Remote Cortex Research Articles

Disturbance of perineuronal nets in the perilesional area after photothrombosis is not associated with neuronal death

Perineuronal nets (PNNs) are a condensed form of extracellular matrix that covers the surface of a subset of neurons. Their presence limits neuronal plasticity and may protect neurons against harmful agents. Here we analyzed the relationship between spatiotemporal changes in PNN expression and cell death markers after focal cortical photothrombotic stroke in rats. We registered a substantial decrease in PNN density using Wisteria floribunda agglutinin staining and CAT-315 and brevican immunoreactivity; the decrease occurred not only in the lesion core but also in the perilesional and remote cortex as well as in homotopic contralateral cortical regions. Fluoro Jade C and TUNEL staining in perilesional and remote areas, however, showed a low density of dying cells. Our results suggest that the PNN reduction was not a result of cellular death and could be considered an attempt to create conditions favorable for synaptic remodeling.

Hippocampal malrotation in pediatric patients with epilepsy associated with complex prefrontal dysfunction

The cognitive consequences of hippocampal malrotation (HIMAL) were investigated in a matched control study of children with epilepsy. Seven children with HIMAL were compared on a range of memory and attention tasks with 21 control children with epilepsy without temporal role pathology and 7 children with epilepsy and magnetic resonance imaging (MRI)-documented hippocampal sclerosis. In addition, in a statistical morphometric analysis, MRI studies from four children with HIMAL were compared to similar images of 20 age-matched typically developing control children. Although the task battery was sensitive to the memory deficit of the children with hippocampal sclerosis, it did not reveal memory impairment in the patients with HIMAL. In contrast, the patients with HIMAL were impaired on the attentionally more demanding dual tasks, compared to both the control and the hippocampal sclerosis group. The structural MRI analysis revealed morphometric abnormalities in the tail of the affected hippocampus, the adjacent neocortex, and the ipsilateral medial thalamus. The basal forebrain was bilaterally affected. Abnormalities in remote cortex were found in the ipsilateral temporal lobe, the contralateral anterior cingulate gyrus, and bilateral in the dorsolateral and lateral-orbitofrontal prefrontal cortex. Because the prefrontal cortical regions have been shown to be active during dual-task performance, the MRI results converge with the neuropsychological findings of impairment on these tasks. We conclude that HIMAL had no direct memory repercussions, but was secondary to subtle but widespread neurologic abnormalities that also affected morphology and functioning of the prefrontal cortex.

A Case Series of Epilepsy-derived Memory Impairment Resembling Alzheimer Disease

We report 4 cases of epilepsy-derived progressive memory disturbances that clinically resembled Alzheimer disease. The patients were 3 women and 1 man, aged 56 to 79 years. The greatest disturbance was in recent memory. The patients' remote memory and orientation were relatively intact. Mental dullness and a decline in daily activities were also observed. No overt seizures were observed in any of the patients. Electroencephalography (EEG) revealed spikes in the left temporal region in 3 patients and in the left central region in the other patient. Single photon emission computed tomography or positron emission tomography revealed focal areas of hypofunction in the frontal, parietal, and parietotemporal regions. Performance of activities and memory improved rapidly in all patients after treatment with carbamazepine; the improvement was maintained after more than a year. It might be speculated that epileptic discharges caused dysfunction in the temporal lobe and the remote cortex through the neocortical and mesiotemporal network. EEG would be useful to rule out the possibility of a reversible condition in patients with cognitive disturbance. Moreover, investigation of this epilepsy-related condition with the combination of EEG and neurofunctional imaging might provide clues to clarify the pathophysiology of Alzheimer disease.

