Real-world evidence data on the monoclonal antibody erenumab in migraine prevention: perspectives of treating physicians in Germany.

BACKGROUND: Erenumab, the first-in-class fully human monoclonal antibody targeting the calcitonin gene-related peptide receptor, was shown to be efficacious and safe for the prophylactic treatment of migraine in adults in randomized clinical trials. Large-scale, real-world evidence in multi-centre settings is still needed to confirm these results. Erenumab patient profiles outside clinical trials and physicians' treatment patterns, as well as data from patients treated in Germany, a severely impacted population, are not published yet. METHODS: TELESCOPE was a multi-centre survey gathering real-world data from 45 German headache centres between July 2019 and December 2019. The project consisted of two parts. In the first part, treating physicians shared their experiences on current erenumab treatment with regard to patient profiles, treatment patterns and treatment responses. In the second part, a retrospective chart review was conducted of 542 migraine patients treated with erenumab for at least three months. Treatment responses focused on various aspects of patients' quality of life. RESULTS: The analysis of 542 patients' charts revealed that three-month treatment with erenumab significantly reduced monthly headaches, migraine and acute medication days. Furthermore, headache intensity and frequency were reduced in over 75 % and accompanying aura in 35 % of patients. The clinical global impression scale revealed a general improvement in 91 % of patients. According to the treating physicians' professional judgement, 83 % of patients responded to erenumab and 80 % were satisfied with the treatment. Physicians evaluated restricted quality of life, the number of monthly migraine days and previous, prophylactic treatments as the main components of the current patient profile for monoclonal antibody recipients. Based on the assessment of physicians, erenumab reduced migraine symptoms in 65 % and increased quality of life in more than 75 % of their patients. CONCLUSIONS: TELESCOPE confirms positive treatment responses with erenumab shown in clinical trials in a real-world multi-centre setting. The results show consistently positive experiences of physicians utilizing erenumab in clinical practice and underline that therapy with this monoclonal antibody is effective in migraine patients, particular in those, who have failed several prophylactic therapies.

[Joint position error in patients with headache : Systematic review of the literature and experimental data for patients with chronic migraine]. / Zervikaler "joint position error" bei Kopfschmerzen : Systematische Literaturübersicht und empirische Daten bei chronischer Migräne.

BACKGROUND: Chronic migraine (CM) is a primary headache type associated with a severe reduction in the quality of life. The association of sensorimotor dysfunction in the neck, measured with the joint position error test (JPE), and CM is largely unknown, even though up to 60% of migraine patients report neck pain accompanying the migraine. METHODS: This manuscript reports a systematic review of the literature on JPE in patients with headache as well as data on an observational study. To determine the JPE of migraine patients, 37 subjects with CM were tested and compared with a control group (CG; n = 22). In an additional analysis, CM patients were divided into two subgroups based on the medical treatment approach. The measurements were taken in the three movement dimensions with five repetitions in each direction using a laser pointer fixed to the head. RESULTS: The mean JPE in the sagittal plane was 3.7° (SD ± 1.4°) and 3.1° (SD ± 1.1°) for CM (n = 37) and CG, respectively. In the transverse plane it was measured as 3.7° (SD ± 1.5°) for CM and 3.2° (SD ± 1°) for the CG, while it was 3.6° (SD ± 1.2°; CM) and 3.3° (SD ± 1.1°; CG) in the frontal plane. The between group difference was not significant for all movement planes. When groups according to the treatment regimen, both groups showed similar migraine and neck pain features but the JPE was significantly larger in the CM + BTh group compared to the CM without BTh group and the CG. In the sagittal plane, the JPE was 4.21° (SD ± 1.8°) for the CM + BTh compared to 2.99° (SD ± 1.2°) in CM without BTh and 3.21° (SD ± 1.2°) in the CG (p = 0.0053). The difference between CM + BTh and CM without BTh was 1.52° (p = 0.016) after propensity score matching in the sagittal plane. CONCLUSIONS: Only patients in the CM + BTh group showed a statistically increased JPE. The influence of neck pain does not explain the between group difference. A possible factor is the degree of chronification. This study indicates that the JPE might discriminate a subgroup of migraine patients.

