Dead reckoning (path integration) requires the hippocampal formation: evidence from spontaneous exploration and spatial learning tasks in light (allothetic) and dark (idiothetic) tests.

Animals navigate using cues generated by their own movements (self-movement cues or idiothetic cues), as well as the cues they encounter in their environment (distal cues or allothetic cues). Animals use these cues to navigate in two different ways. When dead reckoning (deduced reckoning or path integration), they integrate self-movement cues over time to locate a present position or to return to a starting location. When piloting, they use allothetic cues as beacons, or they use the relational properties of allothetic cues to locate places in space. The neural structures involved in cue use and navigational strategies are still poorly understood, although considerable attention is directed toward the contributions of the hippocampal formation (hippocampus and associated pathways and structures, including the fimbria-fornix and the retrosplenial cortex). In the present study, using tests in allothetic and idiothetic paradigms, we present four lines of evidence to support the hypothesis that the hippocampal formation plays a central role in dead reckoning. (1) Control but not fimbria-fornix lesion rats can return to a novel refuge location in both light and dark (infrared) food carrying tasks. (2). Control but not fimbria-fornix lesion rats make periodic direct high velocity returns to a starting location in both light and dark exploratory tests. Control but not fimbria-fornix rats trained in the light to carry food from a fixed location to a refuge are able to maintain accurate outward and homebound trajectories when tested in the dark. (3). Control but not fimbria-fornix rats are able to correct an outward trajectory to a food source when the food source is moved when allothetic cues are present. These, tests of spontaneous exploration and foraging suggest a role for the hippocampal formation in dead reckoning.     

NMDA lesions of Ammon's horn and the dentate gyrus disrupt the direct and temporally paced homing displayed by rats exploring a novel environment: evidence for a role of the hippocampus in dead reckoning

Dead reckoning, a form of navigation used to locate a present position and to return to a starting position, is used by rats to return to their home base. The present experiment examined whether dead reckoning is displayed by rats during their first exploratory excursions in a novel environment and also examined whether the behaviour requires the integrity of the cells of the hippocampus. Experimental rats, those with NMDA (N-methyl d-aspartate) lesions of Ammon's horn and the dentate gyrus, and control rats could leave a cage to explore a large circular table under light and dark conditions. Home base behaviour, use of olfactory cues, and thigmotaxic- based navigation were evaluated. Temporal, topographical and kinematic analyses were conducted on the first three exploratory excursions that extended at least halfway across the table. Groups did not differ in numbers of exits from the home base, lingering near the home base, distance travelled, or the use of surface cues as might be exemplified by thigmotaxic and olfactory behaviour. Temporal, topographical and kinematic reconstructions of homing behaviour, however, indicated that control rats, but not hippocampal rats, made direct high velocity return trips to the home base in both the light and the dark. Peak velocity of the trips occurred at the trip midpoint, independent of trip distance, suggesting the movements were preplanned. These results are discussed in relation to the ideas that dead reckoning is used in the homing of exploring rats and that this form of navigation involves the hippocampus.     

Functional interaction between the associative parietal cortex and hippocampal place cell firing in the rat

The hippocampus and associative parietal cortex (APC) both contribute to spatial memory but the nature of their functional interaction remains unknown. To address this issue, we investigated the effects of APC lesions on hippocampal place cell firing in freely moving rats. Place cells were recorded from APC-lesioned and control rats as they performed a pellet-chasing task in a circular arena containing three object cues. During successive recording sessions, cue manipulations including object rotation in the absence of the rat and object removal in the presence of the rat were made to examine the control exerted by the objects or by non-visual intramaze cues on place field location, respectively. Object rotations resulted in equivalent field rotation for all cells in control rats. In contrast, a fraction of place fields in APC-lesioned rats did not rotate but remained stable relative to the room. Object removal produced different effects in APC-lesioned and control rats. In control rats, most place fields remained stable relative to the previous object rotation session, indicating that they were anchored to olfactory and/or idiothetic cues. In APC-lesioned rats, a majority of place fields shifted back to their initial, standard location, thus suggesting that they relied on uncontrolled background cues to maintain place field stability. These results provide strong evidence that the hippocampus and the APC cooperate in the formation of spatial memory and suggest that the APC is involved in elaboration of a hippocampal map based on proximal landmarks.     

