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Abnormalities in Ipsilateral Silent Period in the High-Risk for Alcohol
Dependence: A TMS Study
Kesavan Muralidharan*, Ganesan Venkatasubramanian, Pramod K Pal and Vivek Benegal
Department of Psychiatry, National Institute of Mental Health and Neuro Sciences [NIMHANS], Bangalore, India
Dr. Kesavan Muralidharan
Department of Psychiatry
National Institute of Mental Health and Neuro Sciences
[NIMHANS] Bangalore-560029, India Tel: 00 91 80 26995252 Fax: 00 91 80
26564830/26562121 E-mail: email@example.com
Received July 16, 2012; Accepted July 27, 2012; Published August 02, 2012
Citation: Muralidharan K, Venkatasubramanian G, Pal PK, Benegal V (2012)
Abnormalities in Ipsilateral Silent Period in the High-Risk for Alcohol Dependence:
A TMS Study. J Addict Res Ther 3:129.
Central Nervous System (CNS) disinhibition has been reported to
underlie the vulnerability to alcohol dependence (AD) in individuals
with a high-family loading of AD . Maturational lag and defective
myelination of particular brain regions, including the corpus callosum
(CC), have been reported in these individuals . Morphometric
studies reported significantly smaller total CC, genu and isthmus areas
in these individuals after controlling for age and intracranial area .
Conduction across the CC can be investigated using a Transcranial
Magnetic Stimulation (TMS) parameter called Ipsilateral Silent
Period (iSP). iSP is recorded by applying a suprathreshold cortical
motor stimulus ipsilateral to a partially activated target muscle
. In patients with lesions of the posterior half of the trunk of CC
or agenesis of the CC, the iSP is reduced or absent. iSP, therefore,
represents the functional integrity of the transcallosal inhibitory/
conduction mechanisms . Abnormal transcallosal inhibition 
and interhemispheric interactions have been reported in children with
ADHD  using TMS.
We attempted to investigate transcallosal conduction in individuals
at high-risk for alcohol dependence using single-pulse TMS.
‘High risk’ (HR) denoted alcohol-naïve offspring of early-onset alcoholdependent
fathers with two or more alcohol-dependent first-degree relatives
and ‘Low Risk’ (LR) was defined as alcohol-naïve individuals without
family history of AD or psychiatric disorders . Right-handed, HR
(n=31) and LR (n=27) subjects, aged 13 – 25 years, matched for age and
gender, were assessed for psychopathology and family-history of AD,
using the Semi-Structured Assessment for the Genetics of Alcoholism
II (SSAGA II)  and the Family Interview for Genetic Studies .
Contraindications to TMS were ruled out . Following single pulse
stimulation at 100% stimulator output, iSP was recorded from the right
First Dorsal Interosseus muscle, at maximal voluntary contraction
 using auditory feedback . 10–12 recordings were obtained with
a 6 second interstimulus interval. iSP was considered to be present
if there was at least a 70% reduction in background EMG activity
following cortical stimulation and resumption of prestimulation EMG
activity subsequently . For each trial, the onset and offset of a silent
period were manually defined, and the duration of a silent period was
calculated as the difference in milliseconds of the onset of EMG silence
and the return of EMG activity [6,8].
The Institute Ethics Committee approved the study. Written
informed consent was obtained from all subjects and parents of
subjects under 18 years of age.
Statistical Package for Social Sciences (SPSS, version 13.0) was used
for analysis. iSP duration was reduced in HR subjects [mean ± SD=13.
18 ± 10. 72 milliseconds] as compared to LR subjects [mean ± SD =15.
11 ± 10. 50 milliseconds], though not statistically significant (t =0.47; P
=0.649). In the summation of all iSP trials in HR and LR subjects, iSP
was absent more often in the HR subjects (124 times out of 340 trials;
36.47%) as compared to the LR subjects (63 times out of 300 trials;
21%) and this was statistically significant (χ2=18.4; p< 0.0001). Of the two output pathways from the primary motor cortex (M1) –
corticospinal output and transcallosal output, the transcallosal output
gives rise to inhibition of the contralateral M1 [4,5,12-14]. Transcallosal
conduction can be measured either as iSP or as interhemispheric
inhibition. Both have been shown to be absent in some patients with
callosal lesions or agenesis of the CC, and are reported to involve
transcallosal pathways [5,14,15]. Patients with agenesis or surgical
lesions of the CC had delayed or absence of iSP [5,14,16]. iSP is
reportedly preserved in patients with subcortical cerebrovascular
lesions that interrupted the corticospinal tract but not CC . In
preschool children, who have yet to develop a functionally competent
CC, iSP was absent . In short, absence of iSP could indicate a
defective conduction across or developmental delay or structural
damage to CC. The greater absence of iSP in our alcohol-naïve HR
group probably indicates defective conduction across CC, which could
reflect a delay in development/maturation of the CC as compared to
the age-matched LR group, and may underlie the vulnerability to AD.
This study was funded by a research grant [NIMH/TMS/KM/040] from the
Centre for Addiction Medicine, NIMHANS, Bangalore- 560029, India.
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