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The hypothalamic hamartoma: a model of subcortical epileptogenesis and encephalopathy.

Although uncommon, the hypothalamic hamartoma (HH) is often associated with a devastating clinical syndrome, which may include refractory epilepsy, progressive cognitive decline, and deterioration in behavioral and psychiatric functioning. Contrary to conventional thinking which attributed seizure origin to cortical structures, the hamartoma itself has now been firmly established as the site of intrinsic epileptogenesis for the gelastic seizures (i.e., characterized by unusual mirth) peculiar to this disorder. It also appears that the HH contributes to a process of secondary epileptogenesis, with eventual cortical seizure onset of multiple types in some patients. Anticonvulsant medications are known to be poorly effective in this disorder. Treatment, including some innovative approaches to surgical resection, is now targeted directly at the HH itself, with impressive results. Younger patients, in particular, may avoid the deteriorating course described earlier. Access to tissue from larger numbers of patients at single or collaborating centers specializing in HH surgery will allow for research into the fundamental mechanisms producing this little understood disorder. Refractory epilepsy associated with HH is the premier human model for subcortical epilepsy and an excellent model for secondary epileptogenesis and epileptic encephalopathy.

Animals↗

Estrogen formation and binding in the cerebral cortex of the developing rhesus monkey.

These studies were undertaken to determine whether estrogen receptors and the microsomal enzyme system called the aromatase complex, which is responsible for conversion of androgen to estrogen, are present in the brain of the rhesus monkey during perinatal life. Four monkeys (three females--one fetus removed on day 153 of gestation and two infants, 5 and 6 days postnatal--and 1 male, 2 days postnatal) were studied. Cytosol estrogen receptors were detected in all brain regions examined. The apparent equilibrium dissociations constants for reaction of these sites with [3H]moxestrol were similar to those for uterine and pituitary cytosol estrogen receptors (0.3-1.1 nM). Within the brain, highest levels of binding were observed in the hypothalamus-preoptic area, with fairly even, lower concentrations throughout the cortical structures. Aromatase complex activity was detected in the majority of the tissue specimens. The highest levels of estrogen formation were observed in the hypothalamus. However, the amygdala, the hippocampus, and several of the cortex samples also contained measurable aromatase complex activity. Among the cortical samples, the highest levels of aromatase complex activity were found in regions of the association cortex (the dorsolateral-prefrontal, orbital-prefrontal, anterior cingulate, and parietal cortices). The lowest levels of aromatase activity were found in the somatosensory and motor cortices of the postnatal animals. These results suggest that locally-formed estrogen may be involved in the effects of circulating androgens on the developing primate neocortex.

Animals↗

Role of cerebral cortex in human postural control: an EEG study.

OBJECTIVE: It was our primary objective to provide evidence supporting the existence of neural detectors for postural instability that could trigger the compensatory adjustments to avoid falls. METHODS: Twelve young healthy subjects performed self-initiated oscillatory and discrete postural movements in the anterior-posterior (AP) directions with maximal range of motion predominantly at ankle joint. Movements were recorded by the system and included force plate and EMG, and EEG measures from 25 electrode sites. The center of pressure dynamics and stability index were calculated, and EEG potentials both in voltage and frequency domains were extracted by averaging and Morlet wavelet techniques, respectively. RESULTS: The initiation of self-paced postural movement was preceded by slow negative DC shift, similar to movement-related cortical potentials (MRCP) accompanying voluntary limb movement. A burst of gamma activity preceded the initiation of compensatory backward postural movement when balance was in danger. This was evident for both oscillatory and discrete AP postural movements. The spatial distribution of EEG patterns in postural actions approximated that previously observed during the postural perceptual tasks. CONCLUSIONS: The results suggest an important role of the higher cortical structures in regulation of posture equilibrium in dynamic stances. Postural reactions to prevent falls may be triggered by central command mechanisms identified by a burst of EEG gamma activity. SIGNIFICANCE: The results from this study contribute to our understanding of neurophysiological mechanisms underlying the cortical control of human upright posture in normal subjects.

Adaptation, Physiological↗

A window on the normal development of sensitivity to global form in Glass patterns.

