Publications

Abstract

Knowing what is going to happen next, that is, the capacity to predict upcoming events, modulates the extent to which aversive stimuli induce stress and anxiety. We explored this issue by manipulating the temporal predictability of aversive events by means of a visual cue, which was either correlated or uncorrelated with pain stimuli (electric shocks). Subjects reported lower levels of anxiety, negative valence and pain intensity when shocks were predictable. In addition to attenuate focus on danger, predictability allows for correct temporal estimation of, and selective attention to, the sensory input. With functional magnetic resonance imaging, we found that predictability was related to enhanced activity in relevant sensory-discriminative processing areas, such as the primary and secondary sensory cortex and posterior insula. In contrast, the unpredictable more aversive context was correlated to brain activity in the anterior insula and the orbitofrontal cortex, areas associated with affective pain processing. This context also prompted increased activity in the posterior parietal cortex and lateral prefrontal cortex that we attribute to enhanced alertness and sustained attention during unpredictability.

Abstract

The human brain supports acquisition mechanisms that extract structural regularities implicitly from experience without the induction of an explicit model. It has been argued that the capacity to generalize to new input is based on the acquisition of abstract representations, which reflect underlying structural regularities in the input ensemble. In this study, we explored the outcome of this acquisition mechanism, and to this end, we investigated the neural correlates of artificial syntactic classification using event-related functional magnetic resonance imaging. The participants engaged once a day during an 8-day period in a short-term memory acquisition task in which consonant-strings generated from an artificial grammar were presented in a sequential fashion without performance feedback. They performed reliably above chance on the grammaticality classification tasks on days 1 and 8 which correlated with a corticostriatal processing network, including frontal, cingulate, inferior parietal, and middle occipital/occipitotemporal regions as well as the caudate nucleus. Part of the left inferior frontal region (BA 45) was specifically related to syntactic violations and showed no sensitivity to local substring familiarity. In addition, the head of the caudate nucleus correlated positively with syntactic correctness on day 8 but not day 1, suggesting that this region contributes to an increase in cognitive processing fluency.

Abstract

There is evidence for cognitive as well as neural plasticity across the adult life span, although aging is associated with certain constraints on plasticity. In the current paper, we argue that the age-related reduction in cognitive plasticity may be due to (a) deficits in general processing resources, and (b) failure to engage in task-relevant cognitive operations. Memory-training research suggests that age-related processing deficits (e.g., executive functions, speed) hinder older adults from utilizing mnemonic techniques as efficiently as the young, and that this age difference is reflected by diminished frontal activity during mnemonic use. Additional constraints on memory plasticity in old age are related to difficulties that are specific to the task, such as creating visual images, as well as in binding together the information to be remembered. These deficiencies are paralleled by reduced activity in occipito-parietal and medial–temporal regions, respectively. Future attempts to optimize intervention-related gains in old age should consider targeting both general processing and task-specific origins of age-associated reductions in cognitive plasticity.

Abstract

The apolipoprotein E {varepsilon}4 (APOE {varepsilon}4) is the main known genetic risk factor for Alzheimer's disease. Genetic assessments in combination with other diagnostic tools, such as neuroimaging, have the potential to facilitate early diagnosis. In this large-scale functional MRI (fMRI) study, we have contrasted 30 APOE {varepsilon}4 carriers (age range: 49–74 years; 19 females), of which 10 were homozygous for the {varepsilon}4 allele, and 30 non-carriers with regard to brain activity during a semantic categorization task. Test groups were closely matched for sex, age and education. Critically, both groups were cognitively intact and thus symptom-free of Alzheimer's disease. APOE {varepsilon}4 carriers showed reduced task-related responses in the left inferior parietal cortex, and bilaterally in the anterior cingulate region. A dose-related response was observed in the parietal area such that diminution was most pronounced in homozygous compared with heterozygous carriers. In addition, contrasts of processing novel versus familiar items revealed an abnormal response in the right hippocampus in the APOE {varepsilon}4 group, mainly expressed as diminished sensitivity to the relative novelty of stimuli. Collectively, these findings indicate that genetic risk translates into reduced functional brain activity, in regions pertinent to Alzheimer's disease, well before alterations can be detected at the behavioural level.

