Between- and within-site variability of fMRI localizations.

This study provides first data about the spatial variability of fMRI sensorimotor localizations when investigating the same subjects at different fMRI sites. Results are comparable to a previous patient study. We found a median between-site variability of about 6 mm independent of task (motor or sensory) and experimental standardization (high or low). An intraclass correlation coefficient analysis using data quality measures indicated a major influence of the fMRI site on variability. In accordance with this, within-site localization variability was considerably lower (about 3 mm). We conclude that the fMRI site is a considerable confound for localization of brain activity. However, when performed by experienced clinical fMRI experts, brain pathology does not seem to have a relevant impact on the reliability of fMRI localizations. Hum Brain Mapp 37:2151-2160, 2016. © 2016 Wiley Periodicals, Inc.

Flow diversion with hydrophilic polymer coating with prasugrel as single antiplatelet therapy in the treatment of acutely ruptured intracranial aneurysms: a multicenter case series, complication and occlusion rates.

BACKGROUND: This study reports a multicenter experience of using hydrophilic polymer-coated (HPC) flow diverters with prasugrel single antiplatelet therapy to treat ruptured aneurysms with subarachnoid hemorrhage (SAH). METHODS: Patients treated for intracranial aneurysms within 30 days after SAH with a p64/p48 MW HPC flow diverter were prospectively identified. Clinical presentation and outcomes, periprocedural and postprocedural complications, and degree of occlusion at follow-up were evaluated. RESULTS: A total of 84 patients were treated in 88 sessions (54.5% women; mean age 53.3 years). Four patients (4.7%) experienced flow diverter-dependent complications. No cases of aneurysm re-rupture or hemorrhagic complications related to antiplatelet therapy were recorded. Immediate complete occlusion was achieved in 27.4% of cases (23/84). The rate of complete occlusion among survivors was 83% in early follow-up, 90.2% in mid-term follow-up, and 92.3% in the latest possible follow-up. CONCLUSION: p64/p48 MW HPC flow diverters with prasugrel single antiplatelet therapy were associated with safety from aneurysm re-rupture and high occlusion rates at medium- and long-term follow-up in managing ruptured aneurysms. Adequate management of single antiplatelet therapy with prasugrel is crucial, particularly with higher doses than usual, to avoid both ischemic and hemorrhagic complications.

Variability of clinical functional MR imaging results: a multicenter study.

PURPOSE: To investigate intersite variability of clinical functional magnetic resonance (MR) imaging, including influence of task standardization on variability and use of various parameters to inform the clinician whether the reliability of a given functional localization is high or low. MATERIALS AND METHODS: Local ethics committees approved the study; all participants gave written informed consent. Eight women and seven men (mean age, 40 years) were prospectively investigated at three experienced functional MR sites with 1.5- (two sites) or 3-T (one site) MR. Nonstandardized motor and highly standardized somatosensory versions of a frequently requested clinical task (localization of the primary sensorimotor cortex) were used. Perirolandic functional MR variability was assessed (peak activation variability, center of mass [COM] variability, intraclass correlation values, overlap ratio [OR], activation size ratio). Data quality measures for functional MR images included percentage signal change (PSC), contrast-to-noise ratio (CNR), and head motion parameters. Data were analyzed with analysis of variance and a correlation analysis. RESULTS: Localization of perirolandic functional MR activity differed by 8 mm (peak activity) and 6 mm (COM activity) among sites. Peak activation varied up to 16.5 mm (COM range, 0.4-16.5 mm) and 45.5 mm (peak activity range, 1.8-45.5 mm). Signal strength (PSC, CNR) was significantly lower for the somatosensory task (mean PSC, 1.0% ± 0.5 [standard deviation]; mean CNR, 1.2 ± 0.4) than for the motor task (mean PSC, 2.4% ± 0.8; mean CNR, 2.9 ± 0.9) (P < .001, both). Intersite variability was larger with low signal strength (negative correlations between signal strength and peak activation variability) even if the task was highly standardized (mean OR, 22.0% ± 18.9 [somatosensory task] and 50.1% ± 18.8 [motor task]). CONCLUSION: Clinical practice and clinical functional MR biomarker studies should consider that the center of task-specific brain activation may vary up to 16.5 mm, with the investigating site, and should maximize functional MR signal strength and evaluate reliability of local results with PSC and CNR.

