Biomedical subjects

Mortimer Mishkin

Publications and source records attributed to Mortimer Mishkin.

16 recordsLinked to original sources

PubMed2006

Using semantic memory to boost 'episodic' recall in a case of developmental amnesia.

We report two experiments that investigated factors that might boost 'episodic' recall for Jon, a developmental amnesic whose episodic memory is gravely impaired but whose semantic memory seems relatively normal. Experiment 1 showed that Jon's recall improved following a semantic study task compared with a non-semantic study task, as well as following four repeated study trials compared with only one. Experiment 2 additionally revealed that Jon's recall improved after acting compared with reading action phrases at study, but only if the phrases were well integrated semantically. The results provide some support for the hypothesis that Jon's 'episodic' recall depends on the extent to which he is able to retrieve events using semantic memory.

Adult↗

PubMed2006

Human memory development and its dysfunction after early hippocampal injury.

Cognitive memory involves long-term memories for facts (semantic memory) and personal experiences (episodic memory) that can be brought to mind. There is consensus that the hippocampus and related medial temporal lobe (MTL) structures are crucial for adult cognitive memory, but much less is known about their contribution to memory during infancy and childhood. We argue that the MTL is involved in memory from early in life, supporting recognition memory within the first postnatal months and recall memory within the first year. We propose that normal development involves a sequence in which a form of semantic-like memory emerges first, whereas the characteristics of episodic memory develop only later with progressive development of the hippocampus. Early bilateral injury to the hippocampus disrupts this normal pattern such that memory skills cannot develop beyond the stage of semantic memories. This review is part of the INMED/TINS special issue "Nature and nurture in brain development and neurological disorders", based on presentations at the annual INMED/TINS symposium (http://inmednet.com/).

Brain Injuries↗

PubMed2006

Effects of hippocampal lesions on the monkey's ability to learn large sets of object-place associations.

Earlier studies found that recognition memory for object-place associations was impaired in patients with relatively selective hippocampal damage (Vargha-Khadem et al., Science 1997; 277:376-380), but was unaffected after selective hippocampal lesions in monkeys (Malkova and Mishkin, J Neurosci 2003; 23:1956-1965). A potentially important methodological difference between the two studies is that the patients were required to remember a set of 20 object-place associations for several minutes, whereas the monkeys had to remember only two such associations at a time, and only for a few seconds. To approximate more closely the task given to the patients, we trained monkeys on several successive sets of 10 object-place pairs each, with each set requiring learning across days. Despite the increased associative memory demands, monkeys given hippocampal lesions were unimpaired relative to their unoperated controls, suggesting that differences other than set size and memory duration underlie the different outcomes in the human and animal studies.

Animals↗

PubMed2006

Brain and cognitive-behavioural development after asphyxia at term birth.

Perinatal asphyxia occurs in approximately 1-6 per 1000 live full-term births. Different patterns of brain damage can result, though the relation of these patterns to long-term cognitive-behavioural outcome remains under investigation. The hippocampus is one brain region that can be damaged (typically not in isolation), and this site of damage has been implicated in two different long-term outcomes, cognitive memory impairment and the psychiatric disorder schizophrenia. Factors in addition to the acute episode of asphyxia likely contribute to these specific outcomes, making prediction difficult. Future studies that better document long-term cognitive-behavioural outcome, quantitatively identify patterns of brain injury over development and consider additional variables that may modulate the impact of asphyxia on cognitive and behavioural function will forward the goals of predicting long-term outcome and understanding the mechanisms by which it unfolds.

Asphyxia Neonatorum↗

PubMed2005

Projections from the entorhinal cortex, perirhinal cortex, presubiculum, and parasubiculum to the medial thalamus in macaque monkeys: identifying different pathways using disconnection techniques.

