Reasoning about the implications of facial expressions: a behavioral and fMRI study on low and high social impact.

Inferring the cause of another person's emotional state is relevant for guiding behavior in social interactions. With respect to their potentially evoked behavioral reactions some emotional states like anger or happiness are considered to have high social impact while others such as fear and sadness have low social impact. We conducted a functional magnetic resonance imaging study to map the brain activation patterns related to reasoning about facial expressions of emotions with high or low social impact in twenty-six healthy volunteers with good emotional competence, self-reported empathy, and explicit facial affect recognition abilities. Our data show that empathic reasoning was faster and more accurate for high impact emotional states than for low impact emotional states. Activated brain areas involved brain circuits associated with basic and higher order empathy and decision-making in the dorsomedial and dorsolateral frontal cortex. However, activation in higher order areas was less during reasoning about emotional states of high social impact. Taken together, reasoning of high and low impact emotional states relied on similar empathy-related brain areas with reasoning about emotional states of low social impact being more erroneous and requiring more cognitive resources.

A functional magnetic resonance imaging study of visuomotor processing in a virtual reality-based paradigm: Rehabilitation Gaming System.

The Rehabilitation Gaming System (RGS) has been designed as a flexible, virtual-reality (VR)-based device for rehabilitation of neurological patients. Recently, training of visuomotor processing with the RGS was shown to effectively improve arm function in acute and chronic stroke patients. It is assumed that the VR-based training protocol related to RGS creates conditions that aid recovery by virtue of the human mirror neuron system. Here, we provide evidence for this assumption by identifying the brain areas involved in controlling the catching of approaching colored balls in the virtual environment of the RGS. We used functional magnetic resonance imaging of 18 right-handed healthy subjects (24 ± 3 years) in both active and imagination conditions. We observed that the imagery of target catching was related to activation of frontal, parietal, temporal, cingulate and cerebellar regions. We interpret these activations in relation to object processing, attention, mirror mechanisms, and motor intention. Active catching followed an anticipatory mode, and resulted in significantly less activity in the motor control areas. Our results provide preliminary support for the hypothesis underlying RGS that this novel neurorehabilitation approach engages human mirror mechanisms that can be employed for visuomotor training.

Peripheral blood levels of matrix metalloproteinase-9 predict lesion volume in acute stroke.

Matrix metalloproteinases (MMPs) have been implicated to play an important role in the destruction of the extracellular matrix in diseases of the central nervous system. This study investigated whether the expression of one of these proteases, MMP-9 in blood, is related to the size of human brain infarcts assessed with magnetic resonance imaging. Consecutively, twenty-one acute stroke patients were included prospectively into our study. In blood samples drawn within 24 h after onset, MMP-9 RNA-expression and proteolytic-activity were analyzed by quantitative polymerase chain reaction and gelatin zymography, respectively. The ischemic lesion volumes in time to peak perfusion maps and diffusion weighted imaging were measured morphometrically. RNA-expression levels of MMP-9 in peripheral blood mononuclear cells (PBMCs) correlated with the brain infarct lesion (TTP-delay 4 s, r = -0.61, p = 0.007; TTP-delay 6 s: r = -0.58, p = 0.012; DWI r = -0.47; p = 0.047). Our preliminary results demonstrate that MMP-9 RNA is upregulated in PBMCs in proportion to ischemia. These findings suggest that MMP-9 might contribute to the manifestation of ischemic brain damage. Since MMP-9 is upregulated in acute ischemia inhibition of MMP-9 may represent a complementary treatment target in acute stroke therapy.

A neural basis for general intelligence.

Universal positive correlations between different cognitive tests motivate the concept of "general intelligence" or Spearman's g. Here the neural basis for g is investigated by means of positron emission tomography. Spatial, verbal, and perceptuo-motor tasks with high-g involvement are compared with matched low-g control tasks. In contrast to the common view that g reflects a broad sample of major cognitive functions, high-g tasks do not show diffuse recruitment of multiple brain regions. Instead they are associated with selective recruitment of lateral frontal cortex in one or both hemispheres. Despite very different task content in the three high-g-low-g contrasts, lateral frontal recruitment is markedly similar in each case. Many previous experiments have shown these same frontal regions to be recruited by a broad range of different cognitive demands. The results suggest that "general intelligence" derives from a specific frontal system important in the control of diverse forms of behavior.

