Generation Of Slow Potentials Research Articles

Individual topographic variability is inherent to cortical physiology but task-related differences may be noise.

The observation of highly variable sets of association neocortical areas across individuals, containing the estimated generators of Slow Potentials (SPs) and beta oscillations, lead to the persistence in individual analyses. This brought to notice an unexpected within individual topographic similarity between task conditions, despite our original interest in task-related differences. A recent related work explored the quantification of the similarity in beta topography between largely differing tasks. In this article, we used Independent Component Analysis (ICA) for the decomposition of beta activity from a visual attention task, and compared it with quiet resting, recorded by 128-channel EEG in 62 subjects. We statistically tested whether each ICA component obtained in one condition could be explained by a linear regression model based on the topographic patterns from the other condition, in each individual. Results were coherent with the previous report, showing a high topographic similarity between conditions. From an average of 12 beta component maps obtained for each task, over 80% were satisfactorily explained by the complementary task. Once more, the component maps including those considered unexplained, putatively “task-specific”, had their scalp distribution and estimated cortical sources highly variable across subjects. These findings are discussed along with other studies based on individual data and the present fMRI results, reinforcing the increasingly accepted view that individual variability in sets of active neocortical association areas is not noise, but intrinsic to cortical physiology. Actual ‘noise’, mainly stemming from group “brain averaging” and the emphasis on statistical differences as opposed to similarities, may explain the overall hardship in replication of the vast literature on supposed task-specific forms of activity, and the ever inconclusive status of a universal functional mapping of cortical association areas. A new hypothesis, that individuals may use the same idiosyncratic sets of areas, at least by their fraction of activity in the sub-delta and beta range, in various non-sensory-motor forms of conscious activities, is a corollary of the discussed variability.

Cellular mechanism of the voltage-dependent change in slow potentials generated in circular smooth muscle of the guinea-pig gastric corpus.

The cellular mechanism of the voltage-dependent properties of slow potentials were investigated in single bundles of circular smooth muscle isolated from the gastric corpus of guinea-pig using conventional microelectrode recordings. Hyperpolarization of the membrane by current injection decreased the frequency and increased the amplitude of slow potentials linearly. At potentials negative of -80 mV, slow potential generation was abolished and a periodic generation of clustered unitary potentials was evident. Application of cyclopiazonic acid (CPA, 20 microM) or thapsigargin (1 microM; inhibitors of Ca(2+)-ATPase), carbonyl cyanide m-chlorophenyl hydrazone (CCCP, 0.1 microM; mitochondrial protonophore) or 2-aminoethoxydiphenyl borate (2-APB, 20 microM; inhibitor of IP(3) receptor-mediated Ca(2+) release) depolarized the membrane and reduced or inhibited the amplitude and frequency of slow potentials: repolarization of the membrane to the resting level by current injection resulted in a recovery of the amplitude of slow potentials in the presence of CPA or CCCP, but not 2-APB. The slow potentials abolished by thapsigargin did not recover upon membrane repolarization. The altered frequency of slow potentials by 2-APB, CPA or CCCP was not reversed by membrane repolarization to control potentials. Depolarization of the membrane by about 10 mV with high-potassium solution also reduced the amplitude and increased the frequency of slow potentials in a manner restored by repolarization to control potentials upon current injection, suggesting that membrane depolarization did not affect the voltage dependency of pacemaker activity. The results indicate that in corpus circular muscles the voltage dependency of the frequency and amplitude of slow potentials requires a functional Ca(2+) store and mitochondria.

Effects of 5-hydroxytryptamine on electrical responses of circular smooth muscle isolated from the guinea-pig gastric antrum

The effects of 5-hydroxytryptamine (5-HT) on electrical responses of the membrane were investigated in circular smooth muscle isolated from the guinea-pig stomach antrum. Small segment of circular muscle tissue produced a periodical generation of slow potentials at frequency of 0.1-2 cycles min(-1), during random generation of unitary potentials. Application of 5-HT (10(-7)-10(-5) M) hyperpolarized the membrane and either increased or decreased the frequency of slow potentials, both with associated increase in amplitude of slow potential. These effects of 5-HT were abolished by methysergide. N(omega)-nitro-L-arginine (L-NA) increased the frequency of spontaneously generated slow potentials and also increased the frequency of slow potentials generated during stimulation with 5-HT, suggesting an involvement of the increased production of nitric oxide (NO) by 5-HT. Atropine did not alter spontaneous and 5-HT-induced electrical responses. The hyperpolarization produced by 5-HT was associated with a decrease in input resistance and time constant of the membrane. The amplitude of the 5-HT-induced hyperpolarization was increased in low [K(+)](o) solution and decreased in high [K(+)](o) solution or in the presence of glybenclamide, suggesting that the hyperpolarization was produced by activation of ATP-sensitive K-channels. The increase in amplitude of slow potentials by 5-HT may be secondary due to hyperpolarization of the membrane. The inhibition by 5-HT of the frequency of slow potentials may be partly due to the increased release of NO, however the mechanism by which dual effects of 5-HT on the frequency of slow potentials remains unsolved.

