Real-life memory and spatial navigation in patients with focal epilepsy: ecological validity of a virtual reality supermarket task.

Ecological assessment and training of real-life cognitive functions such as visual-spatial abilities in patients with epilepsy remain challenging. Some studies have applied virtual reality (VR) paradigms, but external validity of VR programs has not sufficiently been proven. Patients with focal epilepsy (EG, n=14) accomplished an 8-day program in a VR supermarket, which consisted of learning and buying items on a shopping list. Performance of the EG was compared with that of healthy controls (HCG, n=19). A comprehensive neuropsychological examination was administered. Real-life performance was investigated in a real supermarket. Learning in the VR supermarket was significantly impaired in the EG on different VR measures. Delayed free recall of products did not differ between the EG and the HCG. Virtual reality scores were correlated with neuropsychological measures of visual-spatial cognition, subjective estimates of memory, and performance in the real supermarket. The data indicate that our VR approach allows for the assessment of real-life visual-spatial memory and cognition in patients with focal epilepsy. The multimodal, active, and complex VR paradigm may particularly enhance visual-spatial cognitive resources.

Neuropsychological and neural correlates of autobiographical deficits in a mother who killed her children.

We report a case of a delusional patient who had killed two of her children in an attempted 'extended suicide'. She was convinced of a genetic defect that caused autobiographical memory and emotional deficits and made life 'senseless'. Neuropsychological tests revealed dysfunctions in remembering emotional details of personal episodes and theory of mind. Water positron emission tomography (15O) with a paradigm used in a former study by Fink et al. (1996) with healthy controls elicited abnormal activations during autobiographical memory retrieval characterised by a lack of prefrontal and limbic activity. We conclude that these imaging findings reflect neural correlates of the self-reported and objectified autobiographical dysfunctions. Furthermore, they indicate that beliefs or prejudices may have a major impact on the brain's processing of the personal past.

Memory beyond the hippocampus.

Improved neuroanatomical knowledge, technical and methodological innovations (such as PET), and more refined conceptualizations of memory have inspired a reappraisal of theoretical beliefs regarding the role of the hippocampus in memory. In the past few years, it has become apparent that the influence of the medial temporal lobe regions extends beyond memory and that memory processes (such as encoding, consolidation and retrieval) involve not only the hippocampus and the medial temporal and diencephalic regions, but also widely distributed neocortical and perhaps even cerebellar regions.

The neuropathology of amnesia.

Relations between brain damage and memory disturbance are outlined with emphasis on the so-called amnesic syndrome. Following a brief introduction into forms of memory and memory failures, the basic causes of brain damaage (with relevance to amnestic failures) are described. Thereafter, the two best-known forms of brain damage-amnesia relations are reviewed: the consequences of damage to medial temporal lobe structures and to diencephalic regions. For the cases with medial temporal lobe damage, evidence is reported in greater detail for H.M., who has been examined more than any other amnesic patient for more than 30 years now, as a considerable amount of literature has accumulated on his behavior in diverse situations. Other cases with more or less circumscribed damage to medial temporal lobe structures are reviewed so as to outline criteria for or against the hypothesis that there are regions within the medial temporal lobe whose damage might be critical for the amnesic syndrome. Two cases of diencephalic amnesia are summarized in particular (cases of Mair et al., 1979) as they have received extensive neuropsychological and neuropathological investigation. Other cases with, for example, Korsakoff's disease are reviewed, as well as cases with diencephalic, or combined mesencephalic-diencephalic damage without nutritional causes. A third group of patients with massive, but still selective amnesic disturbances are then described: cases of basal forebrain damage, followed by descriptions of Alzheimer's disease which has similarities in the underlying neuropathology. This leads over to cases with more generalized intellectual deteriorations (dementia), which may have developed on the basis of primarily cortical damage or damage principally to basal ganglia structures. After reviewing cases with mainly material-specific memory failures--usually as a consequence of restricted neocortical damage--a separate section follows on patients in whom retrograde amnesia is the prominent symptom. The contribution of animal models of human amnesia is critically reviewed and discrepancies are analyzed between human and animal memory disturbances. This section emphasizes the value of investigating inter-dependencies between brain structures by pointing out that relations between memory disturbances and brain damage may be more complicated than apparent from a simple structure-function assignment. This aspect is further followed up in the conclusions.