Egocentric spatial orientation in a water maze by rats subjected to transection of the fimbria-fornix and/or ablation of the prefrontal cortex

The acquisition of a water maze based task requiring egocentric spatial orientation in the absence of distal cues was studied in four groups of rats: animals in which the fimbria-fornix had been transected, rats that received bilateral ablations of the anteromedial prefrontal cortex, animals in which both of these structures had been lesioned, and a sham-operated control group. Isolated lesions of both the anteromedial prefrontal cortex and the hippocampus were associated with a significantly impaired task acquisition. Both of these individually lesioned groups did, however, eventually demonstrate full functional recovery by reaching the task proficiency of the sham-operated control group. In contrast, the group in which both of these structures had been lesioned failed to demonstrate full functional recovery and was severely and long-lastingly impaired when compared to all other groups. Behavioural challenges in the form of a no-platform session and two reversals of platform position demonstrated that while the sham-operated control group and the group subjected to fimbria-fornix transections in isolation utilized rather pure egocentric orientation strategies, the two prefrontally lesioned groups (and especially the combined lesion group) employed a different set of solution strategies which at least partly relied on a "circling" method. Even in the behaviour of the prefrontally lesioned groups, however, indications of a certain level of cognitive representations of the platform positions were seen. It is concluded that both the prefrontal cortex and the hippocampus contribute to the mediation of egocentric spatial orientation. Furthermore, the hippocampus is a significant and potentially irreplaceable part of the neural substrate of functional recovery of the presently studied task after prefrontal lesions--while the prefrontal cortex may play a similar role with respect to hippocampal lesions.     

Functional asymmetry of left and right avian piriform cortex in homing pigeons' navigation

It has been shown that homing pigeons rely on olfactory cues to navigate over unfamiliar areas and that any kind of olfactory impairment produces a dramatic reduction of navigational performance from unfamiliar sites. The avian piriform cortex is the main projection field of olfactory bulbs and it is supposed to process olfactory information; not surprisingly bilateral lesions to this telencephalic region disrupt homing pigeon navigation. In the present study, we attempted to assess whether the left and right piriform cortex are differentially involved in the use of the olfactory navigational map. Therefore, we released from unfamiliar locations pigeons subjected, when adult, to unilateral ablation of the piriform cortex. After being released, the pigeons lesioned to the right piriform cortex orientated similarly to the intact controls. On the contrary, the left lesioned birds were significantly more scattered than controls, showing a crucial role of the left piriform cortex in processing the olfactory cues needed for determining the direction of displacement. However, both lesioned groups were significantly slower than controls in flying back to the home loft, showing that the integrity of both sides of the piriform cortex is necessary to accomplish the whole homing process.     

Rats can track odors, other rats, and themselves: implications for the study of spatial behavior

In order to demonstrate that rats solve dead reckoning (path integration) tasks in which they return to a starting location using self-movement (idiothetic) cues, it is necessary to remove external (allothetic) cues. Odor cues, especially those generated by a rat on a single passage, are difficult to control and they can potentially serve as a cue to guide a homeward trip. Because it is presently unknown whether rats can track the cues that they themselves leave, as opposed to the odor trails left by other rats, we investigated this question in the present study. A tracking task was used in which rats: (1) followed a scented string from a refuge to obtain a food pellet located on a large circular table; (2) followed odors left on the table; (3) followed odors left by the passage of another rat; or (4) followed odors left by themselves. Groups of rats were presented with strings scented with either the rat's own odor (Group Own), a conspecific's odor (Group Other), or another scent, vanilla (Group Vanilla). After training, a series of discrimination tests were given to determine the nature of the stimulus that controls scent tracking. The results indicated that Own, Other, and Vanilla groups were equally proficient in discriminating and following their respective odors. The rats were also able to follow odor trails on the table surface as well as a trail left by the single passage of another rat or their own passage. This is the first study to demonstrate that rats can discriminate between conspecific odors and their own odor left during a single passage. The results are discussed in relation to their implications for experimental methodology and olfactory contributions to spatial navigation in general and dead reckoning in particular.     

