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Control of semantic interference in episodic memory retrieval is associated with an anterior cingulate-prefrontal activation pattern.

Prefrontal activation is a consistent finding in functional neuroimaging studies of episodic memory retrieval. In the present study we aimed at a further analysis of prefrontal neural systems involved in the executive control of context-specific properties in episodic memory retrieval using an event-related fMRI design. Nine subjects were asked to learn two 20-item word lists that consisted of concrete nouns assigned to four semantic categories. Ten items of both word lists referred to the same semantic category. Subjects were instructed to determine whether nouns displayed in random order corresponded to the first 20-item target list. The interference evoked by the retrieval of semantically related items of the second list resulted in significantly longer reaction times compared to the noninterference condition. Contrasting the interference against the noninterference retrieval condition demonstrated an activation pattern that comprised a right anterior cingulate and frontal opercular area and a left-lateralized dorsolateral prefrontal region. Trial averaged time series revealed that the PFC areas were selectively activated at the interference condition and did not respond to the familiarity of learned words. These findings suggest a functionally separable role of prefrontal cortical areas mediating processes associated with the executive control of interfering context information in episodic memory retrieval.

Adult↗

Bilateral activation of the prefrontal cortex after strategic semantic cognitive training.

The prefrontal cortex (PFC) has been implicated in the ability to apply semantic organizational strategies during verbal encoding and episodic learning. However, there has been no direct evidence demonstrating which specific areas in the PFC are engaged after cognitive training using semantic organizational strategies in healthy adult human subjects. In this study, we investigated the effects of semantic strategic training on brain activity and changes in behavioral performance, after cognitive training, using functional MRI (fMRI). There was a significant activation in bilateral dorsolateral prefrontal (DLPF) and orbitofrontal (OFC) areas after cognitive training. These results demonstrate the engagement of bilateral DLPF and OFC cortex during strategic memory processes, particularly when mobilization and effort of effective use of strategies are required. The functional adaptations observed here may also shed light on some of the processes underlying recovery with cognitive rehabilitation in patient populations with brain injury.

Adult↗

Differential effects of caffeine on free recall after semantic and rhyming tasks in high and low impulsives.

The effects of caffeine on free recall after acquisition on semantic and rhyming tasks were examined. Following a between-subjects design, high and low impulsive male postgraduate students were administered placebo and four doses of caffeine citrate (1, 2, 3 and 4 mg/kg body weight) in a laboratory situation. A double blind procedure was adopted for drug administration. The study supports the following conclusions: (1) under no drug condition, high impulsives recall more after semantic acquisition while their counterparts, the low impulsives, recall more after rhyming acquisition; (2) caffeine facilitates recall in high impulsives after rhyming acquisition but hinders it after semantic acquisition; (3) caffeine does not reliably influence recall of low impulsives.

Adult↗

Autistic children's use of semantic common sense and theory of mind: a comparison with typical and mentally retarded children.

To compare Japanese autistic children's use of semantic knowledge and theory of mind with mentally retarded and typically developing children's, they were tested on their comprehension of active and passive sentences and false belief understanding. Autistic children were sensitive to plausibility levels of semantic bias as were 4-year-olds with typical development when comprehending sentences, although impaired in belief understanding as compared with mentally retarded children and typically developing 5-year-olds. Children's sentence comprehension had no association with belief understanding. Results suggest that autistic children with certain verbal intelligence can utilize semantic common sense to comprehend sentences as can typically developing children and that the ability to comprehend sentences is relatively independent of theory of mind.

Adolescent↗

Semantic memory is impaired in schizophrenia.

Memory is emerging as a key area of neuropsychological deficit in schizophrenia, with evidence suggesting that the impairment is restricted to long-term memory. Semantic memory, the component of long-term memory containing stored representations of the meanings of words and knowledge about the world, was examined in 46 schizophrenic patients and 40 normal controls using a recently devised battery of tests. Evidence of semantic memory impairment was found which was wide ranging and substantial; in some cases it approached the levels seen in a group of 22 patients with mild-to-moderate Alzheimer's disease. Both group analysis and a more detailed examination of two single cases suggested that semantic memory impairment represents a disproportionate and possibly specific neuropsychological deficit in schizophrenia.

Adolescent↗

Differentiation, ageing, and terminal differentiation: a semantic analysis.