The History of Endovascular Stroke Treatment: From Local Intraarterial Fibrinolysis to Stent Retriever Thrombectomy.

BACKGROUND: Acute thromboembolic occlusions of large intracranial arteries are associated with high rates of permanent disability and mortality. Intravenous thrombolysis (IVT) in these patients resulted in an inadequate rate of recanalization and has had limited clinical success. Various endovascular procedures have been attempted to remove intracranial thrombi and reopen occluded vessels. These technical innovations led to the publication of initial case reports, but the methods ultimately did not endure. Endovascular treatment of acute cerebral ischemia was performed only rarely and in selected centers as part of individualized curative attempts. The Solitaire stent was originally developed to treat intracranial aneurysms through stent-assisted coil occlusion. The suggestion that this stent could also be used for intracranial thrombectomy was made as early as 2003 and was clinically confirmed in 2008. Releasing a Solitaire stent into an embolically occluded large cerebral artery, with an incubation time of approximately 3 minutes and slow retraction of the stent, has led to unprecedented success rates of thrombus removal and (sub)total recanalization in more than 90 % of patients. METHODS: This review article aimed to describe the steps in the development of endovascular stroke therapy, beginning with intra-arterial thrombolysis and early technical innovations leading to the eventual success of stent retriever thrombectomy. CONCLUSION: The potential for mechanical recanalization of acutely occluded large cerebral arteries could not be fully exploited until the advent of stent retriever thrombectomy. The entire concept of stroke treatment fundamentally changed after complete and rapid recanalization first became possible. Randomized controlled trials have shown superiority of stent retriever thrombectomy over IVT. An unparalleled boom in endovascular stroke therapy followed. KEY POINTS: · The history of endovascular stroke treatment was marked by setbacks in the first three decades.. · Stent retriever thrombectomy is the first procedure enabling recanalization of acute large intracranial artery occlusions in more than 90 % of patients.. · Stent retriever thrombectomy has transformed stroke care and neuroradiology in unprecedented ways.. · Further technical improvements will enable even faster, safer, complete recanalization in the near future.. · Further improvements in clinical outcomes will probably be determined by aspects beyond endovascular methods alone..

Non-Invasive Intracranial Pressure Monitoring.

(1) Background: Intracranial pressure (ICP) monitoring plays a key role in the treatment of patients in intensive care units, as well as during long-term surgeries and interventions. The gold standard is invasive measurement and monitoring via ventricular drainage or a parenchymal probe. In recent decades, numerous methods for non-invasive measurement have been evaluated but none have become established in routine clinical practice. The aim of this study was to reflect on the current state of research and shed light on relevant techniques for future clinical application. (2) Methods: We performed a PubMed search for "non-invasive AND ICP AND (measurement OR monitoring)" and identified 306 results. On the basis of these search results, we conducted an in-depth source analysis to identify additional methods. Studies were analyzed for design, patient type (e.g., infants, adults, and shunt patients), statistical evaluation (correlation, accuracy, and reliability), number of included measurements, and statistical assessment of accuracy and reliability. (3) Results: MRI-ICP and two-depth Doppler showed the most potential (and were the most complex methods). Tympanic membrane temperature, diffuse correlation spectroscopy, natural resonance frequency, and retinal vein approaches were also promising. (4) Conclusions: To date, no convincing evidence supports the use of a particular method for non-invasive intracranial pressure measurement. However, many new approaches are under development.

Results of the pToWin Study: Using the pCONUS Device for the Treatment of Wide-Neck Intracranial Aneurysms.