Abstract

Literacy and education represent essential aspects of contemporary society and subserve important aspects of socialization and cultural transmission. The study of illiterate subjects represents one approach to investigate the interactions between neurobiological and cultural factors in cognitive development, individual learning, and their influence on the functional organization of the brain. In this chapter we review some recent cognitive, neuroanatomic, and functional neuroimaging results indicating that formal education influences important aspects of the human brain. Taken together this provides strong support for the idea that the brain is modulated by literacy and formal education, which in turn change the brains capacity to interact with its environment, including the individual's contemporary culture. In other words, the individual is able to participate in, interact with, and actively contribute to the process of cultural transmission in new ways through acquired cognitive skills.

Abstract

The irrelevant speech effect illustrates that sounds that are irrelevant to a visually presented short-term memory task still interfere with neuronal function. In the present study we explore the functional and effective connectivity of such interference. The functional connectivity analysis suggested an interaction between the level of irrelevant speech and the correlation between in particular the left superior temporal region, associated with verbal working memory, and the left medial temporal lobe. Based on this psycho-physiological interaction, and to broaden the understanding of this result, we performed a network analysis, using a simple network model for verbal working memory, to analyze its interaction with the medial temporal lobe memory system. The results showed dissociations in terms of network interactions between frontal as well as parietal and temporal areas in relation to the medial temporal lobe. The results of the present study suggest that a transition from phonological loop processing towards an engagement of episodic processing might take place during the processing of interfering irrelevant sounds. We speculate that, in response to the irrelevant sounds, this reflects a dynamic shift in processing as suggested by a closer interaction between a verbal working memory system and the medial temporal lobe memory system.

Abstract

Doubts have been cast on the strict dissociation between short- and long-term memory systems. Specifically, several neuroimaging studies have shown that the medial temporal lobe, a region almost invariably associated with long-term memory, is involved in active short-term memory maintenance. Furthermore, a recent study in hippocampally lesioned patients has shown that the hippocampus is critically involved in associating objects and their locations, even when the delay period lasts only 8 s. However, the critical feature that causes the medial temporal lobe, and in particular the hippocampus, to participate in active maintenance is still unknown. This study was designed in order to explore hippocampal involvement in active maintenance of spatial and non-spatial associations. Eighteen participants performed a delayed-match-to-sample task in which they had to maintain either object–location associations, color–number association, single colors, or single locations. Whole-brain activity was measured using event-related functional magnetic resonance imaging and analyzed using a random effects model. Right lateralized hippocampal activity was evident when participants had to maintain object–location associations, but not when they had to maintain object–color associations or single items. The present results suggest a hippocampal involvement in active maintenance when feature combinations that include spatial information have to be maintained online.

Abstract

Previous work has shown that illiterate subjects are better at naming two-dimensional representations of real objects when presented as colored photos as compared to black and white drawings. This raises the question if color or textural details selectively improve object recognition and naming in illiterate compared to literate subjects. In this study, we investigated whether the surface texture and/or color of objects is used to access stored object knowledge in illiterate subjects. A group of illiterate subjects and a matched literate control group were compared on an immediate object naming task with four conditions: color and black and white (i.e., grey-scaled) photos, as well as color and black and white (i.e., grey-scaled) drawings of common everyday objects. The results show that illiterate subjects perform significantly better when the stimuli are colored and this effect is independent of the photographic detail. In addition, there were significant differences between the literacy groups in the black and white condition for both drawings and photos. These results suggest that color object information contributes to object recognition. This effect was particularly prominent in the illiterate group

Abstract

Retrieval of recently acquired declarative memories depends on
the hippocampus, but with time, retrieval is increasingly sustainable
by neocortical representations alone. This process has been
conceptualized as system-level consolidation. Using functional
magnetic resonance imaging, we assessed over the course of three
months how consolidation affects the neural correlates of memory
retrieval. The duration of slow-wave sleep during a nap/rest
period after the initial study session and before the first scan
session on day 1 correlated positively with recognition memory
performance for items studied before the nap and negatively with
hippocampal activity associated with correct confident recognition.
Over the course of the entire study, hippocampal activity for
correct confident recognition continued to decrease, whereas activity
in a ventral medial prefrontal region increased. These findings,
together with data obtained in rodents, may prompt a
revision of classical consolidation theory, incorporating a transfer
of putative linking nodes from hippocampal to prelimbic prefrontal
areas.