Complex slow potential generators in a simplified attention paradigm

We have recently obtained evidence for complex multifocal, individually variable generators of slow cortical potentials, elicited during performance of visual tasks involving expecting attention, comparison and memory [Basile, L.F.H., Ballester, G., Castro, C.C., and Gattaz, W.F., 2002. Multifocal slow potential generators revealed by high-resolution EEG and current density reconstruction. Int. J. Psychophysiol., 45 (3), 227–240; Basile, L.F.H, Baldo, M.V., Castro, C.C., and Gattaz, W.F. 2003. The generators of slow potentials obtained during verbal, pictorial and spatial tasks. Int. J. Psychophysiol., 48, 55–65]. The cue–target aspect of traditional paradigms for attention studies is equivalent to ‘warning S1’–‘imperative S2’ in slow potential designs. We simplified Posner's spatial cueing task [Posner, M.I. 1980. Orienting of attention.Q. J. Exp. Psychol. Feb;32 (1), 3–25; Posner, M.I., Snyder, C.R., Davidson, B.J. 1980. Attention and the detection of signals. J Exp Psychol. Jun; 109 (2), 160–174] to temporal cuing only, by using visual cues to indicate the mere presence, on a known central position, of the eventual target (17 ms duration, ± 0.3° grey circle). We recorded slow potentials on 12 healthy subjects, by 124-channel EEG system (Neuroscan Inc.), and modeled their generators using current density reconstruction (CDR) by L p 1.2 norm minimization (“Curry V4.6”, Neurosoft Inc.) applied to the target onset time. MRIs were obtained for each subject for constraining source models to individual brain anatomy. Average slow potentials were computed from above 60 artifact-free EEG-epochs (ISI = 1.6 s, average ITI = 2.5 s). We tabulated individual cortical current distributions by cytoarchitectonic area of Brodmann, after scaling into negligible, low, moderate and strong local density, based on percentile bands with respect to absolute maximum current. Despite the task's simplicity, the main result was individual variability and complexity in both scalp voltage and cortical current distributions. As observed in our previous studies, there was strong intersubject variability in the exact distribution of task-related cortical activity. Only parietal area 7 bilaterally was non-negligibly active in all subjects (currents above 10% maximum). As opposed to drawing conclusions based on group averaged data, we propose that activity by cytoarchitectonic area be ranked and statistically analysed only after being scaled on each individual. Based on the present results, the concept of a universal attention-related set of cortical areas if restricted to common areas across subjects is challenged, since even area 7 may no longer be common when the sample size becomes larger. We discuss the fact that group averaging may de-emphasize weakly but consistently active areas, and emphasize strongly but inconsistently active ones.

The effects of flufenamic acid on spontaneous activity of smooth muscle tissue isolated from the guinea-pig stomach antrum

The effects of flufenamic acid were investigated on slow waves, follower potentials and pacemaker potentials recorded respectively from circular smooth muscle cells, longitudinal smooth muscle cells and interstitial cells of Cajal distributed in the myenteric layers (ICC-MY) of the guinea-pig stomach antrum. Flufenamic acid (>10(-5) M) inhibited the amplitude and rate of rise of the upstroke phase of the slow waves, with no marked alteration in their frequency of occurrence. The inhibitory actions of flufenamic acid appeared to be mainly on slow potentials recorded from circular smooth muscle cells, but not on follower or pacemaker potentials. After abolishing spontaneous slow potentials with flufenamic acid, depolarizing current stimuli could evoke slow potentials with an amplitude that was much smaller than in the absence of flufenamic acid, with no significant alteration to the input resistance of the membrane. The time elapsed for the generation of the 2nd component of the slow waves or the slow potentials evoked during depolarizing current pulse stimulation was increased by flufenamic acid. The rate of rise of unitary potentials, but not the frequency of occurrence, was inhibited by flufenamic acid. These results indicate that the inhibitory actions of flufenamic acid appear to be mainly on the circular muscle layer including the interstitial cells of Cajal distributed within the muscle bundles (ICC-IM). Nifedipine-sensitive spike potentials were not inhibited by flufenamic acid. It is concluded that the selective inhibition of the 2nd component of slow waves by flufenamic acid may be mainly due to the inhibition of ion channels, possibly Ca2+-sensitive Cl--channels, activated during generation of slow potentials in the ICC-IM distributed in the circular muscle layer.

