You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
until recently , primary headaches such as migraine and cluster headache ( ch ) were described as vasomotor headaches .
initial positron emission tomography ( pet ) images shed light on the origins of these syndromes , documenting activation in the mesencephalic and pons regions for migraine , and in the grey hypothalamus for ch and others of trigeminal autonomic cephalalgias ( tacs ) [ 24 ] .
tacs include ch , paroxysmal headache and short - lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing ( sunct syndrome ) .
it is interesting to note that the common clinical aspects of this primary headaches , where posterior hypothalamic activation has been reported , concern the important cranial autonomic symptoms .
the concept of tacs indicates a possible common physiopathological base for these syndromes , not shared with other primary headaches , such as migraine or tension - type headache .
pet and functional magnetic resonance imaging ( f - mri ) may be regarded as of little or no importance within a clinical context , but they offer great potential for the exploration of headache physiopathology and the effects of pharmacological treatment . in recent years , f - mri studies have been conducted in tacs , but to date , no studies dealing with ch are available . in the present study
we have investigated the cerebral activation centre during a ch attack in four patients with episodic ch , using f - mri .
we enroled four patients ( 45    4  years ) diagnosed with episodic ch in accordance with the international headache society ( ihs ) classification ( code 3.1.1 ) .
all patients were in the active phase of the illness , and had an average frequency of two episodes a day . in three patients , one of the two attacks had a very regular recurrence ( 2 p.m. ) , while in the other patient it happened at night ( 11  p.m. ) .
the average headache duration , without recourse to treatment , was 110    12  min .
the patients reported no cardiovascular ( hypertension and/or ischaemic cardiopathy ) , cerebrovascular risk factors , or internal pathological symptoms .
a prerequisite for patient enrolment , established on the basis of medical history , was a dramatic response to subcutaneous sumatriptan administration ( 6  mg ) .
the functional study of each individual patient took place in a single continuative session , without interruptions . a priori ,
the duration of the functional examination was established ( the same amount of time for each patient ) to be long enough to allow registration of the asymptomatic state , the onset of pain and the pain relief - state ( provided by administration of drugs ) .
the patients in the study presented attacks at around the same time each day , and this allowed us to place them in the scanner , 15  min before the onset .
when pain occurred they should communicate the onset by pressing buttons on a nonmagnetic button - box .
after 5  min , in order to avoid movements of the patients due to the pain and to induce the state of pain - relief , sumatriptan was subcutaneously injected .
functional datasets were obtained by means of a t2 * weighted gradient echo - epi pulse sequence ( tr / te / fa 3,000  ms/60  ms/30 , tr delay 20  ms , fov 20  cm , matrix 64    64 , voxel 3.125    3.125    5  mm , gap 1.25  mm ) .
we acquired 20 oblique axial slices , parallel to the anterior - posterior commissure plane , extending from the foramen magnum to the vertex .
anatomical datasets were obtained using a t1 mp - rage 3d pulse sequence ( tr / ti / te / fa 2,160  ms/1,100  ms/3.93  ms/10 , voxel 1    1    1.4  mm , gap 0.7  mm ) .
first , functional data was processed in order to increase the snr ratio and reduce artefacts .
we performed slice scan time correction and 3d motion correction by means of rigid body transformations ( the estimated displacement in each direction was less than 3 voxels in each subject ) and spatial smoothing with a gaussian kernel of 4  mm fwhm ( full - width - half - maximum ) .
anatomical data was re - sampled to obtain isometric voxels of 1    1    1  mm then normalised to the talairach and tournaux standard space   to allow intersession statistical analysis .
functional and anatomical datasets were co - registered by translation , rotation and zoom operations on the x , y and z axis .
condition specific effects ( pain vs. no pain ) were estimated using a boxcar approach connected with the hemodynamic response function .
processed functional data obtained from the patients underwent single - subject and multi - subject general linear model ( gml ) analysis .
a statistical map was generated as t - contrast with a threshold value of p  <  0.001 .
the functional study of each individual patient took place in a single continuative session , without interruptions . a priori ,
the duration of the functional examination was established ( the same amount of time for each patient ) to be long enough to allow registration of the asymptomatic state , the onset of pain and the pain relief - state ( provided by administration of drugs ) .
the patients in the study presented attacks at around the same time each day , and this allowed us to place them in the scanner , 15  min before the onset .
when pain occurred they should communicate the onset by pressing buttons on a nonmagnetic button - box .
after 5  min , in order to avoid movements of the patients due to the pain and to induce the state of pain - relief , sumatriptan was subcutaneously injected .
functional datasets were obtained by means of a t2 * weighted gradient echo - epi pulse sequence ( tr / te / fa 3,000  ms/60  ms/30 , tr delay 20  ms , fov 20  cm , matrix 64    64 , voxel 3.125    3.125    5  mm , gap 1.25  mm ) .
we acquired 20 oblique axial slices , parallel to the anterior - posterior commissure plane , extending from the foramen magnum to the vertex .
anatomical datasets were obtained using a t1 mp - rage 3d pulse sequence ( tr / ti / te / fa 2,160  ms/1,100  ms/3.93  ms/10 , voxel 1    1    1.4  mm , gap 0.7  mm ) .
first , functional data was processed in order to increase the snr ratio and reduce artefacts .
we performed slice scan time correction and 3d motion correction by means of rigid body transformations ( the estimated displacement in each direction was less than 3 voxels in each subject ) and spatial smoothing with a gaussian kernel of 4  mm fwhm ( full - width - half - maximum ) .
