Georg Bohner

Differential activation of the dorsal striatum by high-calorie visual food stimuli in obese individuals

The neural systems regulating food intake in obese individuals remain poorly understood. Previous studies applied positron emission tomography and manipulated hunger and satiety to investigate differences in appetitive processing between obese and normal-weight individuals. However, it is not known whether manipulation of stimulus value may yield different neural activity in obese as compared to control subjects when intrinsic physiological states are kept constant. We used functional magnetic resonance imaging to investigate 13 obese and 13 normal-weight subjects and manipulated food motivation by presenting visual food stimuli differing in their caloric content and energy density. In contrast to controls, obese women selectively activated the dorsal striatum while viewing high-caloric foods. Moreover, in the high-calorie condition body mass index (BMI) predicted activation in the dorsal striatum, anterior insula, claustrum, posterior cingulate, postcentral and lateral orbitofrontal cortex. The results indicate that in obese individuals simple visual stimulation with food stimuli activates regions related to reward anticipation and habit learning (dorsal striatum). Additionally, high-calorie food images yielded BMI-dependent activations in regions associated with taste information processing (anterior insula and lateral orbitofrontal cortex), motivation (orbitofrontal cortex), emotion as well as memory functions (posterior cingulate). Collectively, the results suggest that the observed activation is independent of the physiological states of hunger and satiation, and thus may contribute to pathological overeating and obesity. Some of the observed activations (dorsal striatum, orbitofrontal cortex) are likely to be dopamine-mediated.

Cortical spreading ischaemia is a novel process involved in ischaemic damage in patients with aneurysmal subarachnoid haemorrhage

The term cortical spreading depolarization (CSD) describes a wave of mass neuronal depolarization associated with net influx of cations and water. Clusters of prolonged CSDs were measured time-locked to progressive ischaemic damage in human cortex. CSD induces tone alterations in resistance vessels, causing either transient hyperperfusion (physiological haemodynamic response) in healthy tissue; or hypoperfusion [inverse haemodynamic response = cortical spreading ischaemia (CSI)] in tissue at risk for progressive damage, which has so far only been shown experimentally. Here, we performed a prospective, multicentre study in 13 patients with aneurysmal subarachnoid haemorrhage, using novel subdural opto-electrode technology for simultaneous laser-Doppler flowmetry (LDF) and direct current-electrocorticography, combined with measurements of tissue partial pressure of oxygen (ptiO2). Regional cerebral blood flow and electrocorticography were simultaneously recorded in 417 CSDs. Isolated CSDs occurred in 12 patients and were associated with either physiological, absent or inverse haemodynamic responses. Whereas the physiological haemodynamic response caused tissue hyperoxia, the inverse response led to tissue hypoxia. Clusters of prolonged CSDs were measured in five patients in close proximity to structural brain damage as assessed by neuroimaging. Clusters were associated with CSD-induced spreading hypoperfusions, which were significantly longer in duration (up to 144 min) than those of isolated CSDs. Thus, oxygen depletion caused by the inverse haemodynamic response may contribute to the establishment of clusters of prolonged CSDs and lesion progression. Combined electrocorticography and perfusion monitoring also revealed a characteristic vascular signature that might be used for non-invasive detection of CSD. Low-frequency vascular fluctuations (LF-VF) (f < 0.1 Hz), detectable by functional imaging methods, are determined by the brains resting neuronal activity. CSD provides a depolarization block of the resting activity, recorded electrophysiologically as spreading depression of high-frequency-electrocorticography activity. Accordingly, we observed a spreading suppression of LF-VF, which accompanied spreading depression of high-frequency-electrocorticography activity, independently of whether CSD was associated with a physiological, absent or inverse haemodynamic response. Spreading suppressions of LF-VF thus allow the differentiation of progressive ischaemia and repair phases in a fashion similar to that shown previously for spreading depressions of high-frequency-electrocorticography activity. In conclusion, it is suggested that (i) CSI is a novel human disease mechanism associated with lesion development and a potential target for therapeutic intervention in stroke; and that (ii) prolonged spreading suppressions of LF-VF are a novel ‘functional marker’ for progressive ischaemia.

Gray matter abnormalities in subjects at ultra-high risk for schizophrenia and first-episode schizophrenic patients compared to healthy controls

Neuroimaging studies have revealed gray matter abnormalities in schizophrenia in various regions of the brain. It is, however, still unclear whether such abnormalities are already present in individuals at ultra-high risk (UHR) for transition into psychosis. We investigated this issue using voxel-based morphometry of structural magnetic resonance images (MRI) and compared UHR patients with first-episode patients with schizophrenia and healthy controls. Gray matter volume maps from high-resolution MR T1-weighted whole brain images were analyzed in a cross-sectional study in 30 UHR patients, 23 first-episode schizophrenic patients and 29 controls. UHR patients showed significantly lower gray matter volume in the cingulate gyrus bilaterally, in the right inferior frontal and right superior temporal gyrus, as well as in the left and right hippocampus in comparison to healthy subjects. First-episode patients with schizophrenia showed smaller gray matter volume in the cingulate cortex bilaterally, in the left orbitofrontal gyrus, in the right inferior frontal and superior temporal gyrus, in the right temporal pole, in the left and right hippocampus, in the left parahippocampus, left amygdala, and in the left fusiform gyrus compared to the UHR patients. This study provides further evidence that gray matter brain volume, especially in the anterior cingulate cortex, is already reduced in the prodromal state of schizophrenia.