Sphenopalatine ganglion stimulation for cluster headache, results from a large, open-label European registry.

BACKGROUND: Cluster headache (CH) is a disabling primary headache disorder characterized by severe periorbital pain. A subset of patients does not respond to established pharmacological therapy. This study examines outcomes of a cohort of mainly chronic CH patients treated with sphenopalatine ganglion (SPG) stimulation. METHODS: Patients were followed in an open-label prospective study for 12 months. Ninety-seven CH patients (88 chronic, 9 episodic) underwent trans-oral insertion of a microstimulator targeting the SPG. Patients recorded stimulation effect prospectively for individual attacks. Frequency, use of preventive and acute medications, headache impact (HIT-6) and quality of life measures (SF-36v2) were monitored at clinic visits. Per protocol, frequency responders experienced ≥ 50% reduction in attack frequency and acute responders treated ≥ 50% of attacks. HIT-6 responders experienced an improvement ≥ 2.3 units and SF-36 responders ≥ 4 units vs. baseline. RESULTS: Eighty-five patients (78 chronic, 7 episodic) remained implanted and were evaluated for effectiveness at 12 months. In total, 68% of all patients were responders, 55% of chronic patients were frequency responders and 32% of all patients were acute responders. 67% of patients using acute treatments were able to reduce the use of these by 52% and 74% of chronic patients were able to stop, reduce or remain off all preventive medications. 59% of all patients were HIT-6 responders, 67% were SF-36 responders. CONCLUSIONS: This open-label registry corroborates that SPG stimulation is an effective therapy for CH patients providing therapeutic benefits and improvements in use of medication as well as headache impact and quality of life.

Increased thalamic glutamate/glutamine levels in migraineurs.

BACKGROUND: Increased cortical excitability has been hypothesized to play a critical role in various neurological disorders, such as restless legs syndrome, epilepsy and migraine. Particularly for migraine, local hyperexcitability has been reported. Levels of regional excitatory and inhibitory neurotransmitters are related to cortical excitability and hence may play a role in the origin of the disease. Consequently, a mismatch of the excitatory-inhibitory neurotransmitter network might contribute to local hyperexcitability and the onset of migraine attacks. In this study we sought to assess local levels of glutamate / glutamine (GLX) and gamma-aminobutyric acid (GABA) in the occipital cortex and right thalamus of migraineurs and healthy subjects. METHODS: We measured interictally local biochemical concentrations in the occipital lobe and the right thalamus in patients with migraine (without aura) and healthy controls (HCs) using proton magnetic resonance spectroscopy at 3 T. GLX levels were acquired using PRESS and GABA levels using the GABA-sensitive editing sequence MEGA-PRESS. Regional GLX and GABA levels were compared between groups. RESULTS: Statistical analyses revealed significantly increased GLX levels in both the primary occipital cortex and thalamus. However, we found no group differences in GABA levels for these two regions. Correlation analyses within the migraine group revealed no significant correlations between pain intensity and levels of GLX or GABA in either of the two brain regions. CONCLUSIONS: Further research is needed to investigate the role of GABA/GLX ratios in greater depth and to measure changes in neurotransmitter levels over time, i.e. during migraine attacks and interictally.

Case report of an alleviation of pain symptoms in hypnic headache via greater occipital nerve block.

Background Hypnic headache is a rare primary headache disorder with a few hundred described cases so far. Due to the fact that this headache disease is rare, there are no placebo-controlled oral medication studies. After all reported oral medication failed to control pain symptoms of a hypnic headache disease, we were able to reduce pain intensity and frequency via two greater occipital nerve (GON) blocks. Case We report on a 74-year-old patient diagnosed with hypnic headache in our headache outpatient department two years ago. Over a course of nine months none of the recommended oral drugs had an effect in pain alleviation and we decided to try an occipital nerve injection therapy. Two GON-blocks then led to a stable and significant pain reduction over the course of six months during monthly follow-ups. Conclusion GON block can be a successful therapeutic approach for the treatment of hypnic headache when oral medication fails.

A single dose of lorazepam reduces paired-pulse suppression of median nerve evoked somatosensory evoked potentials.

