Background: Amygdalae play a central role in emotional processing by interconnecting frontal cortex and other brain structures. Unilateral amygdala enlargement (AE) is associated with mesial temporal lobe epilepsy (mTLE). In a relatively large sample of patients with mTLE and AE, we aimed to evaluate functional integration of AE in emotion processing and to determine possible associations between fMRI activation patterns in amygdala and deficits in emotion recognition as assessed by neuropsychological testing. Methods: Twenty-two patients with drug resistant unilateral mTLE due to ipsilateral AE were prospectively recruited in a large epilepsy unit and compared with 17 healthy control subjects in terms of amygdala volume, fMRI activation patterns and performance in emotion recognition as assessed by comprehensive affect testing system (CATS) and Ekman faces. All patients underwent structural and functional 1.5 Tesla MRI, electro-clinical assessment and neuropsychological testing. Results: We observed BOLD signal ipsilateral to AE ( n = 7; group PAT1); contralateral to AE ( n = 6; group PAT2) and no activation ( n = 9; group PAT3). In the region of interest (ROI) analysis, beta estimates for fearful face > landscape contrast in the left amygdala region did not differ significantly in patients with left TLE vs. patients with right TLE [ T (16) = −1.481; p = 0.158]. However, beta estimates for fearful face > landscape contrast in the right amygdala region were significantly reduced in patients with right TLE vs. patients with left TLE [ T (16) = −2,922; p = 0.010]. Patients showed significantly lower total scores in CATS and Ekman faces compared to healthy controls. Conclusion: In our cohort, patients with unilateral mesial TLE and ipsilateral AE, an amygdala could display either functional integration in emotion recognition or dysfunction as demonstrated by fMRI. Perception and recognition of emotions were impaired more in right-sided mTLE as compared to left-sided mTLE. Neuropsychological tests showed deficits in emotion recognition in patients as compared to healthy controls.

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 = (VL – VR)/(VL + VR) × 100, where VL and VR 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.

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. (C) 2016 Wiley Periodicals, Inc.

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.

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.

Previous studies have reported decision-making deficits in patients affected by mesial temporal lobe epilepsy (TLE). The aim of the study described here was to assess the specificity of these deficits by comparing performance of patients with neocortical TLE, patients with mesial TLE, and healthy controls. The mesial TLE group performed lower than healthy controls and the neocortical TLE group in decision making under initial ambiguity. Although patients with neocortical TLE and controls showed a significant learning effect over the blocks of the Iowa gambling task, performance of patients with mesial TLE did not improve from the first to the last block of trials. Results suggest that TLE associated with neocortical brain abnormalities does not have deleterious effects on decision making as is found for epilepsy caused by mesial temporal lobe pathologies. The present findings highlight the specificity of the mesial temporal lobes in reward-based, adaptive learning and decision making.

There is no consensus as to whether mesial temporal lobe epilepsy (MTLE) leads to executive function deficits. In this study, we adopted an extensive neuropsychological test battery and assessed different executive functions in chronic, unilateral MTLE. Performance of MTLE patients was compared with that of healthy peers and with normative data. Several MTLE patients had scores below cut-off or below the 10th percentile of normative data. Scores of the whole patient group were overall in the average range of normative data. Relative to controls, MTLE patients performed poorly in tests of working memory, cognitive flexibility, categorical verbal fluency, set-shifting, categorization, and planning. These findings raise an important methodological issue as they suggest that executive function deficits in chronic MTLE may be individually variable and that their assessment should include different tests. Deficits in chronic MTLE are not limited to temporal lobe functions, such as memory, but may extend to extra temporal cognitive domains, such as executive functions.

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.

