***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Migraine is associated with stimulus hypersensitivity , increased evoked cortical responses , and abnormal 5-HT levels in peripheral blood . We studied cortical auditory evoked potentials ( AEPs ) between attacks in 35 patients suffering from migraine without aura ( MO , n = 25 ) or with aura ( MA , n = 10 ) and in 25 healthy volunteers .  Binaural tones were delivered at 40 , 50 , 60 , and 70 dB sensation level ( SL ) in a pseudor and omized order . The intensity dependence of the auditory Nl-P2 component was significantly greater in MO ( p = 0.003 ) and MA ( p = 0.02 ) patients than in healthy controls , result ing in a much steeper amplitudeistimulus intensity function slope . When three sequential blocks of 40 averaged responses were analyzed at the 40- and 70-dB SL intensities , N1–P2 amplitude decreased in second and third blocks at both intensities in controls , but increased in migraineurs , a difference that was significant in both blocks for the 70-dB SL stimulus . The strong interictal dependence of AEPs on stimulus intensity may thus be due to potentiation ( instead of habituation ) of the response during repetition of the high-intensity stimulation . In concordance with previous studies of visual evoked potentials , these results confirm that migraine is characterized between attacks by an abnormality of cortical information processing , which might be a consequence of low 5-HT transmission and favor cortical energy dem and Purpose The tracer 123I-2-([2-({dimethylamino}methyl)phenyl]thio)-5-iodophenylamine ( [123I]ADAM ) has been developed to image serotonin transporters ( SERTs ) with SPECT . Pre clinical studies have shown that [123I]ADAM binds selectively to SERTs . Moreover , initial human studies have shown that [123I]ADAM binding could be blocked by selective serotonin reuptake inhibitors ( SSRIs ) . However , in humans it has not been proven that [123I]ADAM binds selectively to SERTs . Methods We examined the in vivo availability of SERTs in 12 healthy young volunteers 5 h after bolus injection of [123I]ADAM . To evaluate the selectivity of binding , four participants were pretreated ( double-blinded design ) with placebo  , four with paroxetine ( 20 mg )  and  four with the dopamine/norepinephrine blocker methylpheni date ( 20 mg ) . SPECT studies were performed on a brain-dedicated system ( Neurofocus ) , and the SPECT images were coregistered with individual MR scans of the brain . ADAM binding in SERT-rich brain areas and cerebellar cortex ( representing non-specific binding ) was assessed by drawing regions of interest ( ROIs ) on the individual MR images . Specific to non-specific ratios were used as the outcome measure . Results We found that specific to non-specific ratios were statistically significantly lower in paroxetine-pretreated participants than in placebo- or methylpheni date -pretreated participants . No such difference was found between groups pretreated with placebo or methylpheni date . Conclusion Our preliminary findings suggest that [123I]ADAM binds selectively to SERTs in human brain Identification of a biomarker that can inform on extracellular serotonin ( 5-HT ) levels in the brains of living humans would enable greater underst and ing of the way brain circuits are modulated by serotonergic neurotransmission . Substantial evidence from studies in animals and humans indicates an inverse relationship between central 5-HT tonus and 5-HT type 4 receptor ( 5-HT4R ) density , suggesting that 5-HT4R receptor density may be a biomarker marker for 5-HT tonus . Here , we investigated whether a 3-week administration of a selective serotonin reuptake inhibitor , expected to increase brain 5-HT levels , is associated with a decline in brain 5-HT4R binding . A total of 35 healthy men were studied in a placebo-controlled , r and omized , double-blind study . Participants were assigned to receive 3 weeks of oral dosing with placebo or fluoxetine , 40 mg per day . Brain 5-HT4R binding was quantified at baseline and at follow-up with [11C]SB207145 positron emission tomography ( PET ) .  