Paired-pulse behaviour in the somatosensory cortex is an approach to obtain insights into cortical processing modes and to obtain markers of changes of cortical excitability attributable to learning or pathological states. Numerous studies have demonstrated suppression of the response to the stimulus that follows a first one after a short interval, but the underlying mechanisms remain elusive, although there is agreement that GABAergic mechanisms seem to play a crucial role. We therefore aimed to explore the influence of the GABAA agonist lorazepam on paired-pulse somatosensory evoked potentials (SEPs). We recorded and analysed SEPs after paired median nerve stimulation in healthy individuals before and after they had received a single dose of 2.5 mg of lorazepam as compared with a control group receiving placebo. Paired-pulse suppression was expressed as a ratio of the amplitudes of the second and the first peaks. We found that, after lorazepam application, paired-pulse suppression of the cortical N20 component remained unchanged, but suppression of the N20-P25 complex was significantly reduced, indicative of GABAergic involvement in intracortical processing. Our data suggest that lorazepam most likely enhances inhibition within the cortical network of interneurons responsible for creating paired-pulse suppression, leading to reduced inhibitory drive with a subsequently reduced amount of suppression. The results provide further evidence that GABAA -mediated mechanisms are involved in the generation of median nerve evoked paired-pulse suppression.

Early Use of Erenumab vs Nonspecific Oral Migraine Preventives: The APPRAISE Randomized Clinical Trial.

Importance: Patients with migraine often cycle through multiple nonspecific preventive medications due to poor tolerability and/or inadequate efficacy leading to low adherence and increased disease burden. Objective: To compare the efficacy, tolerability, patient adherence, and patient satisfaction between erenumab and nonspecific oral migraine preventive medications (OMPMs) in patients with episodic migraine (EM) who had previously failed 1 or 2 preventive treatments. Design, Setting, and Participants: The 12-month prospective, interventional, global, multicenter, active-controlled, randomized clinical trial comparing sustained benefit of 2 treatment paradigms (erenumab qm vs oral prophylactics) in adult episodic migraine patients (APPRAISE) trial was a 12-month open-label, multicenter, active-controlled, phase 4 randomized clinical trial conducted from May 15, 2019, to October 1, 2021. This pragmatic trial was conducted at 84 centers across 17 countries. Overall, participants 18 years or older with a 12-month or longer history of migraine, and 4 or more but fewer than 15 monthly migraine days (MMDs) were included. Interventions: Patients were randomized (2:1) to receive erenumab or OMPMs. Dose adjustment was permitted (label dependent). Main Outcomes and Measures: The primary end point was the proportion of patients completing 1 year of the initially assigned treatment and achieving a reduction of 50% or greater from baseline in MMDs at month 12. Secondary end points included the cumulative mean change from baseline in MMDs during the treatment period and the proportion of responders according to the Patients' Global Impression of Change (PGIC) scale at month 12 for patients taking the initially assigned treatment. Results: A total of 866 patients were screened, of whom 245 failed the screening and 621 completed the screening and baseline period. Of the 621 randomized patients (mean [SD] age, 41.3 [11.2] years; 545 female [87.8%]; 413 [66.5%] in the erenumab group; 208 [33.5%] in the OMPM group), 523 (84.2%) completed the treatment phase, and 98 (15.8%) discontinued the study. At month 12, significantly more patients assigned to erenumab vs OMPM achieved the primary end point (232 of 413 [56.2%] vs 35 of 208 [16.8%]; odds ratio [OR], 6.48; 95% CI, 4.28-9.82; P <.001). Compared with OMPMs, treatment with erenumab showed higher responder rate (314 of 413 [76.0%] vs 39 of 208 [18.8%]; OR, 13.75; 95% CI, 9.08-20.83; P <.001) on the PGIC scale (≥5 at month 12). Significant reduction in cumulative average MMDs was reported with erenumab treatment vs OMPM treatment (-4.32 vs -2.65; treatment difference [SE]: -1.67 [0.35] days; P < .001). Substantially fewer patients in the erenumab arm compared with the OMPM arm switched medication (9 of 413 [2.2%] vs 72 of 208 [34.6%]) and discontinued treatment due to adverse events (12 of 408 [2.9%] vs 48 of 206 [23.3%]). No new safety signals were identified. Conclusions and Relevance: Results of this randomized clinical trial demonstrated that earlier use of erenumab in patients with EM who failed 1 or 2 previous preventive treatments provided greater and sustained efficacy, safety, and adherence than continuous OMPM. Trial Registration: ClinicalTrials.gov Identifier: NCT03927144.