Effects of inhibitors of nonselective cation channels on the acetylcholine-induced depolarization of circular smooth muscle from the guinea-pig stomach antrum

In circular smooth muscle bundles isolated from the guinea-pig stomach antrum, the effects of quinidine, Ni2+, flufenamic acid, niflumic acid, La3+, SKF-96365 and 4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS) on acetylcholine (ACh)-induced depolarization were investigated. Recording membrane potentials from smooth muscle cells with intracellular microelectrodes revealed that ACh (1 microM) depolarized the membrane by 5-8 mV and increased the amplitude and frequency of slow potentials. These effects were inhibited by atropine. Quinidine (10 microM) increased the amplitude of ACh-induced depolarization, with no alteration to the properties of slow potentials. Ni2+ (50 microM) transiently (5-10 min) depolarized the membrane by about 5 mV, with an associated increase in frequency and amplitude of slow potentials. In the stabilized condition with Ni2+, the amplitude of ACh-induced depolarization remained unchanged. Flufenamic acid (10 microM) inhibited the generation of slow potentials, with no change in either the amplitude of ACh-induced depolarization or of the amplitude and frequency of slow potentials generated during ACh stimulation. A high concentration of flufenamic acid (100 microM) depolarized the membrane and increased the amplitude of ACh-induced depolarization. Niflumic acid (10 microM) hyperpolarized the membrane and increased the amplitude and frequency of slow potentials and also the amplitude of ACh-induced depolarization. DIDS (100 microM) hyperpolarized the membrane and inhibited the amplitude and frequency of slow potentials, with no alteration to the amplitude of ACh-induced depolarization. SKF-96365 (3-50 microM) depolarized the membrane in a concentration-dependent manner, but did not change the level of ACh-induced depolarization. La3+ (50 microM) did not alter the properties of the slow potentials or the ACh-induced responses. These results provide evidence that ACh-induced depolarization is not inhibited by chemicals known to inhibit non-selective cation channels. We suggest that muscarinic receptor-mediated signal transduction may be different in smooth muscle and interstitial cells.

Role of protein kinase C in the excitatory action of cholinergic nerve stimulation on spontaneous activity of circular smooth muscle isolated from the guinea-pig stomach antrum

Following inhibition of NO production with nitroarginine, circular muscle isolated from the guinea-pig gastric antrum generated periodic slow potentials and unitary potentials. Transmural nerve stimulation (TNS) during the interval between slow potentials evoked an apamin-sensitive inhibitory junction potential (IJP) followed by an atropine-sensitive depolarization; the latter was either a transient depolarization with enhanced generation of unitary potentials or a slow potential. After inhibition of unitary potentials and slow potentials with 1 mM caffeine, TNS evoked an IJP and subsequent cholinergic depolarization, the latter developing slowly and lasting for about 10 s. TNS was unable to elicit a slow potential until a certain period of time had elapsed following the cessation of a slow potential. The period during which TNS could not evoke slow potentials (termed the high-threshold period) was about 10 s, and this period was increased by chelerythrine and decreased by phorbol esters. It is concluded that cholinergic nerve-mediated excitation of gastric muscle involves the activation of protein kinase C (PKC), and that the high-threshold period, during which the generation of slow potentials by TNS is inhibited, may be a consequence of reduced activity of PKC.