Increased local and decreased remote functional connectivity at EEG alpha and beta frequency bands in opioid-dependent patients

Although researchers now have a working knowledge of key brain structures involved in realization of actions of substance abuse and addiction, deeper understanding will require examination of network interactions between cortical neuronal assemblies and their subcortical tails in the effects of opioid dependence. Given that repeated exposure to opiates initiates a widespread reorganization of cortical regions, we predict that opioid dependence would result in a considerable reorganization of local and remote functional connectivity in the neocortex. We applied the novel operational architectonics approach that enables us to estimate two local and remote functional cortex connectivities by means of electroencephalogram structural synchrony measure. In 22 opioid-dependent patients, we found the evidence that brain functional connectivity was indeed disrupted by chronic opioid abuse (i.e., the local functional connectivity increased and remote functional connectivity decreased in opioid abusers). This significant difference between "opioid" and "control" populations was the same for alpha and beta frequency bands. Additionally, significant negative relations between duration (years) of daily opioid abuse and the number/strength of functional connections in the posterior section of the cortex were found.

The factors affecting thermal necrosis secondary to the application of the Ilizarov transosseous wire

We investigated thermal changes associated with the application of the Ilizarov transosseous wires, the extent of necrosis, and the factors affecting necrosis. We used a pair of tibiae from a 1-year-old cow. After removal of metaphyseal areas, each of four equal diaphyseal zones marked on both tibiae was drilled at 600, 900, 1,200 and 1,800 rpm, each time with a new wire. Heat changes were recorded with heat electrodes during the application and the speed of the wire was calculated. For histopathological examination, specimens were obtained at the access and exit sites to assess the extent of necrosis. Thermal changes between the zones and immediate and remote cortices were compared. The most significant factor affecting the heat changes was analyzed by linear regression. Heat changes varied between 48.4 degrees C (at 1,200 rpm) and 151.9 degrees C (at 600 rpm). The thickness of the immediate cortex, the time and speed for the wire to pass the cortex were found as significant parameters in heat changes (p=0.003, p=0.01, and p=0.01, respectively). A negative correlation was found between the speed of the wire and the thickness of the necrotic area (r=-0.901, p=0.001). Regression analysis showed that the time for the wire to pass through the cortex was the most significant factor in inducing heat changes in both cortices (p=0.001, p=0.003, respectively). Histopathologically, the extent of necrosis and bone erosion was associated with lower drill speeds. Necrosis was significantly notable in the immediate cortex than that of the remote one (p=0.006). Transosseous wires should be passed at high drill speeds and with earliest time elapses to reduce thermal necrosis.

Changes in regional energy metabolism after closed head injury in the rat.

We examined in the present investigation regional ATP, glucose, and lactate content in the cortical and subcortical structures, in a rat model of closed head injury (CHI). In serial tissue sections bioluminescence imaging of ATP, glucose, and lactate was performed at 4 h, 12 h and 24 h (n = 4/5 per time point with) after the induction of CHI or sham surgery. Bioluminescence images were analyzed by computer-assisted densitometry, at the lesion site, in remote cortical areas, and in the subcortical structures (thalamus and caudate nucleus). ATP content was significantly decreased at the lesion site after 4 h and in the remote cortex at 12 h post-injury. At 12 h, the ATP content reached baseline levels on the ipsilateral side and at 24 h also at remote lateral parietal sites. In the contralateral cortex, ATP increased transiently above the baseline at 12 h. No significant changes in ATP were found in the thalamus and caudate nucleus. Cortical glucose and lactate contents could not be discerned over time. Following CHI there is an acute and progressive, yet transient, ischemic cortical profile, which is not reflected in subcortical areas.

Changes in the cerebrocortical capillary network following venous sinus occlusion in cats