Morphological Differentiation of Corneal Inflammatory Cells: Proposal of Pragmatic Protocol.

PURPOSE: Corneal confocal microscopy is a noninvasive imaging technique to analyze corneal nerve fibers and corneal inflammatory cells (CICs). The amount of CICs is a potential biomarker of disease activity in chronic autoinflammatory diseases. To date, there are no standardized criteria for the morphological characterization of CICs. The aim was to establish a protocol for a standardized morphological classification of CICs based on a literature search and to test this protocol for applicability and reliability. METHODS: A systematic review of the literature about definitions of CICs was conducted. Existing morphological descriptions were translated into a structured algorithm and applied by raters. Subsequently, the protocol was optimized by reducing and defining the criteria of the cell types. The optimized algorithm was applied by 4 raters. The interrater reliability was calculated using Fleiss kappa (K). RESULTS: A systematic review of the literature revealed no uniform morphological criteria for the differentiation of the individual cell types in CICs. Our first protocol achieved only a low level of agreement between 3 raters (K = 0.09; 1062 rated cells). Our revised protocol was able to achieve a higher interrater reliability with 3 (K = 0.64; 471 rated cells) and 4 (K = 0.61; 628 rated cells) raters. CONCLUSIONS: The indirect use of criteria from the literature leads to a high error rate. By clearly defining the individual cell types and standardizing the protocol, reproducible results were obtained, allowing the introduction of this protocol for the future evaluation of CICs in the corneal confocal microscopy.

Increased excitability of somatosensory cortex in aged humans is associated with impaired tactile acuity.

Aging affects all levels of neural processing, including changes of intracortical inhibition and cortical excitability. Paired-pulse stimulation, the application of two stimuli in close succession, is a useful tool to investigate cortical excitability in humans. The paired-pulse behavior is characterized by the second response being significantly suppressed at short stimulus onset asynchronies. While in rat somatosensory cortex, intracortical inhibition has been demonstrated to decline with increasing age, data from human motor cortex of elderly subjects are controversial and there are no data for the human somatosensory cortex (SI). Moreover, behavioral implications of age-related changes of cortical excitability remain elusive. We therefore assessed SI excitability by combining paired-pulse median nerve stimulation with recording somatosensory evoked potentials in 138 healthy subjects aged 17-86 years. We found that paired-pulse suppression was characterized by substantial interindividual variability, but declined significantly with age, confirming reduced intracortical inhibition in elderly subjects. To link the age-related increase of cortical excitability to perceptual changes, we measured tactile two-point discrimination in a subsample of 26 aged participants who showed either low or high paired-pulse suppression. We found that tactile performance was particularly impaired in subjects showing markedly enhanced cortical excitability. Our data demonstrate that paired-pulse suppression of human SI is significantly reduced in older adults, and that age-related enhancement of cortical excitability correlates with degradation of tactile perception. These findings indicate that cortical excitability constitutes an important mechanism that links age-related neurophysiological changes to behavioral alterations in humans.

Temporal summation of trigeminal pain in human anterior cingulate cortex.

Temporal summation of nociceptive inputs in trigeminal networks can induce central sensitization and maintain chronic pain. We combined functional magnetic resonance imaging and electrically evoked pain-related potentials (PREP) in healthy human subjects to identify brain regions involved in temporal summation of nociceptive inputs. We stimulated the skin innervated by the ophthalmic division of the trigeminal nerve with trains of three, seven and eleven similar nociceptive pulses, while recording evoked hemodynamic or electrical brain responses. We found that PREP amplitudes and pain ratings increased in parallel with increasing train length. Strikingly, only hemodynamic responses in the posterior part of the anterior cingulate cortex (pACC) scaled with individual pain ratings on a verbal rating scale (VRS) and electrically evoked responses (i.e., PREP amplitudes for the three train lengths). These findings indicate that pACC codes temporal summation of trigeminal nociception and in this regard may be important for the development of central sensitization observed in chronic head and facial pain.