Valuating other people's emotional face expression: a combined functional magnetic resonance imaging and electroencephalography study.

Reading the facial expression of other people is a fundamental skill for social interaction. Human facial expressions of emotions are readily recognized but may also evoke the same experiential emotional state in the observer. We used event-related functional magnetic resonance imaging and multi-channel electroencephalography to determine in 14 right-handed healthy volunteers (29+/-6 years) which brain structures mediate the perception of such a shared experiential emotional state. Statistical parametric mapping showed that an area in the dorsal medial frontal cortex was specifically activated during the perception of emotions that reflected the seen happy and sad emotional face expressions. This area mapped to the pre-supplementary motor area which plays a central role in control of behavior. Low resolution brain electromagnetic tomography-based analysis of the encephalographic data revealed that the activation was detected 100 ms after face presentation onset lasting until 740 ms. Our observation substantiates recently emerging evidence suggesting that the subjective perception of an experiential emotional state-empathy-is mediated by the involvement of the dorsal medial frontal cortex.

CT-perfusion imaging of the human brain: advanced deconvolution analysis using circulant singular value decomposition.

According to indicator dilution theory tissue time-concentration curves have to be deconvolved with arterial input curves in order to get valid perfusion results. Our aim was to adapt and validate a deconvolution method originating from magnetic resonance techniques and apply it to the calculation of dynamic contrast enhanced computed tomography perfusion imaging. The application of a block-circulant matrix approach for singular value decomposition renders the analysis independent of tracer arrival time to improve the results.

Asymptomatic motor cortex displacement due to a giant arachnoid cyst.

Cerebral lesions are held to induce plastic changes of the brain. Less well established, however, is how much space-occupying brain lesions may only displace functional representations. In a 66-year-old man we show, by means of functional magnetic resonance imaging and transcranial magnetic stimulation, a profound displacement of the motor cortex due to a large asymptomatic arachnoid cyst. Thus, the chronically compressed brain is capable of sustaining normal brain function without utilizing the potential of cortical plasticity.

EFNS guideline on neuroimaging in acute stroke. Report of an EFNS task force.

Neuroimaging techniques are necessary for the evaluation of stroke, one of the leading causes of death and neurological impairment in developed countries. The multiplicity of techniques available has increased the complexity of decision making for physicians. We performed a comprehensive review of the literature in English for the period 1965-2005 and critically assessed the relevant publications. The members of the panel reviewed and corrected an initial draft, until a consensus was reached on recommendations stratified according to the European Federation of Neurological Societies (EFNS) criteria. Non-contrast computed tomography (CT) scan is the established imaging procedure for the initial evaluation of stroke patients. However, magnetic resonance imaging (MRI) has a higher sensitivity than CT for the demonstration of infarcted or ischemic areas and depicts well acute and chronic intracerebral hemorrhage. Perfusion and diffusion MRI together with MR angiography (MRA) are very helpful for the acute evaluation of patients with ischemic stroke. MRI and MRA are the recommended techniques for screening cerebral aneurysms and for the diagnosis of cerebral venous thrombosis and arterial dissection. For the non-invasive study of extracranial vessels, MRA is less portable and more expensive than ultrasonography but it has higher sensitivity and specificity for carotid stenosis. Transcranial Doppler is very useful for monitoring arterial reperfusion after thrombolysis, for the diagnosis of intracranial stenosis and of right-to-left shunts, and for monitoring vasospasm after subarachnoid hemorrhage. Currently, single photon emission computed tomography and positron emission tomography have a more limited role in the evaluation of the acute stroke patient.

Cingulate cortex activation and competing responses: the role of preparedness for competition.