The projections from the perirhinal cortex, entorhinal cortex, parasubiculum, and presubiculum to the thalamus were examined using both anterograde and retrograde tracers. Attention focused on the routes taken by these projections, which were delineated by combining surgical tract section with the placement of a tracer. Projections to the anterior thalamic nuclei almost exclusively used the fornix. These relatively light projections, which arose from all areas of the entorhinal cortex, from the presubiculum, parasubiculum, and area 35 of the perirhinal cortex, terminated mainly in the anterior ventral nucleus. In contrast, the projections to the lateral dorsal nucleus from the entorhinal cortex, presubiculum and parasubiculum were denser than those to the anterior thalamic nuclei. The projections to the lateral dorsal nucleus used two routes. While nearly all of the projections from the subicular complex used the fornix, many of the entorhinal cortex projections passed caudally in the temporopulvinar bundle to reach the lateral dorsal nucleus. The perirhinal cortex, as well as the entorhinal cortex, also projects to nucleus medialis dorsalis. These projections exclusively used the external capsule and thence the inferior thalamic peduncle. Other temporal-thalamic projections included those to the medial pulvinar, via the temporopulvinar bundle, from the perirhinal and entorhinal cortices, and those to the paraventricular nucleus from the entorhinal cortex. By identifying these routes, it is possible to appreciate how different lesions might disconnect temporal-diencephalic pathways and so contribute to memory disorders.

Amidines↗

PubMed2005

In search of an auditory engram.

Monkeys trained preoperatively on a task designed to assess auditory recognition memory were impaired after removal of either the rostral superior temporal gyrus or the medial temporal lobe but were unaffected by lesions of the rhinal cortex. Behavioral analysis indicated that this result occurred because the monkeys did not or could not use long-term auditory recognition, and so depended instead on short-term working memory, which is unaffected by rhinal lesions. The findings suggest that monkeys may be unable to place representations of auditory stimuli into a long-term store and thus question whether the monkey's cerebral memory mechanisms in audition are intrinsically different from those in other sensory modalities. Furthermore, it raises the possibility that language is unique to humans not only because it depends on speech but also because it requires long-term auditory memory.

Animals↗

PubMed2005

Effects of cholinergic deafferentation of the rhinal cortex on visual recognition memory in monkeys.

Excitotoxic lesion studies have confirmed that the rhinal cortex is essential for visual recognition ability in monkeys. To evaluate the mnemonic role of cholinergic inputs to this cortical region, we compared the visual recognition performance of monkeys given rhinal cortex infusions of a selective cholinergic immunotoxin, ME20.4-SAP, with the performance of monkeys given control infusions into this same tissue. The immunotoxin, which leads to selective cholinergic deafferentation of the infused cortex, yielded recognition deficits of the same magnitude as those produced by excitotoxic lesions of this region, providing the most direct demonstration to date that cholinergic activation of the rhinal cortex is essential for storing the representations of new visual stimuli and thereby enabling their later recognition.

Acetylcholine↗

PubMed2005

FOXP2 and the neuroanatomy of speech and language.

That speech and language are innate capacities of the human brain has long been widely accepted, but only recently has an entry point into the genetic basis of these remarkable faculties been found. The discovery of a mutation in FOXP2 in a family with a speech and language disorder has enabled neuroscientists to trace the neural expression of this gene during embryological development, track the effects of this gene mutation on brain structure and function, and so begin to decipher that part of our neural inheritance that culminates in articulate speech.

Animals↗

PubMed2005

Deferred imitation of action sequences in developmental amnesia.

The aims of this study were to investigate whether patients with developmental amnesia (DA) associated with bilateral hippocampal volume reduction show an impairment in incidental nonverbal recall of action sequences, and whether the severity of this memory impairment is influenced by the sequence structure (causal vs. arbitrary). Like adult-onset cases of amnesia (McDonough, Mandler, McKee, & Squire, 1995), patients with DA did not differ significantly from their age-, sex-, and IQ-matched controls in spontaneous production of the sequences prior to modeling but recalled fewer target actions and action pairs than the control group after a 24-hour delay, independent of sequence structure. Unlike the patients with adult-onset amnesia, however, the patients with DA showed some memory for both types of sequences after a 24-hour delay. This difference in severity of memory impairment might reflect differences in extent of pathology and/or age at injury.

