Biomedical subjects

H J Markowitsch

Publications and source records attributed to H J Markowitsch.

At least 91 records · Page 5Linked to original sources

PubMed1986

[Possibilities and weaknesses of psychopathometric diagnosis of dementia].

As cognitive deficiencies in aged people constitute a growing factor in our societies, the possibilities for diagnosing dementia are described and analyzed critically. Based on a discussion of those changes in intellectual performance which are typical for normal aging (e.g., reduction in so-called fluid intelligence combined with preservation of so-called crystallized intelligence), the pathological forms of aging, especially Alzheimer's disease, are outlined. The present, internationally favored psychometrical measures for recording dementia in the aged and for evaluating and diagnosing it differentially are listed. Finally, certain requirements which have to be imposed on a diagnostic test for dementia are discussed.

Aged↗

PubMed1986

Recognition memory and psychophysiological responses to stimuli with neutral or emotional content: a study of Korsakoff patients and recently detoxified and longterm abstinent alcoholics.

Possible relations between chronic alcohol abuse and impairments in cognitive functioning were tested in six groups of subjects, groups A1, A2, CGy, AA, KO, and CGo: The first three groups were about 35 years old, the last three about 50 years. Groups A1 and A2 each consisted of ten men hospitalized for the treatment of alcohol dependency, group A1 having been detoxified for less than one week, and group A2 for more than five months. Group CGy constituted the matched control group. Group AA consisted of six Alcoholics Anonymous, sober for more than five years, nine Korsakoff patients made up group KO, and group CGo was the control group matched for groups AA and KO. As the main tests, all subjects were given a number of slides showing scenes, humans, or animals, half of which had been rated as neutral while the other half was emotionally arousing (in either a negative or a positive way). In two tests, one after ten minutes, and one after two days, the subjects were required to reidentify those slides which they had seen before, and their galvanic skin response was measured simultaneously. Several psychological tests including one for paired associate learning were given as well. The main results were that alcoholics, whether they had been abstinent for a longer time or not, were inferior to nonalcoholics, but that a prolonged period of soberness nevertheless most likely leads to the recovery of cognitive functions. Though the underlying causes of the cognitive deficits found in the four experimental groups (A1, A2, AA, KO) may be due at least in part to different or even contradictory underlying causes, they provide support for "simple versions" of the so-called continuity and premature aging hypotheses.

Adult↗

PubMed1986

Memory related role of the posterior cholinergic system.

In order to establish a model for the possible neuropathology of patients with Alzheimer's disease, various behaviors of rats with different chemical lesions in cholinergic regions were studied and compared with those of sham-operated control rats. A battery of neurological tests was used as well as activity measurements and two learning tasks: a positively reinforced place-learning task with delay periods of Os, 1 min, 15 min, and 2h, and a shock-motivated two-way active avoidance task. While in general no intergroup differences were obtained in performance on the neurological test battery or the rats' activity in an open field, there were marked impairments in the three lesioned groups compared to the control group in the two learning tasks. These deficits were less severe in the two groups with lesions of the medial septal/vertical diagonal band of Broca region and the nucleus basalis of Meynert region, but rather marked in the group with lesions of neurons situated in the pontomesencephalic region, although the amount of ibotenic acid injected had been the same for all groups. We conclude from these data that changes in mesencephalic cholinergic regions might play a significant role in the pathology of Alzheimer's disease. The existence of such regions was recently established for primates as well, thus providing a basis for justifying an animal model of this human disease.

Alzheimer Disease↗

PubMed1986

Afferent connections of the substantia innominata/basal nucleus of Meynert in carnivores and primates.

Afferent connections to the substantia innominata/nucleus basalis complex of monkeys and cats were traced by using the method of retrograde transport of horseradish peroxidase (HRP). Altogether ten injections of HRP were performed in four monkeys (Saimiri sciureus, Callithrix jacchus, Galago senegalensis) and in four cats, with either vertical or oblique needle approaches. The entire brains excluding the olfactory bulbs and the cerebellum were then screened for labeled neurons. In both monkey and cat brains, many retrogradely labeled neurons could be detected in the amygdala, hypothalamus, midline thalamus, zona incerta, and the fields of Forel. Further but weaker labeling occurred in the medial septal nucleus, diagonal band of Broca, olfactory tubercle, paraventricular, anterior, mediodorsal, and central lateral thalamic nuclei, lateral habenula, ventral tegmental area of Tsai, interpeduncular nucleus, parabrachial, raphe, dorsal tegmental nucleus and the locus caeruleus. Cortically, prefrontal, insular, entorhinal, prepiriform, and periamygdaloid areas of both species showed considerable labeling as well as the whole temporal lobe of the monkeys used. The perirhinal and basal temporal cortex of all cats showed moderate labeling. In both monkeys and cats, extremely scarce labeling occurred within the cingulate, retrosplenial, and subicular cortex. From an anatomical point of view, the manifold connections of the substantia innominata/basal nucleus of Meynert found in this study underscore the participation of these nuclear groups in motivational, emotional, and cognitive (e.g. mnemonic) functions. Considering the widespread cortical efferents of this complex, it is suggested that the substantia innominata/nucleus basalis of Meynert serves the transmission of information arising within the limbic system to the whole neocortex.

