[Neuroscience of creativity or can the ungraspable be captured?] / A kreativitás idegtudománya, avagy megragadható-e a megfoghatatlan?

Creativity is a particularly complex entity that can be best conceptualized along dimensions of opposite polarities. It can simultaneously be considered as a phenomenon that comprises a multitude of processes but also be interpreted as a complex construct which indeed does not have a uniformly accepted definition despite extensive literature on creativity. Creativity researchers of various approaches offer alongside methodological diversity a vast array of paradigms and definitions, leading, on the other hand, to contradictions of results. Nevertheless, the concept of creativity is to be maintained in the sense that it encompasses the ability to produce innovatively original, valuable, adaptive solutions breaking with pre-existing categories and developing unconventional alternatives. Since creativity cannot definitely be subject of scientific investigations as an overarching entity and its essence has not been grasped so far, some of its components can be measured and defined such as specific cognitive processes (divergent and convergent thinking, remote associations, conceptual expansion, working memory), motivational factors, emotional/affective conditions or personality traits considered as predictors of creative performance (schizotypal, autistic spectrum traits). Even though definitional inconsistencies persist, gradually neurobiological approaches have become the main issue of creativity research. Recently, the analysis of brain network activity applying methods of electrophysiology and brain imaging seems to promote the understanding of the functional localization of creative performance. Certain brain regions were initially identified as correlates of creativity, such as lateral prefrontal cortex, inferior parietal lobe, insula, striatum. More recent studies emphasize the activation and effective functional connectivity of large brain networks (default mode network, frontoparietal executive control, and others) as well as highlight the importance of their brain and neurochemical substrate (gray matter volume, white matter integrity, dopamine), connecting with cognitive processes of opposite style (flexibility versus persistence). While this paradigm seems to converge toward the delineation of a coherent neurobiological model of creativity, obviously we would not infer the essence of such a complex phenomenon from a simplified sub-process. Orv Hetil. 2023; 164(18): 683-693.

[The facets of creativity in the light of bipolar mood alterations]. / A kreativitás arculatai a bipoláris hangulatzavar tükrében.

The link between creativity, as the highest expression form of human achievement, and bipolar disorder came into focus of scientific investigations and research. Accomplished writers, composers and visual artists show a substantially higher rate of affective disorders, prodominantly bipolar mood disorders, comparing to the general population. Then again, patients afflicted with bipolar II subtype (hypomania and depression), as well as persons presenting the mildest form of bipolar mood swings (cyclothymia) possess higher creative skills. It evokes therefore that certain forms and mood states of bipolar disorder, notably hypomania might convey cognitive, emotional/affective, and motivational benefits to creativity. The aim of this paper is to display expression forms of creativity (writing, visual art, scientific work) as well as productivity (literary and scientific work output, number of artworks and exhibitions, awards) in the light of clinically diagnosed mood states at an eminent creative individual, treated for bipolar II disorder. Analysing the affective states, we found a striking relation between hypomanic episodes and visual artistic creativity and achievement, as well as scientific performance, whereas mild-moderate depressed mood promoted literary work. Severe depression and mixed states were not associated with creative activities, and intriguingly, long-term stabilised euthymic mood, exempted from marked affective lability, is disadvantageous regarding creativity. It seems, thereby, that mood functions as a sluice of creativity. Nevertheless, it is likely that there is a complex interaction between bipolar mood disorder spectrum and psychological factors promoting creativity, influenced also by individual variability due to medication, comorbid conditions, and course of disorder.

The "blue" side of glutamatergic neurotransmission: NMDA receptor antagonists as possible novel therapeutics for major depression.

In spite of the wide-ranging, continuously expanding arsenal of antidepressants and intensive research on depression, the treatment of severe, recurrent mood disorders as well as antidepressant-resistant refractory mood disturbances has not yet entirely been solved. In this article we attempt to review some data from the growing body of evidence that underlie the presumed implication of the glutamatergic neurotransmission in severe mood disorders and thereby some strategies allowing reinstatement of the normal functioning of the glutamatergic system, particularly through N-methyl-d-aspartate (NMDA) receptors. Thus, here we focus on one of the most promising ones, the NMDA receptor-modulating agents including competitive NMDA antagonists, glycine site partial antagonists and channel site antagonists: high- and low-affinity non-competitive NMDA receptor blockers. The glutamate-modulating therapies that specifically affect this system, above all low-affinity non-competitive NMDA receptor antagonists such as amantadine and its derivative memantine which are clinically well tolerated and currently used in other indications hold considerable promise for the development of new, improved antidepressants to treat severe, recurrent and refractory mood disorders.