Functional (dissociative) retrograde amnesia.

Retrograde amnesia is described as condition which can occur after direct brain damage, but which occurs more frequently as a result of a psychiatric illness. In order to understand the amnesic condition, content-based divisions of memory are defined. The measurement of retrograde memory is discussed and the dichotomy between "organic" and "psychogenic" retrograde amnesia is questioned. Briefly, brain damage-related etiologies of retrograde amnesia are mentioned. The major portion of the review is devoted to dissociative amnesia (also named psychogenic or functional amnesia) and to the discussion of an overlap between psychogenic and "brain organic" forms of amnesia. The "inability of access hypothesis" is proposed to account for most of both the organic and psychogenic (dissociative) patients with primarily retrograde amnesia. Questions such as why recovery from retrograde amnesia can occur in retrograde (dissociative) amnesia, and why long-term new learning of episodic-autobiographic episodes is possible, are addressed. It is concluded that research on retrograde amnesia research is still in its infancy, as the neural correlates of memory storage are still unknown. It is argued that the recollection of episodic-autobiographic episodes most likely involves frontotemporal regions of the right hemisphere, a region which appears to be hypometabolic in patients with dissociative amnesia.

A single high dose of dexamethasone affects the phosphorylation state of glutamate AMPA receptors in the human limbic system.

Glucocorticoids (GC) released during stress response exert feedforward effects in the whole brain, but particularly in the limbic circuits that modulates cognition, emotion and behavior. GC are the most commonly prescribed anti-inflammatory and immunosuppressant medication worldwide and pharmacological GC treatment has been paralleled by the high incidence of acute and chronic neuropsychiatric side effects, which reinforces the brain sensitivity for GC. Synapses can be bi-directionally modifiable via potentiation (long-term potentiation, LTP) or depotentiation (long-term depression, LTD) of synaptic transmission efficacy, and the phosphorylation state of Ser831 and Ser845 sites, in the GluA1 subunit of the glutamate AMPA receptors, are a critical event for these synaptic neuroplasticity events. Through a quasi-randomized controlled study, we show that a single high dexamethasone dose significantly reduces in a dose-dependent manner the levels of GluA1-Ser831 phosphorylation in the amygdala resected during surgery for temporal lobe epilepsy. This is the first report demonstrating GC effects on key markers of synaptic neuroplasticity in the human limbic system. The results contribute to understanding how GC affects the human brain under physiologic and pharmacologic conditions.

No morning cortisol response in patients with severe global amnesia.

Activity of the hypothalamus pituitary adrenal (HPA) axis is characterized by a pronounced circadian rhythm. An acute increase in cortisol levels occurs after awakening in the morning with continuously declining levels over the course of the remaining day. The morning cortisol increase probably reflects an activational response of the HPA axis aimed at preparing the body for the day. Some studies found patterns of enhanced or blunted waking cortisol responses observed under chronic stress, burnout, or post traumatic stress disorder. The present study wanted to characterize the morning cortisol response and the circadian cortisol day profile in a sample of six male patients with severe amnesia due to hypoxia, herpes simplex encephalitis or closed head injury. Age and gender matched relatives or friends served as controls. Cortisol was measured from saliva samples collected at home on two consecutive days. The patients were woken up in the morning by their partners or caregivers. The morning cortisol increase typically observed in healthy subjects and also observed in the control group was absent in the amnesic patients. In contrast, a normal circadian day profile was found in the amnesic patients, with a pronounced circadian cortisol decrease. Further studies are needed to understand the neurological or psychological mechanisms leading to a missing morning cortisol response in amnesic patients.

Transient global amnesia.

The syndrome of transient global amnesia (TGA) is defined and described. Characteristic features, epidemical data, variables possibly provoking TGA, its possible etiology and anatomical basis are reviewed. A transient disturbance in the formation of lasting new memories (usually of less than one day) and a retrograde amnesia (which includes the period of the attack and possibly a short time before) are considered as the main features of TGA. A further trait of TGA is the high age of most of the patients subjected to it (58 years on the average). TGA most likely is based on a transient change in the blood supply of certain regions of the brain. The mechanism by which this change happens is still hypothetical. Regions of the limbic system, in particular the area of the temporal lobe and the hippocampal formation, appear to be affected most likely. Uncertain are: the existence of factors provoking the outbreak of an amnesic attack, the likeliness of multiple episodes of TGA and the neuropsychological alterations in patients who suffered a transient global amnesic attack. The outcome of this review suggests, however, that the incidence of recurrent attacks of TGA is higher than previously assumed and that a transient global amnesic attack may be followed by lasting behavioral deteriorations.