Coil embolization has become a well-established option for the treatment of intracranial aneurysms. Yet, wide-neck bifurcation aneurysms (WNBAs) remain a challenge. The pCONUS is the first generation of a stent-like implant for the bridging of WNBAs to enable coiling. The pToWin study was a prospective, single-arm, multicenter study conducted to analyze the safety and efficacy of the pCONUS in the treatment of WNBAs. The primary effectiveness endpoint was the rate of adequate occlusion of the aneurysm at 3-6 and 7-12 months. The primary safety endpoint was the occurrence of major ipsilateral stroke or neurological death during the follow-up. A total of 115 patients were included. Aneurysm locations were the middle cerebral artery in 52 (45.2%), the anterior communicating artery in 35 (30.4%), the basilar artery in 23 (20%), the internal carotid artery terminus in three (2.6%), and the pericallosal artery in two (1.7%) patients. Treatment was successfully performed in all but one patient. The morbi-mortality rate was 1.9% and 2.3% at 3-6 and 7-12 months, respectively. Of the aneurysms, 75.0% and 65.6% showed adequate occlusion at 3-6 and 7-12 months, respectively. pCONUS offers a safe and reasonably effective treatment of WNBAs, demonstrated by acceptable adequate aneurysm occlusion and low rates of adverse neurologic events.

Language Dominance in Patients With Malformations of Cortical Development and Epilepsy.

Background: Language function may be reorganized in patients with malformations of cortical development (MCD). This prospective cohort study aimed in assessing language dominance in a large group of patients with MCD and epilepsy using functional MRI (fMRI). Methods: Sixty-eight patients (40 women) aged 10-73 years (median, 28.0; interquartile range, 19) with MCD and epilepsy underwent 1.5 T MRI and fMRI (word generation task). Single-subject image analysis was performed with statistical parametric mapping (SPM12). Language lateralization indices (LIs) were defined for statistically significantly activated voxels in Broca's and Wernicke's areas using the formula: LI = (V L - V R)/(V L + V R) × 100, where V L and V R were sets of activated voxels on the left and on the right, respectively. Language laterality was considered typical if LI was between +20 and +100 or atypical if LI was between +19 and -100. Results: fMRI signal was elicited in 55 of 68 (81%) patients. In 18 of 55 (33%) patients, language dominance was typical, and in 37 of 55 (67%) patients, atypical (in 68%, right hemispheric; in 32%, bilateral). Language dominance was not influenced by handedness, electroclinical, and imaging features. Conclusions: In this prospective study on a large group of patients with MCD and epilepsy, about two-thirds had atypical language dominance. These results may contribute to assessing risks of postsurgical language deficits and could assist in planning of "cortical mapping" with intracranial electrodes in patients who undergo presurgical assessment.

Neural correlates of transmeatal cochlear laser (TCL) stimulation in healthy human subjects.

Transmeatal cochlear laser (TCL) treatment has recently been proposed as a therapeutic procedure for cochlear dysfunction such as chronic cochlear tinnitus or sensorineural hearing loss. The aim of this study was to investigate whether TLC has any influence on the central nervous system using functional MRI with healthy young adults. The laser stimulation device was placed on the tympanic membrane of both ears. A laser stimulation run and a placebo run were performed in random order. The participants were unable to differentiate between verum and placebo stimulation. In the comparison of verum to placebo runs, we observed significant activations within the left superior frontal gyrus, the right middle and medial frontal gyrus, the right superior parietal lobule, the left superior occipital gyrus, the precuneus and cuneus bilaterally, the right anterior and the left and right middle and posterior cingulate gyrus and the left thalamus. This network of brain areas corresponds well to results from previous PET studies of patients with tinnitus. Though TCL seems to have a clinically measurable effect on the central nervous system the neurophysiological mechanism leading to the observed activated neuronal network remains unknown.

Shank Muscle Strength Training Changes Foot Behaviour during a Sudden Ankle Supination.