Although the important protective effect of venous collateral pathways in sinus occlusion on parenchymal injury has been demonstrated in previous works, the vascular response in the capillary microcirculation itself after cerebral venous occlusion has not been fully elucidated. We examined the morphology of the capillary network after venous occlusion by relating stereologic morphometric parameters to changes in local cerebral blood flow and the development of brain edema. Experimental venous sinus occlusion was induced by injection of 0.5 mL of cyanoacrylate into the superior sagittal sinus and by immediate ligation of both external jugular veins in chloralose-urethane anesthetized cats (n = 24). Capillaries in the adjacent cortex (marginal and suprasylvian cortex) and remote cortex (piriform cortex) were injected with Evans blue dye 2 minutes before sacrifice at 15-minute and 120-minute postsinus occlusion. The stereologic morphometric parameters including volume density, minimum intercapillary distance, capillary diameter, and number of perfused capillaries were computed on a fluorescence microscopic photograph using an image analysis system. Cerebral blood flow (CBF) was measured by hydrogen clearance method, and brain tissue water content was measured using the dry-wet method. In the cortex adjacent to the superior sagittal sinus, the volume density and the number of perfused capillaries were increased significantly (p < 0.02, and p < 0.05, respectively) and the minimum intercapillary distance was decreased significantly (p < 0.02) at 15 minutes after venous occlusion (n = 10). Cerebral blood flow (CBF) was also decreased to 53% of that in the control group (p < 0.01). Although the morphologic parameters returned to the control level by 120 minutes after venous occlusion, the CBF remained decreased after venous occlusion. No change was observed in the water content of the adjacent gray matter at 15 minutes after venous occlusion; however, it was increased (p < 0.05) at 120 minutes. These results indicate that the recruitment of reserve capillaries occurs during the early phase of venous occlusion. While CBF decreased to half of the control after venous occlusion, capillary perfusion remained above or near the control level until 120 minutes postocclusion, suggesting that venous recruitment would be potentially beneficial in clinical patients in the early stage of venous occlusion.

Intracerebral propagation of interictal activity in partial epilepsy: implications for source localisation.

The hypothesis that focal scalp EEG and MEG interictal epileptiform activity can be modelled by single dipoles or by a limited number of dipoles was examined. The time course and spatial distribution of interictal activity recorded simultaneously by surface electrodes and by electrodes next to mesial temporal structures in 12 patients being assessed for epilepsy surgery have been studied to estimate the degree of confinement of neural activity present during interictal paroxysms, and the degree to which volume conduction and neural propagation take part in the diffusion of interictal activity. Also, intrapatient topographical correlations of ictal onset zone and deep interictal activity have been studied. Correlations between the amplitudes of deep and surface recordings, together with previous reports on the amplitude of scalp signals produced by artificially implanted dipoles suggest that the ratio of deep to surface activity recorded during interictal epileptiform activity on the scalp is around 1:2000. This implies that most such activity recorded on the scalp does not arise from volume conduction from deep structures but is generated in the underlying neocortex. Also, time delays of up to 220 ms recorded between interictal paroxysms at different recording sites show that interictal epileptiform activity can propagate neuronally within several milliseconds to relatively remote cortex. Large areas of archicortex and neocortex can then be simultaneously or sequentially active via three possible mechanisms: (1) by fast association fibres directly, (2) by fast association fibres that trigger local phenomena which in turn give rise to sharp/slow waves or spikes, and (3) propagation along the neocortex. The low ratio of deep-to-surface signal on the scalp and the simultaneous activation of large neocortical areas can yield spurious equivalent dipoles localised in deeper structures. Frequent interictal spike activities can also take place independently in areas other than the ictal onset zone and their interictal propagation to the surface is independent of their capacity to trigger seizures. It is concluded that: (1) the deep-to-surface ratios of electromagnetic fields from deep sources are extremely low on the scalp; (2) single dipoles or a limited number of dipoles are not adequate for surgical assessment; (3) the correct localisation of the onset of interictal activity does not necessarily imply the onset of seizures in the region or in the same hemisphere. It is suggested that, until volume conduction and neurophysiological propagation can be distinguished, semiempirical correlations between symptomatology, surgical outcome, and detailed presurgical modeling of the neocortical projection patterns by combined MEG, EEG, and MRI could be more fruitful than source localization with unrealistic source models.

Effects of dexamethasone on tumor-induced brain edema and its distribution in the brain of monkeys.