Three weeks of intervention with fluoxetine was associated with a 5.2 % reduction in brain 5-HT4R binding ( P=0.017 ) , whereas placebo intervention did not change 5-HT4R binding ( P=0.52 ) . Our findings are consistent with a model , wherein the 5-HT4R density adjusts to changes in the extracellular 5-HT tonus . Our data demonstrate for the first time in humans that the imaging of central 5-HT4R binding may be used as an in vivo biomarker of the central 5-HT tonus Objective : The 5-HT1B/D agonists ( triptans ) are specific headache medications that have no effect on pain as such . Although they are routinely used in the treatment of acute migraine attacks , the underlying mechanisms of action are still a matter of debate . Methods : Forty-three healthy participants underwent fMRI while receiving trigemino-nociceptive stimulation and control stimuli in a st and ardized fMRI paradigm . Using a crossover , double-blind , placebo-controlled design , 21 participants ( 10 women , mean age 26.9 , range 20–37 years ) received sumatriptan and 22 participants ( 11 women , mean age 25.5 , range 22–32 years ) received acetylsalicylic acid ( ASA ) . Administration of medication and saline was r and omized between participants of each group result ing in half of the participants receiving saline and the other half receiving the respective medication during the first fMRI data acquisition . Results : While mean pain intensity ratings did not differ significantly between control and medication nor between medications , we found a significant blood oxygen level – dependent signal increase in the trigeminal nuclei and the thalamus after sumatriptan treatment compared with placebo or ASA . In addition , we specifically looked for the pharmacologic modulation of functional coupling between trigeminal nuclei and higher brain areas , i.e. , trigemino-cortical pathways , and found a strong coupling during the saline condition , which was altered by sumatriptan but not after ASA administration . Conclusion : These data suggest that a specific functional inhibition of trigemino-cortical projections is one of the reasons that triptans , unlike pain killers , act highly specifically on headache and migraine but not pain as such Background : Altered serotonin ( 5-HT ) neurotransmission has been implicated in the pathophysiology of migraine headache . Objectives : To test this hypothesis in migraine patients in vivo using PET and α-[11C]methyl-l-tryptophan as a surrogate marker of brain 5-HT synthetic rate during different phases of their migraine attack and after acute antimigraine therapy with sumatriptan , and to compare them with normal controls . Methods : Six patients were scanned 1 ) within 6 hours after the onset of a spontaneous migraine attack , 2 ) 2 hours after subcutaneous sumatriptan  , and 3 ) interictally when migraine free for at least 3 days  . Head pain was rated before each scan , and before and every 15 minutes after sumatriptan . Results : Brain 5-HT synthesis was highest during attacks , lowest after sumatriptan , and intermediate when patients were migraine free . All states were statistically different from the others in virtually all brain regions examined . 5-HT synthetic rates in patients during migraine attacks did not differ from those of age- and sex-matched controls , whereas they were significantly lower after sumatriptan in a majority of regions . Interictally , global brain 5-HT synthetic rate was slightly , albeit not significantly , lower ( −14 % ) in migraine patients than in controls , with specific cortical areas exhibiting proportionally more severe reductions ( −28 % to 31 % ) . Conclusions : These findings point to a low cortical serotonergic tone in migraine patients interictally . Further , they demonstrate widespread increases in brain serotonin ( 5-HT ) synthetic rate in migraine patients during attacks , and that triptans exert a negative feedback regulation of brain 5-HT synthesis concurrently with modulation of pain pathways Objective .—To investigate the effects of fluoxetine in migraine prophylaxis on habituation of visually evoked potentials Abstract Objective : Triptans are highly effective in the treatment of migraine . Both central and peripheral mechanisms of action have been suggested . Until now , firm data about the passage of triptans into the CNS in humans have been lacking . The aim of the current study was to evaluate , using positron emission tomography ( PET ) , the uptake and distribution of zolmitriptan into the CNS after intranasal administration . Subjects and methods : Eight healthy volunteers , five males and three females ( mean ages 23 and 26 years , respectively ) , were included .  