Regional cerebral blood flow (rCBF) was studied in a task, where a preparatory stimulus (S1) cued for an imperative second stimulus (S2) which was associated with a response. Two preparatory stimuli cued unequivocally each for one response. In contrast, a third preparatory stimulus cued for two response alternatives which appeared for the same ratio (each in 50% of all trials) introducing response competition. In a first experimental condition, non-arbitrary, unambiguous stimuli were used as S1 to enable the subjects to prepare their responses. In a second and third scan, arbitrary preparatory stimuli were used during different stages of awareness for the S1-S2 association. Subjects performed this task "naive" without knowledge about the S1-S2 association and also in an experimental condition being aware of the S1-S2 association. Button presses after unambiguous, non-arbitrary preparatory stimuli activated the right middle frontal gyrus and inferior parietal lobe if S1 was associated with a definite response. When the subjects did not know the S1-S2 relation, left prefrontal cortex activation was associated with trials including definite responses. Performing the same S1-S2 response condition after subjects knew their relation right prefrontal and left parietal areas became additionally engaged. However, in the first experimental condition using unambiguous, non-arbitrary stimuli and in the third, "aware" experimental condition when S1 was coupled with two response alternatives, the anterior cingulate cortex was activated. As these experimental conditions have in common, that the preparatory stimulus shares information about the upcoming competing response alternatives they highlight the evaluative role of the anterior cingulate cortex for competing actions.

Reorganization of cerebral circuits in human brain lesion.

Recovery after focal brain lesions is supposed to be mediated by cerebral reorganization. Stroke is a powerful model to study these processes in the human brain, since middle cerebral artery infarction is a common neurological disease with a clearly defined onset of a lateralized sensorimotor deficit syndrome. Brain tumours constitute a further model differing from stroke by their slow lesion dynamics. Evidence from functional neuroimaging and transcranial magnetic stimulation will be presented showing that recovery of hand function is related to reorganization of local perilesional and large-scale circuits involving the contralesional hemisphere.

Intravenous levetiracetam in clinical practice--Results from an independent registry.

PURPOSE: Most common clinical studies with antiepileptic drugs do not reflect medical everyday practice due to their strict in- and exclusion criteria and specifications of treatment regimens. Here we present a large non-interventional registry with the intention to evaluate the spectrum of applications in daily use and the efficacy and tolerability of intravenously given levetiracetam (LEV-iv). METHODS: In a prospective approach of 17 neurological and neuropediatric centres in Germany LEV-iv treated patients of all ages were included over a period of 10 months. The observational period was 10 days with daily documentation of LEV-iv administration, type and frequency of seizures, currently used drugs and doses, and adverse events (AEs). In addition, treatment efficacy and tolerability were assessed by patients and physicians at study end as well as practicability of LEV-iv using a five-step scale. RESULTS: In 95 patients LEV-iv was administered, 93 were included into the analysis. The median LEV-iv dose was 1500 mg (range 110-6000 mg) per day. Median age was 66 years (range 0.7-90.3 years). The majority of patients (n=70, 75%) suffered from status epilepticus (SE, n=55, 59%) and acute seizure clusters (n=15, 16%). Of those with SE, 41 patients (75%) had SE for the first time. Acute seizure clusters and SE terminated in 83% after LEV-iv administration. A total of 29 adverse events were reported in 17 of the 95 patients from the safety set. Ten of these were at least possibly related to LEV-iv treatment. Slight decrease of blood pressure during the infusion (3 patients each) was captured most frequently. No serious side effect was observed. Physicians rated the efficacy and tolerability of LEV-iv treatment as good or very good in 78% and 82% of the cases, respectively. CONCLUSION: In this large observational study of everyday practise the use of LEV-iv exhibited a remarkable good response and tolerability in patients with acute onset seizures (mostly SE). Further randomized controlled studies, like the established status epilepticus trial (ESET) are needed to confirm these findings.

Individual integration of positron emission tomography and high-resolution magnetic resonance imaging.