BACKGROUND: The peroneal muscles are the most effective lateral stabilisers whose tension braces the ankle joint complex against excessive supination. The purpose of this study was to identify the morphological and biomechanical effects of two machine-based shank muscle training methods. METHODS: Twenty-two healthy male recreationally active sports students performed ten weeks of single-set high resistance strength training with 3 training sessions per week. The subjects conducted subtalar pronator/supinator muscle training (ST) with the right leg by using a custom-made apparatus; the left foot muscles were exercised with machine-based talocrural plantar and dorsiflexor training (TT). Muscle strength (MVIC), muscle volume and foot biomechanics (rearfoot motion, ground reaction forces, muscle reaction times) during a sudden ankle supination were recorded before and after the intervention. RESULTS: Compared to TT, ST resulted in significantly higher pronator (14% vs. 8%, P<0.01) and supinator MVIC (25% vs. 12%, P<0.01). During sudden foot inversions, both ST and TT resulted in reduced supination velocity (-12%; P<0.01). The muscle reaction onset time was faster after the training in peroneus longus (PL) (P<0.01). Muscle volume of PL (P<0.01) and TA (P<0.01) increased significantly after both ST and TT. CONCLUSION: After both ST and TT, the ankle joint complex is mechanically more stabilised against sudden supinations due to the muscle volume increase of PL and TA. As the reduced supination velocities indicate, the strength training effects are already present during free-fall. According to a sudden ankle supination in standing position, both machine-based dorsiflexor and pronator strength training is recommended for enhancing the mechanical stability of the ankle.

Neural correlates of episodic encoding and recognition of words in unmedicated patients during an acute episode of schizophrenia: a functional MRI study.

OBJECTIVE: Memory impairment has been well documented in schizophrenia. In a previous study, the authors investigated patterns of brain activity during episodic encoding and recognition of words in remitted, stable schizophrenia outpatients being treated with novel antipsychotics. The same procedure was used in this study to investigate unmedicated patients during an acute episode of schizophrenia. METHOD: Functional magnetic resonance imaging was used to study regional brain activation in 10 unmedicated patients experiencing an acute episode of schizophrenia and 10 healthy comparison subjects during performance of a modified version of the words subtest of Warrington's Recognition Memory Test. RESULTS: Despite intact recognition performance, patients with schizophrenia showed reduced activation of anterior prefrontal, posterior cingulate, and retrosplenial areas relative to comparison subjects during word encoding. During word recognition, reduced activation was found in the patients' dorsolateral prefrontal and limbic/paralimbic regions. On the other hand, higher metabolism in bilateral anterior prefrontal cortices was observed. CONCLUSIONS: The results suggest that different neural pathways are engaged during episodic encoding and recognition of words in patients experiencing an acute episode of schizophrenia relative to healthy comparison subjects. Furthermore, acute psychosis may prevent practice effects, reflected in a failure to engage brain regions associated with successful episodic memory retrieval in healthy subjects.

An FMRI study of episodic encoding and recognition of words in patients with schizophrenia in remission.

OBJECTIVE: Verbal memory deficits are among the most severe cognitive deficits observed in patients with schizophrenia. This study examined patterns of brain activity during episodic encoding and recognition of words in patients with schizophrenia. METHOD: Functional magnetic resonance imaging (fMRI) was used to study regional brain activation in 10 healthy male comparison subjects and 10 male outpatients with schizophrenia during performance of a modified version of the words subtest of Warrington's Recognition Memory Test. RESULTS: Despite having intact performance in word recognition, the patients with schizophrenia had less activation of the right dorsolateral and anterior prefrontal cortex, right anterior cingulate, and left lateral temporal cortex during word encoding, compared with the healthy comparison subjects. During word recognition, the patients had impairments in activation of the bilateral dorsolateral prefrontal and lateral temporal cortices. CONCLUSIONS: Schizophrenia was associated with attenuated frontotemporal activation during episodic encoding and recognition of words. These results from an fMRI study replicate earlier findings derived from a positron emission tomography study.

Functional magnetic resonance imaging detects activation of the visual association cortex during laser acupuncture of the foot in humans.

