Clinical Neuroscience

[The role of ventromedial prefrontal cortex in addictological disorders]

KELEMEN Oguz, MÁTTYÁSSY Adrienn, KÉRI Szabolcs

FEBRUARY 10, 2004

Clinical Neuroscience - 2004;57(01-02)

[Recently a significant conceptual change emerged in the interpretation of addictological disorders. Despite this significant progress, the exact neuronal mechanisms of these disorders are still unknown. By the development of cognitive neuroscience novel clinical tests became available which are devoted to the evaluation of more properly defined neuronal structures. These novel approaches are designed to separately investigate memory/attention-related and affective processes in decision- making. These investigations along with animal models and functional neuroimaging approaches suggest the crucial role of a complex neuronal network in the pathomechanism of addictolo-gical disorders, including the ventromedial prefrontal cortex and the amygdala-accumbens system. The aim of this paper is to review these novel findings in order to gain insight into the neurocognitive mechanisms of addictological disorders.]



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Clinical Neuroscience

[Effect of mental arithmetic and verbal fluency on the flow velocity in the middle cerebral arteries]


[Introduction - Using transcranial Doppler sonography (TCD), changes in blood flow velocity (BFV) can be measured in the Medial Cerebral Artery (MCA) during cognitive effort. Our goal was to define the time-course and laterality of BFV in healthy vo-lunters during arithmetic and verbal fluency tasks according to handedness. Methods - Twelve subjects (8 right-handed, 4 left-handed) were assessed. The TCD registered BFV in both MCA simultaneously. Heart rate was also recorded using TCD. Finally we included a 16-channel EEG. BFV laterality index (LI) was calculated. Participants were asked to count silently and generate words beginning with a specified letter. To estimate hemispheric differences in BFV, two-tailed Wilcoxon tests were utilized along with correlational analyses. Results - During cognitive effort the BFV changed in a triphasic manner in all participants. A 6-8% elevation of BFV was observed in MCAs without latency at the time of the evoking signal. Laterality of BFV developed after 5-13 seconds during cognitive effort in right-, and several seconds later in left-handed subjects. During tasks the BFV increased in the dominant hemis-phere up to 2.6-4.7% compared to the subdominant one. We also calculated the LI. During the verbal task the LI agreed with the handedness in 9 out of 12 subjects. During the mental arithmetic task, agreement was found in 6 out of 12 subjects. According to LI results we found a discrepancy between verbal and arithmetic tests in 3 out of 12 subjects. Conclusion - Cognitive effort elicites significant bilateral BFV increases in the MCAs, which suggests fast neurogenic regulation. The course of BFV during mental arithmetic proved to be different from course BFV assessed during the word fluency task. Based on the laterality of the BFV, the word-generation task was more sensitive in determining the dominant hemisphere when compared to the mental arithmetic task. The use of LI may help to estimate hemispheric functions even in pathologic circumstances.]

Clinical Neuroscience

[Multiple sclerosis to date: diagnosis, epidemiology, new aspects of the pathomechanism and the therapy]

BENCSIK Krisztina

Clinical Neuroscience

[A novel analgesic made from cannabis]


[Bayer AG has recently announced that it acquired exclusive rights for the marketing of GW Pharmaceuticals´ new medicine Sativex® in Europe and in other regions. Sativex is a sublingual spray on Cannabis extract basis, and is equipped with an electronic tool to facilitate accurate dosing and to prevent misuses. It is standardized for the THC and CBD. The new analgesic is proposed for the treatment of muscle spasticity and pains accompanying multiple sclerosis and as an efficient analgetic for neurogenic pain not responding well to opioids and to other therapies available. The entirely new mechanism of action through the recently discovered cannabinoid receptor system may offer a real therapeutic potential to the drug. Although the Government of Netherlands has authorized the sale of pharmaceutical grade Cannabis herb by pharmacies in the Netherlands, the availability on the pharmaceutical market of the registered preparation may render requests for the authorization of the smoking of Cannabis herb (marihuana) by individuals suffering of multiple sclerosis, neurogenic pain, AIDS wasting syndrome unnecessary. Nevertheless, the ”old chameleon” plant Cannabis appears to gradually regain its previous status in mainstream therapy and pharmacy. As long as the plant Cannabis and its products continue to be classified as narcotic drugs, medical use of the new preparation will need close supervision.]