Visual paired-pulse stimulation reveals enhanced visual cortex excitability in migraineurs.

Migraine is a common ictal disorder with an interindividual heterogeneous characteristic, whose underlying mechanisms remain elusive. On the one hand migraine is associated with abnormal cortical hyperexcitability. On the other hand, studies reported lower amplitudes of visual-evoked potentials (VEPs) and concluded that low preactivation levels imply decreased excitability. Here we measured visual cortex excitability and paired-pulse suppression in subjects suffering from migraine without aura and in a group of aged- and gender-matched healthy subjects to address the relation between activation levels and excitability. To that aim, we analysed amplitudes of VEPs and paired-pulse suppression evoked by a paired-pulse stimulation paradigm using stimulus onset asynchronies (SOAs) between 80 and 133 ms. We found that in migraineurs in the interictal state the amplitudes of the first VEP were reduced as compared with healthy subjects by approximately 20%. In the case of paired-pulse suppression comparable to healthy controls, the second response amplitude should be reduced as well, which was not the case. Instead, the ratio between the first and second VEP was higher than in healthy controls and did not depend on SOA in the range tested, which demonstrates reduced paired-pulse suppression and therefore implicates increased cortical excitability. Our data show that in migraineurs VEPs were reduced presumably due to reduced activation levels. However, paired-pulse suppression using short SOAs in the range of 100 ms or less was even higher than in normal subjects. Thus, our data show that signatures of both hyper- and hypoexcitability can be found depending on stimulation condition.

Habituation of the auditory startle response in cervical dystonia and Parkinson's disease.

The auditory startle response (ASR) is a brainstem reflex elicited by an unexpected acoustic stimulus. In focal dystonia (FD), the excitability of brainstem neurons is abnormally enhanced. To identify a possible impact of this pathology on the processing of acoustic stimuli, we studied the habituation of the ASR in patients (n = 11) with FD and compared the findings to those of patients with Parkinson's disease (PD; n = 11) and controls (n = 11). Latencies in FD patients did not differ from those of controls but were delayed in PD patients compared to controls (p < 0.0001). Habituation was normal at the orbicularis oculi muscles but reduced at the sternocleidomastoid muscles in FD (p = 0.005). Habituation in PD was comparable to controls. Normal latencies and sequence activation indicate intact neural pathways mediating the ASR in FD. Impaired habituation of the ASR points towards a reduced inhibition of acoustic stimuli in FD.

Activity of attention related structures in multiple sclerosis patients.

AIMS: It was investigated whether the cortical activity during tasks requiring focused or divided attention is reduced in multiple sclerosis patients with prominent deficits (MS(+D)) and increased in patients without impairment (MS(-D)) in these specific attention functions. METHODS: Six MS(+D) patients with attention deficits, six unimpaired MS(-D) patients, and age-, gender-, and education-matched healthy control subjects were examined with functional magnetic resonance imaging (fMRI). The experimental paradigm consisted of visual tasks requiring focused or divided attention. RESULTS: Performance accuracy and reaction times were impaired in MS(+D) patients. This subgroup showed reduced activation within superior and inferior frontal gyrus during focused attention. Under conditions of divided attention decreased activity was found within middle and inferior frontal gyrus, inferior parietal structures, and occipital areas. No compensatory activity was observed. MS(-D) patients did neither differ in behavioral data nor in cortical activity in attention related structures from control subjects. CONCLUSIONS: The study found evidence for the neural correlate of attentional deficits in MS patients. In patients with specific attention deficits, reduced cortical activity in prefrontal and parietal areas, which are associated with attention and executive control, reflects the patients' reduced performance on a behavioral level. Our findings also suggest impaired top-down attentional control on sensory structures in these patients. In patients without verifiable attention deficits a normal functioning of structures relevant for executive attention was observed. Compensatory activity in these structures as a marker of reorganization in less pronounced stages of the disease was not found.