The aim of this study was to investigate the effect of laser acupuncture on cerebral activation. Using functional magnetic imaging (fMRI) cortical activations during laser acupuncture at the left foot (Bladder 67) and dummy acupuncture, were compared employing a block design in ten healthy male volunteers. All experiments were done on a 1.5 Tesla magnetic resonance scanner equipped with a circular polarized head coil. During laser acupuncture, we found activation in the cuneus corresponding to Brodmann Area (BA) 18 and the medial occipital gyrus (BA 19) of the ipsilateral visual cortex. Placebo stimulation did not show any activation. We could demonstrate that laser acupuncture of a specific acupoint, empirically related to ophthalmic disorders, leads to activation of visual brain areas, whereas placebo acupuncture does not. These results indicate that fMRI has the potential to elucidate effects of acupuncture on brain activity.

A new pneumatic vibrator for functional magnetic resonance imaging of the human sensorimotor cortex.

The aim of the study was to implement a vibrotactile stimulator using functional magnetic resonance imaging (fMRI). A fMRI compatible vibration device consisting of a pneumatically driven dual membrane pump was developed. Brain activation during 50 Hz vibrotactile stimulation of the right hand-palm were compared to a right 2 Hz finger-to-thumb-tapping in ten healthy, right-handed male volunteers. The vibration paradigm showed a comparable activation pattern with respect to finger-to-thumb-tapping in the contralateral perirolandic region. The advantage of the new vibration device is the possibility to elicit the vibratory-tonic-reflex due to the higher amplitude in context with the high frequency than established devices. This reflex is considered to be responsible for the activation in the primary motor cortex and the current paradigm might prove useful in future neurosurgical planning in patients with perirolandic lesions.

Endovascular coil occlusion of 1811 intracranial aneurysms: early angiographic and clinical results.

OBJECTIVE: We sought to evaluate the early angiographic and clinical outcomes of the first session of endovascular coil occlusion of a large number of patients with intracranial aneurysms treated by five neurointerventionalists during a decade at a single center. METHODS: We performed retrospective analyses of pre- and postprocedural angiographic studies and early clinical outcomes. Enrolled patients underwent endovascular treatment of intracranial aneurysms with detachable coils. RESULTS: A total of 1811 aneurysms in 1579 patients were treated with coil occlusion. Of these, 90 to 100% occlusion of 86.5% of the aneurysms was achieved. In 82.3% of the procedures, no complications occurred. The clinical outcome profile at primary discharge according to the Glasgow Outcome Scale was as follows: Grade V, 74.6%; Grade IV, 6.7%; Grade III, 11.1%; Grade II, 3.1%; and Grade I, 4.5%. In patients with large aneurysms with wide necks, a lower occlusion rate and an increased complication rate were encountered. The use of three-dimensional and fibered coils resulted in higher occlusion rates. Balloon remodeling and stent deployment increased the complication rate. Previous aneurysm rupture, procedural complications, and vasospasm correlated with poor outcome. Of the patients in poor grade after aneurysm rupture, 42% recovered to Glasgow Outcome Scale Grade IV or V, as opposed to 90% of patients who were treated for unruptured aneurysms. The ischemic complication rate was 9%, and the hemorrhagic complication rate was 3%. The early procedural morbidity rate was 5.3%, and the procedural mortality rate was 1.5%. The management mortality rate was 4.4%. CONCLUSION: These data confirm the safety and efficacy of endovascular coil occlusion for patients with intracranial aneurysms.

Treatment of extracranial and intracranial aneurysms and arteriovenous fistulae using stent grafts.