Dual concentration-dependent effects of phorbol 12,13-dibutyrate on spontaneous and acetylcholine-induced electrical responses recorded from isolated circular smooth muscle of the guinea-pig stomach antrum

Intracellular recordings of electrical activity were made from circular smooth muscle cells in small segments of tissue isolated from the guinea-pig stomach antrum. Every cell that was impaled exhibited a rhythmic generation of slow potentials. Experiments were carried out to test the effects of three different concentrations (1, 10 and 100 nM) of phorbol 12, 13-dibutyrate (PDBu) on these slow potentials and on the responses produced by acetylcholine (ACh), in the presence of nifedipine and N(omega)-nitro-L-arginine (nitroarginine), known inhibitors of L-type Ca-channels and nitric oxide synthase, respectively. The resting membrane potential was -62 +/- 7 mV, while the frequency and amplitude of the slow potentials were 1.6 +/- 0.1 cycle per min (cpm) and 33 +/- 1 mV, respectively. Application of 1 nM PDBu increased the frequency of slow potentials, with no significant change in the membrane potential and amplitude of slow potentials. At a concentration of 100 nM, PDBu depolarized the membrane by about 6 mV, and either decreased the amplitude and frequency of the slow potentials or abolished them. The amplitude and frequency of the slow potentials were not significantly changed in the presence of 10 nM PDBu. In the presence of chelerythrine (1-2 microM), a known inhibitor of protein kinase C (PKC), the increase in frequency of slow potentials by 1 nM PDBu and depolarization produced by 100 nM PDBu were not elicited. The increase in frequency of slow potentials by 100 nM ACh was inhibited by PDBu, in a concentration-dependent manner, and ACh-responses were abolished in the presence of 100 nM PDBu. These results indicate that PDBu has dual actions on the spontaneous activity of antral circular muscle, with low concentrations increasing and high concentrations inhibiting the frequency of the slow potentials. The former may be produced by activation of protein kinase C (PKC). As the ACh-induced excitation of slow potentials is inhibited by PDBu, a possible causal relationship between the inhibition and over-activation of PKC is considered.

Effects of endogenous and exogenous nitric oxide on electrical responses of circular smooth muscle isolated from the guinea-pig stomach antrum

The effects of endogenous and exogenous nitric oxide (NO) on electrical activity were investigated in circular smooth muscle preparations isolated from the guinea-pig stomach antrum. The actions of endogenous NO were evaluated from the effects of inhibition of NO synthesis by N(omega)-nitro-L-arginine (nitroarginine), while those of exogenous NO were assessed from the effects of SIN-1, an NO donor. Antral circular smooth muscle generated slow potentials periodically at a frequency of about 1 cycle per min (cpm), and unitary potentials were also generated in a random fashion in the interval between slow potentials. Application of nitroarginine (10(-5) M) increased the frequency of slow potentials, with no significant alteration of the resting membrane potential and amplitude of slow potentials. Frequency analysis of unitary potentials revealed that nitroarginine also increased the spectral density at 0.01-1 Hz frequency. The refractory period for the generation of slow potentials evoked by depolarizing pulses was about 10 s, but was decreased to 6 s by nitroarginine. In the presence of nitroarginine, SIN-1 (10(-9)-10(-7) M) reduced the amplitude and frequency of slow potentials: low concentrations (<10(-8) M) reduced only the frequency of slow potentials, while higher concentrations (10(-8)-10(-7) M) reduced both the amplitude and frequency of slow potentials, in a concentration-dependent manner, before abolishing the slow potentials. The power spectrum of the unitary potentials indicated that SIN-1 (>10(-8) M) reduced the spectral density at 0.01-1 Hz frequency. The refractory period for the generation of slow potentials was increased again to about 10 s by SIN-1. Thus, the excitatory effects of nitroarginine could be antagonized by SIN-1, suggesting that the inhibitory effects of endogenous NO are comparable to those of exogenous NO produced by SIN-1. The results also suggested that the effects of NO on smooth muscle are insignificant and NO selectively inhibits the activity of intramuscular interstitial cells of Cajal (ICC-IM).

Inhibitory actions of cilostazol on electrical responses of smooth muscle isolated from the guinea-pig stomach antrum.