Abstract

Positron emission tomography (PET) was performed in normal volunteers during a serial recall task under the influence of irrelevant speech comprising both single item repetition and multi-item sequences. An interaction approach was used to identify brain areas specifically related to the irrelevant speech effect. We interpreted activations as compensatory recruitment of complementary working memory processing, and decreased activity in terms of suppression of task relevant areas invoked by the irrelevant speech. The interaction between the distractors and working memory revealed a significant effect in the left, and to a lesser extent in the right, superior temporal region, indicating that initial phonological processing was relatively suppressed. Additional areas of decreased activity were observed in an a priori defined cortical network related to verbalworking memory, incorporating the bilateral superior temporal and inferior/middle frontal corticesn extending into Broca’s area on the left. We also observed a weak activation in the left inferior parietal cortex, a region suggested to reflect the phonological store, the subcomponent where the interference is assumed to take place. The results suggest that the irrelevant speech effect is correlated with and thus tentatively may be explained in terms of a suppression of components of the verbal working memory network as outlined. The results can be interpreted in terms of inhibitory top–down attentional mechanisms attenuating the influence of the irrelevant speech, although additional studies are clearly necessary to more fully characterize the nature of this phenomenon and its theoretical implications for existing short-term memory models

Abstract

The posterior medial parietal cortex and the left prefrontal cortex have both been implicated in the recollection of past episodes. In order to clarify their functional significance, we performed this functional magnetic resonance imaging study, which employed event-related source memory and item recognition retrieval of words paired with corresponding imagined or viewed pictures. Our results suggest that episodic source memory is related to a functional network including the posterior precuneus and the left lateral prefrontal cortex. This network is activated during explicit retrieval of imagined pictures and results from the retrieval of item-context associations. This suggests that previously imagined pictures provide a context with which encoded words can be more strongly associated.

Abstract

Regions of the prefrontal cortex (PFC) are typically activated in many different cognitive functions. In most studies, the focus has been on the role of specific PFC regions in specific cognitive domains, but more recently similarities in PFC activations across cognitive domains have been stressed. Such similarities may suggest that a region mediates a common function across a variety of cognitive tasks. In this study, we compared the activation patterns associated with tests of working memory, semantic memory and episodic memory. The results converged on a general involvement of four regions across memory tests. These were located in left frontopolar cortex, left mid-ventrolateral PFC, left mid-dorsolateral PFC and dorsal anterior cingulate cortex. These findings provide evidence that some PFC regions are engaged during many different memory tests. The findings are discussed in relation to theories about the functional contribition of the PFC regions and the architecture of memory.

Abstract

Cognitive studies show that both younger and older adults can increase their memory performance after training in using a visuospatial mnemonic, although age-related memory deficits tend to be magnified rather than reduced after training. Little is known about the changes in functional brain activity that accompany training-induced memory enhancement, and whether age-related activity changes are associated with the size of training-related gains. Here, we demonstrate that younger adults show increased activity during memory encoding in occipito-parietal and frontal brain regions after learning the mnemonic. Older adults did not show increased frontal activity, and only those elderly persons who benefited from the mnemonic showed increased occipitoparietal activity. These findings suggest that age-related differences in cognitive reserve capacity may reflect both a frontal processing deficiency and a posterior production deficiency.

