Aberrant functional connectivity of resting state networks in subclinical hypothyroidism
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 patients

Target 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 moods1. 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 SCH2, 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.

Figures

Resting-state networks (1A) Right fronto-parietal attention network. (1B)Anterior DMN network

Output of the randomised analysis for the control versus SCH patient group contrast threshold at P < 0.05 . Reduced connectivity was observed in regions of the (2A) right fronto-parietal network, (2B) Anterior DMN. Results are shown on a Montreal Neurological Institute 1mm standard atlas. R, right; L, left.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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