Abstract
The pathomechanism of cluster headache (CH) is not entirely understood, but central and peripheral components were suggested. A recent report showed that transcranial magnetic stimulation measured cortical excitability was increased in the hemisphere ipsilalteral to the pain. In the current study we set out to investigate the amplitude of resting brain fMRI activity to find signatures of the increased excitability. High resolution T1 weighted and resting state functional MRI images were acquired from seventeen patients with CH in pain free period and from twenty-six healthy volunteers. Patients’ data were normalized (e.g. inverted along the midsagittal axis) according to the headache side. Independent component analysis and a modified dual regression approach were used to reveal the differences between the resting state networks. Furthermore, the timecourses were decomposed into five frequency bands by discrete wavelet decomposition and were also re-regressed to the original data to reveal frequency specific resting activity maps. Two of the identified resting state networks showed alterations in CH. When the data were inverted to have patients’ headaches on the left, the ipsilateral attention network showed increased connectivity in 0.08–0.04 Hz frequency band in the in CH group. In the same dataset, cerebellar network showed higher functional connectivity in 0.02–0.01 Hz range in the ipsilateral cerebellum. When the data of patients having headache on the left were inverted to the right, similar increased signal was found in the ipsilateral attention network in 0.08–0.04 Hz band. The cerebellar network showed increased connectivity in the cerebellum in 0.02–0.01 Hz band in patients. The Fourier analysis of these area revealed increased power in CH at all cases. Our results showed alterations of brain functional networks in CH. The alterations of resting state activity were found in the hemisphere ipsilateral to the pain, signifying the altered cortical processing in the pathomechanism of CH.
This is a preview of subscription content, access via your institution.
References
Absinta M, Rocca MA, Colombo B, Falini A, Comi G, Filippi M (2012) Selective decreased grey matter volume of the pain-matrix network in cluster headache. Cephalalgia 32:109–115. doi:10.1177/0333102411431334
Baliki MN, Mansour AR, Baria AT, Apkarian AV (2014) Functional reorganization of the default mode network across chronic pain conditions. PLoS ONE 9:e106133. doi:10.1371/journal.pone.0106133
Beckmann CFFN, Smith SM (2009) Group comparison of resting-state FMRI data using multi-subject ICA and dual regression. Neuroimage 47:S39–S41
Beckmann CF, DeLuca M, Devlin JT, Smith SM (2005a) Investigations into resting-state connectivity using independent component analysis. Philos Trans R Soc Lond B 360:1001–1013. doi:10.1098/rstb.2005.1634
Beckmann CF, DeLuca M, Devlin JT, Smith SM (2005b) Investigations into resting-state connectivity using independent component analysis. Philos Trans R Soc B 360:1001–1013. doi:10.1098/Rstb.2005.1634
Boyacioglu R, Beckmann CF, Barth M (2013) An investigation of RSN frequency spectra using ultra-fast generalized inverse imaging. Front Hum Neurosci 7:156. doi:10.3389/fnhum.2013.00156
Casale MS, Baratto M, Cervera C, Gallamini M, Lynch G, Gjini K, Boutros NN (2008) Auditory evoked potential abnormalities in cluster headache. NeuroReport 19:1633–1636. doi:10.1097/WNR.0b013e328314e0dd
Chadaide Z, Arlt S, Antal A, Nitsche MA, Lang N, Paulus W (2007) Transcranial direct current stimulation reveals inhibitory deficiency in migraine. Cephalalgia 27:833–839. doi:10.1111/j.1468-2982.2007.01337.x
Cosentino G, Brighina F, Brancato S, Valentino F, Indovino S, Fierro B (2015) Transcranial magnetic stimulation reveals cortical hyperexcitability in episodic cluster headache. J Pain 16:53–59. doi:10.1016/j.jpain.2014.10.006
Dietrichs E, Haines DE (2002) Possible pathways for cerebellar modulation of autonomic responses: micturition. Scand J Urol Nephrol Suppl 36:16–20