We have investigated the effects of cilostazol, a type III phosphodiesterase inhibitor, on the electrical responses of smooth muscle tissue isolated from the guinea-pig stomach antrum. Cilostazol (10(-5) M) inhibited slow waves recorded from circular muscle cells, but did not significantly alter the pacemaker potentials and follower potentials recorded from myenteric interstitial cells and longitudinal muscle cells respectively. Slow potentials generated in isolated circular muscle bundles without attached myenteric interstitial cells were inhibited by cilostazol (>10(-7) M), while all membrane activities were abolished by 10(-5) M cilostazol. In circular muscle bundles, the input resistance of smooth muscle cells and the refractory period for the generation of slow potentials were not altered during the inhibition of spontaneous activity with cilostazol. While cilostazol at 10(-7) and 10(-6) M did not elevate the tissue content of cyclic AMP, at 10(-5) M cyclic AMP was elevated by about 30%. A similar elevation was also produced by 10(-7) M forskolin. The content of cyclic AMP was not significantly increased in preparations stimulated with 10(-3) M caffeine. The potency for inhibiting slow waves was in the order caffeine (10(-3) M) > forskolin (10(-7) M) > cilostazol (10(-5) M). The frequency of slow waves was decreased by caffeine or forskolin but not by cilostazol, while the duration was reduced by caffeine but not by cilostazol or forskolin. Follower potentials were modulated by caffeine and forskolin, but not by cilostazol: the duration was reduced by caffeine, the frequency was reduced by caffeine or forskolin, and the amplitude was not significantly altered by any of them. The results indicate that cilostazol has high selectivity in inhibiting the activity of circular muscle much more than that of longitudinal muscle or pacemaker cells, with no causal relation to the tissue content of cyclic AMP as appears to be the case for the inhibitory actions of caffeine and forskolin.

Topographic abnormality of slow cortical potentials in schizophrenia.

A recent study from our laboratory has provided evidence for the generation of slow potentials occurring in anticipation to task-performance feedback stimuli, in multiple association cortical areas, consistently including two prefrontal areas. In the present study, we intended to determine whether these slow potentials would indicate some abnormality (topographic) in schizophrenic patients, and thus serve as an indication of abnormal association cortex activity. We recorded slow potentials while subjects performed a paired-associates memory task. A 123-channel EEG montage and common average reference were used for 20 unmedicated schizophrenic (mean duration of illness: 11.3 +/- 9.2 years; mean number of previous hospitalizations: 1.2 +/- 1.9) and 22 healthy control subjects during a visual paired-associates matching task. For the topographic analysis, we used a simple index of individual topographic deviation from normality, corrected for absolute potential intensities. Slow potentials were observed in all subjects. Control subjects showed a simple spatial pattern of voltage extrema (left central positive and right prefrontal negative), whereas schizophrenic patients presented a more complex, fragmented pattern. Topographic deviation was significantly different between groups (P<0.001). The increased topographic complexity in schizophrenics could be visualized in grand averages computed across subjects. Increased topographic complexity could also be seen when grand averages were computed for subgroups of patients assembled either according to task-performance (high versus low) or by their scores on psychopathological scales. There was no significant correlation between topographic deviation and psychopathology scores. We conclude that the slow potential topographic abnormalities of schizophrenia indicate an abnormality in the configuration of large-scale electrical activity in association cortices.

The generators of slow potentials obtained during verbal, pictorial and spatial tasks

The purpose of this study was to test whether slow cortical electrical activity is specific to performance on verbal, pictorial and spatial tasks. Twenty-nine healthy subjects were required to compare pairs of visual stimuli separated by a delay of 2.5 s in a S1–S2 contingent negative variation-type paradigm. Slow potentials (SPs) were recorded by high-resolution EEG (123 channels) and their generators modeled by current density reconstruction using individual MRIs as source space models. Activity in each architectonic area of Brodmann was scored with respect to individual maximum current by a percentile method. Results showed a multifocal pattern of current density foci comprising the SP generators, including frontal and posterior cortices in all subjects, with the most active areas being common to the three tasks. In spite of the intersubject variability in the sets of active areas for each given task, a few cortical areas were observed to discriminate between tasks in a statistically significant way: the verbal task corresponded to stronger electrical activity in right area 45 than the other tasks; the spatial to weaker activity in right area 38 and left area 5 than the other tasks; the pictorial, compared to the spatial task, to stronger activity in left area 39; the verbal, compared to the spatial task, to stronger activity in left area 10, and compared to the pictorial, to weaker activity in right area 20. The present method of SP analysis may aid in the functional mapping of human association cortices in individual cases. We discuss our results emphasizing intersubject variability in cortical activity patterns and the possibility of finding more universal patterns.

