"What" and "where" in visual working memory: a computational neurodynamical perspective for integrating FMRI and single-neuron data

Single-neuron recordings, functional magnetic resonance imaging (fMRI) data, and the effects of lesions indicate that the prefrontal cortex (PFC) is involved in some types of working memory and related cognitive processes. Based on these data, two different models of the topographical and functional organization of the PFC have been proposed: organization-by-stimulus-domain, and organization-by-process. In this article, we utilize an integrate-and-fire network to model both single-neuron and fMRI data on short-term memory in order to understand data obtained in topologically different parts of the PFC during working memory tasks. We explicitly model the mechanisms that underlie working memory-related activity during the execution of delay tasks that have a "what"-then-"where" design (with both object and spatial delayed responses within the same trial). The model contains different populations of neurons (as found experimentally) in attractor networks that respond in the delay period to the stimulus object, the stimulus position, and to combinations of both object and position information. The pools are arranged hierarchically and have global inhibition through inhibitory interneurons to implement competition. It is shown that a biasing attentional input to define the current relevant information (object or location) enables the system to select the correct neuronal populations during the delay period in what is a biased competition model of attention. The processes occurring at the AMPA and NMDA synapses are dynamically modeled in the integrate-and-fire implementation to produce realistic spiking dynamics. It is shown that the fMRI data characteristic of the dorsal PFC and linked to spatial processing and manipulation of items can be reproduced in the model by a high level of inhibition, whereas the fMRI data characteristic of the ventral PFC and linked to object processing can be produced by a lower level of inhibition, even though the network is itself topographically homogeneous with no spatial topology of the neurons. This article, thus, not only presents a model for how spatial versus object short-term memory could be implemented in the PFC, but also shows that the fMRI BOLD signal measured during such tasks from different parts of the PFC could reflect a higher level of inhibition dorsally, without this dorsal region necessarily being primarily spatial and the ventral region object-related.     

Different cortical activity in reading of Kanji words, Kana words and Kana nonwords

We report a positron emission tomography study on reading of Japanese Kanji (morphograms) words, Kana (phonograms) words and Kana nonwords using statistical parametric mapping. Activity was more pronounced in the lateral fusiform gyrus (Area 37) in Kanji, in contrast to the greater activation in the middle and inferior occipital gyri (Areas 18 and 19) and the deep perisylvian temporo-parietal area (Areas 40/22 and 22/21) in Kana, suggesting that Kanji and Kana are processed differently.     

Double dissociations of word and number processing in auditory and written modalities: a case study

We report an individual with a massive left-hemisphere lesion, who showed reverse patterns of dissociations between word and number processing in two modalities (auditory comprehension and written production). His performance in auditory comprehension was perfect for words, but severely impaired for numbers. In written production, he performed significantly better at writing numbers (both Arabic numbers and word numbers) than writing words. His visual comprehension fell into normal range for words and numbers while his oral production was at floor for both. This case profile adds further evidence to the functional/neural segregation of word and number processing systems.     

Cortical control of inhibition of return: Causal evidence for task-dependent modulations by dorsal and ventral parietal regions

Inhibition of return (IOR) reflects a bias to preferentially attend to non-previously attended or inspected spatial locations. IOR is paramount to efficiently explore our environment, by avoiding repeated scanning of already visited locations. Patients with left visual neglect after right parietal damage or fronto-parietal disconnection demonstrated impaired manual, but not saccadic, IOR for right-sided targets (Bourgeois et al., 2012). Here we aimed at investigating in healthy participants the causal role of distinct cortical sites within the right hemisphere in manual and saccadic IOR, by evaluating the offline effects of repetitive Transcranial Magnetic Stimulation (rTMS) on the right intra-parietal sulcus (IPS) and the right temporo-parietal junction (TPJ). Our results show that rTMS over both sites lastingly interfered with manual but not saccadic IOR for right-sided targets. This behavioral pattern closely mimicked the performance of neglect patients evaluated with the same paradigm. In contrast, for left-sided targets, rTMS over the right IPS impaired both manual and saccadic IOR, while rTMS over the right TPJ produced no modulation in either task. We concluded that distinct parietal nodes of the dorsal and ventral spatial attention networks of the right hemisphere make different contributions to exogenous orienting processes implicated in IOR, and that such effects are hemifield- and task-dependent.     

Specialization of phonological and semantic processing in Chinese word reading

The purpose of this study was to examine the neurocognitive network for processing visual word forms in native Chinese speakers using functional magnetic resonance imaging (fMRI). In order to compare the processing of phonological and semantic representations, we developed parallel rhyming and meaning association judgment tasks that required explicit access and manipulation of these representations. Subjects showed activation in left inferior/middle frontal gyri, bilateral medial frontal gyri, bilateral middle occipital/fusiform gyri, and bilateral cerebella for both the rhyming and meaning tasks. A direct comparison of the tasks revealed that the rhyming task showed more activation in the posterior dorsal region of the inferior/middle frontal gyrus (BA 9/44) and in the inferior parietal lobule (BA 40). The meaning task showed more activation in the anterior ventral region of the inferior/middle frontal gyrus (BA 47) and in the superior/middle temporal gyrus (BA 22,21). These findings are consistent with previous studies in English that suggest specialization of inferior frontal regions for the access and manipulation of phonological vs. semantic representations, but also suggest that this specialization extends to the middle frontal gyrus for Chinese. These findings are also consistent with the suggestion that the left middle temporal gyrus is involved in representing semantic information and the left inferior parietal lobule is involved in mapping between orthographic and phonological representations.     