We have developed, validated, and employed a technique of retrospective spatial alignment and integrated display of positron emission tomographic (PET) and high-resolution magnetic resonance (MR) brain images. The method was designed to improve the anatomical evaluation of functional images obtained from single subjects. In the first computational step, alignment of PET and MR data sets is achieved by iteratively matching in three orthogonal views the outermost scalp contours derived from front-to-back projections of each data set. This procedure avoids true three-dimensional modeling, runs without user interaction, and tolerates missing parts of the head circumference in the image volume, as usually the case with PET. Thereafter, high-resolution MR sections corresponding to the PET slices are reconstructed from the spatially transformed MR data. In a phantom study of this method, PET/MR alignment of the phantom's surface was accurate with average residual misfits of 2.17 to 2.32 mm as determined in three orthogonal planes. In-plane alignment of the phantom's insertion holes was accurate with an average residual misfit of 2.30 mm. In vivo application in six subjects allowed the individual anatomical localization of regional CBF (rCBF) responses obtained during unilateral manual exploration. In each subject, the maxima of the rCBF activations in the hand area were precisely allocated to gray matter in the anterior or posterior wall of the central sulcus. The configuration of the rCBF responses closely followed the gyral structures. The technique provided a better topographical understanding of rCBF changes in subtraction images of PET activation studies. It opens the perspective for studies of structural-functional relationships in individual subjects.

Quantitation of regional cerebral blood flow with 15O-butanol and positron emission tomography in humans.

We describe the implementation and validation of a combined dynamic-autoradiographic approach for measuring the regional cerebral blood flow (rCBF) with 15O-butanol. From arterial blood data sampled at a rate of 1 s and list mode data of the cerebral radioactivity accumulated over 100 s, the time shift between blood and tissue curves, the dispersion constant DC, the partition coefficient p, and the CBF were estimated by least squares fitting. Using the fit results, a pixel-by-pixel parametrization of rCBF was computed for a single 40-s (autoradiographic) 15O-butanol uptake image. The mean global CBF found in 27 healthy subjects was 49 +/- 8 ml 100 g-1 min-1. Gray and white matter rCBF were 83 +/- 20 and 16 +/- 3 ml 100 g-1 min-1, respectively, with a corresponding partition coefficient p of 0.77 +/- 0.18 and 0.77 +/- 0.29 ml/g in both compartments. The quantitative images resulted in a significantly higher gray matter rCBF than the autoradiographic images.

Accuracy and precision of the computerized brain atlas programme for localization and quantification in positron emission tomography.

The computerized brain atlas programme (CBA) provides a powerful tool for the anatomical analysis of functional images obtained with positron emission tomography (PET). With a repertoire of simple transformations, the data base of the CBA is first adapted to the anatomy of the subject's brain represented as a set of magnetic resonance (MR) or computed tomography (CT) images. After this, it is possible to spatially standardize (reformat) any set of tomographic images related to the subject, PET images, as well as CT and MR images, by applying the inverse atlas transformations. From these reformatted images, statistical images, such as average images and associated error images corresponding to different groups of subjects, may be produced. In all these images, anatomical structures can be localized using the atlas data base and the functional values can be evaluated quantitatively. The purpose of this study was to determine the spatial and quantitative accuracy and precision of the calculated regional mean values. Therefore, the CBA was applied to regional CBF (rCBF) measurements with [11C]fluoromethane and PET on 26 healthy male volunteers during rest and during three different physiological stimulation tasks. First, the spatial accuracy and precision of the reformation process were determined by measuring the spread of defined anatomical structures in the reformatted MR images of the subjects. Second, the mean global CBF and the mean rCBF in the average PET images were compared with the global CBF and rCBF in the original PET images. Our results demonstrate that the reformation process accurately transformed the individual brains of the subjects into the standard brain anatomy of the CBA. The precision of the reformation process had an SD of approximately 1 mm for the lateral dislocation of midline structures and approximately 2-3 mm for the dislocation of the inner and outer brain surfaces. The quantitative rCBF values of the original PET images were accurately represented in the reformatted PET images. Moreover, this study shows that the application of the CBA improves the analysis of functional PET images: (a) The average PET images had a low background noise [0.4 ml/100 g/min +/- 0.7 (SD)] compared to the mean rCBF changes specifically induced by physiological stimulation. (b) The reformatted PET images had a voxel volume of 10.9 mm3. Owing to this high sampling resolution, it was possible to differentiate the mean rCBF changes in adjacent activated fields such as the left motor hand area from the sensory hand area and the left premotor cortex.(ABSTRACT TRUNCATED AT 400 WORDS)

Potential time course of human immunodeficiency virus type 1-associated minor motor deficits: electrophysiologic and positron emission tomography findings.