Single-dose and chronic corticosterone treatment alters c-Fos or FosB immunoreactivity in the rat cerebral cortex.

The aim of this study was to examine the effects of single-dose and chronic corticosterone treatment on the inducible transcription factor c-Fos and FosB, and thereby to estimate the effects of high-doses of corticosterone on calcium-dependent neuronal responses in the rat cerebral cortex. At the same time we investigated the distribution of interneurons containing calretinin (CR), vasoactive intestinal polypeptide (VIP) and neuropeptide Y (NPY) in chronically treated animals in order to collect data on the involvement of inhibitory neurons in this process. Adult male rats were injected subcutaneously with 10mg corticosterone, whereas controls received the vehicle (sesame oil). The animals were fixed by transcardial perfusion 12 and 24h following single corticosterone injection, and the brains were processed for c-Fos and FosB immunohistochemistry. To investigate the effects of repeated corticosterone administration, rats were daily treated with the same amount of corticosterone (10mg/animal, subcutaneously) for 21 days. Controls were injected with vehicle. At the end of the experiment, the rats were perfused and immunohistochemistry was used to detect the presence of the FosB protein, CR, VIP and NPY. Quantitative evaluation of immunolabelled cells was performed in the neocortex and the hippocampus. The number of immunoreactive nuclei per unit area was used as a quantitative measure of the effects of corticosterone. It was found that a single-dose administration of corticosterone resulted in a significant, time-dependent increase of c-Fos protein immunoreactivity in the granule cell layer of the dentate gyrus, as well as in regions CA1 and CA3 of the hippocampus 12 and 24h post-injection with respect to control animals. Significant enhancement of c-Fos immunoreactivity was also observed in the neocortex at 12 and 24h post-injection. Single-dose treatment did not significantly alter FosB immunolabelling. Repeated administration of corticosterone produced a complex pattern of changes in FosB immunolabelling: significant increase in FosB immunoreactivity was detected in the granule cell layer of the dentate gyrus, with no significant changes in the CA1 and CA3 layers of the hippocampus and in the neocortex. However, a significant decrease of FosB induction in the neocortex was observed in chronically treated rats in comparison to single-dose injected animals (12h before immunohistochemistry). Analysis of immunohistochemical detection of interneuronal markers revealed a significant reduction of the CR immunolabelling in the CA3 area of the hippocampus. No changes in VIP or NPY immunoreactivity were found in the Ammon's horn 3 weeks following daily corticosterone treatment. NPY immunoreactivity was significantly attenuated in the neocortex. The present data suggest that single-dose corticosterone treatment increases immunoreactivity of c-Fos protein in a time-dependent manner, 12 and 24h post-injection in the rat hippocampus and the neocortex, whereas chronic corticosterone treatment influences FosB immunoreactivity, primarily in the dentate gyrus. Chronic corticosterone administration seems to affect CR levels in the CA3 area of the hippocampus.

[Amnesic syndrome following lesion of the fornix or does reversible Korsakow's syndrome exist?]. / Fornix léziót követo amnesztikus szindróma, avagy létezik-e reverziblis Korsakow szindróma?

The 53-year-old female patient had suffered massive subarachnoid bleeding due to rupture of left-localized aneurysm of the anterior communicant artery. Following the neurosurgical intervention, deterioration of consciousness related to strong vasospasm occurred. Cerebral CT examination was performed, showing a 0.5 cm ischaemic lesion of the left hippocampal fornix. Due to intensive therapy, the patient recovered gradually, however considerable short-time memory deficit and severe anterograde amnesia remained. Admission of the patient in psychiatric care 5 weeks after the operation was necessary since acute deterioration had been added to memory disturbance and anterograde amnesia. Clinical features included severe short-time memory deficit, continuous and severe anterograde amnesia, disorientation, alterations of verbal fluency and abstraction. The amnesic syndrome was probably related to the hippocampal damage, but considering the development of cognitive deficits, cerebral CT was performed again, which verified internal hydrocephalus. A ventriculo-peritoneal shunt has been implanted and the patient was re-admitted in psychiatry care because of her memory deficit, anterograde amnesia and disorientation. Thereafter, low doses of citalopram and donepezil therapy was started together with temporarily used antipsychotic medication (risperidone). Gradual, but continuous improvement of memory and cognitive function could be detected, with total recovery after one year. The deficits in long- and short-term memory, orientation and cognition were totally restored.