Multifocal slow potential generation revealed by high-resolution EEG and current density reconstruction

In this work we used high-resolution EEG (123 channels) and current density reconstruction (CDR) to analyze the generators of slow potentials (SPs) in 31 healthy individuals. SPs were obtained during a task–performance feedback anticipation paradigm. The task consisted of a visual paired-associate memory test, with correct performance on single trials indicated by pleasant visual stimuli and incorrect performance by an unpleasant sound. We used realistic models of each subject's head based on their magnetic resonance images (MRIs) to estimate the potentials in the intracranial compartments and to define the source space using individual cortical geometry. Source reconstruction was performed by an Lp-norm minimization algorithm. Results showed a multifocal pattern of current density foci in various association cortices, including prefrontal areas 9 and 10 of Brodmann in all subjects. Posterior cortical areas also contributed importantly to the SP, for instance extrastriate area 19 and parietal area 7, in 90% of the subjects. According to our modeling, we conclude that even the pure stimulus-anticipation SP obtained here, as opposed to traditional motor-task contigent negative variation (CNVs), is not exclusively prefrontal in origin, being generated by multiple association areas. We discuss our results with respect to new possibilities in large-scale cortical physiology and with respect to their application in psychiatry.

Effects of RHC-80267, an inhibitor of diacylglycerol lipase, on excitation of circular smooth muscle of the guinea-pig gastric antrum.

In small segments of circular smooth muscle isolated from the guinea-pig gastric antrum, the effects of RHC-80267, an inhibitor of diacylglycerol lipase, were investigated both on regenerative slow potentials (either occurring spontaneously or as the result of a depolarizing intracellular current injection) and on the actions of acetylcholine (ACh). As diacylglycerol is a known activator of protein kinase C (PKC), it would therefore be expected that RHC-80267 would activate PKC indirectly. In circular smooth muscle bundles, spontaneously generating slow potentials recorded simultaneously from two given cells were synchronized, indicating that these two cells were electrically coupled. RHC-80267 (0.3-1 microM) increased the frequency of slow potential generation, with no alteration to the amplitude of either the slow potentials or the resting membrane potential. Synchronous electrical activity in a given pair of cells was also unchanged by RHC-80267, indicating that intercellular electrical coupling was not altered. The input resistance of smooth muscle cells calculated from the amplitude of electrotonic potentials produced by injection of current was not significantly altered by RHC-80267. The refractory period for the generation of slow potentials evoked by depolarizing stimuli was about 8 s, and it was decreased to about 5 s by RHC-80267, with no significant alteration to the amplitude of spontaneous or evoked slow potentials. ACh (0.5 microM) depolarized the membrane by about 5 mV and increased the amplitude and frequency of slow potentials. The actions of ACh on the frequency of slow potentials were enhanced by RHC-80267, with no alteration to the amplitudes of both the ACh-induced depolarization and slow potentials. These results support the idea that PKC is involved in determining the frequency of slow potentials, by shortening the refractory period for excitation of gastric smooth muscle cells.

Assessment of association cortex activity by high-resolution EEG and current density reconstruction

We analyzed the electrical generators of CNV-type potentials obtained during a visual paired-associates memory task, using Lp norm minimization constrained by individual cortical anatomy. The task that we designed maximized the chances of verifying prefrontal cortex activity, by combining the anticipation of interesting, relatively arousing stimuli with the uncertain expectation based on memory recall. We tested a set of topographical hypotheses on the relation between activity in particular prefrontal domains and task conditions. The task consisted in two types of blocks: 1) memorization, when pairs of words, or abstract figures or positions on the screen were separated in time by 2,5 seconds @l-S2 stimuli); 2) execution with feedback for each trial, when subjects had to decide whether the upcoming pair (S2) of a given stimulus (Sl), just seen in the previous memorization block, formed or not a category match. Sl remained on the screen until a button press indicated the subject’s decision. Two and a half seconds after button press, S2 was presented, and 2,5 seconds after S2 onset, the feedback stimulus (S3) was presented. An interesting, relatively arousing visual stimulus indicated correct and an unpleasant sound indicated incorrect performance. We recorded the EEG using a 123-channel montage in 19 healthy subjects We used a realistic, three compartments model of the head, based on segmentation of individual TZweighed MRI sets and approximation by few milimeter side triangles. Approximately 20.000 points distributed over the cortical surface supported possible model equivalent current dipoles. The average slow potentials were then transformed into signal-to-noise ratios, and the intracranial electrical generators modeled as distributed current sources. For solving the inverse problem (finding the best fitting current distributions that explain the surface data), we applied a minimization algorithm to the Lp (p= 1.2) norms of data and model terms. The generators of the feedback anticipation CNVs consisted in a set of cortical association areas, including prefrontal Brodmann areas 9 and 10 in all subjects. We also obtained preliminary evidence, by analyzing potentials averaged across subjects, for task-specific (verbal, spatial and pictorial) topography of the memorization CNVs. The generators of such group average potentials were also a collection of cortical areas, with some areas appearing to be specifically active during the spatial subtask (left areas 9,10, lateral 6,5,39 and right 19), as opposed to some areas active during the verbal subtask (right 9,22 and 7). The pictorial subtask seemed to combine activity from the other two subtasks. We propose the use of current density reconstruction of the generators of slow potentials as a method for evaluating the functional integrity of cortical association areas in neuropsychiatric clinical conditions. We have started to use such method in a group of schizophrenic patients, and found preliminary evidence, using group averaged potentials, for important abnormalities in signalto-noise ratios and in the topography of all CNVs in the schizophrenic group. The global field power of the memorization CNVs was enhanced in the three subtasks. Finally, preliminary source reconstruction, by the projection of group potentials onto representative head models, indicated a larger degree of generator dispersion in the group of patients.