Decision making is essential in everyday life. Though the importance of the mesial temporal lobe in emotional processing and feedback learning is generally recognized, decision making in mesial temporal lobe epilepsy (mTLE) is almost unexplored so far. Twenty-eight consecutive epilepsy patients with drug resistant mTLE and fifty healthy controls performed decision tasks under initial ambiguity (participants have to learn by feedback to make advantageous decisions) and under risk (advantageous choices may be made by estimating risks and by rational strategies). A subgroup analysis compared the performance of patients affected by MRI-verified abnormalities of the hippocampus or amygdala. The effect of lesion side was also assessed. In decision under ambiguity, mTLE patients showed marked deficits and did not improve over the task. Patients with hippocampus abnormality and patients with amygdala abnormality showed comparable deficits. No difference was found between right and left TLE groups. In decision under risk, mTLE patients performed at the same level as controls. Results suggest that mTLE patients have difficulties in learning from feedback and in making decisions in uncertain, ambiguous situations. By contrast, they are able to make advantageous decisions when full information is given and risks, possible gains and losses are exactly defined.

[Case records of Epileptic Disorders. Anatomo-electro clinical correlations. Case 01-2009]. Tuberous sclerosis complex (TSC) is a multisystem genetic disorder with variable phenotypic expression, caused by mutations in one of the two tumor suppressor genes, TSC1 or TSC2. Epilepsy is the most common neurological presentation and seizures are often medically intractable. Definition of the epileptogenic zone during presurgical evaluation is challenging given the multiple potentially epileptogenic lesions visible on MRI. However, TSC patients may nevertheless achieve seizure freedom, when preoperative evaluation yields concordant results. The strategies used in these patients vary substantially among different epilepsy surgery centres. We present a 21-year-old right-handed, intellectually not impaired woman with TSC and medically intractable seizures since the age of 15 years. Careful multi-stage presurgical evaluation, including prolonged video-EEG-monitoring, cerebral high resolution MRI, ictal and interictal [99m Tc]HMPAO-SPECT, [18 F]FDG-PET and further invasive recordings with subdural and depth electrodes led to the identification of an epileptogenic tuber with concordant seizure onset zone in the right neocortical temporal lobe. A tailored resection was performed leading to excellent surgical outcome (follow-up 12 months, Engel class I).

Neurodevelopmental changes regarding interference and magnitude processing were assessed in 3 age groups (children, n = 10; young adults, n = 11; elderly participants, n = 9) by using an functional magnetic resonance imaging version of the numerical Stroop task. Behaviorally, comparable distance and size congruity effects were found in all 3 age groups. Distance effects were most pronounced in the more difficult numerical task, whereas size congruity effects were comparable across tasks. In response to interference, an age-linear trend in the pattern of activation in left and right prefrontal and left middle temporal regions of the brain was observed. This implicates that with increasing age interference control requires increasing effort (possible explanations for children's relatively lower interference effects are provided). In contrast, the distance effect produced a negative linear trend in right prefrontal, supplementary motor area, and intraparietal cortex. This suggests that relative to old adults, children and young adults had to recruit a larger network upon processing magnitude. The latter findings are even more remarkable considering that the behavioral effects were similar across groups. In summary, the developmental trajectories of interference control and magnitude processing differ, although these cognitive functions activate partially overlapping brain regions.

Polymicrogyria is a malformation of cortical organisation morphologically marked by an irregular brain surface with multiple excessively folded small gyri. Cortical thickness is reduced but appears increased in some areas as a result of the fusion of small gyri. On magnetic resonance imaging polymicrogyria is delineated by an abnormal gyral pattern, increased cortical thickness and irregularity of the cortical-white matter junction.