Afferent Pathways↗

PubMed1985

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.

Afferent Pathways↗

PubMed1985

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.

Animals↗

PubMed1985

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.

Alcohol Amnestic Disorder↗

PubMed1985

The amygdala's role in human mnemonic processing.

The possible role played by the human amygdaloid complex in the processing of mnemonic information is examined. First, evidence is reviewed from case reports in which amygdaloid damage occurred due to surgical intervention or pathological or age-related changes. Then, studies are evaluated in which the amygdala was stimulated or in which electrical potentials were recorded from it. Based on this survey an hypothesis on the possible involvement of the amygdala in mnemonic information processing is proposed. In essence, it is argued that the human amygdala is responsible for activating or reactivating those mnemonic events which are of an emotional significance for the subjects' life history and that this (re-)activation is performed by charging sensory information with appropriate emotional cues. Supportive evidence for this hypothesis is given based on human case reports, on studies in animals in which information processing was determined following amygdaloid lesions, and on evidence of neuroanatomical connections of the primate amygdala.

Adult↗

PubMed1985

Involvement of the amygdala in learning and memory: a critical review, with emphasis on anatomical relations.

The amygdala has been attributed with a considerable number of very diverse functions. Its involvement in learning and memory, though, has found increased attention. Following a short description of the connections of the amygdala and its critical neurotransmitters, studies are reviewed here in which the amygdala's activity was manipulated or observed by different methods (lesions, electrical brain stimulation, neurochemical intra-amygdaloid injections, single-unit recordings). Some of the major conclusions resulting from this data analysis indicate an advantage in performing subtotal amygdaloid lesions over an amygdalectomy, a point of view that is especially supported by the heterogeneous anatomical connections of different amygdaloid nuclei. Thereafter, an evaluation is made of different tasks with respect to their discriminative sensitivity to amygdaloid manipulations. Some species-specific differences in performing certain tasks after amygdaloid injuries are discussed in relation to the different expansion of amygdalo-cortical connections in higher and less highly encephalized species. Finally, some general assumptions are made on the specific role of each of the amygdaloid nuclei during the mnemonic processes attributed to the amygdala. It is concluded that emotionally significant information is encoded and can be retrieved on the basis of the structures and connections of the basolateral limbic circuit.

Amygdala↗

PubMed1985

Collateralization in the mammalian nervous system.

After reviewing the loci of origin for neurons with collateralized axons, some hypotheses on their distribution in the mammalian nervous system, on their functional contributions and on their significance in the course of encephalization are discussed. In principle, the distribution of collateralized neurons seems to be restricted to anatomical circuits subserving unspecific activation of forebrain regions and controlling body balance and movements. Concerning the limbic system, a minor degree of collateralization seems to exist only in less encephalized species. Based on a number of anatomical and functional arguments, it is assumed that the significance of collateralization fades in the course of encephalization.

Animals↗

PubMed1985

Hypotheses on mnemonic information processing by the brain.

From a neuropsychological point of view, hypotheses are offered on the possible action of the brain in the processing of mnemonic information for long-term storage (or for retrieval of long-term stored information). It is argued that strict relations between damage of circumscribed brain structures and amnesia, as they have been suggested in recent case reports, are questionable for several reasons: Firstly, the involved regions differ between cases; secondly, there is some counter-evidence from other cases in which similar neuronal damage failed to result in lasting amnesic disturbances; thirdly, it is hypothesized that even from circumscribed brain damage it is not justifiable to conclude that the lesioned structure is solely or principally responsible for the observed mnemonic changes, as the brain acts in an integrative way, that is, on the basis of a wide-spread network of neuronal information processing. On the basis of these and related arguments, hypotheses and models on mnemonic information processing in the intact and in the damaged brain are derived. With these hypotheses even the frequent observation of interindividual differences in mnemonic information processing finds a possible explanation which is in conformity to known anatomical circuits and connections and to principles of neuronal coding.

Amnesia↗

PubMed1985

Consequences of serial cortical, hippocampal, and thalamic lesions and of different lengths of overtraining on the acquisition and retention of learning tasks.

