Functional differentiation in the dorsal hippocampus with local electrical stimulation during learning by rats

Rats were given stimulation through bipolar electrodes to the CA1 region of the dorsal hippocampus during the learning of a brightness descrimination. Animals stimulated only during cue presentation showed a pattern of disruption comparable to that of animals in an earlier experiment receiving stimulation throughout the whole learning period. Stimulation 10 sec after each response produced a similar effect to such stimulation given 5 sec after in the earlier experiment with disruption slightly less than with the 5 sec delay. Stimulation to the overlying cortex produced no significant effects. Results further support the view that the CA1 region mediates two distinct processes in this discrimination, namely a short term memory process in consolidation and a retrieval or comparison process. Both appear likely to be related through an attentional mechanism.     

Electrical stimulation of the human hippocampus produces verbal intrusions during memory testing

Verbal memory testing was conducted during electrical stimulation of the human hippocampus in 12 epilepsy surgery candidates with unilateral temporal lobe seizure onset. Performance was assessed during baseline, left hippocampal stimulation and right hippocampal stimulation. Verbal intrusion errors were greater during electrical stimulation of the hippocampus contralateral to the seizure focus. These findings suggest that verbal intrusions are related to memory deficits, and that patients with cerebral disease who intrude words from an earlier portion of a learning test are likely to have bilateral cerebral dysfunction.     

Behavioral effects of high frequency electrical stimulation of the hippocampus on electrical kindling in rats

Experiments were designed to evaluate the effects of high frequency electrical stimulation (HFS) applied in ventral hippocampus during the hippocampal kindling process, as well as on the expression of fully kindled seizures and the refractoriness for subsequent convulsions during their postictal period. Male Wistar rats, stereotactically implanted in both ventral hippocampus, received daily bilateral HFS (pulses of 60 micros width at 130 Hz at subthreshold current intensity) during 1h immediately after each kindling stimulation (1s train of 60 Hz biphasic square waves, each 1 ms) during 40 days or until the kindled state was achieved. Rats were classified as follows: (a) Responder animals, who required low current intensity for HFS (208+/-38.2 microA), did not show progress of the kindling process and remained in stages II and III seizures. (b) Nonresponders rats, in which the current intensity for HFS was higher (434.5+/-51.7 microA), developed the kindling process as the kindling control group. When HFS was applied before the kindling stimulation in fully kindled rats, animals presented a reduced expression of the fully kindled seizures (nonresponders animals) and an enhanced refractoriness for subsequent seizures during the postictal period (kindling control and nonresponder animals). There was no correlation between the area where the HFS was applied and the effects induced. It was concluded that HFS at 130 Hz in ventral hippocampus is able to modify the epileptogenesis induced by the hippocampal kindling process and the refractoriness to subsequent seizures during the postictal period in rats.     

Changes in the electrical activity of the ventral hippocampus during stimulation of the anterior cingulate gyrus of the cat cortex

The results of anterior cingulate gyrus stimulation and cutting of the main cortical input to hippocampus (the entorhinal cortex) lead to the suggestion that the entorhinal cortex and the limbic thalamic nuclei are involved in the genesis of ventral hippocampus responses to anterior cingulate gyrus stimulation.     

The effects of electrical (blocking) stimulation to the dorsal hippocampus of the rat of learning of a simultaneous brightness discrimination

Twenty-four rats were chronically implanted with bilateral bipolar electrodes in the CA1 region of the dorsal hippocampus. Animals were then trained on a simultaneous visual discrimination task under several conditions of stimulation. Compared with 8 operated and 8 unoperated controls, 8 rats receiving $\text{1}\text{2}$ sec train of pulses every 3·0 sec given continuously throughout the learning period showed severe disruption of learning. A further 8 rats given 2·0 sec of stimulation 5·0 sec after each response also showed disruption of learning but some learning took place. After criterion performance was achieved “continuous” stimulation resulted in a significant increase in errors but “2 sec” stimulation led to no significant change in the number of correct responses. Stimulation during learning resulted in a strong persevarative response tendency. These results were considered in terms of a registration-consolidation-retrieval continuum.     

Visual illusions during the electrical stimulation of the labyrinth

Transcutaneous electrical stimulation of the labyrinth induced apparent motion of a stationary light source in darkness in normal subjects. This effect is similar to the oculogyric illusion induced by rotatory vestibular stimulation. Monaural anodal stimulation of the right labyrinth evoked apparent movement of the target to the left, whereas cathodal stimulation induced opposite illusion. The threshold current was 0.35-0.6 mA. Binaural bipolar stimuli induced illusory target motion directed to the side of the cathode, the threshold decreased 1.5-2.5 times. Binaural monopolar stimulation induced vertical apparent displacement of a target, the threshold being 1.4-3.0 mA. The amplitude and velocity of illusory target motion increased with current. The subject eyes began to move with much higher currents than those necessary for illusory sensation. It is therefore suggested that the visual illusion is related not to vestibulo-visual interaction but to vestibular effects on the spatial perception system.     