Filippini N et al (2009) Distinct patterns of brain activity in young carriers of the APOE-epsilon4 allele. Proc Natl Acad Sci USA 106:7209–7214. doi:10.1073/pnas.0811879106
Fox MD, Raichle ME (2007) Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging. Nat Rev Neurosci 8:700–711. doi:10.1038/nrn2201
Gao L et al (2015) Frequency-dependent changes of local resting oscillations in sleep-deprived brain. PLoS ONE 10:e0120323. doi:10.1371/journal.pone.0120323
Greicius MD, Srivastava G, Reiss AL, Menon V (2004) Default-mode network activity distinguishes Alzheimer’s disease from healthy aging: evidence from functional MRI. Proc Natl Acad Sci USA 101:4637–4642. doi:10.1073/pnas.0308627101
Headache Classification Committee of the International Headache S (2013) The international classification of headache disorders, 3rd edn (beta version) Cephalalgia 33:629–808. doi:10.1177/0333102413485658
Jenkinson M, Bannister P, Brady M, Smith S (2002) Improved optimization for the robust and accurate linear registration and motion correction of brain images. Neuroimage 17:825–841
Kim JY et al (2013) Increased power spectral density in resting-state pain-related brain networks in fibromyalgia. Pain 154:1792–1797. doi:10.1016/j.pain.2013.05.040
Kublbock M et al (2014) Stability of low-frequency fluctuation amplitudes in prolonged resting-state fMRI. NeuroImage 103C:249–257. doi:10.1016/j.neuroimage.2014.09.038
Lemaire JJ et al (2011) White matter connectivity of human hypothalamus. Brain Res 1371:43–64. doi:10.1016/j.brainres.2010.11.072
Malinen S et al (2010) Aberrant temporal and spatial brain activity during rest in patients with chronic pain. Proc Natl Acad Sci USA 107:6493–6497. doi:10.1073/pnas.1001504107
Mantini D, Perrucci MG, Del Gratta C, Romani GL, Corbetta M (2007) Electrophysiological signatures of resting state networks in the human brain. Proc Natl Acad Sci USA 104:13170–13175. doi:10.1073/pnas.0700668104
May A, Bahra A, Buchel C, Frackowiak RS, Goadsby PJ (1998) Hypothalamic activation in cluster headache attacks. Lancet 352:275–278. doi:10.1016/S0140-6736(98)02470-2
May A, Bahra A, Buchel C, Frackowiak RS, Goadsby PJ (2000) PET and MRA findings in cluster headache and MRA in experimental pain. Neurology 55:1328–1335
Morelli N, Pesaresi I, Cafforio G, Maluccio MR, Gori S, Di Salle F, Murri L (2009) Functional magnetic resonance imaging in episodic cluster headache. J Headache Pain 10:11–14. doi:10.1007/s10194-008-0085-z
Naegel S, Holle D, Desmarattes N, Theysohn N, Diener HC, Katsarava Z, Obermann M (2014) Cortical plasticity in episodic and chronic cluster headache. NeuroImage 6:415–423. doi:10.1016/j.nicl.2014.10.003
Nichols TE, Holmes AP (2002) Nonparametric permutation tests for functional neuroimaging: a primer with examples. Hum Brain Mapp 15:1–25. doi:10.1002/Hbm.1058
Otti A, Guendel H, Wohlschlager A, Zimmer C, Noll-Hussong M (2013) Frequency shifts in the anterior default mode network and the salience network in chronic pain disorder. BMC Psychiatry 13:84. doi:10.1186/1471-244X-13-84
Owen SL et al (2007) Connectivity of an effective hypothalamic surgical target for cluster headache. J Clin Neurosci 14:955–960. doi:10.1016/j.jocn.2006.07.012
Qiu E et al (2013) Abnormal brain functional connectivity of the hypothalamus in cluster headaches. PLoS ONE 8:e57896. doi:10.1371/journal.pone.0057896
Qiu E, Tian L, Wang Y, Ma L, Yu S (2015) Abnormal coactivation of the hypothalamus and salience network in patients with cluster headache. Neurology. doi:10.1212/WNL.0000000000001442
Risold PY, Thompson RH, Swanson LW (1997) The structural organization of connections between hypothalamus and cerebral cortex brain research. Brain Res Rev 24:197–254
Rocca MA et al (2010) Central nervous system dysregulation extends beyond the pain-matrix network in cluster headache. Cephalalgia 30:1383–1391. doi:10.1177/0333102410365164