Adolescent↗

PubMed2005

One-trial visual recognition in cats.

The ability of normal cats to perform delayed matching- and nonmatching-to-sample with trial-unique stimuli was investigated both in a modified Wisconsin General Testing Apparatus requiring manipulatory responses and in a Nencki-type testing room requiring locomotor responses. Cats trained in the WGTA learned the two tasks at about the same rate, on average, as that reported for monkeys. However, unlike monkeys, whose strong preference for novelty facilitates their learning of the nonmatching rule and retards their learning of the matching rule, the cats learned the two different rules at about the same rate, suggesting that cats do not share the monkey's strong preference for novelty. In contrast to their relatively rapid learning of the manipulatory versions of the two tasks, cats learned the locomotor versions only slowly or even failed to learn. Experimental analysis indicated that a major source of the cats' difficulty on these locomotor versions was interference from a strong tendency in the large testing room to use visuospatial strategies. Nevertheless, once the matching or nonmatching rule was learned at short delays, whether in the WGTA or the testing room, the cats performed at criterion levels without further training even at delays of 10 minutes, indicating that this species, like monkeys, has a highly developed long-term recognition memory ability.

Analysis of Variance↗

PubMed2004

Dissociable functional cortical topographies for working memory maintenance of voice identity and location.

In order to ascertain whether the neural system for auditory working memory exhibits a functional dissociation for spatial and nonspatial information, we used functional magnetic resonance imaging and a single set of auditory stimuli to study working memory for the location and identity of human voices. The subjects performed a delayed recognition task for human voices and voice locations and an auditory sensorimotor control task. Several temporal, parietal, and frontal areas were activated by both memory tasks in comparison with the control task. However, during the delay periods, activation was greater for the location than for the voice identity task in dorsal prefrontal (SFS/PreCG) and parietal regions and, conversely, greater for voices than locations in ventral prefrontal cortex and the anterior portion of the insula. This preferential response to the voice identity task in ventral prefrontal cortex continued during the recognition test period, but the double dissociation was observed only during maintenance, not during encoding or recognition. Together, the present findings suggest that, during auditory working memory, maintenance of spatial and nonspatial information modulates activity preferentially in a dorsal and a ventral auditory pathway, respectively. Furthermore, the magnitude of this dissociation seems to be dependent on the cognitive operations required at different times during task performance.

Acoustic Stimulation↗

PubMed2004

Species-specific calls evoke asymmetric activity in the monkey's temporal poles.

It has often been proposed that the vocal calls of monkeys are precursors of human speech, in part because they provide critical information to other members of the species who rely on them for survival and social interactions. Both behavioural and lesion studies suggest that monkeys, like humans, use the auditory system of the left hemisphere preferentially to process vocalizations. To investigate the pattern of neural activity that might underlie this particular form of functional asymmetry in monkeys, we measured local cerebral metabolic activity while the animals listened passively to species-specific calls compared with a variety of other classes of sound. Within the superior temporal gyrus, significantly greater metabolic activity occurred on the left side than on the right, only in the region of the temporal pole and only in response to monkey calls. This functional asymmetry was absent when these regions were separated by forebrain commissurotomy, suggesting that the perception of vocalizations elicits concurrent interhemispheric interactions that focus the auditory processing within a specialized area of one hemisphere.

Acoustic Stimulation↗

PubMed2003

Language fMRI abnormalities associated with FOXP2 gene mutation.