Thalamic mediodorsal nucleus and memory: a critical evaluation of studies in animals and man.

Following a general description of the anatomical organization of the thalamic mediodorsal nucleus (MD) of animals and man, the involvement of this nucleus in the processing of memory related information has been evaluated by reviewing stimulation, electrophysiological, and lesion studies in animals, and by reviewing research on induced lesions, degenerative changes and vascular damage of MD in humans. Neither the results from animal experiments nor those from studies on humans provide clear-cut evidence for a specific, memory related role of MD. However, the findings here presented do support the theory that MD is one of several, possible memory related relay stations. While therapeutically induced and circumscribed lesions of MD rarely result in long-lasting memory deficits, pathological processes in MD are more likely to be followed by severe memory disturbances if one or more particular structures in addition to MD are included in the lesioned regions. Consequently, it is emphasized that only the disruption of more than one site along memory related pathways will result in severe and enduring memory deficits. To account for apparent inter-species differences in the involvement of MD in memory related processes, it has been argued that MD and its principal cortical target region might basically be involved in arousal and emotional processes, but that for primates and especially for man the phylogenetically young parvocellular sector of MD and its cortical projection region, the dorsolateral prefrontal cortex, are furthermore involved in memory functions, which are modulated by emotional factors via the rest of MD and the prefrontal cortex.

Reduced resistance to progressive extinction in senescent rats: a neuroanatomical and behavioral study.

The behavior of senescent rats and mature-young rats was compared in a learning task which consisted of the acquisition of a visual discrimination task, its reversal, the induction of a progressively increasing extinction, relearning and, finally, a complete extinction training. It was found that young and old rats were statistically indistinguishable during all parts of the task, except the progressively increasing extinction. Here, the senescent animals made a significantly higher number of errors than the mature-young ones. Neuroanatomically, ventricular dilation, commissural changes and neuronal loss were observed in senescent rats. The significantly reduced number of neurons in the medial nucleus of the amygdala in old rats compared to young was not directly related to the changed behavior in the progressively increasing extinction part of the visual discrimination task. Based on the anatomical connections of the amygdala and its possible functions in learning and memory, the hypothesis is made that the medial amygdaloid nucleus is involved in the learning of changing response-reinforcement contingencies.

Cortical and thalamic afferent connections of the insular and adjacent cortex of the rat.

Thalamic and cortical afferents to the insular and perirhinal cortex of the rat were investigated. Unilateral injections of horseradish peroxidase (HRP) were made iontophoretically along the rhinal sulcus. HRP injections covered or invaded areas along the rhinal fissure from about the level of the middle cerebral artery to the posterior end of the fissure. The most anterior injection labeled a few cells in the mediodorsal nucleus. More posterior injections labeled neurons in the basal portion of the nucleus ventralis medialis, thus suggesting that this cortical region constitutes the rat's gustatory (insular) cortex. We consider the cortex situated posterior to the gustatory cortex in and above the rhinal sulcus as the core region of the rat's (associative) insular cortex, as this cortex receives afferents from the regions of and between the nuclei suprageniculatus and geniculatus medialis, pars magnocellularis. It includes parts of the cortex termed perirhinal in other studies. The cortex dorsal and posterior to the insular cortex we consider auditory cortex, as it receives afferents from the principal part of the medial geniculate nucleus, and the cortex ventral to the insular cortex (below the fundus of the rhinal sulcus) we consider to constitute the prepiriform cortex, which is athalamic. The posterior part of the perirhinal cortex (area 35) receives afferents from nonspecific thalamic nuclei (midline nuclei). Cortical afferents to the injection loci arise from a number of regions, above all from regions of the medial and sulcal prefrontal cortex. Those injections confined to the projection cortex of the suprageniculate-magnocellular medial geniculate nuclear complex also led to labeling in contralateral prefrontal regions, particularly in area 25 (infralimbic region). A comparison of our results with those on the insular cortex of cats and monkeys suggests that on the basis of thalamocortical connections, topographical relations, and involvements of neurons in information processing and overt behavior, the insular cortex has to be regarded as a heterogeneous region which may be separated into prefrontal insular, gustatory (somatosensory) insular, and associative insular portions.