Aim of this functional magnetic resonance imaging (fMRI) study was to dissociate normal aging and minimal cognitive impairment (MCI) concerning magnitude processing and interference control. We examined the neural correlates of a numerical Stroop task in elderly individuals with and without MCI. Fifteen elderly participants (six patients with MCI and nine controls) were subjected to a numerical Stroop task requiring numerical/physical magnitude classifications while inhibiting task-irrelevant stimulus dimensions. Effects of distance and congruity were examined. Behaviourally, robust distance and congruity effects were observed in both groups and tasks. Imaging baseline conditions revealed stronger and more distributed activations in MCI patients relative to controls which could not be explained by the higher error rates committed by patients. Across tasks, conjunction analysis revealed highly significant activations in intra-parietal and prefrontal regions suggesting that both groups recruit comparable brain regions upon processing magnitude and interference, respectively. MCI patients exhibited stronger pre-/postcentral and thalamic activations, possibly reflecting more effortful response-selection processes or alternatively, deficient inhibitory control. Moreover, MCI patients exhibited additional activations in fronto-parietal (magnitude) and occipital/cerebellar (congruity) regions. To summarize, though MCI patients needed to recruit more distributed activation patterns conjunction analysis revealed common activation sites in response to magnitude processing and interference control.

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.

Background: Patients with alcohol addiction show a number of transient or persistent neurological and psychiatric deficits. The complexity of these brain alterations suggests that several brain areas are involved, although the definition of the brain alteration patterns is not yet accomplished.Aim: To determine brain atrophy patterns in patients with alcohol dependence.Methods: Voxel-based morphometry (VBM) of grey matter (GM) and white matter (WM) was performed in 22 patients with alcohol dependence and in 22 healthy controls matched for age and sex.Results: In patients with alcohol dependence, VBM of GM revealed a significant decrease in density (p < 0.001) in the precentral gyrus, middle frontal gyrus, insular cortex, dorsal hippocampus, anterior thalamus and cerebellum compared with controls. Reduced density of WM was found in the periventricular area, pons and cerebellar pedunculi in patients with alcohol addiction.Conclusions: Our findings provide evidence that alcohol addiction is associated with altered density of GM and WM of specific brain regions. This supports the assumption that alcohol dependence is associated with both local GM dysfunction and altered brain connectivity. Also, VBM is an effective tool for in vivo investigation of cerebral atrophy in patients with alcohol addiction.

In this functional MRI experiment, encoding of objects was associated with activation in left ventrolateral prefrontal/insular and right dorsolateral prefrontal and fusiform regions as well as in the left putamen. By contrast, correct recognition of previously learned objects (R judgments) produced activation in left superior frontal, bilateral inferior frontal, and right cerebellar regions, whereas correct rejection of distractor objects (N judgments) was associated with activation in bilateral prefrontal and anterior cingulate cortices, in right parietal and cerebellar regions, in the left putamen, and in the right caudate nucleus. The R minus N comparison showed activation in the left lateral prefrontal cortex and in bilateral cingulate cortices and precunei, while the N minus R comparison did not reveal any positive signal change. These results support the view that similar regions of the frontal lobe are involved in episodic encoding and retrieval processes, and that the successful episodic retrieval of newly learned objects is mainly based on a frontoparietal network.

The present functional magnetic resonance imaging (fMRI) study investigates modifications of brain activation patterns related to the training of two different arithmetic operations, multiplication and subtraction. Healthy young adults were trained in five sessions to answer multiplication and subtraction problems. In the following fMRI session, trained and new untrained problems closely matched for difficulty were presented in blocked order. Contrasts between untrained and trained operations showed stronger activation of inferior frontal and parietal regions, especially along the banks of the intraparietal sulcus. The reverse contrasts, trained minus untrained operations, yielded significantly higher activation in the left angular gyrus for multiplication but no significantly activated area for subtraction. This suggests that training leads to a reduction of general purpose processes, such as working memory and executive control in both operations, indicated by the decrease of activation in inferior frontal areas. For multiplication, however, the increase of activation in the left angular gyrus indicates a switching of cognitive processes. Trained subtraction therefore seems to lead to faster and more efficient strategies, while trained multiplication showed a shift from quantity-based processing (supported by the areas along the intraparietal sulci) to more automatic retrieval (supported by the left angular gyrus). The same training method caused changes in brain activation patterns that depended on the given operation. The effects of learning on the brain therefore seem not only to depend on the method of learning but also on its content.