Roosendaal SD, Schoonheim MM, Hulst HE, Sanz-Arigita EJ, Smith SM, Geurts JJG, Barkhof F (2010) Resting state networks change in clinically isolated syndrome. Brain 133:1612–1621. doi:10.1093/Brain/Awq058
Salvador R et al (2008) A simple view of the brain through a frequency-specific functional connectivity measure. NeuroImage 39:279–289. doi:10.1016/j.neuroimage.2007.08.018
Smith SM (2002) Fast robust automated brain extraction. Hum Brain Mapp 17:143–155. doi:10.1002/hbm.10062
Smith SM, Nichols TE (2009) Threshold-free cluster enhancement: addressing problems of smoothing, threshold dependence and localisation in cluster inference. NeuroImage 44:83–98. doi:10.1016/j.neuroimage.2008.03.061
Sprenger T, Boecker H, Tolle TR, Bussone G, May A, Leone M (2004) Specific hypothalamic activation during a spontaneous cluster headache attack. Neurology 62:516–517
Sprenger T et al (2007) Altered metabolism in frontal brain circuits in cluster headache. Cephalalgia 27:1033–1042. doi:10.1111/j.1468-2982.2007.01386.x
Szabo N, Kincses ZT, Pardutz A, Toth E, Szok D, Csete G, Vecsei L (2013) White matter disintegration in cluster headache. J Headache Pain 14:64. doi:10.1186/1129-2377-14-64
Tajti J, Szok D, Majláth Z, Tuka B, Csáti A, Vécsei L (2015) Migraine and neuropeptides. Neuropeptides 52:19–30. doi:10.1016/j.npep.2015.03.006
Teepker M et al (2012) Diffusion tensor imaging in episodic cluster headache. Headache 52:274–282. doi:10.1111/j.1526-4610.2011.02000.x
Tian L, Kong Y, Ren J, Varoquaux G, Zang Y, Smith SM (2013) Spatial vs temporal features in ICA of resting-state fMRI—a quantitative and qualitative investigation in the context of response inhibition. PLoS ONE 8:e66572. doi:10.1371/journal.pone.0066572
Tracey I (2008) Imaging pain. Br J Anaesth 101:32–39. doi:10.1093/bja/aen102
Tuka B et al (2013) Alterations in PACAP-38-like immunoreactivity in the plasma during ictal and interictal periods of migraine patients. Cephalalgia 33:1085–1095. doi:10.1177/0333102413483931
van Vliet JA, Vein A, Le Cessie S, Ferrari MD, van Dijk JG, Group DRR (2003) Impairment of trigeminal sensory pathways in cluster headache. Cephalalgia 23:414–419
Xue T et al (2012) Intrinsic brain network abnormalities in migraines without aura revealed in resting-state fMRI. PLoS ONE 7:e52927. doi:10.1371/journal.pone.0052927
Yang FC et al (2013) Altered gray matter volume in the frontal pain modulation network in patients with cluster headache. Pain 154:801–807. doi:10.1016/j.pain.2013.02.005
Yang FC et al (2014) Altered hypothalamic functional connectivity in cluster headache: a longitudinal resting-state functional MRI study. J Neurol Neurosurg Psychiatry 86(4):437–445. doi:10.1136/jnnp-2014-308122
Zou QH et al (2008) An improved approach to detection of amplitude of low-frequency fluctuation (ALFF) for resting-state fMRI: fractional ALFF. J Neurosci Methods 172:137–141. doi:10.1016/j.jneumeth.2008.04.012
Acknowledgements
The study was supported by the “Neuroscience Research Group of the Hungarian Academy of Sciences and University of Szeged”, project FNUSA-ICRC (No. CZ.1.05/1.1.00/02.0123) from the European Regional Development Fund, the National Brain Research Program (Grant No. KTIA_13_NAP-A-II/20.) and an OTKA [PD 104715] Grant. Dr. Szabó and Dr. Kincses were supported by European Regional Development Fund—Project FNUSA-ICRC (No. CZ.1.05/1.1.00/02.0123) and by European Union—Project ICRC-ERA-HumanBridge (No. 316345). Dr. Párdutz was supported by the Bolyai Scholarship Program of the Hungarian Academy of Sciences.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that there are no conflicts of interest.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Faragó, P., Szabó, N., Tóth, E. et al. Ipsilateral Alteration of Resting State Activity Suggests That Cortical Dysfunction Contributes to the Pathogenesis of Cluster Headache. Brain Topogr 30, 281–289 (2017). https://doi.org/10.1007/s10548-016-0535-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10548-016-0535-x
Keywords
- Cluster headache
- MRI
- Resting state networks
- Dual regression
- Frequency analysis