Abstract

In a within-subject design we investigated the levels-of-processing (LOP) effect using visual material in a behavioral and a corresponding PET study. In the behavioral study we characterize a generalized LOP effect, using pleasantness and graphical quality judgments in the encoding situation, with two types of visual material, figurative and nonfigurative line drawings. In the PET study we investigate the related pattern of brain activations along these two dimensions. The behavioral results indicate that instruction and material contribute independently to the level of recognition performance. Therefore the LOP effect appears to stem both from the relative relevance of the stimuli (encoding opportunity) and an altered processing of stimuli brought about by the explicit instruction (encoding mode). In the PET study, encoding of visual material under the pleasantness (deep) instruction yielded left lateralized frontoparietal and anterior temporal activations while surface-based perceptually oriented processing (shallow instruction) yielded right lateralized frontoparietal, posterior temporal, and occipitotemporal activations. The result that deep encoding was related to the left prefrontal cortex while shallow encoding was related to the right prefrontal cortex, holding the material constant, is not consistent with the HERA model. In addition, we suggest that the anterior medial superior frontal region is related to aspects of self-referential semantic processing and that the inferior parts of the anterior cingulate as well as the medial orbitofrontal cortex is related to affective processing, in this case pleasantness evaluation of the stimuli regardless of explicit semantic content. Finally, the left medial temporal lobe appears more actively engaged by elaborate meaning-based processing and the complex response pattern observed in different subregions of the MTL lends support to the suggestion that this region is functionally segregated.

Abstract

The objectives of this article are to characterize the performance and to discuss the performance differences between literate and illiterate participants in a well-defined study population.We describe the participant-selection procedure used to investigate this population. Three groups with similar sociocultural backgrounds living in a relatively homogeneous fishing community in southern Portugal were characterized in terms of socioeconomic and sociocultural background variables and compared on a simple neuropsychological test battery; specifically, a literate group with more than 4 years of education (n = 9), a literate group with 4 years of education (n = 26), and an illiterate group (n = 31) were included in this study.We compare and discuss our results with other similar studies on the effects of literacy and illiteracy. The results indicate that naming and identification of real objects, verbal fluency using ecologically relevant semantic criteria, verbal memory, and orientation are not affected by literacy or level of formal education. In contrast, verbal working memory assessed with digit span, verbal abstraction, long-term semantic memory, and calculation (i.e., multiplication) are significantly affected by the level of literacy. We indicate that it is possible, with proper participant-selection procedures, to exclude general cognitive impairment and to control important sociocultural factors that potentially could introduce bias when studying the specific effects of literacy and level of formal education on cognitive brain function.

Abstract

Is there a relation between socioeconomic factors and aphasia severity and recovery? Connor, Obler, Tocco, Fitzpatrick, and Albert (2001) describe correlations between the educational level and socioeconomic status of aphasic subjects with aphasia severity and subsequent recovery. As stated in the introduction by Connor et al. (2001), studies of the influence of educational level and literacy (or illiteracy) on aphasia severity have yielded conflicting results, while no significant link between socioeconomic status and aphasia severity and recovery has been established. In this brief note, we will comment on their findings and conclusions, beginning first with a brief review of literacy and aphasia research, and complexities encountered in these fields of investigation. This serves as a general background to our specific comments on Connor et al. (2001), which will be focusing on methodological issues and the importance of taking normative values in consideration when subjects with different socio-cultural or socio-economic backgrounds are assessed.

Abstract

In the present PET study we explore some functional aspects of the interaction between attentional/control processes and learning/memory processes. The network of brain regions supporting recall of abstract designs were studied in a less practiced and in a well practiced state. The results indicate that automaticity, i.e., a decreased dependence on attentional and working memory resources, develops as a consequence of practice. This corresponds to the practice related decreases of activity in the prefrontal, anterior cingulate, and posterior parietal regions. In addition, the activity of the medial temporal regions decreased as a function of practice. This indicates an inverse relation between the strength of encoding and the activation of the MTL during retrieval. Furthermore, the pattern of practice related increases in the auditory, posterior insular-opercular extending into perisylvian supra marginal region, and the right mid occipito-temporal region, may reflect a lower degree of inhibitory attentional modulation of task irrelevant processing and more fully developed representations of the abstract designs, respectively. We also suggest that free recall is dependent on bilateral prefrontal processing, in particular non-automatic free recall. The present results cofirm previous functional neuroimaging studies of memory retrieval indicating that recall is subserved by a network of interacting brain regions. Furthermore, the results indicate that some components of the neural network subserving free recall may have a dynamic role and that there is a functional restructuring of the information processing networks during the learning process.