OBJECTIVE: Treatment of 11 patients with aneurysms or arteriovenous fistulae of the craniocervical arteries with stent grafts. METHODS: Peripheral stent grafts were deployed in two extracranial internal carotid arteries. Coronary stent grafts were used to treat two giant aneurysms, five direct carotid-cavernous fistulae, one vertebrojugular fistula, and two dissecting aneurysms of the vertebral artery (V2 and V4). RESULTS: Stent grafts were used successfully in two extracranial internal carotid and two extracranial vertebral arteries, one dissecting aneurysm of the intracranial vertebral artery, one giant aneurysm and one pseudoaneurysm of the cavernous internal carotid artery, and five direct carotid-cavernous sinus fistulae. Angiographic follow-up examinations (available in nine patients; obtained at 3 mo to 5 yr; average, 24 mo) revealed normal vessel caliber, and the stent grafts in all 9 of 11 initial patients were patent. There was a recurrent saccular aneurysm adjacent to the stent graft in the patient with the intracranial vertebral artery aneurysm. The following five complications were encountered: transient hemiparesis (n = 2), increased hemiparesis, postprocedural management-related fatality, and ICA dissection. In six patients, stent graft deployment was accomplished without any technical or clinical complication. There were no permanent neurological deficits consequent to stent graft placement. CONCLUSION: Stent grafts are a useful tool for the endovascular treatment of head and neck aneurysms and direct arteriovenous fistulae in selected patients. The major disadvantage of the currently available stent grafts is their lack of mechanical flexibility. Maneuvering stent grafts in the intracranial arteries carries the risk of iatrogenic vessel dissection and may require supportive measures and protection of the target site by conventional stents.

Brain activation patterns during a selective attention test-a functional MRI study in healthy volunteers and patients with schizophrenia.

Functional magnetic resonance imaging was used to compare cortical activation patterns in healthy volunteers with those in patients with schizophrenia during a modified verbal Stroop task. Healthy subjects (n=13) and patients with schizophrenia (n=13) on stable antipsychotic treatment, matched on demographic variables, were included. Patients were preselected on the basis of good performance on a selective attention test. Patients with schizophrenia showed a significantly increased pattern of activation in the left and right inferior frontal cortex and the anterior cingulate cortex. A significant negative correlation between activation of the left prefrontal cortex and accuracy in the modified Stroop test was observed for healthy controls but not schizophrenia patients. Although both groups recruited the prefrontal cortex during the modified Stroop task, for the schizophrenia patients this activation was bilateral, whereas for the controls this activation was primarily in the left hemisphere, suggesting that patients with schizophrenia recruited more prefrontal regions to perform the task with the same accuracy as healthy controls. Our findings of increased activity across multiple areas of the brain, including dorsolateral frontal cortex and anterior cingulate, in patients with schizophrenia who perform relatively well on a task of selective attention give further evidence that task performance may be a confounding factor in the interpretation of neuroimaging results.

The influence of hyperoxia on regional cerebral blood flow (rCBF), regional cerebral blood volume (rCBV) and cerebral blood flow velocity in the middle cerebral artery (CBFVMCA) in human volunteers.

Conflicting results reported on the effects of hyperoxia on cerebral hemodynamics have been attributed mainly to methodical and species differences. In the present study contrast-enhanced magnetic resonance imaging (MRI) perfusion measurement was used to analyze the influence of hyperoxia (fraction of inspired oxygen (FiO2) = 1.0) on regional cerebral blood flow (rCBF) and regional cerebral blood volume (rCBV) in awake, normoventilating volunteers (n = 19). Furthermore, the experiment was repeated in 20 volunteers for transcranial Doppler sonography (TCD) measurement of cerebral blood flow velocity in the middle cerebral artery (CBFV(MCA)). When compared to normoxia (FiO2 = 0.21), hyperoxia heterogeneously influenced rCBV (4.95 +/- 0.02 to 12.87 +/- 0.08 mL/100g (FiO2 = 0.21) vs. 4.50 +/- 0.02 to 13.09 +/- 0.09 mL/100g (FiO2 = 1.0). In contrast, hyperoxia diminished rCBF in all regions (68.08 +/- 0.38 to 199.58 +/- 1.58 mL/100g/min (FiO2 = 0.21) vs. 58.63 +/- 0.32 to 175.16 +/- 1.51 mL/100g/min (FiO2 = 1.0)) except in parietal and left frontal gray matter. CBFV(MCA) remained unchanged regardless of the inspired oxygen fraction (62 +/- 9 cm/s (FiO2 = 0.21) vs. 64 +/- 8 cm/s (FiO2 = 1.0)). Finding CBFV(MCA) unchanged during hyperoxia is consistent with the present study's unchanged rCBF in parietal and left frontal gray matter. In these fronto-parietal regions predominantly fed by the middle cerebral artery, the vasoconstrictor effect of oxygen was probably counteracted by increased perfusion of foci of neuronal activity controlling general behavior and arousal.

