Neuropsychology and early diagnosis

The presence of histopathological lesions characteristic of Alzheimer's disease, senile plaques and neurofibrillar degeneration in the brains of cognitively normal individuals has been well documented in several longitudinal clinicopathological studies over the last two decades. Clinical and pathological epidemiological data suggest that Alzheimer's disease can begin to develop almost a decade before the first clinical manifestations appear. The present article reviews the studies investigating cognitive alterations before the disease manifests. All these studies reveal the presence of alterations in preclinical phases in cognitive functions other than memory, such as those related to attention, processing speed and verbal fluency. Assessment of memory with tools sensitive to hippocampal memory impairment is recommended. The best predictor is having each individual's baseline performance, which can then be used for comparison with subsequent performance. Once reduced performance is detected (even when within the "normal" range), affected persons should be referred to specific units able to diagnose the disease in the early stages.     

The perineuronal net component of the extracellular matrix in plasticity and epilepsy

During development the extracellular matrix (ECM) of the central nervous system (CNS) facilitates proliferation, migration, and synaptogenesis. In the mature nervous system due to changes in the ECM it provides structural stability and impedes proliferation, migration, and synaptogensis. The perineuronal net (PN) is a specialized ECM structure found primarily surrounding inhibitory interneurons where it forms a mesh-like structure around points of synaptic contact. The PN organizes the extracellular space by binding multiple components of the ECM and bringing them into close proximity to the cell membrane, forming dense aggregates surrounding synapses. The PN is expressed late in postnatal development when the nervous system is in the final stages of maturation and the critical periods are closing. Once fully expressed the PN envelopes synapses and leads to decreased plasticity and increases synaptic stability in the CNS. Disruptions in the PN have been studied in a number of disease states including epilepsy. Epilepsy is one of the most common neurologic disorders characterized by excessive neuronal activity which results in recurrent spontaneous seizures. A shift in the delicate balance between excitation and inhibition is believed to be one of the underlying mechanisms in the development of epilepsy. During epileptogenesis, the brain undergoes numerous changes including synaptic rearrangement and axonal sprouting, which require structural plasticity. Because of the PNs location around inhibitory cells and its role in limiting plasticity, the PN is an important candidate for altering the progression of epilepsy. In this review, an overview of the ECM and PN in the CNS will be presented with special emphasis on potential roles in epileptogenesis.     

Neuropsychology of fear and loathing

For over 60 years, ideas about emotion in neuroscience and psychology have been dominated by a debate on whether emotion can be encompassed within a single, unifying model. In neuroscience, this approach is epitomized by the limbic system theory and, in psychology, by dimensional models of emotion. Comparative research has gradually eroded the limbic model, and some scientists have proposed that certain individual emotions are represented separately in the brain. Evidence from humans consistent with this approach has recently been obtained by studies indicating that signals of fear and disgust are processed by distinct neural substrates. We review this research and its implications for theories of emotion.     

Quality of life in childhood epilepsy with lateralized epileptogenic foci

Background  

Measuring quality of life (QOL) helps to delineate mechanisms underlying the interaction of disease and psychosocial factors. In adults, epileptic foci in the left temporal lobe led to lower QOL and higher depression and anxiety as compared to the right-sided foci. No study addressed the development of QOL disturbances depending on the lateralization of epileptogenic focus. The objective of our study was to examine QOL in children with lateralized epileptiform discharges.     

Neuropsychology: the touchy, feely side of vision

Some visual attributes, such as colour, are purely visual, but others, such as orientation and movement, can be perceived by touch or audition. A magnetic stimulation study has now shown that the perception of tactile orientation may be influenced by visual Information.     

Morphogenesis, plasticity and irreversibility

The dynamical systems theory of morphogenesis is surveyed, in which positional information is generated through intracellular reaction dynamics and cell-cell interaction. Cells differentiate because of these dynamics. In addition, these differentiated cells form an ordered spatial pattern, which further stabilizes the cellular states, leading to robust morphogenesis and irreversibility in the differentiation. Induction, community effect, gastrulation and activin-controlled artificial tissue-genesis are discussed from the perspective of this theory and the relevance of dynamics of cellular plasticity is stressed.     