Saccade induced cortical activation in patients with post-stroke visual field defects.

Substantial disability in patients with hemianopia results from reduced visual perception. Several studies have shown that these patients have impaired saccades but may improve search strategies with appropriate training of saccades. We used fMRI to study the representation of saccades in patients with post-stroke hemianopia to the left. Brain activation during visually guided saccades was measured in 10 patients with a pure occipital cortical lesion causing homonymous hemianopia and in 10 healthy control subjects. Differences in activation between rest and saccades and between controls and patients were assessed with statistical parametric mapping (SPM'99). In normal subjects, significant activation was found in the frontal and parietal eye fields bilaterally and in the supplementary eye field. These areas were also activated in patients, however, to a lesser degree. In contrast, an area of increased activation in patients was found in the posterior parietal cortex of the (non-affected) left hemisphere. Visual field defects after striate lesions are associated with changes in the frontoparietal network underlying the cortical control of saccades.

Improved surgical procedure using intraoperative navigation for the implantation of the SPG microstimulator in patients with chronic cluster headache.

INTRODUCTION: The ATI SPG microstimulator is designed to be fixed on the posterior maxilla, with the integrated lead extending into the pterygopalatine fossa to electrically stimulate the sphenopalatine ganglion (SPG) as a treatment for cluster headache. Preoperative surgical planning to ensure the placement of the microstimulator in close proximity (within 5 mm) to the SPG is critical for treatment efficacy. The aim of this study was to improve the surgical procedure by navigating the initial dissection prior to implantation using a passive optical navigation system and to match the post-operative CBCT images with the preoperative treatment plan to verify the accuracy of the intraoperative placement of the microstimulator. METHODS: Custom methods and software were used that result in a 3D rotatable digitally reconstructed fluoroscopic image illustrating the patient-specific placement with the ATI SPG microstimulator. Those software tools were preoperatively integrated with the planning software of the navigation system to be used intraoperatively for navigated placement. Intraoperatively, the SPG microstimulator was implanted by completing the initial dissection with CT navigation, while the final position of the stimulator was verified by 3D CBCT. Those reconstructed images were then immediately matched with the preoperative CT scans with the digitally inserted SPG microstimulator. This method allowed for visual comparison of both CT scans and verified correct positioning of the SPG microstimulator. RESULTS: Twenty-four surgeries were performed using this new method of CT navigated assistance during SPG microstimulator implantation. Those results were compared to results of 21 patients previously implanted without the assistance of CT navigation. Using CT navigation during the initial dissection, an average distance reduction of 1.2 mm between the target point and electrode tip of the SPG microstimulator was achieved. Using the navigation software for navigated implantation and matching the preoperative planned scans with those performed post-operatively, the average distance was 2.17 mm with navigation, compared to 3.37 mm in the 28 surgeries without navigation. CONCLUSION: Results from this new procedure showed a significant reduction (p = 0.009) in the average distance from the SPG microstimulator to the desired target point. Therefore, a distinct improvement could be achieved in positioning of the SPG microstimulator through the use of intraoperative navigation during the initial dissection and by post-operative matching of pre- and post-operatively performed CBCT scans.

Reorganization of motor execution rather than preparation in poststroke hemiparesis.

BACKGROUND AND PURPOSE: The aim of the present study was to examine movement-related potentials (MRPs) in patients in the "chronic" stage after cortical stroke with recovered hemiparesis compared with healthy control subjects. METHODS: Right index finger MRPs were derived from 12 patients > or =1 year after infarction in the territory of the left middle cerebral artery as well as from 12 control subjects. MRP components were compared between groups. RESULTS: In the patient group, the component directly preceding movement onset (negative slope [NS]) was significantly reduced over the lesioned hemisphere contralateral to the movement. Furthermore, increased motor potentials (MPs) were observed over the contralesional hemisphere during movement execution. No changes in the early MRP (Bereitschaftspotential) reflecting movement preparation were found. CONCLUSIONS: Because the NS is supposed to be generated by the primary motor cortex, the decreased component over the lesioned hemisphere is interpreted to represent impaired contralateral M1 functioning in stroke patients. Contralesional activity has been reported as a probable sign of brain plasticity by functional imaging studies. Our results broaden these findings, giving new insights into the temporal course of movement-related brain activity in recovered cortical stroke patients. The data point to a functional reorganization of motor execution rather than preparation in poststroke hemiparesis.