We studied the development of sensitivity to global form in 6-year-olds, 9-year-olds, and adults (n = 24 in each group) using Glass patterns with varying ratios of paired signal dots to noise dots. The developmental pattern was similar whether the global structure within the Glass patterns was concentric or parallel. Thresholds were equally immature for both types of pattern at 6 years of age (about twice the adult value) but were adult-like at 9 years of age. Together, the results indicate that the cortical structures involved in the processing of global form achieve functional maturity between 6 and 9 years of age. During middle childhood, the mechanisms mediating sensitivity to concentric structure develop at the same rate as those mediating sensitivity to parallel structure.

Adolescent↗

Effects of neonatal 6-hydroxydopamine treatment on cortical development in mice and rats as monitored by developmental changes of gangliosides.

In a comparative study newborn rats and mice received subcutaneous (s.c.) injections of 6-hydroxydopamine (6-OHDA: 100 mg/kg) on postnatal days (p.d.) 1-3. In rats the treatment permanently reduced synaptosomal 3H-noradrenaline (3H-NA) uptake in the cortex to about 50-60% of control values. Conversely, cortical 3H-NA uptake was only temporarily reduced in treated mice during the first week and central noradrenergic neurons completely recovered during the second and third week. The different response of mice and rats to 6-OHDA is suggested to be due to earlier maturation of the noradrenergic system in mice, making it less vulnerable to neonatal injections of the neurotoxin. To determine whether the development of the cortex would be altered after degeneration of its noradrenergic innervation, developmental changes of cortical ganglioside content and composition of 6-OHDA-treated animals were compared to that of littermate controls. In 18-day-old rats, where reduction of 3H-NA uptake had persisted, ganglioside content was reduced by 16.5%, indicating growth impairment of neuronal membrane structures. Cortical gangliosides of younger rats and all the stages studied in mice were not affected by 6-OHDA treatment.

Animals↗

Stereo-EEG in children.

BACKGROUND: Stereotactic placement of intracerebral multilead electrodes for chronic EEG recording of seizures or stereoelectroencephalography (SEEG) was introduced 50 years ago at Saint Anne Hospital in Paris, France for the presurgical evaluation of patients with drug-resistant focal epilepsy. SEEG explorations are indicated whenever the noninvasive tests fail to adequately localize the epileptogenic zone (EZ). INDICATIONS: Currently, approximately 35% of our operated-on children require a SEEG evaluation. Arrangement of electrodes is individualized according to the peculiar needs of each child, to verify a predetermined hypothesis of localization of the EZ based on pre-SEEG anatomo-electro-clinical findings. Multilead intracerebral electrodes are designed to sample cortical structures on the lateral, intermediate, and mesial aspect of the hemisphere, as well as deep-seated lesions. Stereotactic stereoscopic teleangiograms and coregistered 3-D MRI are employed to plan avascular trajectories and to accurately target the desired structures. Pre-SEEG stereotactic neuroradiology and electrode implantation are usually performed in separate procedures. Electrodes are removed once video-SEEG monitoring is completed. INTRACEREBRAL ELECTRICAL STIMULATIONS: Intracerebral electrical stimulations are used to better define the EZ and to obtain a detailed functional mapping of critical cortical and subcortical regions. MORBIDITY: Surgical morbidity of SEEG is definitely low in children. SEEG-GUIDED RESECTIVE SURGERY: In 90% of evaluated children, SEEG provides a guide for extratemporal or multilobar resections. SEEG-guided resective surgery may yield excellent results on seizures with 60% of patients in Engel's Class I.

Brain Mapping↗

Medial temporal lobe activation during encoding and retrieval of novel face-name pairs.

The human medial temporal lobe (MTL) is known to be involved in declarative memory, yet the exact contributions of the various MTL structures are not well understood. In particular, the data as to whether the hippocampal region is preferentially involved in the encoding and/or retrieval of associative memory have not allowed for a consensus concerning its specific role. To investigate the role of the hippocampal region and the nearby MTL cortical areas in encoding and retrieval of associative versus non-associative memories, we used functional magnetic resonance imaging (fMRI) to measure brain activity during learning and later recognition testing of novel face-name pairs. We show that there is greater activity for successful encoding of associative information than for non-associative information in the right hippocampal region, as well as in the left amygdala and right parahippocampal cortex. Activity for retrieval of associative information was greater than for non-associative information in the right hippocampal region also, as well as in the left perirhinal cortex, right entorhinal cortex, and right parahippocampal cortex. The implications of these data for a clear functional distinction between the hippocampal region and the MTL cortical structures are discussed.

Adult↗

Late responses after transcranial magnetic stimulation in stroke.