LTP,memory and structural plasticity

Our current understanding of the mechanisms of information processing and storage in the brain, based on the concept proposed more than fifty years ago by D. Hebb, is that a key role is played by changes in synaptic efficacy induced by coincident pre- and postsynaptic activity. Decades of studies of the properties of long-term potentiation (LTP) have shown that this form of plasticity adequately fulfills these requirements and is likely to contribute to several models of learning and memory. Recent analyses of the molecular events implicated in LTP are consistent with the view that modifications of receptor properties or insertion of new receptors account for the potentiation of synaptic transmission. These experiments, however, have also uncovered an unexpected structural plasticity of synapses. Dendritic spines appear to be dynamic structures that can be formed, modified in their shape or eliminated under the influence of activity. Furthermore, recent studies suggest that LTP, in addition to changes in synaptic function, is also associated with mechanisms of synaptogenesis. We review here the evidence pointing to this activity-dependent remodeling and discuss the possible role of this structural plasticity for synaptic potentiation, learning and memory.     

The Neuropsychology of Individual Differences

Russian neuropsychology, created by the works of A.R. Luria and his students, is currently undergoing a period of differentiation. In addition to the two main themes—clinical and experimental neuropsychology (with their practical applications, i.e., the diagnosis and restoration of higher mental functions)—developmental neuropsychology (of childhood and old age), the neuropsychology of borderline states, the psychophysiological aspects of neuropsychology, and a number of other areas are also in the midst of a process of formation. Among the new themes that have gained importance in the past few years we have the neuropsychology of individual differences, based on application of the theories, methods, and procedures of neuropsychology to study of the mental functions of normal people.     

Neurotrophins, synaptic plasticity and dementia

The growing realization that neurotrophins, such as brain-derived neurotrophic factor (BDNF), are crucial in modulating synaptic plasticity has broadened the spectrum of their trophic actions. At the same time, it has become clear that Abeta peptides derived from amyloid precursor protein (APP) have dramatic effects on synaptic transmission before the onset of the neurodegenerative disease. Because neurotrophins and Abeta are responsible for affecting both synaptic and cognitive function, it is likely that their mechanisms of action will be related and might even intersect. This review highlights several recent findings that suggest trophic factors and APP use similar pathways to control neuronal activity.     

Neuroactive steroids and GABAA receptor plasticity in the brain of the WAG/Rij rat, a model of absence epilepsy

The role of neuroactive steroids and GABA(A) receptors in the generation of spontaneous spike-and-wave discharges (SWDs) was investigated in the WAG/Rij rat model of absence epilepsy. The plasma, cerebrocortical, and thalamic concentrations of the progesterone metabolite 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha,5alpha-TH PROG) were increased in the WAG/Rij rat at 2 months of age compared with those in control (Wistar) rats. In contrast, the brain and peripheral levels of 3alpha,5alpha-tetrahydrodeoxycorticosterone (3alpha,5alpha-TH DOC) did not differ between the two rat strains at this age. At 6 months of age, when absence epilepsy worsens in WAG/Rij rats, the plasma concentration of 3alpha,5alpha-TH PROG remained high whereas that of 3alpha,5alpha-TH DOC had increased, the cerebrocortical levels of both 3alpha,5alpha-TH PROG and 3alpha,5alpha-TH DOC had increased, and the thalamic concentrations of these metabolites had decreased. At 6 months of age the expression of the alpha(4) and delta subunits of the GABA(A) receptor in relay nuclei was increased. Finally, chronic stress induced by social isolation elicited a reduction in the amount of 3alpha,5alpha-TH PROG in the thalamus of 2-month-old WAG/Rij rats that was associated with a reduction in the number and overall duration of SWDs at 6 months of age. Absence epilepsy in the WAG/Rij rat is thus associated with changes in the abundance of neuroactive steroids and in the expression of specific GABA(A) receptor subunits in the thalamus, a brain area key to the pathophysiology of this condition.