Half the members of the KE family suffer from a speech and language disorder caused by a mutation in the FOXP2 gene. We examined functional brain abnormalities associated with this mutation using two fMRI language experiments, one involving covert (silent) verb generation and the other overt (spoken) verb generation and word repetition. The unaffected family members showed a typical left-dominant distribution of activation involving Broca's area in the generation tasks and a more bilateral distribution in the repetition task, whereas the affected members showed a more posterior and more extensively bilateral pattern of activation in all tasks. Consistent with previously reported bilateral morphological abnormalities, the affected members showed significant underactivation relative to the unaffected members in Broca's area and its right homolog, as well as in other cortical language-related regions and in the putamen. Our findings suggest that the FOXP2 gene is critically involved in the development of the neural systems that mediate speech and language.

Brain Mapping↗

PubMed2003

One-trial memory for object-place associations after separate lesions of hippocampus and posterior parahippocampal region in the monkey.

In earlier studies of one-trial spatial memory in monkeys (Parkinson et al., 1988; Angeli et al., 1993), severe and chronic memory impairment for both object-place association and place alone was found after ablation of the hippocampal formation. The results appeared to provide the first clear-cut evidence in the monkey of the essential role of the hippocampus in spatial memory, but that interpretation neglected the inclusion in the lesion of the underlying posterior parahippocampal region. To determine the separate contributions of the hippocampus and posterior parahippocampal region to these spatial forms of one-trial memory, we trained 10 rhesus monkeys, as before, to remember the spatial positions of either two different trial-unique objects overlying two of the wells in a three-well test tray (object-place trials) or simply two of the three wells (place trials). Six of the monkeys then received ibotenic acid lesions restricted to the hippocampal formation (group H), and the four others received selective ablations of the posterior parahippocampal region (group P), comprising mainly parahippocampal cortex, parasubiculum, and presubiculum. Group H was found to be completely unaffected postoperatively on both types of trials, whereas group P sustained an impairment on both types equal in magnitude to that observed after the combined lesions in the original studies. Thus, contrary to the previous interpretation, one-trial memory for object-place association and, perhaps more fundamentally, one-trial memory for two different places appear to be critically dependent not on the hippocampal formation but rather on the posterior parahippocampal region.

Animals↗

PubMed2003

Functional mapping of the primate auditory system.

Cerebral auditory areas were delineated in the awake, passively listening, rhesus monkey by comparing the rates of glucose utilization in an intact hemisphere and in an acoustically isolated contralateral hemisphere of the same animal. The auditory system defined in this way occupied large portions of cerebral tissue, an extent probably second only to that of the visual system. Cortically, the activated areas included the entire superior temporal gyrus and large portions of the parietal, prefrontal, and limbic lobes. Several auditory areas overlapped with previously identified visual areas, suggesting that the auditory system, like the visual system, contains separate pathways for processing stimulus quality, location, and motion.

Acoustic Stimulation↗

PubMed2002

A room with a view and a polarizing cue: individual differences in the stimulus control of place navigation and passive latent learning in the water maze.

We investigated individual differences in the stimulus control of navigational behavior in the water maze by comparing measures of place learning in one environment to measures of latent learning (via passive placement on the goal platform) in a novel environment. In the first experiment, 12 rats were trained to find a slightly submerged hidden platform at a fixed location in room A for 10 days (4 trials/day). Fast and slow place learners were identified by their mean escape latency and cumulative distance to the goal during acquisition. The same animals were then given a 2-min passive placement on the submerged platform in room B. Latent learning was assessed by the animal's escape latency on a single swim trial immediately following the placement in room B. The results showed that the good latent learners in room B were not necessarily the fast place learners in room A. This weak correlation may be related to the fact that some rats swam near the area in room B that corresponded to the former goal location in room A relative to a common polarizing cue (i.e., the door/entrance to both rooms). When the view of the door was blocked in a second experiment a significant positive correlation between place acquisition and the latent learning test was obtained, although escape performance following passive placement was not improved. These findings suggest that while place navigation and latent learning via passive placement may involve some common cognitive-spatial function, other associative (S-S and/or S-R) processes that occur during place navigation/active movement may be required for animals to exhibit truly accurate navigational behavior characteristic of asymptotic escape performance in the water maze. Additional implications for neurobiological studies using a procedural pretraining design are discussed.

Animals↗