Radioactive [carbonyl-11C]zolmitriptan was infused intravenously for 5 minutes on two occasions : once alone , and once 30–40 minutes after intranasal administration of unlabelled zolmitriptan 5 mg . PET was used to measure the concentration of labelled zolmitriptan  in the brain , from the start of the tracer infusion for 90 minutes . Regional cerebral blood volume was determined with [15O]carbon monoxide . In addition , an MRI scan was performed to obtain anatomical information . The PET images were analysed quantitatively for different areas of the brain , generating [11C]zolmitriptan time-activity data corrected for circulating tracer activity . The rate of uptake of intranasal zolmitriptan into the CNS was estimated by kinetic modelling using the PET data . Results : PET data from this study demonstrate a rapid dose-proportional uptake of [11C]zolmitriptan into the brain . Significant concentrations of [11C]zolmitriptan were found in all brain regions studied . Calculated CNS concentrations after intranasal zolmitriptan administration showed a gradual increase , reaching about 2nM ( 0.5 μg/L ) 30 minutes after administration and 3.5nM ( 1.0 μg/L ) , or one-fifth of the plasma concentration , 1 hour after administration . Five minutes after zolmitriptan administration , the mean CNS concentration had already reached 0.5nM , which is higher than in vitro values for initiation of the agonistic action on 5-HT1B/1D receptors . Conclusion : This study demonstrates by direct measurements that zolmitriptan enters the brain parenchyma in humans , achieving an uptake rate and concentration compatible with a central mode of action As shown in animal studies , 5HT1B/1D agonists can inhibit activity in the trigeminal nucleus caudalis , which may be advantageous for their antimigraine effect . To demonstrate a possible central nervous system ( CNS ) action of these compounds in man we studied their effect on the intensity dependence of the cortical auditory evoked potentials ( IDAPs ) , thought to be inversely related to central serotonergic transmission . An amplitude/stimulus intensity function ( ASF ) slope was computed in healthy volunteers and migraine patients between attacks before and 2 h after oral 311C90 ( zolmitriptan “ Zomig ” ) 10 mg ( n=14 ) , 311C90 5 mg ( n=7 ) , sumatriptan 100 mg ( n=14 ) , dexfenfluramine 15 mg ( n=4 ) , lorazepam 1.25 mg ( n=4 ) and placebo ( n=14 ) . 311C90 10 mg and , to a lesser degree , 5 mg significantly increased the mean ASF slope ( p=0.007 and 0.05 vs placebo ) . There was a significant positive correlation between plasma levels of 311C90 and ASF slope changes .  Sumatriptan and lorazepam had little effect , but dexfenfluramine produced a significant ASF slope decrease .  311C90 is able to modify a CNS activity that is modulated by serotonin , i.e. the IDAP . This effect is probably the consequence of its super or lipophilicity compared to sumatriptan and of activation of prejunctional 5HT1B/1D autoreceptors , which lowers central serotonin release and thus the preactivation level of sensory cortices Background : Migraine is frequently associated with nonheadache symptoms before , during , and after the headache . Premonitory symptoms occurring before the attack have not been rigorously studied . Should these symptoms accurately predict headache , there are considerable implication s for the pathophysiology and management of migraine . Methods : Electronic diaries were used in a 3-month multicenter study to record nonheadache symptoms before , during , and after migraine . The authors recruited subjects who reported nonheadache symptoms in at least two of three attacks that they believed predicted headache . Symptoms were entered in the diaries by patient initiation and through prompted entries at r and om times daily . Entries could not be altered retrospectively . Data recorded included nonheadache symptoms occurring during all three phases of the migraine , prediction of the attack from premonitory symptoms , general state of health , and action taken to prevent the headache . Results : One hundred twenty patients were recruited : 97 provided usable data . Patients correctly predicted migraine headaches from 72 % of diary entries with premonitory symptoms . A range of cognitive and physical symptoms was reported at a similar rate through all three phases 
    Output:
    
The review ed papers collectively support the notion that migraine patients have alterations in serotonergic neurotransmission .
Most likely , migraine patients have a low cerebral serotonin level between attacks , which elevates during a migraine attack .