The clinical and radiological spectrum of posterior reversible encephalopathy syndrome: the retrospective Berlin PRES study

The aim of the study was to characterize the clinical and radiological spectrum of posterior reversible encephalopathy syndrome (PRES) in a large cohort. The radiological report data bases of the authors′ university hospitals were searched for patients with PRES. Various imaging features at onset of symptoms and on follow-up as well as clinical and paraclinical data were tabulated in those patients fulfilling the criteria for PRES. Exploratory univariate analyses were performed. A total of 96 patients with PRES were included into the study. Wide differences in lesion location, diffusivity, distribution pattern, edema severity, hemorrhage, underlying diseases, symptoms, mean arterial pressure (MAP) and coagulation status were encountered. Hemorrhage occurred significantly more frequently in patients with altered coagulation state and was significantly associated with higher edema grades and with the presence of cytotoxic edema. There was a significant difference in MAP between toxic associations with higher MAP in infection, eclampsy and autoimmune disorders, while lower MAP was found in chemotherapy and immunsupression. In 82% of patients complete or near complete resolution of edema was noted during follow-up. Higher MAP levels were associated with incomplete edema resolution. In 43% of patients residual lesions were seen with a relatively even distribution between focal gliosis, infarction, posthemorrhagic residua, atrophy and laminar necrosis. PRES in this large hospital-based retrospective study comprises a wide radiological and clinical spectrum. Residual lesions were encountered more frequently than commonly expected. Our results point towards a differential contribution of high blood pressure to the course of PRES in different underlying etiologies.

Mechanical recanalization in basilar artery occlusion: The ENDOSTROKE study

A study was undertaken to evaluate clinical and procedural factors associated with outcome and recanalization in endovascular stroke treatment (EVT) of basilar artery (BA) occlusion.

4-D Imaging in Cerebrovascular Disorders by Using 320-Slice CT: Feasibility and Preliminary Clinical Experience

RATIONALE AND OBJECTIVES The authors report study protocols and initial clinical experience in assessing patients with acute and chronic cerebrovascular disorders using the recently introduced technique of volume computed tomography (VCT). MATERIALS AND METHODS Thirteen patients with presumptive cerebrovascular insufficiency underwent VCT using a 320-slice scanner (detector width, 160 mm), including time-resolved whole-brain perfusion and cerebral angiography (four-dimensional computed tomographic angiography [CTA] and computed tomographic perfusion [CTP]). Unenhanced cranial CT (cCT) and helical cervicocranial CT (three-dimensional CTA) were added according to clinical requirements. Study protocols are presented, and image quality, data management, and radiation exposure issues are discussed. RESULTS In 12 of 13 patients, the procedure was performed successfully on admission; in the other patient, the study was aborted for clinical reasons and repeated. Total scan time amounted to about 5 minutes, and data reconstruction times were up to 10 minutes. About 9000 primary images were generated, partially in the enhanced Digital Imaging and Communications in Medicine format, thus requiring new data postprocessing and management strategies. Image artifacts restricted the use of single-rotation cCT and incremental VCT (three-dimensional CTA). Overall exposure figures (computed tomographic dose index and dose-length product) were increased by 65% on average when three-dimensional CTA was added to volume cCT and four-dimensional CTA and CTP (5.0 mSv and 2178 mGy . cm, respectively). CONCLUSION Preliminary clinical experience indicates that whole-brain four-dimensional CTA and CTP is a robust technique that provides relevant clinical information with respect to whole-brain perfusion as well as cerebral hemodynamics. The exposure benefit of deriving time-resolved perfusion and vessel images from one source data set is compromised when adding three-dimensional CTA to the protocol. Other acquisition techniques specific to VCT, such as single-rotation cCT and incremental three-dimensional CTA, suffer from restrictions in terms of image quality at present.

White matter abnormalities in subjects at ultra high-risk for schizophrenia and first-episode schizophrenic patients

Schizophrenia is associated with neuroanatomical abnormalities. Gray matter decrease seems to predate first schizophrenic episode. Whether white matter abnormalities predate the onset of psychotic symptoms is unclear. We investigated this issue using voxel-based morphometry (VBM) of structural magnetic resonance images to examine individuals with prodromal symptoms who were at ultra high-risk (UHR) of developing schizophrenia and compared them to first-episode schizophrenic patients and healthy controls. White matter volume maps from high-resolution magnetic resonance T1 weighted whole brain images were analyzed in a cross-sectional study using SPM2 in 30 UHR patients, 23 first-episode schizophrenic patients and 29 healthy controls. UHR patients showed significant lower white matter volume in the right superior temporal lobe compared to healthy controls. First-episode patients with schizophrenia showed widespread smaller white matter volume bilaterally compared to UHR patients. This study provides first evidence for smaller white matter volume in the right temporal lobe of UHR patients, one of the key structures in the pathophysiology of schizophrenia. Furthermore, white matter abnormalities seem to progress after transition into schizophrenia.