Cortical stimulation during learning in rabbits

Rabbits were trained to perform a conditioned avoidance response to a buzzer. Prior to the beginning of training, nonpolarizable electrodes were implanted in the frontal, visual and auditory cortex bilaterally. The effect of cathodal and anodal polarization was tested during the course of training. Cathodal polarization in both the frontal and auditory areas caused a significant decrement in performance, lasting over a period of two days. Cathodal polarization in the visual cortex did not alter the conditioned avoidance response to the buzzer. Anodal polarization produced no consistent effects on performance.     

In vivo neuronal firing patterns during human epileptiform discharges replicated by electrical stimulation

ObjectiveTo describe neuronal firing patterns observed during human spontaneous interictal epileptiform discharges (IEDs) and responses to single pulse electrical stimulation (SPES).MethodsActivity of single neurons was recorded during IEDs and after SPES in 11 consecutive patients assessed with depth EEG electrodes and attached microelectrodes.ResultsA total of 66 neurons were recorded during IEDs and 151 during SPES. We have found essentially similar patterns of neuronal firing during IEDs and after SPES, namely: (a) a burst of high frequency firing lasting less than 100 ms (in 39% and 25% of local neurons, respectively for IED and SPES); (b) a period of suppression in firing lasting around 100–1300 ms (in 19% and 14%, respectively); (c) a burst followed by suppression (in 10% and 12%, respectively); (d) no-change (in 32% and 50%, respectively).ConclusionsThe similarities in neuronal firing patterns associated with IEDs and SPES suggest that, although both phenomena are initiated differently, they result in the activation of a common cortical mechanism, probably initiated by brief synchronised burst firing in some cells followed by long inhibition.SignificanceThe findings provide direct in vivo human evidence to further comprehend the pathophysiology of human focal epilepsy.     

Spreading depression in the thalamus, hippocampus and caudate nucleus of the rat during electrical stimulation of the parietal area of the cortex

Parameters of electrical stimulation (ES) of the rats cerebral cortex which synaptically induced spreading depression (SD) in deep structures were found. The thalamic SD was regularly triggered by short (0.02-0.05 s) high-frequency (200-500 Hz) ES of the parietal cortical surface. In this case the EEG control showed the absence of any seizure activity in the cortical and subcortical structures. Nembutal (20-40 mg/kg) raised the SD thresholds, but did not prevent the short-latency thalamic SD. The ES of the parietal cortex was not sufficiently effective for SD synaptic excitation in the hippocampus and caudate nucleus. In contrast to the thalamic SD, the hippocampal one was accompanied by the episodes of epileptiform activity at certain SD phases. Thus, the low subseizure threshold of the synaptically triggered cortical and subcortical SD should be taken into account when biological purpose of the SD is discussed.     

Direct electrical stimulation of rat soleus during denervation-reinnervation

The effect of direct, low-frequency electrical stimulation (at 10 Hz continuously 8 h daily) of muscle on isometric twitch contractile properties of adult rat soleus was observed during denervation and reinnervation. The normal and the bilaterally sciatic nerve crush-denervated groups were implanted with unilateral juxtamuscular electrodes to stimulate the soleus muscle in one limb. After 10, 15, 20, 25, and 30 days of electrical stimulation (2- to 4-mA pulses at 4 ms duration) the normal control, normal-stimulated, crush-denervated control, and crush-denervated-stimulated soleus muscles (N = 6) were evaluated in vitro by massively field stimulating the muscles in physiologic buffer (pH 7.2) at 23 to 24°C. The parameters of isometric twitch contraction measured were latent period (LP), maximum isometric twitch tension (P_t), contraction time (CT), maximum rate of isometric twitch tension (V_t^max), and half-relaxation time (HRT). In normal muscle, 25 and 30 days of electrical stimulation produced significant (P < 0.05) changes: muscle hypertrophy (26.5 and 16.6%, respectively), decline in the P_t (23.4 and 12.1%, respectively), and decrease in the (V_t^max) (17.3 and 21.6%, respectively). For the same periods, compared with the crush-denervated control, the crush-denervated-stimulated muscles also showed significant (P < 0.05) changes: prolongation of the LP. (22.9 and 26.5%), decline in the P_t (24.5 and 31.6%), and decrease in the V_t^max (27.7 and 33.3%). These results, therefore, suggest that the long-term (200 to 240 h) direct, lowfrequency (10 Hz) electrical stimulation may impair the mechanism of isometric twitch development in slow-twitch muscle of the rat. However, our study does not prove that this pattern of electrostimulation can significantly alter the course of self-reinnervation in muscle.     

Physostigmine reverses memory deficits produced by pretraining electrical stimulation of the dorsal hippocampus in mice

The aim of the present experiments was to test the validity of the hypothesis that presynaptic cholinergic activity has a functional significance for memory formation. The results show that electrical stimulation of the dorsal hippocampus delivered before learning in BALB/c mice which induces a decrease of about 40% in hippocampal choline acetyltransferase (ChAT) activity at the time of learning results in deficits in retention scores in two appetitive learning tasks (operant conditioning in the Skinner box or a spatial memory task using a 4-hole board). In both behavioral tasks intraventricular injection of 1 microgram of physostigmine 20 min before the acquisition session reverses the disruptive effect of pretraining hippocampal stimulation. Our results seem to indicate that the memory deficits produced by pretraining electrical stimulation of the hippocampus result from both a decrease in ChAT activity and a corresponding reduction of acetylcholine availability in the hippocampal formation.     