Abstract

Recent event-related FMRI studies indicate that the prefrontal (PFC) and the medial temporal lobe (MTL) regions are more active during effective encoding than during ineffective encoding. The within-subject design and the use of well-educated young college students in these studies makes it important to replicate these results in other study populations. In this PET study, we used an auditory word-pair association cued-recall paradigm and investigated a group of healthy upper middle-aged/older illiterate women. We observed a positive correlation between cued-recall success and the regional cerebral blood flow of the left inferior PFC (BA 47) and the MTLs. Specifically, we used the cuedrecall success as a covariate in a general linear model and the results confirmed that the left inferior PFC and the MTLare more active during effective encoding than during ineffective encoding. These effects were observed during encoding of both semantically and phonologically related word pairs, indicating that these effects are robust in the studied population, that is, reproducible within group. These results generalize the results of Brewer et al. (1998, Science 281, 1185– 1187) and Wagner et al. (1998, Science 281, 1188–1191) to an upper middle aged/older illiterate population. In addition, the present study indicates that effective relational encoding correlates positively with the activity of the anterior medial temporal lobe regions.

Abstract

A fundamental problem in the study of learning is that learning-related changes may be confounded by nonspecific time effects. There are several strategies for handling this problem. This problem may be of greater significance in functional magnetic resonance imaging (fMRI) compared to positron emission tomography (PET). Using the general linear model, we describe, compare, and discuss two approaches for separating learning-related from nonspecific time effects. The first approach makes assumptions on the general behavior of nonspecific effects and explicitly models these effects, i.e., nonspecific time effects are incorporated as a linear or nonlinear confounding covariate in the statistical model. The second strategy makes no a priori assumption concerning the form of nonspecific time effects, but implicitly controls for nonspecific effects using an interaction approach, i.e., learning effects are assessed with an interaction contrast. The two approaches depend on specific assumptions and have specific limitations. With certain experimental designs, both approaches may be used and the results compared, lending particular support to effects that are independent of the method used. A third and perhaps better approach that sometimes may be practically unfeasible is to use a completely temporally balanced experimental design. The choice of approach may be of particular importance when learning related effects are studied with fMRI.

Abstract

The objective of this study was to investigate the central processing of dynamic mechanical allodynia in patients with mononeuropathy. Regional cerebral bloodflow, as an indicator of neuronal activity, was measured with positron emission tomography. Paired comparisons were made between three different states; rest, allodynia during brushing the painful skin area, and brushing of the homologous contralateral area. Bilateral activations were observed in the primary somatosensory cortex (S1) and the secondary somatosensory cortex (S2) during allodynia compared to rest. The S1 activation contralateral to the site of the stimulus was more expressed during allodynia than during innocuous touch. Significant activations of the contralateral posterior parietal cortex, the periaqueductal gray (PAG), the thalamus bilaterally and motor areas were also observed in the allodynic state compared to both non-allodynic states. In the anterior cingulate cortex (ACC) there was only a suggested activation when the allodynic state was compared with the non-allodynic states. In order to account for the individual variability in the intensity of allodynia and ongoing spontaneous pain, rCBF was regressed on the individually reported pain intensity, and significant covariations were observed in the ACC and the right anterior insula. Significantly decreased regional blood flow was observed bilaterally in the medial and lateral temporal lobe as well as in the occipital and posterior cingulate cortices when the allodynic state was compared to the non-painful conditions. This finding is consistent with previous studies suggesting attentional modulation and a central coping strategy for known and expected painful stimuli. Involvement of the medial pain system has previously been reported in patients with mononeuropathy during ongoing spontaneous pain. This study reveals a bilateral activation of the lateral pain system as well as involvement of the medial pain system during dynamic mechanical allodynia in patients with mononeuropathy.