The largely unsolved problems in the theoretical analysis of differentiation and ageing involve a substantial component of linguistic (semantic) difficulties. Some of these are simple traps of ambiguity, resulting from metaphorical or analogical employment of established terms--for example, "terminal differentiation" (loss of division potential in vitro) as a borrowing from "differentiation" as used by developmental biologists, or "commitment" by analogy with "determination". Some difficulties represent a failure to adopt (at least provisionally) an operational (empirical) view--for example, failure to ask what is the nature of the evidence for the view that a fertilized ovum is totipotential, or to scrutinize the evidence for the view that cells "terminally differentiated" in vitro in a conventional medium are in fact moribund under all conditions, or to examine more closely the view that the differentiated state and the cycling state are mutually exclusive. With respect to the problem of ageing, we review some of the critical experiments on "terminal differentiation" or "clonal senescence". We then proceed to consider some of the models that have been proposed, including a molecular model proposed by the author which appears to overcome some of the objections to other models. Some of the models exemplify the results of what are ultimately semantic vices. The problems with which these remarks began should indeed yield to the immense and novel resources of molecular biology. But the development of complete analyses demands not only good luck and delicate technique but also critical semantic clarity and severity. Given the best tools, we shall solve major theoretical problems only if we understand quite fully what problem it is that we are trying to solve--and the history of science illustrates that this is not as elementary a matter as it sounds.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Differentiation↗

Neuronal correlate of the higher-order semantic code in human prefrontal cortex in language tasks.

Recently, Posner et al. (Science, 1988, 240: 1627-1631) have shown by means of positron-emission tomography (PET) that the highest activation related to the higher-order semantic encoding in language tasks is revealed in the anterior inferior region of the left prefrontal cortex. We had a case where we explored the neuronal activity in this cerebral area in a patient with diagnostic intracerebral electrodes. Neurons of the left cortical areas 10 and 46 exhibited responses related to the processing of semantic and grammatic signs of the presented phrases. Specific responses in neuronal activity of the same cells in other higher-order language tasks, in discrimination of concrete and abstract words, and the absence of significant responses in other relatively simpler language tasks, such as object naming and lexical decision, supports the PET finding on the selective participation of this cerebral area in the higher-order semantic encoding and discovers new neuronal mechanisms of this encoding.

Adult↗

The effects of physical and semantic incongruities on auditory event-related potentials.

Twenty subjects listened to a series of simple sentences, spoken by a male voice, in which the last word was on occasions either made semantically incongruous or was unexpectedly spoken by a female voice. Averages of ERPs to the last words revealed that a consistent late negative component (N456) was associated with semantic incongruity and a late positive component (P416) with physical (voice) incongruity. The results were consistent with those in the visual modality by Kutas and Hillyard (1980a,b) and are interpreted in terms of the facilitatory and inhibitory effects of contextual priming on the processing of the words concerned. In a subsidiary experiment 6 subjects were required to repeat the last words of the same set of sentences as rapidly as possible. Verbal response latency increased by 62 msec to physically incongruous words and by 185 msec to semantically incongruous words.

Auditory Perception↗

Cognition in Alzheimer's disease: disorders of attention and semantic knowledge.

Alzheimer's disease leads to a selective decline of cognitive skills, particularly semantic knowledge and visuospatial attention. Recent advances suggest that, although the two systems responsible for these skills can interact, the semantic memory deficit seen in Alzheimer's disease cannot be solely attributed to attention or retrieval deficiencies. This is consistent with a modular view of cognition, which postulates that disruption to these systems is selective in Alzheimer's disease. Cortico-cortical disconnection of association areas may disrupt widespread networks mediating attention and semantic knowledge in Alzheimer's disease.

Alzheimer Disease↗

Episodic and semantic memory influences on picture naming in Alzheimer's disease.

This study investigated the relationship between semantic and episodic memory as they support lexical access by healthy younger and older adults and individuals with Alzheimer's disease (AD). In particular, we were interested in examining the pattern of semantic and episodic memory declines in AD (i.e., word-finding difficulty and impaired recent memory) vis-à-vis more preserved remote memories. We administered a picture naming task in which the episodic period of the pictures and whether the pictured items were unique to one period or commonly used across periods were varied. Groups of younger adults (N=40), healthy older adults (N=20) and older adults with AD (N=18) were asked to name drawings of objects in four conditions: dated unique, contemporary unique, dated common, and contemporary common. The results indicated that all participants named items that were common to both episodic periods more successfully than items unique to one period. An interaction was observed such that the healthy older and AD groups were more successful in retrieving names of objects presented in the dated compared to contemporary unique conditions, whereas the younger adults showed the reverse pattern. These results indicate that naming ability is affected both by the cumulative frequency of using an item over a lifetime and by when an item was first acquired. The findings support a theoretical stance which proposes an enduring reciprocal link between semantic and episodic memory. This theoretical relationship has practical implications for the development of intervention strategies when interacting with persons who have AD.