Cortical and thalamic afferent connections of the insular and adjacent cortex of the cat.

The thalamo-cortical and cortico-cortical afferents of the cat's insular cortex were investigated with the retrograde horseradish peroxidase technique. The most prominent loci of thalamic labeling were the suprageniculate nucleus and parts of the posterolateral nucleus. Injections into the anterior part of the insular cortex also resulted in labeled cells in the ventromedial posterior nucleus and in the intralaminar nuclei, while injections into posterior parts revealed projections from the medial and dorsal parts of the medial geniculate nucleus. Only the anterior and most ventral parts of the insular cortex overlying the anterior rhinal sulcus were connected with the mediodorsal nucleus of the thalamus. All injections into the gyrus sylvius anterior showed a specific pattern of cortical afferents: With the exception of the labeling in the prefrontal cortex and the inferotemporal region, the labeled cells were very narrowly restricted to the presylvian, the suprasylvian, and the splenial sulcus. The thalamic neurons projecting to the cortex were generally organized in a bandlike pattern which crossed nuclear borders. The majority of the cortico-cortical connections originated from sulcal areas next to the prefrontal, parietal, and cingulate cortex, that is, next to so-called association cortices. In the light of the present results the role of the insular cortex as a multifunctional association area is discussed, as well as its relation to other cortical centers.

Collateral innervation of the medial and lateral prefrontal cortex by amygdaloid, thalamic, and brain-stem neurons.

The distribution of the afferents to the rat's prefrontal cortex originating in the thalamic mediodorsal nucleus and the amygdala was investigated with two fluorescent tracers. Special emphasis was laid on detecting the loci of neurons which project via axonal collaterals into both lateral and medial portions of the prefrontal cortex. It was found that a high number of neurons of the anterior portion of the basolateral amygdaloid nucleus terminate via collaterals in both the medial and lateral subfields of the prefrontal cortex. On the other hand, only a small number of mediodorsal thalamic cells were found to project to both sides of the prefrontal hemisphere via bifurcating axonal collaterals. These cells were situated exclusively in the lateral part of the medial segment of the mediodorsal nucleus. The majority of both thalamic and amygdaloid neurons with bifurcating axons originate from subregions whose cells innervate primarily the medial prefrontal cortex. In brain-stem, neurons of the nucleus raphé dorsalis also project via collaterals to the medial and lateral prefrontal regions. Furthermore, neurons of the dorsal and ventral premamillary nuclei, the lateral mamillary nucleus, the ventral tegmental area of Tsai, and the ventral tegmental nucleus of Gudden were found to project to the medial prefrontal cortex. Our results indicate a differential collateral organization of thalamic and amygdaloid afferents to prefrontal cortical fields. The anterior basolateral amygdala (which innervates via collaterals both the medial and lateral prefrontal subfields) may add a common input to either subfield, such as information on the significance of incoming stimuli to the animal's behavior, while the mediodorsal nucleus (whose segments are principally connected to only one prefrontal subfield) may add segment-specific information, for example, of a spatial-cognitive nature for the lateral segment and of an emotional nature for the central and medial segments. The existence of a basolateral limbic circuit, composed of the amygdala, the thalamic mediodorsal nucleus, and the prefrontal cortex, is confirmed and knowledge on its interconnectivity is extended. From an anatomical point of view these data provide arguments for both unitary and diverging functions of the prefrontal cortex.

Convergence of intra- and interhemispheric cortical afferents: lack of collateralization and evidence for a subrhinal cell group projecting heterotopically.