Homing behavior of hippocampus and parahippocampus lesioned pigeons following short-distance releases

The avian hippocampal formation has been proposed to play a critical role in the neural regulation of a navigational system used by homing pigeons to locate their loft once in the familiar area near home. In support of this hypothesis, the homing performance of pigeons with target lesions of either the hippocampus or parahippocampus was found to be impaired compared to controls following releases of about 10 km. Further, radio tracking revealed that the in-flight behavior of the hippocampal lesioned homing pigeons was characterized by numerous direction changes and generally poor orientation with respect to the home loft. The results identify a local navigational impairment on the part of the hippocampal lesioned pigeons in the vicinity of the loft where landmark cues are thought to be important. Additionally, target lesions of the hippocampus or parahippocampus were found to be similarly effective in causing homing deficits.     

Processing idiothetic cues to remember visited locations: hippocampal and vestibular contributions to radial-arm maze performance

This research examined whether rats can use idiothetic cues to form spatial memories in the radial-arm maze (RM) and whether the hippocampus is involved in such ability. A possible contribution of the vestibular system to RM performance was also investigated. Rats with excitotoxic hippocampal lesions and sham-operated controls were trained on two versions of the RM task. In the Light condition, a unique visual insert was apposed on each arm floor and rats could choose which arm to enter next by relying on visual and/or idiothetic stimuli. In the Dark condition, the task was administered in darkness and success required processing of idiothetic cues to remember visited locations on the maze. In experiment 1, the performance of lesioned rats was impaired in the Light condition, but both control and lesioned rats learned to avoid already visited arms. In the Dark condition, the performance of controls improved over time whereas a severe deficit was observed in rats with hippocampal lesions. Thus, control rats, but not hippocampal lesioned rats, can form spatial memories by processing idiothetic inputs. Experiment 2 showed that vestibular lesions disrupt performance in both the Light and the Dark conditions and confirmed that rats use idiothetic information, especially vestibular cues, while navigating in the RM. Therefore, cues generated during locomotion play an important role in hippocampal-dependent spatial memory.     

Lesions of nucleus basalis alter ChAT activity and EEG in rat frontal neocortex.

The EEG was recorded from frontal, parietal and visual cortices of sham-operated control rats and rats having ibotenic acid lesions of the nucleus basalis. Recordings were made during a period of rest and during stimulus-evoked desynchronization. Spectral power was determined using a Fast Fourier Transform routine; 3 artifact-free 4 sec epochs of resting activity and two 4 sec epochs of activated EEG were analyzed. Choline acetyltransferase activity (ChAT) was measured in each cortical area and was reduced in lesioned animals an average of 25% in frontal cortex, 19% in the parietal region and 10% in visual cortex. The percent of low frequency activity (1-12 Hz) in the frontal EEG was significantly greater in lesioned animals than in the control group during quiet rest; a significant correlation was found between ChAT activity and power in this band. Desynchronized activity was largely unaffected except for a reduction in 25-31 Hz activity in the frontal cortex of lesioned animals. EEG activity in both the parietal and visual areas was unchanged from control values.     

A lateralized avian hippocampus: preferential role of the left hippocampal formation in homing pigeon sun compass-based spatial learning

The hippocampal formation (HF) plays a crucial role in amniote spatial cognition. There are also indications of functional lateralization in the contribution of the left and right HF in processes that enable birds to navigate space. The experiments described in this study were designed to examine left and right HF differences in a task of sun compass-based spatial learning in homing pigeons (Columba livia). Control, left (HFL) and right (HFR) HF lesioned pigeons were trained in an outdoor arena to locate a food reward using their sun compass in the presence or absence of alternative feature cues. Subsequent to training, the pigeons were subjected to test sessions to determine if they learned to represent the goal location with their sun compass and the relative importance of the sun compass vs. feature cues. Under all test conditions, the control pigeons demonstrated preferential use of the sun compass in locating the goal. By contrast, the HFL pigeons demonstrated no ability to locate the goal by the sun compass but an ability to use the feature cues. The behaviour of the HFR pigeons demonstrated that an intact left HF is sufficient to support sun compass-based learning, but in conflict situations and in contrast to controls, they often relied on feature cues. In conclusion, only the left HF is capable of supporting sun compass-based learning. However, preferential use of the sun compass for learning requires an intact right HF. The data support the hypothesis that the left and right HF make different but complementary contributions toward avian spatial cognition.     

Similar memory impairments found in medial septal-vertical diagonal band of Broca and nucleus basalis lesioned rats: are memory defects induced by nucleus basalis lesions related to the degree of non-specific subcortical cell loss?