Primary afferent-evoked synaptic responses and slow potential generation in rat substantia gelatinosa neurons in vitro.

1. Primary afferent fiber-evoked synaptic responses and the mechanisms of spike and slow potential generation have been examined in adult rat substantia gelatinosa (SG) neurons in an in vitro transverse spinal cord slice preparation in which an attached dorsal root is retained. Intracellular recordings were made from SG neurons identified by morphological and electrophysiological criteria. Afferent fiber-evoked fast excitatory postsynaptic potentials (fast EPSPs) and slow EPSPs have been analyzed. 2. SG neurons had mean resting membrane potentials of -67.1 +/- 0.5 mV (mean +/- SE), mean input resistance of 257 +/- 17.7 (SE) M omega, and a mean time constant of 21.3 +/- 1.9 ms and exhibited spontaneous EPSPs. 3. Single low-intensity stimuli applied to the dorsal root using a suction electrode produced, in 70% of SG neurons, short-latency, presumed monosynaptic fast EPSPs which had a half decay time of 10-30 ms and an amplitude of 8-28 mV. The conduction velocity of afferent fibers evoking fast EPSPs was 2-7 m/s, corresponding to that of thinly myelinated A-delta-fibers. Dorsal root stimulation at higher intensities evoked, in 10% of SG neurons, long-latency and apparently monosynaptic EPSPs which had a time course and amplitude similar to that evoked by low-intensity stimulation. The conduction velocity of fibers evoking long-latency EPSPs was 0.4-2 m/s, suggesting that they constitute predominantly C-fibers. A-delta- and C-fiber-mediated fast EPSPs were detected in 20% of SG neurons examined. 4. Low-intensity stimuli produced slow EPSPs in 20% of SG neurons. Slow EPSPs were 3-15 mV in amplitude and of up to 2 min in duration. A-delta-fibers appeared to be responsible for the generation of slow EPSPs. Slow EPSPs were associated with an increase in membrane resistance and were decreased in amplitude with membrane hyperpolarization. 5. Action potentials in SG neurons had a mean amplitude of 76.3 +/- 1.1 mV and a mean duration of 1.0 +/- 0.07 ms. Na+ ions represent the main charge carrier during the rising phase of the action potential and Ca2+ ions contribute to the shoulder on the falling phase. 6. In 20% of SG neurons, subthreshold depolarizing pulses were followed by long-lasting slow-inactivating depolarizing potentials which were able to initiate spikes. The slow depolarizing potentials were blocked by TTX and enhanced by application of TEA and Ba2+, suggesting that Na+ and K+ are involved in this slow-inactivating potential.(ABSTRACT TRUNCATED AT 400 WORDS)

Cortical slow potentials and the occipital EEG in congenital blindness

In a group of 7 congenitally blind adults, electroencephalographic occipital alpha rhythms were absent, but slow negative cortical potentials (CNV) were recorded over the visual cortex and were similar to those of normally sighted controls. Frontal and central CNV amplitudes, but not auditory evoked potentials or reaction times, were decreased significantly in the blind. The results confirm the presence of a developmental EEG abnormality following early blindness, and demonstrate the independance of slow potential generation from rhythmic 8–12 c/sec EEG activity in deafferented visual cortex. Non-sensory specific, event-related potentials such as the Contingent Negative Variation may prove to be useful psychophysiological probes of residual cortical function in brain regions which are deprived of primary sensory input.