The distribution of corticocortical projecting neurons in the rat's brain was investigated with fluorescent dyes and the retrograde transport of horseradish peroxidase. Although the fluorescent techniques especially revealed the existence of a considerable number of neurons interconnecting the limbic areas (sub- and perirhinal cortex, prefrontal, cingulate, and retrosplenial cortex) both intra- and interhemispherically, only a negligibly small number of neurons with collateralized axons could be detected. In the rat's anterior dorsolateral cortex an area is described whose neurons are organized in a columnlike fashion and project intra- and interhemispherically to the limbic areas examined. The density of efferent connections differed between areas, with an especially high density found in a small region of the subrhinal cortex. Injections of horseradish peroxidase into different regions of the cingulate and retrosplenial cortex confirmed the existence of widespread heterotopic interhemispheric connections originating from this defined subrhinal area, though the number of retrogradely labeled cells remained consistently smaller than that obtained following the injection of fluorescent dyes. Among the regions studied with horseradish peroxidase injections, those into the retrosplenial cortex showed the highest density of labeled cells within this subrhinal area. A more detailed examination of the subrhinal region containing the densely labeled neurons (projecting to the contralateral hemisphere) made use of Nissl stains and revealed a morphologically separable area which was characterized by medium-sized, dark-staining neurons whose long axons were oriented mediolaterally. The region includes portions of the insular-perirhinal, entorhinal, and piriform cortex. It is suggested that the corticocortical projections are basically noncollateralized in the rat. However, there apparently is a dense interhemispheric interconnectivity between the limbic areas. Functional evidence for the defined subrhinal area suggests a prominent role of its neurons in cognitive information processing. The present evidence for considerable interhemispheric cortical projections may provide a new impetus for studying the intercommunication of the two sides of the brain with both anatomical and behavioral methods.

Cortical and subcortical afferent connections of the primate's temporal pole: a study of rhesus monkeys, squirrel monkeys, and marmosets.

The afferent connections of the primate's temporopolar cortex were investigated with the retrograde horseradish peroxidase technique. Old World and New World monkeys received small unilateral injections of horseradish peroxidase. These labeled cells in a number of cortical, thalamic, and brainstem regions and in a few further telencephalic and diencephalic regions. Cortically, the neighboring areas of the inferior and superior temporal gyrus and the insula contained a considerable number of labeled cells. Furthermore, a substantial projection arose from the orbitofrontal and the frontopolar cortex. The cingulate gyrus contained only very few labeled cells. Interhemispherically, corticocortical connections arose mainly from temporal lobe areas. Labeled cells were seen in various regions of the basal forebrain and cells labeled only faintly in the lateral and basal accessory nuclei of the amygdala. The claustrum contained labeled neurons only in one rhesus monkey. On the diencephalic level, the caudal medial portion of the medial pulvinar was the principal thalamic source of afferents to the temporopolar cortex. Furthermore, labeled cells were found in the neighboring, caudal part of the mediodorsal nucleus, within and along the nucleus limitans, in the medial geniculate nucleus, and in several nuclei of the nonspecific system. The fields of Forel, the zona incerta, and lateral and dorsomedial hypothalamic areas contained a few labeled cells. Within the brainstem of the rhesus monkeys those regions projecting diffusely to the cortex contained a few labeled neurons. Furthermore, these brains had some labeled cells in the regions of the nuclei medialis annuli aqueductus, tractus mesencephalicus nervi trigemini, and trochlearis. Although among the three species differences in the cortical and thalamic projection patterns were observed, the regions projecting most densely to the temporal pole were similar in principle. This statement holds in particular for cortical and thalamic sites. However, the greatest number of labeled cells was found in the rhesus monkey, a fact that cannot be attributed solely to the size of the horseradish peroxidase injections and the size of the brain, but that appears rather to represent a true species difference. From our results we conclude that the temporopolar cortex constitutes a cortical area necessary for effective affectional-sensory integration.

Cortical projections originating from the cat's insular area and remarks on claustrocortical connections.

The cortical projections originating in the cat's insular cortex and claustrum were investigated with the aid of the horseradish peroxidase retrograde tracing technique. Twenty small injections of horseradish peroxidase were distributed along lateral and medial regions of the hemisphere. Labeling in the insular cortex occurred following all injections except those six situated along the lateral gyrus--that is, within the visual cortex. In the claustrum labeled neurons were found following all injections, except following the injection situated in the posterior temporal area. Claustral labeling was frequently more intense than insular labeling. The injections into the occipital cortex that revealed no insular innervation nevertheless received a considerable number of claustral projections. As the insular cortex itself receives at most a minor projection from the claustrum the differing cortical projection patterns of insula and claustrum have to be considered unrelated. Our findings confirm the view that the claustrum projects to most regions of the cerebral cortex; these projections are at least in part topographically organized. A topographical pattern can also be constructed for the insular cortex, though it is less stringent than for the claustrocortical connections. Both the afferent and efferent connections of the insula show similarities to those of the prefrontal cortex. Nevertheless, the insula differs in that it receives strong input from the sensory associative nuclei of the thalamus. Consequently, and in line with behavioral observations following its ablation, we consider the insula as involved in the temporal structuring of perceived patterns.