anatomical data was re - sampled to obtain isometric voxels of 1    1    1  mm then normalised to the talairach and tournaux standard space   to allow intersession statistical analysis .
functional and anatomical datasets were co - registered by translation , rotation and zoom operations on the x , y and z axis .
condition specific effects ( pain vs. no pain ) were estimated using a boxcar approach connected with the hemodynamic response function .
processed functional data obtained from the patients underwent single - subject and multi - subject general linear model ( gml ) analysis .
a statistical map was generated as t - contrast with a threshold value of p  <  0.001 .
during execution of functional mri ( three afternoon sessions and one night session ) all the patients suffered from ch attacks , and the administration of sumatriptan brought pain relief after 4    1  min ( average values and standard deviation ) . in all attacks
( single - subject gml study ) , comparing the pain state with the pain - free state , we detected significant cerebral activation ( p  <  0.05 , corrected for multiple comparisons ) in the ipsilateral hypothalamic grey matter ( fig .  1 ) . the coordinates and the z - score of the activation zones
figure 2 shows the temporal course of the bold signals in the hypothalamus ipsilaterally to the pain - side in patient 2 .
additionally , with a less conservative threshold of p  <  0.001 uncorrected , trends of activation were observed in the pre - frontal cortex , anterior cingulate cortex , contralateral thalamus , ipsilateral basal ganglia and bilaterally in the insula and the cerebellar hemispheres .
however , these areas were not subject to more detailed analysis because the study was not designed to investigate the activation of the pain matrix ( stereotactic co - ordinates were not shown).fig . 
1multi - subject gml analysis shows cerebral activation area in the posterior grey hypothalamus , ipsilateral to the pain side ( p  <  0.001 uncorrected for descriptive purposes ) , superimposed on a t1-weighted anatomical reference mr image in axial ( a ) and coronal ( b ) planestable  1bold - signal increases during spontaneous ch attack compared with the pain - free state ( p  <  0.05 , corrected for multiple comparisons)talairach coordinatesz - score p  <  0.05 ( corrected)xyzpatient 161014.89patient 23814.83patient 35644.91patient 44724.32multi - subject study5816.93fig . 
2temporal course of the bold signals in the hypothalamus ipsilaterally to the pain - side in patient 2 .
the number of the 400 ge - epi acquisitions , is indicated multi - subject gml analysis shows cerebral activation area in the posterior grey hypothalamus , ipsilateral to the pain side ( p  <  0.001 uncorrected for descriptive purposes ) , superimposed on a t1-weighted anatomical reference mr image in axial ( a ) and coronal ( b ) planes bold - signal increases during spontaneous ch attack compared with the pain - free state ( p  <  0.05 , corrected for multiple comparisons ) temporal course of the bold signals in the hypothalamus ipsilaterally to the pain - side in patient 2 .
this study documents the activation of cerebral areas normally attributed to the analysis of painful stimuli ( pre - frontal cortex , basal ganglia , thalamus , cingulate cortex , insula and cerebellum ) as reported in a comprehensive review   and of the hypothalamic region ipsilaterally to the pain - side as documented in previous functional studies carried out using pet methods   in ch . to date , f - mri has only been used in the study of patients affected by other tacs .  
previously , in short - lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing , f - mri studies have shown both hypothalamic activation ipsilateral to the pain side   and bilateral activation of the hypothalamus . in one case of atypical
tac , activation of the hypothalamus , ipsilateral to the pain side , has been reported using f - mri .
overall , we have demonstrated the anatomical location of central nervous system activation with the first f - mri study during a ch attack .
the diencephalon - hypothalamic region seems to be an activation area specific to ch , and for this reason , the possible role of attack generator centres has been suggested . as suggested by clinical , biohumoral and electrophysiological data ,
there is great need to investigate ch and other related idiopathic headache syndromes using f - mri which offers a good balance of spatial and temporal resolution .
the f - mri presents major advantages in comparison with the pet : it does not use radioisotope administrative tracers ( intravenously ) , but endogenous tracers ( deoxy - haemoglobin ) .
furthermore f - mri allows to effect anatomical and functional acquisitions in the same recording session .
this study method seems appropriate for investigation of pathogenetic aspects in the primary headaches , particularly for analysis of functional data immediately prior to attack onset .
we have investigated the cerebral activation centre in four patients with episodic cluster headache ( ch ) with functional magnetic resonance imaging ( f - mri ) . 
 the patients underwent mri scans for anatomical and functional data acquisition in the asymptomatic state , during a headache attack and after subcutaneous administration of sumatriptan . 
 anatomical images were acquired by means of 3d - mprage sequences and f - mri images were obtained by means of echo - planar imaging . 
 data was analysed using the brainvoyager qx version 1.7.81 software package . in all patients , 
 the data showed significant hypothalamic activation of the hypothalamus ipsilateral to the pain side , attributable to a headache attack . 
 overall , we have demonstrated the anatomical location of central nervous system activation by means the first f - mri study in ch patients . 
 f - mri offers a good balance of spatial and temporal resolution , and this method of study appears appropriate for investigating the pathogenetic aspects of primary headaches . 
 positron emission tomography and f - mri may be regarded as little or no importance in a clinical context , they do , however , offer great potential for the exploration of headache physiopathology and the effects of pharmacological treatment .