Obstructive sleep apnoea syndrome: ‘‘through the looking glass”  of transcranial
Obstructive sleep apnoea syndrome (OSAS) is an insidious and
chronic condition characterized by repetitive upper airway closure
during sleep that includes a constellation of symptoms, commonly
excessive daytime somnolence and cognitive defects . OSAS rep-
resents one of the most important issues of public health because it
affects a large proportion of the population at all ages, with in-
creased morbidity and mortality and high medical and social costs
. The impact of OSAS is potentially profound and wide-ranging
both in physical, emotional, and intellectual capacities , causing
a worsening in quality of life . Cognitive defects represent some
of the most serious symptoms of OSAS, as they include attention
deﬁcits, impaired concentration and memory problems [2,4]. The
pathophysiology of OSAS has not been completely understood.
Transcranial magnetic stimulation (TMS) is a widely used, non-
invasive neurophysiological technique capable of assessing motor
cortex excitability painlessly and safely . For the past 20 years,
many researchers have investigated the responses to electromag-
netic stimulation of the primary motor cortex in a number of dif-
ferent physiological and pathological states . The main body of
data in sleep was gathered to understand its physiology, but re-
lated diseases or syndromes were also studied in detail. Although
the ﬁrst TMS report in OSAS patients showed a widespread defect
in corticomotor system conductivity , subsequent studies dem-
onstrated that the corticospinal tract was unaffected [8,9]. The
main TMS ﬁnding of OSAS patients, at least in the awake state,
was an increase of the cortical silent period duration, while relaxed
motor threshold was not signiﬁcantly affected [8,9]. Cortical silent
period is an inhibitory intracortical phenomena mediated through
a GABA-B inhibitory neuromodulator. In previous reports a reduc-
tion of cortical excitability was related to the metabolic changes
chronically induced by OSAS (e.g., decrease of SaO
 or increase
). In this issue of Sleep Medicine Joo and colleagues 
described the largest group of OSAS patients ever evaluated with
TMS. They conﬁrmed the previous observation of an increase of
CSP duration mediated by GABA-B mechanism. They also com-
pleted the neurophysiological characterization of cortical excitabil-
ity using ‘‘one of the most popular neurophysiological tools,” the
so-called short-latency intracortical inhibition (SICI)  along
with short-latency intracortical facilitation (SICF). In OSAS, SICI
and SICF were not affected, thus intracortical inhibitory and facili-
tatory phenomena—mediated by GABA-A and NMDA, respec-
tively—were not signiﬁcantly involved .
The authors also observed a slight but signiﬁcantly increased re-
laxed motor threshold not previously reported. Joo and colleagues
proposed that in OSAS patients changes in cortical excitability
were related to awake cerebral hypoperfusion (reported by these
authors previously ). Recently, the same group described
reduced brain gray matter concentration in OSAS patients .
These combined changes in brain perfusion and morphology could
lead to cortical hypoexcitability . Moreover, TMS delivered
during apnea caused a dramatic reduction of cortical excitability
(reduction of 90% compared with the awake state) . These re-
peated and chronic changes in cortical excitability could represent
the neurophysiological substrate leading to a modiﬁcation of brain
perfusion and morphology of brain gray matter as previously re-
TMS is a powerful tool able to detect speciﬁc changes in motor
cortex output due to different conditions caused by disease, drugs
or physiological state . Despite all these premises, it is quite dis-
appointing that in OSAS, as well as in all other sleep research stud-
ies, there is lack of correlation between TMS ﬁndings, sleepiness
and cognitive function. Further investigation must be planned to
explore whether cortical changes are indeed related to the chronic
effect of OSAS or if they are primarily related to the pathophysiol-
ogy of the disorder or if they are reversible with treatment. In my
opinion, the work of Joo and colleagues  represents an impor-
tant contribution of TMS application in OSAS using a large sample
and a well-deﬁned cohort of patients and different TMS variables
to test cortical excitability.
In conclusion, transcranial magnetic stimulation is a novel tech-
nique to explore the dynamic changes of cortical excitability in
sleep physiology and its disorders .
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Sleep Medicine 11 (2010) 820–821
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