Afferents to the ventral tegmental nucleus of Gudden in the mouse, rat, and cat.

Afferents to the ventral tegmental nucleus of Gudden (VT) were investigated in mice, rats, and cats. Unilateral and bilateral injections or iontophoretical applications of horseradish peroxidase (HRP) were made into the region of the VT. The entire cerebrum was then screened for labeled neurons. Following injections situated principally within the VT, in all three species many retrogradely labeled neurons were observed in the mamillary bodies and the lateral habenular nuclei. Fewer labeled cells were observed in the prefrontal cortex, the basal forebrain, various hypothalamic nuclei, the interpeduncular nucleus, nucleus of the posterior commissure, nucleus of Darkschewitsch and interstitial nucleus of Cajal, vestibular nucleus, and nucleus praepositus hypoglossi. Scant but consistent labeling occurred in the cingular, retrosplenial, and insular cortices, within the medial forebrain bundle, fields of Forel, zona incerta, ventral tegmental area of Tsai, substantia nigra, pretectal area, periaqueductal gray, dorsal tegmental nucleus, locus ceruleus, and raphe complex. Our results show a high similarity in the distribution of afferent connections converging on the VT of mice, rats, and cats. They indicate furthermore that the VT is reached by a variety of cortical and subcortical afferents, which belong either to the limbic system or to brain stem regions related to motor, sensory, and autonomic functions. It is suggested that the VT subserves as a midbrain core structure of the limbic system, which is responsible for the transfer of motor, sensory, and autonomic informations arising within the brain stem to limbic forebrain structures.

Individual prediction of change in delayed recall of prose passages after left-sided anterior temporal lobectomy.

Prognostic variables for individual memory outcome after left anterior temporal lobectomy (ATL) were studied in 27 patients with refractory temporal lobe epilepsy. The difference between pre- and postoperative performance in the delayed recall of two prose passages (Story A and B) from the Wechsler Memory Scale served as measure of postoperative memory change. Fifteen independent clinical, neuropsychological, and electrophysiological variables were submitted to a multiple linear regression analysis. Preoperative immediate and delayed recall of story content and right hemisphere Wada memory performance for pictorial and verbal items explained very well postoperative memory changes in recall of Story B. Delayed recall of Story B, but not of Story A, had high concurrent validity to other measures of memory. Patients who became seizure-free did not differ in memory change from patients who continued to have seizures after ATL. The variables age at epilepsy onset and probable age at temporal lobe damage provided complementary information for individual prediction but with less effectiveness than Wada test data. Our model confirmed that good preoperative memory functioning and impaired right hemispheric Wada memory performance for pictorial items predict a high risk of memory loss after left ATL. The analyses demonstrate that the combination of independent measures delivers more information than Wada test performance or any other variable alone. The suggested function can be used routinely to estimate the individual severity of verbal episodic memory impairment that might occur after left-sided ATL and offers a rational basis for the counseling of patients.

Left hemispheric neuronal heterotopia: a PET, MRI, EEG, and neuropsychological investigation of a university student.

A 21-year-old left-handed medical student had a prominent unilateral cerebral cortical malformation due to an ontogenetic migration disorder. We performed neuropsychological studies, EEG, T1- and T2-weighted and proton-density MRI, and positron emission tomography (PET) (under both the resting condition and neuropsychological activation). Neuropsychological testing revealed normal intelligence and generally normal memory functioning but selective deficits in tests of verbal fluency and spatial-figural relationships. Proton-density and T2-weighted MRI revealed extensive left cortical heterotopia that included parts of the Wernicke area. PET under the resting condition revealed a small interhemispheric difference with slightly reduced glucose metabolism in the left temporoparietal cortical zone. An activation PET (with the patient performing a verbal fluency test) resulted in a normal overall increase in metabolism but marked deviations in cortical areas. The highest activity changes were in the Broca and Wernicke areas of the right hemisphere, and there was very little activation in those regions of the left hemisphere that were expected to respond well to the activation--the temporal, parietal, and temporo-occipital cortical zones. We conclude that there can be large compensations for unilateral heterotopia.