The ability of the rat brain to acquire or to retain specific learning tasks was tested under conditions of multiple lesions and widely different amounts of practice. Lesion targets were (a) the medial prefrontal and cingulate cortex, (b) the anterior and mediodorsal thalamus, and (c) the dorsal and ventral hippocampus. Rats were divided into seven groups. The first group received lesions of all three structural complexes prior to training in a delayed alternation and an active avoidance task. Groups 2-4 received lesions in different combinations of two of the three structural complexes prior to task acquisition. Group 5 first learned both tasks and then received the medial cortical lesion; thereafter it was retrained to criterion. Then, the thalamic lesion was made, and relearning was tested a second time. Finally, the hippocampal region was damaged, and a last relearning test was given. Groups 6 and 7 also first acquired both tasks; however, after that, they received 240 (Group 6) or 1,280 (Group 7) trials of overtraining. Following this, all three structural complexes were given lesions serially before relearning of the two tasks was tested. Nine of the ten animals of Group 1 failed to acquire the alternation task, but all learned the avoidance task. In Groups 2-4, all rats acquired both tasks. Postoperatively, rats of Group 5 were inferior to those of Group 6 in both tasks, and rats of Group 7 were the most successful animals of the last three groups. These results question the assumption that serial lesions with intermittent training between lesions have beneficial effects, and they also stress the importance of task practice, that is, of behavioral experience. It is argued that prolonged training will lead to a widely distributed storage of information within the brain. The process of wide diffusion of information will, however, be disturbed (or at least retarded) by lesions made shortly after task acquisition or task reacquisition (as was the case for animals of Group 5).

Animals↗

PubMed1984

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.

Afferent Pathways↗

PubMed1984

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.

Animals↗

PubMed1984

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.

Amygdala↗

PubMed1984

Claustral efferents to the cat's limbic cortex studied with retrograde and anterograde tracing techniques.

The claustral projections to the cat's limbic cortex were investigated with horseradish peroxidase retrograde tracing technique and with autoradiography. Autoradiographic injections covered small portions of either the dorsal anterior claustrum or intermediate to posterior regions of the claustrum. Injections of horseradish peroxidase were made into the subicular, insular, entorhinal, prepiriform, cingulate, retrosplenial and prefrontal cortex. Both methods revealed fully consistent data for substantial claustral efferents to the cingulate, retrosplenial, entorhinal and subicular cortex. For the prepiriform cortex claustral efferents could be established unequivocally only with the horseradish peroxidase technique. Only a rather minor projection could be traced for the claustro-insular projection. Unilateral injections of horseradish peroxidase revealed the existence of a minor number of labeled claustral cells in the contralateral hemisphere for all loci except insular and prepiriform ones. Our data show that claustral cells reach the majority of the allocortical areas of the brain. They thereby confirm the view that the claustrum projects to most regions of the cortex and furthermore that a certain kind of topography exists in the claustro-cortical afferents with a minor number of claustral cells sending afferents to the contralateral cortical hemisphere. In addition, our data reveal that the distribution of claustro-cortical afferents is uneven and that the ventral claustrum (or nucleus endopiriformis) sends fibers to more cortical regions than previously assumed. It is suggested that the claustrum participates in the integration of sensory, motivational, emotional and mnemonic information via its reciprocal claustro-neocortical and its claustro-limbic connections.

Animals↗

PubMed1984

The prefrontal cortex of a prosimian (Galago senegalensis) is reached by efferent neurons originating in the nucleus basalis of Meynert.

Efferent projections from the basal forebrain to the prefrontal cortex of the lesser bush baby (Galago senegalensis) were traced with the retrograde horseradish peroxidase technique. Different areas of the prefrontal cortex of six bush babies were injected with small amounts of horseradish peroxidase. The entire basal forebrain was then screened for labeled neurons. Following all six injections, many retrogradely labeled neurons could be detected in the nucleus basalis of Meynert. These results indicate a strong innervation of the bush baby's prefrontal cortex by the nucleus basalis of Meynert. The observed projections seem comparable in strength and topography to those found in another primate species, the rhesus monkey. Anatomical and functional implications of these projections in the bush baby are discussed and related to findings in other primates and species of other orders.

Animals↗

PubMed1984

Basal forebrain efferents reach the whole cerebral cortex of the cat.

Efferent projections from the basal forebrain to the cat's cerebral cortex were traced with the retrograde horseradish peroxidase technique. Different areas of the cerebral cortex of 51 cats were injected with small amounts of horseradish peroxidase. The entire basal forebrain was screened for labeled neurons. Following all injections, retrogradely labeled neurons could be detected in either the medial septum, or the vertical and horizontal limb of the diagonal band of Broca, or the substantia innominata, or in several of these structures. All three basal forebrain structures project heavily to allocortical regions, but only weakly to neocortical regions. An exception is the medial prefrontal cortex which is densily innervated by the substantia innominata (i.e., comparably dense as allocortical regions are innervated by the substantia innominata). Large injections into he basal temporal cortex (including the perirhinal cortex) and into the insular cortex also led to a considerable number of labeled cells in the substantia innominata. The results indicate a widespread innervation of the cat's cerebral cortex by the basal forebrain. This diffuse projection to the cortex has recently been found also in monkeys and rats. Anatomical and functional implications of these projections in the cat are discussed and related to findings in other species.

Animals↗