Midbrain-hindbrain malformations in patients with malformations of cortical development and epilepsy: a series of 220 patients.

Midbrain-hindbrain malformations (MHM) may coexist with malformations of cortical development (MCD). This study represents a first attempt to investigate the spectrum of MHM in a large series of patients with MCD and epilepsy. We aimed to explore specific associations between MCD and MHM and to compare two groups of patients: MCD with MHM (wMHM) and MCD without MHM (w/oMHM) with regard to clinical and imaging features. Two hundred and twenty patients (116 women/104 men, median age 28 years, interquartile range 20-44 years at the time of assessment) with MCD and epilepsy were identified at the Departments of Neurology and Pediatrics, Innsbruck Medical University, Austria. All underwent high-resolution MRIs (1.5-T) between 01.01.2002 and 31.12.2011. Midbrain-hindbrain structures were visually assessed by three independent raters. MHM were seen in 17% (38/220) of patients. The rate of patients wMHM and w/oMHM differed significantly (p=0.004) in three categories of MCD (category I - to abnormal neuronal proliferation; category II - to abnormal neuronal migration; and category III - due to abnormal neuronal late migration/organization): MCD due to abnormal neuronal migration (31%) and organization (23%) were more commonly associated with MHM compared to those with MCD due to abnormal neuronal proliferation (9%). Extensive bilateral MCD were seen more often in patients wMHM compared to those w/oMHM (63% vs. 36%; p=0.004). In wMHM group compared to w/oMHM group there were higher rates of callosal dysgenesis (26% vs. 4%; p<0.001) and hippocampal abnormalities (52% vs. 27%; p<0.001). Patients wMHM were younger (median 25 years vs. 30 years; p=0.010) at the time of assessment and had seizure onset at an earlier age (median 5 years vs. 12 years; p=0.043) compared to those w/oMHM. Patients wMHM had higher rates of learning disability (71% vs. 38%; p<0.001), delayed developmental milestones (68% vs. 35%; p<0.001) and neurological deficits (66% vs. 47%; p=0.049) compared to those w/oMHM. The groups (wMHM and w/oMHM) did not differ in their response to antiepileptic treatment, seizure outcome, seizure types, EEG abnormalities and rate of status epilepticus. Presence of MHM in patients with MCD and epilepsy is associated with severe morphological and clinical phenotypes.

Caffeine and cognition in functional magnetic resonance imaging.

Caffeine has been consumed since ancient times due to its beneficial effects on attention, psychomotor function, and memory. Caffeine exerts its action mainly through an antagonism of cerebral adenosine receptors, although there are important secondary effects on other neurotransmitter systems. Recently, functional MRI (fMRI) entered the field of neuropharmacology to explore the intracerebral sites and mechanisms of action of pharmacological agents. However, as caffeine possesses vasoconstrictive properties it may interfere with the mechanisms underlying the functional contrast in fMRI. Yet, only a limited number of studies dealt with the effect of caffeine on measures in fMRI. Even fewer neuroimaging studies examined the effects that caffeine exerts on cognition: Portas and colleagues used fMRI in an attentional task under different levels of arousal (sleep deprivation or caffeine administration), concluding that the thalamus is involved in mediating the interaction of attention and arousal. Bendlin and colleagues found caffeine to stabilize the extent of neuronal activation in repetitive word stem completion, counteracting the general task practice effect. Recently, Koppelstaetter and colleagues assessed the effect of caffeine on verbal working memory demonstrating a modulatory effect of caffeine on brain regions (medial frontopolar and anterior cingulate cortex) that have been associated with attentional and executive functions. This review surveys and discusses neuroimaging findings on 1) how caffeine affects the contrast underlying fMRI techniques, particularly the blood oxygen level dependent contrast (BOLD fMRI), and 2) how caffeine operates on neuronal activity underlying cognition, to understand the effect of caffeine on behavior and its neurobiological underpinnings.