BACKGROUND: We tested whether metabolic abnormalities in the prefrontal-striatal circuitry as demonstrated by positron emission tomography (PET) were present in patients seropositive for human immunodeficiency virus type 1 (HIV-1) with HIV-1-associated minor motor deficits as demonstrated by quantitative motor testing. PATIENTS: We examined 19 HIV-1-positive patients, covering the range from normal results of quantitative motor testing to clearly pathologic psychomotor slowing indicative of HIV-1-associated minor motor deficits. None fulfilled the clinical criteria for HIV-1-associated dementia. Results were compared with those of 15 healthy volunteers. METHODS: All subjects underwent clinical examination, routine magnetic resonance (MR) imaging, and electrophysiologic motor testing at the time of PET. RESULTS: Seven HIV-1-positive patients showed significant hypermetabolism in the basal ganglia. Nine patients showed a significant frontomesial hypometabolism. CONCLUSIONS: The data of our cross-sectional study strongly suggest a characteristic time course in the development of HIV-1-associated minor motor deficits. Hypermetabolism in the basal ganglia is associated initially with normal motor performance. Moderate motor slowing appears at a later stage when basal ganglia hypermetabolism drops toward hypometabolism. More severe functional deficits and highly pathologic motor slowing become manifest when hypometabolism is most widespread in the basal ganglia. This stage leads to dementia.

Visual hallucinations in recovery from cortical blindness: imaging correlates.

OBJECTIVE: To investigate the cerebral metabolic and functional patterns during recovery from cortical blindness. DESIGN: Follow-up study with serial clinical, metabolic, and functional imaging and visual evoked potentials. CASE PRESENTATION: A 24-year-old woman suffered from cortical blindness after cardiac arrest and recovered over a 6-month period. During recovery, she experienced complex visual hallucinations that could be initiated by visual imagery. RESULTS: Initially, the regional cerebral metabolic rate of glucose was severely reduced in the visual and parieto-occipital cortex bilaterally but recovered almost completely. Visual hallucinations led to significant increases of the regional cerebral blood flow in the initially severely hypometabolic parieto-occipital and temporo-lateral cortex. CONCLUSIONS: Recovery of vision was related to normalization of the postlesionally dysfunctional cortex. Visual hallucinations appeared as the clinical correlate of the electrophysiological hyperexcitability of the recovering partially damaged visual cortex.

Role of the premotor cortex in recovery from middle cerebral artery infarction.

OBJECTIVE: To study the mechanisms underlying recovery from middle cerebral artery infarction in 7 patients with an average age of 53 years who showed marked recovery of hand function after acute severe hemiparesis caused by their first-ever stroke. INTERVENTIONS: Assessment of motor functions, transcranial magnetic stimulation, somatosensory evoked potentials, magnetic resonance imaging, and positron emission tomographic measurements of regional cerebral blood flow during finger movement activity. RESULTS: The infarctions involved the cerebral convexity along the central sulcus from the Sylvian fissure up to the hand area but spared the caudate nucleus, thalamus, middle and posterior portions of the internal capsule, and the dorsal part of the precentral gyrus in each patient. After recovery (and increase in motor function score of 57%, P<.001), the motor evoked potentials in the hand and leg muscles contralateral to the infarctions were normal, whereas the somatosensory evoked potentials from the contralateral median nerve were reduced. During fractionated finger movements of the recovered hand, regional cerebral blood flow increases occurred bilaterally in the dorsolateral and medial premotor areas but not in the sensorimotor cortex of either hemisphere. CONCLUSIONS: Motor recovery after cortical infarction in the middle cerebral artery territory appears to rely on activation of premotor cortical areas of both cerebral hemispheres. Thereby, short-term output from motor cortex is likely to be initiated.