On the neural basis of focused and divided attention.

Concepts of higher attention functions distinguish focused and divided attention. The present study investigated whether these mental abilities are mediated by common or distinct neural substrates. In a first experiment, 19 healthy subjects were examined with functional brain imaging (fMRI) while they attended to either one or both of two simultaneously presented visual information streams and responded to repetitive stimuli. This experiment resembled a typical examination of these mental functions with the single task demanding focused and the dual task conditions requiring divided attention. Both conditions activated a widespread, mainly right-sided network including dorso- and ventrolateral prefrontal structures, superior and inferior parietal cortex, and anterior cingulate gyrus. Under higher cognitive demands of divided attention, activity in these structures was enhanced and left-sided homologues were recruited. In a second experiment investigating another 17 subjects with almost the same paradigm, it was accounted for that in most dual task investigations of focused and divided attention the single tasks are easier to process than their combined presentation. Therefore, the task difficulty of focused attention tasks was increased. Almost the same activity pattern observed during division of attention was now found during focusing attention. Comparing both attentional states matched for task difficulty, differences were found in visual but not in prefrontal or parietal cortex areas. Our results suggest that focused and divided attention depend on largely overlapping neuronal substrates. Differences in activation patterns, especially in prefrontal and parietal areas, may result from unequal demands on executive control due to disparate processing requirements in typical tasks of focused and divided attention: Easier conditions begin with mainly right-sided activity within the attention network. As conditions become more difficult, left-lateralized homologue areas activate.

Antinociceptive reflex alteration in acute posttraumatic headache following whiplash injury.

Brainstem-mediated antinociceptive inhibitory reflexes of the temporalis muscle were investigated in 82 patients (47 F, 35 M, mean age 28.3 years, SD 9.4) with acute posttraumatic headache (PH) following whiplash injury but without neurological deficits, bone injury of the cervical spine or a combined direct head trauma on average 5 days after the acceleration trauma. Latencies and durations of the early and late exteroceptive suppression (ES1 and ES2) and the interposed EMG burst (IE) of the EMG of the voluntarily contracted right temporalis muscle evoked by ipsilateral stimulation of the second and third branches of the trigeminal nerve were analyzed and compared to a cohort of 82 normal subjects (43 F, 39 M, mean age 27.7 years, SD 7.1). Highly significant reflex alterations were found in patients with PH with a shortening of ES2 duration with delayed onset and premature ending as the primary parameter of this study, a moderate prolongation of ES1 and IE duration and a delayed onset of IE. The latency of ES1 was not significantly changed. These findings indicate that acute PH in whiplash injury is accompanied by abnormal antinociceptive brainstem reflexes. We conclude that the abnormality of the trigeminal inhibitory temporalis reflex is based on a transient dysfunction of the brainstem-mediated reflex circuit mainly of the late polysynaptic pathways. The reflex abnormalities are considered as a neurophysiological correlate of the posttraumatic (cervico)-cephalic pain syndrome. They point to an altered central pain control in acute PH due to whiplash injury.

Sparse imaging of the auditory oddball task with functional MRI.

Cortical reactions to rare task-related stimuli have been studied with electrophysiological methods in the assessment of the P300 component as well as in functional imaging studies with regard to oddball tasks. While functional magnetic resonance imaging studies using auditory stimuli have to deal with interference between auditory stimuli and scanner noise, the aim of our study was to assess auditory target processing with the sparse imaging method. Single volumes of echo-planar imaging were acquired 4 s following the onset of the stimuli of interest. In keeping with previous studies, target stimuli activated the insula, superior temporal gyrus, cingulate gyrus, middle frontal gyrus, parietal cortex and the cerebellum. Our results encourage the application of the sparse imaging method in experiments on cognitive processing elicited by auditory stimulation in a silent environment.