Subacute electrical stimulation of the hippocampus blocks intractable temporal lobe seizures and paroxysmal EEG activities

PURPOSE: To investigate the clinical, electroencephalographic (EEG), and histopathologic effects of subacute electrical stimulation of the hippocampal formation or gyrus (SAHCS) on 10 patients with intractable temporal lobe seizures. METHODS: Bilateral, depth, hippocampal or unilateral, subdural, basotemporal electrodes were implanted in all 10 patients for a topographic diagnosis of the site and extent of the epileptic focus before a temporal lobectomy. In all patients, antiepileptic drugs (AEDs) were discontinued from 48 to 72 h before a program of continuous SAHCS, which was performed for 2-3 weeks. Stimulation parameters were biphasic Lilly wave pulses, 130/s in frequency, 450 micros in duration, and 200-400 microA in amplitude. The stimuli were delivered 23 of every 24 h for the 2-3-week SAHCS period. The effects of SAHCS on the number of clinical seizures per day and the percentage of interictal EEG spikes per 10-second samples of maximal paroxysmal activity at the epileptic focus were determined daily during the 16 days of SAHCS. At the completion of this program, patients underwent an en bloc temporal lobectomy, and the histopathologic effects of SAHCS on the stimulated tissue were analyzed by means of light-microscopy studies. RESULTS: In seven patients whose stimulation electrode contacts were placed within the hippocampal formation or gyrus and who experienced no interruption in the stimulation program, SAHCS abolished clinical seizures and significantly decreased the number of interictal EEG spikes at the focus after 5-6 days. The most evident and fast responses were found by stimulating either the anterior pes hippocampus close to the amygdala or the anterior parahippocampal gyrus close to the entorhinal cortex. Other surface, hippocampal, and basotemporal EEG signs predicted and accompanied this antiepileptic response. These included an electropositive DC shift and monomorphic delta activity at the medial hippocampal and parahippocampal regions, and a normalization of the background EEG activity and signs of slow-wave sleep in surface. depth, and subdural regions. In contrast, no evident antiepileptic responses or no responses at all were found in three patients when stimulation was either interrupted or when it was administered outside the hippocampus. Light microscopy analysis of the stimulated hippocampal tissue showed histopathological abnormalities attributable to the depth-electrode penetration damage or to the pial surface reaction to the subdural, Silastic electrode plate. However, no evident histopathological differences were found between the stimulated and nonstimulated hippocampal tissue. CONCLUSIONS: SAHCS appears to be a safe procedure that can suppress temporal lobe epileptogenesis with no additional damage to the stimulated tissue.     

Functional contributions and interactions between the human hippocampus and subregions of the striatum during arbitrary associative learning and memory

The hippocampus and striatum are thought to have different functional roles in learning and memory. It is unknown under what experimental conditions their contributions are dissimilar or converge, and the extent to which they interact over the course of learning. In order to evaluate both the functional contributions of as well as the interactions between the human hippocampus and striatum, the present study used high‐resolution functional magnetic resonance imaging (fMRI) and variations of a conditional visuomotor associative learning task that either taxed arbitrary associative learning (Experiment 1) or stimulus‐response learning (Experiment 2). In the first experiment, we observed changes in activity in the hippocampus and anterior caudate that reflect differences between the two regions consistent with distinct computational principles. In the second experiment, we observed activity in the putamen that reflected content specific representations during the learning of arbitrary conditional visuomotor associations. In both experiments, the hippocampus and ventral striatum demonstrated dynamic functional coupling during the learning of new arbitrary associations, but not during retrieval of well‐learned arbitrary associations using control variants of the tasks that did not preferentially tax one system versus the other. These findings suggest that both the hippocampus and subregions of the dorsal striatum contribute uniquely to the learning of arbitrary associations while the hippocampus and ventral striatum interact over the course of learning. © 2015 Wiley Periodicals, Inc.     

Yawning induced by focal electrical stimulation in the human brain

The primary function of yawning is not fully understood. We report a case in which electrical stimulation of the putamen in the human brain consistently elicited yawning. A 46-year-old woman with intractable epilepsy had invasive depth electrode monitoring and cortical stimulation mapping as part of her presurgical epilepsy evaluation. The first two contacts of a depth electrode that was intended to sample the left insula were in contact with the putamen. Stimulation of these contacts at 6 mA and 8 mA consistently elicited yawning on two separate days. Engagement in arithmetic and motor tasks during stimulation did not result in yawning. When considering the role of the putamen in motor control and its extensive connectivity to cortical and brainstem regions, our findings suggest that it plays a key role in the execution of motor movements necessitated by yawning. Furthermore, given the role of the anterior insula in attention and focused tasks, activation of this area while engaged in arithmetic and motor tasks could inhibit the putaminal processing necessary for yawning. Many have hypothesized the function of yawning; however, it remains debatable whether yawning serves a primarily physiological or communicative function or perhaps both.