In addition to early responses after transcranial magnetic stimulation, usually designated as Motor Evoked Potentials (MEP), several late responses have been reported in intervals up to 500 ms following stimulus. Our attention in this work was focused on the response in interval 150-300 ms after stimulus output, which is also designated as S > 150 response. We monitored longitudinally late S > 150 response in group of 19 stroke patient with verified hemispherical ischemic lesion. Our results have shown that the presence of late S > 150 response on the first day after stroke predicts an excellent improvement of clinical deficit and that late S > 150 response is more sensitive to hemispheric lesion than early MEPs. From this point of view, recording of late responses can supplement early MEP recording. Our study demonstrated that supratentorial structures are involved in the origin of the S > 150 response. According to the observation that in some patients a normal early response was present and an S > 150 response was absent on the hemiparetic side, and both responses were present on the unaffected side, we hypothesize that cortical structures play an important role in S > 150 response.

Aged↗

Shared and separate systems in bilingual language processing: converging evidence from eyetracking and brain imaging.

The neurological and cognitive aspects of bilingual language processing were examined in late Russian-English bilinguals using headband-mounted eyetracking and functional neuroimaging. A series of three eyetracking studies suggested that, at early stages of word recognition, bilinguals can activate both languages in parallel, even when direct linguistic input is in one language only. A functional neuroimaging study suggested that, although the same general structures are active for both languages, differences within these general structures are present across languages and across levels of processing. For example, different centers of activation were associated with first versus second language processing within the left Inferior Frontal Gyrus, but not within the Superior Temporal Gyrus. We suggest that parallel activation (as found with eyetracking) and shared cortical structures (as found with fMRI) may be characteristic of early stages of language processing (such as phonetic processing), but the two languages may be using separate structures at later stages of processing (such as lexical processing).

Adult↗

Visual responses of neurons in somatosensory cortex of hamsters with experimentally induced retinal projections to somatosensory thalamus.

These experiments investigate the capacity of thalamic and cortical structures in a sensory system to process information of a modality normally associated with another system. Retinal ganglion cells in newborn Syrian hamsters were made to project permanently to the main thalamic somatosensory (ventrobasal) nucleus. When the animals were adults, single unit recordings were made in the somatosensory cortices, the principal targets of the ventrobasal nucleus. The somatosensory neurons responded to visual stimulation of distinct receptive fields, and their response properties resembled, in several characteristic features, those of normal visual cortical neurons. In the visual cortex of normal animals and the somatosensory cortex of operated animals, the same functional categories of neurons occurred in similar proportions, and the neurons' selectivity for the orientation or direction of movement of visual stimuli was comparable. These results suggest that thalamic nuclei or cortical areas at corresponding levels in the visual and somatosensory pathways perform similar transformations on their inputs.

Animals↗

Learning-induced oscillatory activities correlated to odour recognition: a network activity.

In trained behaving rats, the expression of a prominent beta oscillatory activity in the olfactory system was previously identified as a correlate of odour recognition. The aim of the present study was to assess the putative role of a functional coupling between the olfactory bulb (OB) and higher structures in this activity. We performed a unilateral inactivation of the medial part of the olfactory peduncle by lidocaine infusion. Inactivation deprived the OB from most of its centrifugal afferences, including feedback connections from the piriform cortex (PC) while sparing the ascending fibres from the OB to higher cortical structures. This treatment reduced the amplitude of odour-induced oscillatory beta responses both in OB and PC. In parallel, gamma activity classically observed in these two structures during spontaneous activity displayed a strong enhancement. Results suggest that odour-induced oscillatory response could be the emergent feature of an olfactory functional network set up through learning.

Anesthetics, Local↗

Cerebral decreases in opioid receptor binding in patients with central neuropathic pain measured by [11C]diprenorphine binding and PET.

Central neuropathic pain (CNP) is pain resulting from damage to the central nervous system. Up till now, it has not been possible to identify a common lesion or pharmacological deficit in these patients. This preliminary study in a group of patients with CNP with predominantly post-stroke pain, demonstrates that there is significantly less opioid receptor binding in a number of cortical and sub-cortical structures that are mostly, but not exclusively, within the medial pain system in patients compared to age-matched pain-free controls. The reductions in opioid receptor binding within the medial system were observed mainly in the dorsolateral (Brodman area 10) and anterior cingulate (Brodman area 24 with some extension into area 23) and insula cortices and the thalamus. There were also reductions in the lateral pain system within the inferior parietal cortex (Brodman area 40). These changes in binding could not be accounted for by the cerebral lesions shown by CT or MRI, which were outside the areas of reduced binding and the human pain system. To our knowledge this is the first systematic demonstration of a reduction in opioid receptor-binding capacity in neurones within the human nociceptive system in patients with CNP. This may be a key common factor resulting in undamped nociceptor activity within some of the structures that are predominantly within the medial nociceptive system. If confirmed, these findings may explain why certain patients with CNP require high doses of synthetic opiates to achieve optimum analgesia. The findings also raise the possibility of new pharmacological approaches to treatment.

