain activity primarily This hyperpolarization causes the membrane potential

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 Sleep deprivation ... Khan & Al-Jahdali

Figure 5 - Impaired glymphatic system in the brain after sleep deprivation. Lower AQP4 expression, altered glymphatic clearance, toxic waste buildup, and
higher beta-amyloid levels occur, leading to a dysfunction in cognitive performance.

to become more negative in neurons, and may be an wakefulness, absorbing the surrounding atmosphere
outcome of synaptic surplus due to powerful wake necessitates solidifying networks within the brain.38
plasticity. This can lead to an unevenness of the This requires an increase of the cellular processes for
supply and demand energy, signaled by an increase in energy, learning consolidation, and a reduction of the
extracellular adenosine.34 signal-to-noise ratios.39 Spontaneous activity, which is
It is unclear whether OFF stages are able to undergo any neural activity not driven by a task, can renormalize
a few of the healing roles of sleep, namely synaptic the synaptic strength and restore cellular homeostasis
homeostasis. Nevertheless, the existence of OFF periods during sleep.
during wake periods offer interesting explanations. For The strength reduction of synapses can explain
example, the dissociation between attentiveness and the benefits of sleep on memory acquisition and
specific cognitive functions during SD can be explained consolidation, as energy is saved when counteracting
by the incidence of local sleep in arousal subcortical the network effects of synaptic excitation and increased
promoting systems, and at additional periods in precise neuronal activity following wake periods.40 Differing
cortical regions.35 In addition, if local sleep-in wake results can follow an amplification in the synaptic
occurred in the brainstem and hypothalamic nerve cells strength, comprising faster energy utilization, increased
that apply control in arousal, it could clarify the reasons need for the distribution of cellular components to
for the augmented global impairments and sleepiness in synapses which causes stress to cells, and modifications
attention following SD, especially for less demanding in the glia support cells.41 This increased synaptic power
uninteresting activities. Testing overall performance in can also weaken the selectivity of neuronal reactions
attention and alertness in SD subjects is very unstable, and consolidates the skill to absorb information.
ranging from normal levels to dangerous mistakes.36 Without normalizing the synaptic power, SD will
The synaptic homeostasis hypothesis. Shown in increase the weight of plasticity on the nerve cells and
Figure 4, the synaptic homeostasis hypothesis (SHY) fail to re-establish neuronal selectivity and learning
proposes that during the slow wave stage of NREM abilities, which does not allow enhancing of the signal-
sleep, synapses are decreased throughout the brain to to-noise ratios. As SD continues, the lack of sleep will
counteract the net strengthening of network synapses diminish the brain’s ability to re-establish cellular and
during a waking experience, such as learning.37 During synaptic homeostasis challenged by plastic changes

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which happens during normal wake, resulting in a circulation in the brain, dysregulation of the glucose
consolidation and integration of memories.42,43 metabolism, insulin resistance, resulting in cognitive
Synaptic renormalization displays the many benefits decline. Overtime, these metabolite accumulation and
of sleep, through the desaturation of the synaptic dysregulation can cause severe brain complications.50
networks, the enhancement in energy provision, and PET scans with tracers were used to study the amount
the decrease in cellular pressure causing an improved of amyloid-beta in mice through standard sleep and
learning experience and retention of memories.44 For sleep deprivation. A one-night comparison showed
instance, the coding of new images is compromised that there was a significant increase in the beta-amyloid
after a night of slight SD, which reduces the slow wave levels in the thalamus and the hippocampus of the
activity, exclusive of lessening total SD.45 However, Gais mice, demonstrating in vivo evidence of the effects
et al11 concluded through fMRI studies that declarative of sleep deprivation on recognized neurodegenerative
memory is not affected with long term SD, and processes.51
Voderholzer et al46 that long term SD does not affect Despite these findings, the PET scan technique
long term declarative memory in adolescents. could not distinguish between the soluble and insoluble
Similarly, episodic memory retention can be beta-amyloid, which could affect the findings as soluble,
significantly reduced if a training task is carried out after rather than insoluble amyloid-beta, is more predictive
SD, regardless of no alterations in reaction time during of neurodegenerative disorders such as Alzheimer’s
the training, which suggests a reduction in coding ability disease. Another study with older participants found
because of SD.6 Opposing this, an increased encrypting an inverse relationship between the beta-amyloid and
ability of pictures, word pairs, and lists were observed
performance in several cognitive areas, with an increase
following a short sleep in which slow oscillations were
in the beta-amyloid. This can be indicative of a deficient
boosted by transcranial and sham stimulation. This was
possibly due to the down-scaling of synaptic networks glymphatic system in individuals with SD, which cause
in the hippocampus, that were potentiated towards a lower performance in global cognition, verbal fluency,
saturation during the previous period of wakefulness.47 confrontation naming, and verbal learning.52
The brain’s glymphatic system. The glymphatic system However, SD was not studied in the participants and
consists of a complex of vessels that remove waste from so more research is required to conclude whether the
the central nervous system, typically in the sleep state. increase of beta amyloid is indeed due to an impaired
This happens when the cerebrospinal fluid (CSF) moves glymphatic system, specifically due to sleep loss.
into the para-arterial region, followed by an interstitial Opposing evidence in the Melzer et al study53 fails to
area across the aquaporin 4 (APQ4) water channel find a connection between the beta-amyloid deposition
route. Due to rhythmic pulsations during the stages of and a decline in cognitive performance, suggesting there
sleep, an interchange arises between the interstitial fluid are other factors which could be the primary driver of
(ISF) as well as the CSF. Unused products are relocated the cognitive impairment.
from the arteries to the veins, which travel across to the Conclusion. Sleep is undoubtedly a vital
paravenous region.48 component in a healthy lifestyle. To maintain our
The reduced expression of the water channel bodies in a consistent wake and sleep cycle, the brain
pathway, AQP4 can increase the probability of continually secretes neurological hormones. The
additional secretion of a peptide called beta-amyloid. adverse consequences of SD are evident on overall
The sleep and awake states have different glymphatic behaviour and cognitive performance. Neurological
system roles. During the sleep state, the CSF flows pathways slow down, causing a reduced reaction time
at increased levels, and the interstitial space increases and mental state. Systems in the body enters a state of
by 60%, which can successfully clear toxic cellular life-support as a means of coping until the brain can
molecules. Following a sleep-state, the beta-amyloid be re-stimulated. Fluctuations in the thalamic activity,
levels can be reduced by the CSF. Beta amyloid is a synaptic renormalization, glymphatic system roles,
primary reason for many neurodegenerative diseases DMN activity, amygdala activity and hippocampal
such as Dementia and Alzheimer’s disease. This shows activity can cause unequal stimulation in the brain,
that sleep deprivation can diminish the active process of which results in irregular activities in the brain to
the glymphatic system, leading to toxin build-up which manage SD. As a result, an impairment in attentiveness,
can negatively affect the cognitive performance, motor working memory, consolidation of memories, alertness,
functions and behavioral patterns.49 (Figure 5). judgement, decision-making, and many other
The reduction of the glymphatic activity also diminished cognitive performances will follow. After
results in a dysregulation of the apolipoprotein E having the required quantity of sleep for a specific

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 Sleep deprivation ... Khan & Al-Jahdali

person, the brain will be at an advantage with higher 14. Prince TM, Abel T. The impact of sleep loss on hippocampal
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