Alterations of seizure-induced c-fos immunolabelling and gene expression in the rat cerebral cortex following dexamethasone treatment.

We examined the effects of dexamethasone on the expression of the inducible transcription factor c-fos in 4-aminopyridine (4-AP) seizures. Induction of c-fos mRNA due to 4-AP-elicited convulsion was detected by means of the polymerase chain reaction (PCR) in samples from the neocortex. Adult male rats were pretreated with different doses of dexamethasone (0.5, 1, 3, 5mg/kg body weight); 1h later 5mg/kg 4-AP was injected intraperitoneally. Controls received the solvent of dexamethasone. Pretreatment with dexamethasone provided significant symptomatic protection against 4-AP-induced convulsions. Immunohistochemistry was used to evaluate the presence of the c-fos protein. The number of Fos-immunoreactive nuclei per section area was measured in the neocortex and hippocampus. Pretreatment with dexamethasone resulted in a dose-dependent, significant decrease of seizure-induced Fos-protein immunoreactivity in the neocortex, in the hilum of the dentate fascia, as well as in regions CA1-3 of the hippocampus, compared to control animals. Brains processed for mRNA isolation and PCR, displayed a significant increase of c-fos mRNA following the 4-AP treatment, while pretreatment with dexamethasone did not prevent or decrease this boosted c-fos mRNA expression. We conclude that seizure-induced c-fos expression and intracellular Fos-protein localization are mediated by transmitter and receptor systems, and dexamethasone significantly decreases Fos immunoreactivity, probably by regulating the intracellular traffic of the protein. We also conclude that dexamethasone does not interfere with the genomic regulation of c-fos mRNA synthesis.

Non-competitive NMDA receptor antagonists moderate seizure-induced c-fos expression in the rat cerebral cortex.

We examined the effects of non-competitive NMDA glutamate receptor antagonists on seizures elicited by 4-aminopyridine (4-AP), and in particular, on the expression of the transcription factor c-fos induced by these seizures. Induction of c-fos mRNA due to 4-AP-elicited seizures was ascertained by reverse transcription polymerase chain reaction in samples of the neocortex. Adult rats were pretreated with the NMDA receptor antagonists amantadine (40 mg/kg), ketamine (3mg/kg), dizocilpine (MK-801; 1mg/kg) or dextrometorphan (40 mg/kg); 4-AP (5mg/kg) was then injected i.p. Controls were treated with either antagonist only or with 4-AP only. Pretreatment with the antagonists (with the exception of amantadine) increased the latency of behavioural seizures, but not all of the antagonists caused symptomatic seizure protection. In the brains which were processed for Fos immunohistochemistry, quantitative evaluation of immunostained cells was performed in the neocortex and hippocampus. Treatment with either antagonist did not induce by itself c-fos expression, with the exception of amantadine, which caused slight Fos induction in the neocortex. Pretreatment with all the antagonists resulted in decrease of seizure-induced Fos immunoreactivity with respect to non-pretreated animals. Decrease of immunostained cells was significant in the neocortex, in the granule cell layer and hilus of the dentate gyrus, in hippocampal areas CA1 and CA2. MK-801, ketamine and dextrometorphan decreased significantly Fos immunoreactivity also in area CA3. The decrease of Fos immunostaining was not directly correlated with a suppression of behavioural seizures. The results support an important role of NMDA receptors in c-fos gene induction in acute 4-AP seizures.

Decreased cutaneous vasodilatation to isometric handgrip exercise in Alzheimer's disease.

BACKGROUND: Cutaneous active vasodilatation is a cholinergic nerve mediated function of the sympathetic nervous system and the disturbed function of cholinergic neurotransmission is known as a prominent feature of Alzheimer's disease (AD). METHODS: To assess this relationship, skin blood flow (SkBF) and other haemodynamic parameters were determined by a simple vasodilatory test, isometric handgrip exercise (IHG), in 22 late-onset sporadic type AD and 20 aged control persons (AC). RESULTS: Significantly higher cutaneous vascular resistance and decreased SkBF were found after the stimulus in the AD group. A smaller reduction (p < 0.03) of R wave intervals on the electrocardiogram was observed in the AD group compared to the AC one. After IHG, change in systolic blood pressure was less in the AD (p < 0.01) than in the AC group. CONCLUSION: Our results suggest that autonomic dysfunction affecting active vasodilator sympathetic, as well as parasympathetic functions is present in AD.