Aged↗

Immunolocalization of the exocytosis-sensitive phosphoprotein, PP63/parafusin, in Paramecium cells using antibodies against recombinant protein.

We have localized a structure-bound fraction of the exocytosis-sensitive phosphoprotein, PP63/parafusin (PP63/pf), in Paramecium cells by widely different methods. We combined cell fractionation, western blots, as well as light and electron microscopy (pre- and post-embedding immunolabeling), applying antibodies against the recombinant protein. PP63/pf is considerably enriched in certain cortical structures, notably the outlines of regular surface fields (kinetids), docking sites of secretory organelles (trichocysts) and the membranes of subplasmalemmal Ca2+-stores (alveolar sacs). From our localization studies we tentatively derive several potential functions for PP63/pf, including cell surface structuring, assembly of exocytosis sites, and/or Ca2+ homeostasis.

Animals↗

Neurocircuitries of the basal ganglia studied in organotypic cultures: focus on tyrosine hydroxylase, nitric oxide synthase and neuropeptide immunocytochemistry.

The nigrostriatal and mesolimbic systems of the rat were reconstructed using an organotypic culture model, whereby neonatal brain tissue was grown in vitro for approximately one month. The nigrostriatal system comprised of tissue from the substantia nigra, the dorsal striatum and the frontoparietal cortex, while the mesolimbic system included the ventral tegmental area, ventral striatum (including the fundus striati, accumbens nucleus, olfactory tubercle, lateral septum, ventral pallidum and piriform cortex) and cingulate cortex. These regions were also cultured alone or in pairs. The cultures were monitored in vitro, and after one month fixed in a formalin-picric acid solution, and processed for immunohistochemistry using antibodies raised against tyrosine hydroxylase, nitric oxide synthase, preprocholecystokinin, glutamate decarboxylase, neuropeptide Y, dopamine- and cyclic AMP-regulated phosphoprotein-32 and glial fibrillary acidic protein. The tissue survived in single, double or triple cultures, although differences were found depending upon the source and combination of cultured region. Neurons had localization and shape as in vivo. Local networks were especially prominent in the mesencephalon, where both tyrosine hydroxylase-positive axons spread from the "substantia nigra" to the rest of the tissue, and where nitric oxide synthase-positive networks also surrounded tyrosine hydroxylase-positive neurons. Glutamate decarboxylase-positive nerve terminals formed dense networks around tyrosine hydroxylase-positive neurons. In the striatum, nitric oxide synthase and dopamine- and cyclic AMP-regulated phosphoprotein-32 neurons were surrounded by tyrosine hydroxylase-positive nerve terminals. The nigral and ventral tegmental area dopamine neurons projected to striatal and cortical structures, but the projection from the ventral tegmental area to the cingulate cortex was more prominent. With regard to co-existence, preprochole-cystokinin-like immunoreactivities was found in many tyrosine hydroxylase-positive neurons and neuropeptide Y- and nitric oxide synthase-like immunoreactivity co-existed in striatal and cortical tissues. In general terms, the chemical neuroanatomy in the cultures was similar to that described earlier in vivo. Nitric oxide synthase staining was particularly intense. Taken together, the organotypic model captures many of the morphological and neurochemical features seen in vivo, providing a valuable model for studying neurocircuitries of the brain in detail, where 'normal' and 'pathological' conditions can be simulated.

Animals↗

[How to evaluate recirculation effect on brain function after global ischemia--broad spectral EEG analysis by Fourier method].