The function of nucleus basalis (NB) and medial septal-vertical diagonal band of Broca (MS-VDBB) in a place navigation task requiring reference memory was investigated. Two subclasses of nucleus basalis ibotenic acid-lesioned rats could be identified: a group having both extensive non-specific subcortical damage and severely impaired learning behavior, and a less impaired group with correspondingly less subcortical damage. The depletion of cortical cholinergic enzymes was slightly higher in the group of NB-lesioned rats with extensive subcortical lesions than in the group with smaller lesioned areas. In the hippocampus of both of these NB-lesioned groups, cholinergic innervation remained unchanged. Ibotenic acid lesioning restricted to the MS-VDBB depleted hippocampal cholinergic innervation, but not the innervation of the frontal cortex, and also led to impaired learning behavior. Of all the lesioned rats, the most impaired were the NB-lesioned rats with large non-specific subcortical lesion.     

Involvement of the hippocampus and associative parietal cortex in the use of proximal and distal landmarks for navigation

Rats with dorsal hippocampus or associative parietal cortex (APC) lesions and sham-operated controls were trained on variants of the Morris water maze navigation task. In the 'proximal landmark condition', the rats had to localize the hidden platform solely on the basis of three salient object landmarks placed directly in the swimming pool. In the 'distal landmark condition', rats could rely only on distal landmarks (room cues) to locate the platform. In the 'beacon condition', the platform location was signaled by a salient cue directly attached to it. Rats with hippocampal lesions were impaired in the distal and to a less extent in the proximal landmark condition whereas rats with parietal lesions were impaired only in the proximal landmark condition. None of the lesioned groups was impaired in the beacon condition. These results suggest that the processing of information related to proximal, distal landmarks or associated beacon are mediated by different neural systems. The hippocampus would contribute to both proximal and distal landmark processing whereas the APC would be involved in the processing of proximal landmarks only. Navigation relying on a cued-platform would not require participation of the hippocampus nor the APC. Assuming that the processing of proximal landmarks heavily depends on the integration of visuospatial and idiothetic information, these results are consistent with the hypothesis that the APC plays a role in the combination of multiple sensory information and contributes to the formation of an allocentric spatial representation.     

Hyperglycolysis is exacerbated after traumatic brain injury with fentanyl vs. isoflurane anesthesia in rats

Despite common use of narcotics in the clinical management of severe traumatic brain injury (TBI), in experimental models rats treated with fentanyl have exhibited worse functional outcome and more CA1 hippocampal death than rats treated with standard isoflurane anesthesia. We hypothesized that greater post-traumatic excitotoxicity, reflected by cerebral glucose utilization (CMRglu), may account for detrimental effects of fentanyl vs. isoflurane. Rats were anesthetized with either isoflurane (1% by inhalation) or fentanyl (10 mcg/kg iv bolus then 50 mcg/kg/h infusion). 14C-deoxyglucose autoradiography was performed 45 min after controlled cortical impact (CCI) to left parietal cortex (n=4 per anesthetic group) or in uninjured rats after 45 min of anesthesia (n=3 per anesthetic group). Uninjured rats treated with fentanyl vs. isoflurane showed 35-45% higher CMRglu in all brain structures (p<0.05) except CA3. After TBI in rats treated with isoflurane, CMRglu increased significantly only in ipsilateral CA1 and ipsilateral parietal cortex (p<0.05 vs. isoflurane uninjured). Conversely, after TBI in rats treated with fentanyl, CMRglu increased markedly and bilaterally in CA1 and CA3 (p<0.05 vs. fentanyl uninjured), but not ipsilateral parietal cortex. In contralateral CA1, CMRglu was nearly two times greater after TBI in fentanyl vs. isoflurane treated rats (p<0.05). Hyperglycolysis was exacerbated in CA1 and CA3 hippocampus after TBI in rats treated with fentanyl vs. isoflurane anesthesia. This post-traumatic hyperglycolysis suggests greater excitotoxicity and concurs with reports of worse functional outcome and more CA1 hippocampal death after TBI with fentanyl vs. isoflurane anesthesia.     