A human choriocarcinoma was successfully adapted to grow in the brain of monkeys (Macaca mulatta), thus providing a model of tumor-induced brain edema. Four animals were given dexamethasone (3 mg/kg/day) during 3 to 5 days after the onset of clinical signs, and the other five received no treatment for the same period. Tissue water and electrolyte content of treated and untreated animals were compared in cortex and white matter at various distances from the edge of the tumor. In untreated animals, 67.9% and 23.6% swelling was detected in adjacent and remote white matter, respectively, but only 11.8% swelling was noted in adjacent cortex. In animals treated with dexamethasone these percentages of swelling were improved to 32.4% and 11.9% in the corresponding white matter, and to 4.9% in adjacent cortex. The electrolyte changes shown in edematous brain of control animals also demonstrated significant improvement in the dexamethasone-treated group. Tissue radioactivity of 3H-dexamethasone at 60 minutes after intravenous injection was high in the periphery of tumor, adjacent cortex, and white matter, but low in the center of tumor, remote cortex, and white matter. The sites with high concentrations of dexamethasone also showed significant improvement of brain edema after dexamethasone treatment, suggesting that dexamethasone may act directly at these loci.

METABOLIC RESPONSE TO FOCAL PENICILLIN SEIZURES IN RAT: SPIKE DISCHARGE VS. AFTERDISCHARGE1

Abstract– The correlations among clinical events, electrocorticogram, histology, size of focus, and biochemical changes were examined in a model of focal penicillin seizures in rats. Ten units of penicillin injected into the motor cortex were found to be the threshold dose for producing repetitive spike discharges. These were associated with synchronous contralateral muscle jerks which reached a peak intensity in 10 min and fell off rapidly in 45–90 min. The half‐life of penicillin in the cortex was 15 min, with little diffusion from the site of injection. The size of the metabolic focus was determined by autoradiography with [2‐14C]deoxyglucose and was 6.5 times larger than the diffusion of penicillin. Increased glucose utilization appeared in the focus and in cortical columns in the contralateral homo‐typic cortex.Thirty times more penicillin (&gt;300 units) was required to produce spikes with afterdischarge than to product spikes alone. Afterdischarges correlated with contralateral tonic‐clonic seizures and occurred only after 1 h of exposure to penicillin. These lasted 10‐45 s each and recurred over 3 to 4h. The size of the metabolic focus determined by [2‐14C]deoxyglucose during afterdischarges was 4.6 times larger than the focus exhibiting spike discharges alone.Tissue substrates were measured in the seizure focus, homotypic ‘mirror’ cortex, and cortex remote from the focus in paralyzed ventilated animals. During repetitive spike discharge there was a fall in high energy compounds in the focus (phosphocreatine, 4.91 → 4.24 mmol/kg; ATP, 2.62 → 2.17 mmol/kg) and a rise in lactate (1.41 → 2.79 mmol/kg). Changes were similar but less intense in ‘mirror’ and remote cortex. During spikes with afterdischarge, changes in high energy compounds in the focus were of a similar magnitude (phosphocreatine, 4.91 → 3.86 mmol/kg; ATP, 2.62 → 2.46 mmol/kg) but there was a greater rise in lactate (1.41 → 6.32 mmol/kg) and a fall in glucose (2.38 → 1.81 mmol/kg). In contrast, changes in ‘mirror’ and remote cortex during afterdischarges showed an increase in high‐energy compounds.

DC potentials of temporal lobe seizures in the monkey.

In 8 monkeys, made epileptic by alum or penicillin injection into temporal lobe structures, 40 seizures were studied by both DC cortical potential and subcortical EEG recordings. Eighteen seizures of lateral temporal origin had an abrupt negative DC potential shift of 0.5 to 2.0 mV in and around the focus. The frontal, parietal and occipital cortices did not develop DC potential changes, perhaps due to the limited propagation of the neocortical seizures. Twenty-two seizures of medial temporal origin showed a negative shift of the anterior, inferior or lateral temporal cortex in 85% of seizures. The other 15% had a positive or no shift. In hippocampal seizures, a positive displacement was sometimes seen prior to the main negative shift in the lateral temporal cortex. The remote cortex developed only a minimal positive shift in 30% of the mediotemporal seizures. A marked negative shift in the frontocentral cortex was the first sign of impending generalization, which may result from a series of chain reactions with seizure propagation, involving more and more structures of the brain. Registration of DC potentials in temporal lobe seizures may give insight into the nature of abnormal EEG activities and to some extent into the origin of seizures.