Topography of interictal glucose hypometabolism in unilateral mesiotemporal epilepsy.

We mapped the regional cerebral glucose metabolism (rCMRGlu) in 20 patients suffering from medically refractory focal epilepsy of either left or right mesiotemporal origin (mTLE) during resting wakefulness. After temporal lobectomy, histology demonstrated hippocampal sclerosis in 18 patients. Pixel-by-pixel comparisons with healthy control subjects showed significant (p < 0.001) depressions of the mean rCMRGlu ipsilateral to the epileptic focus in the mesiotemporal region, including the hippocampus and the parahippocampal gyrus and middle temporal gyrus. Additional remote rCMRGlu depressions occurred bilaterally in the fronto-orbital cortex and ipsilaterally in the posterior insula and the thalamus. Patients with left-sided mTLE had additional rCMRGlu depressions in the left inferior frontal gyrus (Broca's region) and superior temporal gyrus at the parietotemporal junction, whereas corresponding rCMRGlu depressions were not present in patients with right mTLE. Neuropsychological testing showed impaired verbal fluency, verbal intelligence, and verbal memory in the left mTLE patients. Correlations of the specific mean rCMRGlu depressions and the neuropsychological deficits suggest that impaired language functions in patients with left mTLE could result from functional changes beyond the temporal lobe.

Ictal motor signs and interictal regional cerebral hypometabolism.

Early motor manifestations are the main components of focal seizures involving the frontal lobe. We examined the relationship between the initial ictal motor manifestations and interictal abnormalities of cerebral glucose consumption (rCMRGlc) as assessed by PET in 48 consecutive patients with focal seizures of neocortical origin. Group data analysis revealed that patients with predominantly unilateral clonic seizures had a significant contralateral perirolandic hypometabolism and to a lesser degree a contralateral frontomesial hypometabolism. Patients with predominantly focal tonic manifestations showed a hypometabolism within the frontomesial and perirolandic regions that was unilateral in all patients with lateralized tonic seizures. Patients with versive seizures had mainly contralateral metabolic depressions without a consistent regional pattern. Patients with hypermotor seizures had metabolic depressions involving frontomesial, anterior cingulate, perirolandic, and anterior insular/frontal operculum areas. In all patient groups, bilateral and symmetric hypometabolism of the thalamus and cerebellum was observed. We propose that this pattern of distinctly abnormal metabolic brain regions demonstrates not only possible epileptogenic zones but also symptomatogenic brain regions as shown by the associations between clinical manifestations and sets of abnormal brain regions, particularly if epileptogenic zones are in a clinically silent neocortical brain region. The detection and possible differentiation of symptomatogenic and epileptogenic zones might improve the effectiveness of presurgical noninvasive studies.

Human anterior intraparietal area subserves prehension: a combined lesion and functional MRI activation study.

It has been shown in nonhuman primates that the posterior parietal cortex is involved in coordination of arm and eye movements in space, whereas the anterior intraparietal area in the anterior lateral bank of the intraparietal sulcus plays a crucial role in fine finger movements, such as grasping. In this study we show by optoelectronic movement recordings that patients with cortical lesions involving the anterior lateral bank of the intraparietal sulcus have selective deficits in the coordination of finger movements required for object grasping, whereas reaching is much less disturbed. Patients with parietal lesions sparing the cortex lining the anterior intraparietal sulcus showed intact grasping behavior. Complementary evidence was obtained from functional MRI in normal control subjects showing a specific activation of the anterior lateral bank of the intraparietal sulcus during grasping. In conclusion, this combined lesion and activation study suggests that the anterior lateral bank of the intraparietal sulcus, possibly including the human homologue of the anterior intraparietal area, mediates the processing of sensorimotor integration of precisely tuned finger movements in humans.