Effects of training on a spatial memory task on high affinity choline uptake in hippocampus and cortex in young adult and aged rats

The relation of forebrain cholinergic function to learning and memory was explored by identification and characterization of a training-induced change in high-affinity choline uptake (HACU), an index of cholinergic activity. Young adult rats were trained to find an invisible escape platform in a water tank using environmental cues. After 4 d of this place-training (16 trials), hippocampal HACU was significantly reduced relative to that observed in rats trained to find a visible platform (cue-training), even when cue- and place-trained rats were yoked for swim time. These place- but not cue-trained rats showed significantly lower hippocampal HACU than did naive rats, and no effect of training was noted after only 1 d of training. Similar results were obtained in parietal cortex. These differential training effects on HACU correspond to previous reports that muscarinic blockade impairs place, but not cue, learning. A further experiment revealed that the decrease in HACU in hippocampus, but not in parietal cortex, occurred only during the acquisition phase of learning and was related to the rate of acquisition for individual animals. Hippocampal HACU in naive young and aged (24-27 months) rats did not differ, but the response of the septohippocampal cholinergic system to training was diminished in the aged rats. Old rats displayed impaired place learning and a corresponding dampening of the training-induced change in HACU. These results suggest that there is a task-specific engagement of cholinergic function in young animals that does not occur in behaviorally impaired aged animals, a finding that is consistent with a role for cholinergic dysfunction in memory impairments associated with aging.     

Exploratory activity and response to a spatial change in rats with hippocampal or posterior parietal cortical lesions.

Rats with bilateral lesions of posterior parietal cortex (PPC: Krieg's Area 7) or dorsal hippocampus (HIP) were compared with controls for their response to environmental change. In the first experiment, following subjects' exploration of a relatively homogeneous open-field environment, a stimulus-rat was introduced at a particular location beneath the glass floor. All groups selectively explored the location of the stimulus-rat, but only the control and PPC groups displayed habituation. On removal of the stimulus-rat, only the control group selectively re-explored the place where the stimulus-rat had been. A second experiment, similar to the first, used additional prominent visual cues beneath the floor. When the cues were spatially separate from the location of the stimulus-rat (Dissociated object condition), the same results were obtained as in the first experiment. When the additional cues were positioned close to the stimulus-rat location (Associated object condition), habituation occurred in all groups including the hippocampal group, and again the removal of the stimulus-rat resulted in a selective re-exploration of its former location in the control group only. However, a selective preference for staying at the stimulus-rat's previous location was found in PPC animals as in controls. Hippocampal rats failed to investigate the location of the missing stimulus in all conditions. The results confirm the role played by the hippocampus in spatial memory and suggest that the posterior parietal cortex is involved in the cognitive-demanding aspects of spatial encoding, particularly in environments that are poorly visually differentiated.     

Prefrontal cortical mediation of rats' place learning in a modified water maze

The acquisition of a place learning task in a water maze modified from the “standard” set-up by restriction of distal cues and addition of “proximal” cues (ping-pong balls in fixed positions on the surface of the water) was tested in three groups of rats: (I) animals subjected to bilateral ablation of the anteromedial prefrontal cortex, (II) rats in which the parietal “association” cortex had been removed bilaterally, and (III) a sham operated control group. The task acquisition of the prefrontaly ablated group was significantly impaired, whereas the animals in which the parietal cortex had been removed acquired the task as quickly as the control group. Upon reaching criterion level performance all animals were tested on “challenge” sessions on which the cues were manipulated. Such “challenges” demonstrated that the animals of all three groups discriminated between the distal cues and utilized such a discrimination for navigational purposes.     

Effects of confinement, previous experience and hippocampal damage on the DRL schedule

Rats with dorsal hippocampal (HIPP) and cortical (CX) lesions and control animals were tested for acquisition of a differential reinforcement of low rate of responding (DRL-20 s) task in a 6-compartment apparatus that permitted running, drinking and other activities. HIPP and CX animals and one group of control rats (NOR) were trained in an 'open' condition which allowed a variety of activities, while another control group (CON) were trained while confined to the food and lever area of the apparatus. In the second stage of the experiment conditions were reversed. DRL performance was significantly better in the 'open' condition for all groups: more pellets were gained with fewer lever presses. Groups HIPP performed worse than groups NOR and CX in both conditions. When NOR and CX rats were confined to the food area they developed a jumping behaviour, (attempts to leave the food area) which increased throughout the testing period, coupled with a progressive deterioration of performance. Rats initially trained in the 'confined' condition did not develop jumping. HIPP animals were significantly more active; they produced more lever presses, entered the different compartments more frequently and showed higher activity in the running wheel. The schedule-induced interim behaviour in the open condition was wheel-running in all groups. In the HIPP group the number of jumps was significantly less than in the NOR and CX groups i.e. they were less affected by confinement. These findings suggest that previous experience in the 'open' condition has a strong anterograde, seemingly irreversible, consequence on subsequent behaviour in the 'confinement' condition for normal and cortical control rats and this anterograde effect is less pronounced in animals with hippocampal damage.     