EEG alterations after 5 or 10 minutes of global ischemia were investigated for 6 hours of postischemic period in 18 adult cats, together with biophysiological parameters such as cerebral blood flow, intracranial pressure, systemic blood pressure, heart rate, and blood gases. Our EEG analytical system is composed of high fidelity pre-amplifier, AA 6 MK II (Medelec Limited, England) and signal processor 7T 08 (NEC-SanEi, Japan). It is qualified to analyze frequencies up to 20 kHz within 3 dB cut-off. Particular features of our EEG analytical method are focused on Fourier analysis about broad frequency bands, frequency and amplitude spectra to be expressed on bi-logarithmic graph and direct EEG recordings from various structures of the brain. On the basis of fluctuation theory following 3 types were divided; Type f which corresponds to 1/f fluctuation, Type L which corresponds to Lorentzian fluctuation, Type f+L which is the sum of Type f and L. The distribution of these types in the central nervous system corresponds with cortical structures, spinal cord and brain stem respectively. In conclusion, there was a good correlation between EEG and blood flow in the motor cortex. The functional reversibility after ischemia was different according to the types. Type f structures, namely the motor cortex, hippocampus and amygdala were vulnerable and Type f+L structures namely ventrolateral nucleus of the thalamus and midbrain reticular formation tended to recover or stay in preservation.

Animals↗

Changes in the cytoplasmic structure of CTLs during target cell recognition and killing.

CTL play a critical role in immune defense by recognizing and killing virally infected or tumor cells. In this report, the structure of cytoplasm within living CTL was monitored during CTL killing of target cells. Living CTL were simultaneously loaded with fluorescent 70,000- and 10,000-kDa dextran particles. The relative distribution of the large and small dextrans within CTL revealed subcellular heterogeneities in the submicroscopic structure of cytoplasm. Localized alterations in cytoplasmic structure correlated with specific events during CTL killing. Recognition of target cells was accompanied by a transient increase in large dextran accessibility over a broad front near the interface between CTL and target cells. This region narrowed to a smaller area from which pseudopodia were extended toward the target. During extension, there was a large difference between regions of high dextran accessibility within the pseudopod and more structured cytoplasm within the cell body. Areas undergoing structural changes showed localized foci of high dextran accessibility. During retraction, cytoplasmic structure became gradually more uniform throughout the protrusion and cell body. These observations revealed subcellular regions undergoing major changes during early stages of the killing response, and addressed the role of cytoplasmic solation in controlling CTL morphology. They support mechanisms of pseudopod extension driven by hydrostatic pressure and demonstrate a precise regulation of cortical structure to control the direction of pseudopod extension.

Animals↗

Consciousness: criteria and possible mechanisms.

There are two sorts of criteria of consciousness--objective and subjective ones. They are the ability for operating with the knowledge which could be addressed to other people in the abstract form and the feeling of 'ego' as a 'host' of these actions, respectively. These two signs of consciousness are provided with the mechanism based on the synthesis in the brain structures of different kinds of information: sensory information, the data extracted from the memory and the signals from the centers of emotions and motivation. As a result of this synthesis, the sense of 'ego' arises and the message designated for others is determined. A significant role in the informational synthesis is played by dynamic cortical structures--foci of interaction. In perception they are localized predominantly in the projectional cortex, in thinking and in the associative areas. Realization is closely connected with communication and appearance of the interaction foci in the verbal zones of the left hemisphere. Pavlov (1951), in his program lecture in Madrid early in the present century, said that he saw the final aim of his study in the revealing of the mechanism and the inner vital sense of human consciousness. It is important, that Pavlov placed the words 'mechanism' and 'vital sense' near each other, i.e., he considered that the sense of consciousness would be realized through revealing its mechanism. This insight attracts our attention now, when the problem on consciousness mechanism is in scientific plans and the search for the meaning of life by the end of the twentieth century, one full of dramatic events, acquires a special value.

Brain↗

Nonlinear EEG dynamics during imagined self-paced movements.

The majority of studies devoted to reveal electrophysiological correlates of words and sentences comprehension, imageability and remembering are based on the event-related potentials and frequency synchronization in different narrow frequency bands. These linear methods reveal some patterns of EEG activity in time and frequency domain. Having in mind that the activation of many cortical structures is a result of mass of nonlinearly interconnected neurons, the linear methods seem to be insufficient to discover the complexity of the information transfer. We revealed recently nonlinear dynamic transients in EEG, long before real performance of goal-directed voluntary movements with different temporal and spatial distributions over frontal, sensorimotor and parietal cortical areas (Popivanov and Dushanova, 1999). The aim of this study was to establish whether similar behavior of the nonlinear characteristics exists when the subject imagines movements of a given type. The Kolmogorov entropy computed over time after the sentence end proved to be an useful characteristic that complement the linear methods.

Eidetic Imagery↗