Clinical Neuroscience

[Brachytherapy of brain stem tumours]

JULOW Jenő, VIOLA Árpád, MAJOR Tibor, VALÁLIK István, SÁGI Sarolta, MANGEL László, KOVÁCS Rita Beáta, REPA Imre, BAJZIK Gábor, NÉMETH György

[Introductions - The optimal therapy of brain stem tumours of different histopathology determines the expected length of survival. Authors report 125Iodine interstitial irradiation of brain stem tumours with stereotactic brachytherapy. Case reports - Two patients having brain stem tumours were suffering from glioma or from metastases of a carcinoma. In Case 1 the tumour volume was 1.98 cm3 at the time of planning interstitial irradiation. The control MRI examination performed at 42 months post-op showed a postirradiation cyst size of 5.73 cm3 indicating 65.5% shrinkage. In Case 2 the shrinkage was more apparent as the tumour vo-lume measured on the control MRI at 8 moths post-op was only 0.16 cm3 indicating 97.4% shrinkage of the 6.05 cm3 target volume at the time of brachytherapy with the metastasis practically disappearing. Quick access to histopathological results of the stereotactic intraoperative biopsy made it possible to carry out the 125Iodine stereotactic brachytherapy immediately after the biopsy, resulting in less inconvience for patients of a second possible intervention. The control MRI scans show significant shrinkage of tumours in both patients. Conclusion - The procedure can be performed as a biopsy. The CT and image fusion guided 125Iodine stereotactic brachytherapy can be well planned dosimetrically and is surgically precise.]

Clinical Neuroscience

[Clinical features and molecular diagnosis of spinocerebellar ataxia]


[In the past decade, a great progress has been made in understanding genetic basis of the spinocerebellar ataxia. Based upon the genotypes, more then 20 subgroups of autosomal dominant spinocerebellar ataxia have been identified with different gene mutations. Neither the pathomechanism nor the function of these genes is fully understood. In these disorders the main clinical sign is ataxia. Other symptoms may be present as well, but no speci-fic clinical feature is known for differentiating subgroups. Specific diagnosis can be made by genetic tests. In this review we summarize the clinical features and genetic backgrounds of the most common spinocerebellar ataxias.]

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[Dual diagnosis of addiction ]


[Psychopathology is significantly high among individuals with addiction problems compared to other populations. We look at the dynamic and nature of these correlations, and address the specific treatments of such comorbidities, as well as the vulnerabilities of professionals working in the field. Few typical cases of interactions between drug use and mental disorders will be presented to provide example of the complexity and importance of dual-diagnosis. ]

Clinical Neuroscience


MÁTYÁS Ferenc, WATANABE Masahiko, MACKIE Ken, KATONA István, FREUND F. Tamás

[Several abused drugs are known to alter glutamatergic signaling in reward pathways of the brain, and these plastic changes may contribute to the establishment of addiction- related behaviour. Glutamatergic synapses of the prefrontal cortical projections to the nucleus accumbens (nAcb) - which are suggested to be under endocannabinoid (eCB) control - play a central role in the addiction process. The most abundant eCB in the brain is 2-arachidonoyl- glycerol (2-AG). It is synthesized by diacylglycerol lipase alpha (DGL-α), and exerts its action via type 1 cannabinoid receptors (CB1). However, the precise localization of DGL-α and CB1 - i.e. the sites of synthesis and action of 2AG - is still unknown. At the light microscopic level, immunocytochemistry revealed a granular pattern of DGL-α distribution in the core of the nAcb. Electron microscopic analysis confirmed that these granules corresponded to the heads of dendritic spines. On the other hand, presynaptic axon terminals forming excitatory synapses on these spineheads were found to express CB1 receptors. Our results demonstrate that the molecular constituents for a retrograde endocannabinoid control of glutamatergic transmission are available in the core of the nAcb, and their relative subcellular location is consistent with a role of 2-AG in addiction-related plasticity of cortical excitatory synapses in this reward area.]

Clinical Neuroscience

Neuroscience highlights: Main cell types underlying memory and spatial navigation

KRABOTH Zoltán, KÁLMÁN Bernadette

Interest in the hippocampal formation and its role in navigation and memory arose in the second part of the 20th century, at least in part due to the curious case of Henry G. Molaison, who underwent brain surgery for intractable epilepsy. The temporal association observed between the removal of his entorhinal cortex along with a significant part of hippocampus and the developing severe memory deficit inspired scientists to focus on these regions. The subsequent discovery of the so-called place cells in the hippocampus launched the description of many other functional cell types and neuronal networks throughout the Papez-circuit that has a key role in memory processes and spatial information coding (speed, head direction, border, grid, object-vector etc). Each of these cell types has its own unique characteristics, and together they form the so-called “Brain GPS”. The aim of this short survey is to highlight for practicing neurologists the types of cells and neuronal networks that represent the anatomical substrates and physiological correlates of pathological entities affecting the limbic system, especially in the temporal lobe. For that purpose, we survey early discoveries along with the most relevant neuroscience observations from the recent literature. By this brief survey, we highlight main cell types in the hippocampal formation, and describe their roles in spatial navigation and memory processes. In recent decades, an array of new and functionally unique neuron types has been recognized in the hippocampal formation, but likely more remain to be discovered. For a better understanding of the heterogeneous presentations of neurological disorders affecting this anatomical region, insights into the constantly evolving neuroscience behind may be helpful. The public health consequences of diseases that affect memory and spatial navigation are high, and grow as the population ages, prompting scientist to focus on further exploring this brain region.