Adult↗

Evidence for the importance of basal ganglia output nuclei in semantic event sequencing: an fMRI study.

Semantic event sequencing is the ability to plan ahead and order meaningful events chronologically. To investigate the neural systems supporting this ability, an fMRI picture sequencing task was developed. Participants sequenced a series of four pictures presented in random order based on the temporal relationship among them. A control object discrimination task was designed to be comparable to the sequencing task regarding semantic, visuospatial, and motor processing requirements but without sequencing demands. fMRI revealed significant activation in the dorsolateral prefrontal cortex and globus pallidus internal part in the picture sequencing task compared with the control task. The findings suggest that circuits involving the frontal lobe and basal ganglia output nuclei are important for picture sequencing and more generally for the sequential ordering of events. This is consistent with the idea that the basal ganglia output nuclei are critical not only for motor but also for high-level cognitive function, including behaviors involving meaningful information. We suggest that the interaction between the frontal lobes and basal ganglia output nuclei in semantic event sequencing can be generalized to include the sequential ordering of behaviors in which the selective updating of neural representations is the key computation.

Basal Ganglia↗

Neural correlates of verbal semantic memory in patients with temporal lobe epilepsy.

Functional imaging data suggest that the core network engaged in verbal semantic memory (SM) processing encompasses frontal and temporal lobe structures, with a strong left lateralization in normal right handers. The impact of long term temporal lobe epilepsy (TLE) on this network has only partly been elucidated. We studied verbal SM in 50 patients with chronic, intractable TLE (left TLE=26, right TLE=24) and 35 right handed normal controls using a verbal fMRI semantic decision paradigm. All patients had language lateralized to the left hemisphere, as verified by the intracarotid amobarbital procedure. Within and between group analyses showed remarkable, group-specific activation profiles. The control group activated frontal and temporal areas bilaterally, with a strong left predominance. Left TLE patients showed a shift of activations of left frontal and medial temporal areas to homologous regions in the right hemisphere. Furthermore, left TLE subjects utilized subcortical structures such as the thalamus and putamen to accomplish the verbal SM task. Contrastively, the activation pattern of right TLE patients resembled that of normal controls, but exhibited "hypofrontality" with a shift from frontal to posterior regions in the temporal, parietal and occipital lobe. Our results show that chronic epileptic activity originating from temporal seizure foci is associated with an alteration of neural circuits which support semantic language processing and that side of seizure focus has a specific impact on the resulting activation network. These findings presumably result from morphological changes and from functional reorganization which are both inherent to chronic TLE.

Adult↗

Effects of ketamine on thought disorder, working memory, and semantic memory in healthy volunteers.

BACKGROUND: The N-methyl-D-aspartate receptor antagonist, ketamine, produces a clinical syndrome of thought disorder, perceptual distortion, and cognitive impairment. METHODS: We have administered ketamine to healthy volunteers to characterize the formal thought disorder and specific memory dysfunction associated with ketamine. Ten healthy volunteers underwent a double-blind, placebo-controlled, ketamine infusion (0.12 mg/kg bolus and 0.65 mg/kg/hour). Thought disorder was evaluated with the Scale for the Assessment of Thought, Language and Communication. Cognitive testing involved working and semantic memory tasks. RESULTS: Ketamine produced a formal thought disorder, as well as impairments in working and semantic memory. The degree of ketamine-induced thought disorder significantly correlated with ketamine-induced decreases in working memory and did not correlate with ketamine-induced impairments in semantic memory. CONCLUSIONS: This study characterizes the formal thought disorder associated with ketamine and may suggest that ketamine-induced deficits in working memory are associated with ketamine-induced thought disorder.

Adult↗

Unconscious semantic priming from pictures.