Variable telomere length across post-mortem human brain regions and specific reduction in the hippocampus of major depressive disorder

Stress can be a predisposing factor to psychiatric disorders and has been associated with decreased neurogenesis and reduced hippocampal volume especially in depression. Similarly, in white blood cells chronic psychological stress has been associated with telomere shortening and with mood disorders and schizophrenia (SZ). However, in previous post-mortem brain studies from occipital cortex and cerebellum, no difference in telomere length was observed in depression. We hypothesized that in psychiatric disorders, stress-driven accelerated cellular aging can be observed in brain regions particularly sensitive to stress. Telomere length was measured by quantitative-PCR in five brain regions (dorsolateral prefrontal cortex, hippocampus (HIPP), amygdala, nucleus accumbens and substantia nigra (SN)) in major depressive disorder (MDD), bipolar disorder, SZ and normal control subjects (N=40, 10 subjects per group). We observed significant differences in telomere length across brain regions suggesting variable levels of cell aging, with SN and HIPP having the longest telomeres and the dorsolateral prefrontal cortex the shortest. A significant decrease (P<0.02) in telomere length was observed specifically in the HIPP of MDD subjects even after controlling for age. In the HIPP of MDD subjects, several genes involved in neuroprotection and in stress response (FKBP5, CRH) showed altered levels of mRNA. Our results suggest the presence of hippocampal stress-mediated accelerated cellular aging in depression. Further studies are needed to investigate the cellular specificity of these findings.     

Effects of medial and dorsal cortex lesions on spatial memory in lizards

In mammals and birds, the hippocampus is a major learning and memory center that plays a prominent role in spatial memory, the use of distal cues to guide navigation. The role of reptilian hippocampal homologues, the medial and dorsal cortex, in spatial memory has not been thoroughly investigated. The medial and dorsal cortex of reptiles is known to play a role in learning both tasks that are hippocampally dependent and tasks that are not hippocampally dependent in mammals and birds. In order to examine the specific role of the medial and dorsal cortex in spatial memory, we trained medial cortex, dorsal cortex, and sham lesioned Cnemidophorus inornatus lizards to locate the one heated rock of four identical rocks spaced evenly around the perimeter of a circular, sand filled, arena in a cool room. We used probe trials to examine the strategies used by lizards to locate the goal. Medial cortex lesions and dorsal cortex lesions slowed acquisition and altered the strategies used to locate the goal. However, none of the lizards adopted a spatial strategy to locate the goal suggesting that the dorsal cortex and medial cortex are involved in using non-spatial strategies for navigation.     

皮质发育障碍大鼠小脑回形态学和海马苔藓纤维发芽的研究

目的 探讨液氮损伤诱导局灶性皮质发育障碍大鼠海马形态学及苔藓纤维发芽的情况。方法 实验随机分为正常对照组、假手术组和液氮损伤组，建立局灶性皮质发育障碍动物模型，察看其行为改变；采用常规HE染色、Nissl染色和Timm’s硫化银组织化学方法染色，肉眼和光镜下观察大鼠脑皮质形态变化，光镜下评估海马苔藓纤维发芽情况，各组数据取苔藓纤维发芽评分，采用非参数秩和Kruskal—Wallis H检验，组间两两比较用Nemenyi法。结果 液氮损伤组大鼠行为轻微改变，鼠脑嘴尾方向形成了一小的脑回，同侧海马CA3区有苔藓纤维发芽．而正常对照组和假手术组却没有。结论 幼鼠早期液氮损伤可导致小脑回形成及海马CA3区苔藓纤维发芽。小脑回周围异常兴奋性突触环路和海马CA3区苔藓纤维发芽形成推测是局灶性皮质发育障碍导致癫痫发生的重要机制。