Experimental and preliminary clinical evidence of an ischemic zone with prolonged negative DC shifts surrounded by a normally perfused tissue belt with persistent electrocorticographic depression

In human cortex it has been suggested that the tissue at risk is indicated by clusters of spreading depolarizations (SDs) with persistent depression of high-frequency electrocorticographic (ECoG) activity. We here characterized this zone in the ET-1 model in rats using direct current (DC)-ECoG recordings. Topical application of the vasoconstrictor endothelin-1 (ET-1) induces focal ischemia in a concentration-dependent manner restricted to a region exposed by a cranial window, while a healthy cortex can be studied at a second naïve window. SDs originate in the ET-1-exposed cortex and invade the surrounding tissue. Necrosis is restricted to the ET-1-exposed cortex. In this study, we discovered that persistent depression occurred in both ET-1-exposed and surrounding cortex during SD clusters. However, the ET-1-exposed cortex showed longer-lasting negative DC shifts and limited high-frequency ECoG recovery after the cluster. DC-ECoG recordings of SD clusters with persistent depression from patients with aneurysmal subarachnoid hemorrhage were then analyzed for comparison. Limited ECoG recovery was associated with significantly longer-lasting negative DC shifts in a similar manner to the experimental model. These preliminary results suggest that the ischemic zone in rat and human cortex is surrounded by a normally perfused belt with persistently reduced synaptic activity during the acute injury phase.

Multi-slice CT angiography in the evaluation of patients with acute cerebrovascular disease – a promising new diagnostic tool

Abstract Single-slice computed tomographic angiography (CTA) is an established imaging method for the cerebrovascular system (CVS), but it suffers from technical limitations with respect to the coherent high resolution visualization of longer vascular segments, such as the extra- and intracranial CVS. The recently introduced multi-slice (MS) technology has been attributed with a superior imaging quality for angiographic procedures due to increased scan speed and improved spatial resolution. The purpose of this study was to evaluate the suitability of multi-slice CTA (MS-CTA) for the assessment of the arteriovenous CVS in patients with acute symptoms of either arterial or venous occlusive diseases. 41 patients with clinically suspected acute cerebral ischaemia (hemispheric in 29 and vertebrobasilar in 12 patients) and 4 patients with suspected cerebral venous thrombosis (CVT) underwent CTA in a MS-CT scanner. In addition, doppler ultrasonography (DUS) was performed in 34, magnetic resonance angiography (MRA) in 5 and digital subtraction angiography (DSA) in 6 patients. All findings were reviewed for stenoses or occlusion of the extra- and intracranial CVS and correlated with the clinical outcome. In 43 (96 %) of 45 patients, MS-CTA yielded images of diagnostic quality with comprehensive visualization of the arterial and venous CVS including the cervical carotid bifurcation, the third segment of the major cerebral arteries and the dural sinus as well as internal cerebral veins. In 2 patients, assessment of the carotid bifurcation was limited because of tooth artefacts. In all patients, in whom imaging and clinical follow-up proved a non-lacunar infarction (n=22), MS-CTA detected the underlying vascular pathology. Suspected CVT could be confirmed in 2 and ruled out in another 2 patients through MS-CTA. In conclusion, multi-slice CT angiography may be a promising new diagnostic tool for the rapid and comprehensive assessment of the arteriovenous CVS in patients with clinical signs of acute cerebrovascular diseases.

Pineal calcification in Alzheimer's disease: an in vivo study using computed tomography.

Melatonin has been postulated to have diverse properties, acting as an antioxidant, a neuroprotector, or a stabilizer within the circadian timing system, and is thus thought to be involved in the aging process and Alzheimers disease (AD). We used computed tomography to determine the degree of pineal calcification (DOC), an intra-individual melatonin deficit marker, as well as the size of uncalcified pineal tissue, in 279 consecutive memory clinic outpatients (AD: 155; other dementia: 25; mild cognitive impairment: 33; depression: 66) and 37 age-matched controls. The size of uncalcified pineal tissue in patients with AD (mean 0.15 cm(2) [S.D. 0.24]) was significantly smaller than in patients with other types of dementia (0.26 [0.34]; P=0.038), with depression (0.28 [0.34]; P=0.005), or in controls (0.25 [0.31]; P=0.027). Additionally, the DOC in patients with AD (mean 76.2% [S.D. 26.6]) was significantly higher than in patients with other types of dementia (63.7 [34.7]; P=0.042), with depression (60.5 [33.8]; P=0.001), or in controls (64.5 [30.6]; P=0.021). These two findings may reflect two different aspects of melatonin in AD. On the one hand, the absolute amount of melatonin excretion capability, as indicated by uncalcified pineal volume, refers to the antioxidant properties of melatonin. On the other hand, the relative reduction in melatonin production capability in the individual, as indicated by DOC, refers to the circadian properties of melatonin.