Mukesh Kumar1, Ritu Tyagi1, Prabhjot Kaur1, Subash Khushu1, Maria M D'souza1, Tarun Sekhri2, Ratnesh Kanwar2, and Poonam Rana1
1NMR Research Center, Institute of Nuclear Medicine and Allied Science, Delhi, India, 2Thyroid research centre, Institute of Nuclear Medicine and Allied Science, Delhi, India
Synopsis
Cognitive
deficit in Subclinical hypothyroidism (SCH) patient is still a topic
to research work upon.
The present study was conducted to examine resting state networks
(RSNs) in SCH using rsfMRI.
SCH
patients showed significantly decreased functional connectivity in
right fronto-parietal network and anterior
default mode network
(DMN) as compared with control subjects. Our finding suggests
cognitive impairment in
resting state networks related to attention and emotional processing
in SCH patientsTarget
audience:
Clinician
and researchers working in the field of thyroid dysfunction.
Purpose
Hypothyroidism
is among the most prevalent endocrine disorder resulting in
cognitive dysfunction,
disturbed attention and depressed moods
1.
However the association between modest thyroid
stimulating hormone (TSH) changes (with normal level of free
tri-iodothyronine (FT3)
and
free thyroxine
(FT4)) i.e. sub
clinical hypothyroidism (SCH) and
altered brain functions is still under debate. Few
neuroimaging studies have reported functional changes in SCH
2,
3 but
the effect on functional connectivity (FC) has not been studied using
resting state functional magnetic resonance imaging (rsfMRI).
Resting-state fMRI (rsfMRI) is technique to investigate the
functional connectivity of the brain which measures coherent
spontaneous low-frequency fluctuations in the blood oxygenation
level-dependent (BOLD) signal during the resting condition. The
primary focus of the present study was to examine whether SCH would
impact alteration in resting state networks (RSNs) using rsfMRI.
Materials
and Methods
In
the present study, 14 healthy controls (mean age ± SD = 34 ± 10.45)
and 14 SCH patients (mean age ± SD= 27.92 ± 5.88) were taken. The
recruited patients were diagnosed with SCH for the first time and had
not been treated earlier.
Informed consent was obtained from all the subjects prior to MRI
study. Thyroid
tests, namely, FT3, FT4 and TSH were carried out in both the groups.
In controls the level of thyroid hormones were (FT3 = 2.8-7.1 pmol/l,
FT4 =12.0-22.0 pmol/l and TSH = 0.27-4.2 μIU/ml). In SCH group,
patients with normal level FT4 and TSH range of 5-10 μIU/ml was
considered. None of the subject had any history of neurological or
psychiatric disorders. The study was approved by the institutional
ethics committee.
The study was carried out using a 3T whole body MR system (Magnetom
Skyra; Siemens, Erfurt, Germany). Functional
brain volumes were acquired using echo-planar T2* -weighted imaging
sequence. Each volume consisted of 30 interleaved 5-mm thick slices
without interslice gap (TE = 30 ms, TR = 2000 ms, FOV = 240 mm, flip
angle = 90°, voxel size = 3.75 X 3.75 X 5 mm3).
For anatomical reference, a T1- weighted 3D gradient echo sequence
(MPRAGE: Magnetization Prepared Rapid Acquisition Gradient Echo, 160
sagittal slices, slice thickness = 1 mm, field of view = 256 mm, TR =
1900 ms, TE = 2.07 ms) image data set was acquired
with total
scanning time of 410 seconds (205 brain volumes), during which the
subjects were asked to keep their eyes closed without thinking of
anything in particular and not falling asleep. Data
analysis was performed using FSL software
(http://fsl.fmrib.ox.ac.in.uk)
and independent component and a dual regression approach was used.
Results
Total
Seven components were identified as RSNs from group MELODIC output
that included right fronto-parietal network, left fronto-parietal
network, default mode network (DMN), medial visual network and motor
network, anterior DMN, auditory network. In our study we have
identified changes in only right fronto-parietal and anterior DMN
RSNs
(Fig. 1A, 1B). SCH patients showed significantly decreased temporal
correlation in the right fronto-parietal network (anterior cingulate
gyrus, paracingulate gyrus) and anterior DMN (juxtapositional lobule
cortex, precentral gyrus, anterior and posterior cingulate gyrus) as
compared with control subject (Fig 2A,2B).
Discussion
To
the best of our knowledge, this is the first study to report
alterations in resting state functional connectivity in subclinical
hypothyroidism. Our findings showed significantly reduced functional
connectivity in right fronto-parietal network and anterior DMN
network in SCH patients. It is reported that the fronto-parietal
networks are implicated in working memory and cognitive attention
processes whereas anterior DMN network is associated with mood and
emotional cognitive function and specific motor function. There are
few functional studies which have shown association of reduced
activations in frontal and parietal areas with cognitive functions in
SCH patients
2,
3.
Therefore, alterations in the resting state connectivity might be
responsible for the cognitive impairments in these patients. These
studies support our finding of reduced resting state functional
connectivity network related to attention and emotional processing.
Conclusion
The
reduced functional connectivity in right fronto-parietal network and
anterior DMN network suggests attention, emotion and motor cognitive
dysfunction in SCH patients. These findings provide an evidence for
further studies on cognitive dysfunctions in SCH.
Acknowledgements
No acknowledgement found.References
1.
S. Singh, M. Kumar, S. Modi et al.
Alterations of Functional Connectivity Among Resting-State Networks
in Hypothyroidism. Journal of Neuroendocrinology, 2015, 0, 1–7
2.
D. Menicucci, L. Sebastiani, A. Comparini et al. Minimal changes
of thyroid axis activity influence brain functions in young females
affected by subclinical hypothyroidism. Archives Italiennes de
Biologie, 151: 1-10, 2013.
3.
De-Fa Zhu, Zhao-Xin Wang, Da-Ren Zhang et al. fMRI revealed
neural substrate for reversible working memory dysfunction in
subclinical hypothyroidism. Brain
(2006) 129, 2923–2930.