Three experiments examined the effects of unconsciously presented picture primes on semantic categorization and naming responses to both word and picture targets. Picture naming and word categorization responses to targets were faster and more accurate when the picture primes belonged to the same semantic category as the targets, so called priming effect. No priming was found when subjects performed a word reading task. When priming was evident, no difference was found between responses to targets that were nominally identical to primes (e.g. the picture of a lion followed by either the word LION or the picture of a lion) compared with nominally different targets from the same semantic category as the primes (e.g. the picture of an ELEPHANT followed by either the word LION or the picture of a lion). Responding did not differ significantly from chance when subjects were asked to categorize the primes as natural objects vs. artifacts or as meaningful vs. meaningless objects in three distinct forced-choice unspeeded tasks.

Adult↗

Lexical-semantic deficits in two patients with dominant thalamic infarction.

Two patients with dominant thalamic infarction, one in the tuberothalamic artery territory, the other in the paramedian artery territory, demonstrated language impairment limited to word retrieval difficulties in spontaneous language and structured naming tasks. Using a cognitive neuropsychological model of lexical processing developed in the study of patients with cortical lesions. We carried out a detailed investigation of their lexical abilities. Both patients demonstrated impairment restricted to oral and written picture naming and oral naming to definition and spared performance on tasks of lexical comprehension, oral word reading, and writing to dictation, as well as syntactic comprehension and production. Naming impairment disproportionately affected lower frequency words, and word substitutions often corresponded to objects that were semantically-related to target words. We propose that our patients' word retrieval impairments reflect a failure of thalamic input to effectively engage the cortical networks subserving lexical semantic processing, leading to degraded levels of activation as the semantic system interfaces with subsequent stages of lexical processing.

Aphasia↗

ERP assessment of semantic memory in Alzheimer's disease.

This study used the technique of Event-Related Potentials (ERPs), specifically the component N400, to evaluate semantic functions in Alzheimer's disease (AD). ERPs of 10 patients with probable AD and 10 asymptomatic elderly control subjects were recorded during a semantic categorization task using pictures as stimuli, 50% of the stimuli were congruent and the other 50% were incongruent. Significant differences for the incongruent ERPs, with a diminished N400 component, was observed in the patients group whereas the amplitude of the congruent ERPs was similar in both groups. The characteristics of the N400 in the patients with probable AD suggest that there is a lack of efficiency in accessing information and shows that there are deficient associative connections within the semantic network.

Aged↗

The N400 in a semantic categorization task across 6 decades.

OBJECTIVES: To characterize the effects of normal aging on the amplitude, latency and scalp distribution of the N400 congruity effect. METHODS: Event-related brain potentials (ERPs) were recorded from 72 adults (half of them men) between the ages of 20 and 80 years (12/decade) as they performed a semantic categorization task. Participants listened to spoken phrases (e.g. 'a type of fruit' or 'the opposite of black') followed about 1 s later by a visually-presented word that either did or did not fit with the sense of the preceding phrase; they reported the word read and whether or not it was appropriate. ERP measurements (mean amplitudes, peak amplitudes, peak latencies) were subjected to analysis of variance and linear regression analyses. RESULTS: All participants, regardless of age, produced larger N400s to words that did not fit than to those that did. The N400 congruity effect (no-fit ERPs - fit ERPs) showed a reliable linear decrease in the amplitude (0.05-0.09 microV per year, r = 0.40) and a reliable linear increase peak latency (1.5-2.1 ms/year, r = 0.60) with age. CONCLUSIONS: In sum, the N400 semantic congruity effect at the scalp gets smaller, slower and more variable with age, consistent with a quantitative rather than qualitative change in semantic processing (integration) with normal aging.

Acoustic Stimulation↗

Tau protein in cerebrospinal fluid from semantic dementia patients.

Apolipoprotein E (APOE) genotypes and cerebrospinal fluid (CSF) tau protein concentration were evaluated in patients suffering from semantic dementia, with the aim of determining whether these markers could help to differentiate this condition from Alzheimer's disease (AD) in early stages. By strictly following diagnostic criteria for semantic dementia, we found a clinically homogeneous group comprising eight patients from a total population of 621 subjects referred for dementia investigation. CSF tau protein concentrations were moderately increased with a small intraindividual variation 437+/-36 pg/ml (mean+/-SD) compared to healthy control individuals. APOE genotype distribution showed an over representation of the epsilon4 allele (69% epsilon3, 31% epsilon4 and no epsilon2), a pattern similar to that found in AD. These results indicate that semantic dementia is a rather uncommon but clinically distinct condition which shows a moderate increase of CSF tau protein levels and for which the epsilon4 allele is a risk factor.

Alzheimer Disease↗