Early coding of reaching: frontal and parietal association connections of parieto-occipital cortex

The ipsilateral association connections of the cortex of the dorsal part of the rostral bank of the parieto-occipital sulcus and of the adjoining posterior part of the superior parietal lobule were studied by using different retrograde fluorescent tracers. Fluoro-Ruby, Fast blue and Diamidino yellow were injected into visual area V6A, and dorso-caudal (PMdc, F2) and dorso-rostral (PMdr, F7) premotor cortex, respectively. The parietal area of injection had been previously characterized physiologically in behaving monkeys, through a variety of oculomotor and visuomanual tasks. Area V6A is mainly linked by reciprocal projections to parietal areas 7m, MIP (medial intraparietal) and PEa, and, to a lesser extent, to frontal areas PMdr (rostral dorsal premotor cortex, F7) and PMdc (F2). All these areas project to that part of the dorsocaudal premotor cortex that has a direct access to primary motor cortex. V6A is also connected to area F5 and, to a lesser extent, to 7a, ventral (VIP) and lateral (LIP) intraparietal areas. This pattern of association connections may explain the presence of visually-related and eye-position signals in premotor cortex, as well as the influence of information concerning arm position and movement direction on V6A neural activity. Area V6A emerges as a potential 'early' node of the distributed network underlying visually-guided reaching. In this network, reciprocal association connections probably impose, through re-entrant signalling, a recursive property to the operations leading to the composition of eye and hand motor commands.     

Re-evaluating split-fovea processing in word recognition: Effects of fixation location within words

It has been claimed that word recognition is affected fundamentally by the precise location at which a word is fixated because a precise split in hemispheric processing at the point of fixation causes all letters to the left and right of fixation to project to different, contralateral hemispheres. To assess this claim, 5-letter words (and nonwords) were presented for lexical decision when participants fixated the space immediately to the left (location 1) or right (location 6) of each stimulus, or one of the four possible inter-letter spaces (locations 2-5). Fixation location was controlled using an eye-tracker linked to a fixation-contingent display and all stimuli were presented entirely within foveal vision to avoid confounding influences of extrafoveal hemispheric projections. Performance was equally poorest when fixating locations 1 and 6 (when words were shown entirely to either the right and left of fixation), intermediate for location 5, and equally superior for locations 2, 3, and 4. Additional word-specific analyses also showed no evidence of the effects of fixation location on optimal word recognition predicted by split-fovea processing. These findings suggest that, while fixation location influences word recognition, word recognition is apparently not affected by a split in hemispheric processing at the point of fixation and does not depend critically on the precise location at which a word is fixated. Implications of these findings for the role of fixation location in word recognition are discussed.     

Subcortical and cerebellar atrophy in mesial temporal lobe epilepsy revealed by automatic segmentation

PURPOSE: To determine the validity and utility of using automated subcortical segmentation to identify atrophy of the hippocampus and other subcortical and cerebellar structures in patients with mesial temporal lobe epilepsy (MTLE). METHODS: Volumetric MRIs were obtained on 21 patients with MTLE (11 right, 10 left) and 21 age- and gender-matched healthy controls. Labeling of subcortical and cerebellar structures was accomplished using automated reconstruction software (FreeSurfer). Multivariate analysis of covariance (MANCOVA) was used to explore group differences in intracranial-normalized, age-adjusted volumes and structural asymmetries. Step-wise discriminant function analysis was used to identify the linear combination of volumes that optimized classification of individual subjects. RESULTS: Results revealed the expected reduction in hippocampal volume on the side ipsilateral to the seizure focus, as well as bilateral reductions in thalamic and cerebellar gray matter volume. Analysis of structural asymmetries revealed significant asymmetry in the hippocampus and putamen in patients compared to controls. The discriminant function analysis revealed that patients with right and left MTLE were best distinguished from one another using a combination of subcortical volumes that included the right and left hippocampus and left thalamus (91-100% correct classification using cross-validation). DISCUSSION: Volumetric data obtained with automated segmentation of subcortical and cerebellar structures approximate data from previous studies based on manual tracings. Our data suggest that automated segmentation can provide a clinically useful means of evaluating the nature and extent of structural damage in patients with MTLE and may increase diagnostic classification of patients, especially when hippocampal atrophy is mild.     

Real and imaginary rotary motion processing: functional parcellation of the human parietal lobe revealed by fMRI

Functional magnetic resonance imaging was performed in 16 healthy subjects while they undertook orientation discrimination tasks of real rotating and mentally rotating alphanumeric characters. Perception of rotating and stationary abstract characters was also performed. Mental rotation and the perception of alphanumeric characters undergoing real rotation activated equivalent cortical areas, in keeping with the analogue hypothesis of mental rotation. In addition, areas along the dorsal stream, including the V5/middle temporal complex and the intraparietal sulcus (IPS), were activated during both the real and imaginary rotary conditions. Within the parietal lobe there were areas of convergence (i.e., recruited by all three motion conditions) and areas of divergence (i.e., selectively activated by a particular condition). Tasks requiring canonical-mirror orientation discrimination revealed involvement of neural substrates localized to the ventrolateral bank of the IPS. Tasks in which this judgment was not performed and during which the subject viewed rotary motion of abstract stimuli recruited activity in the medial bank of the IPS. These results indicate subspecialization of the human posterior parietal lobe according to function.     

Oral reading of words and sentences: Investigating the source of context effects

Background: Aphasic speakers' oral reading of isolated words has been widely studied, yet little is known about how contextual information influences reading ability when words are placed in sentences. Embedding words in sentences or texts has been argued to provide syntactic and/or semantic constraints on oral word reading that are unavailable in word lists, but no details are available about how such constraints might operate. The few studies that have actually compared sentence vs list reading have yielded conflicting results, and fail to show any consistent reading pattern that would predict when and why a reading advantage would arise from sentence context.Aims: We attempted to identify the pattern of aphasia/alexia that is associated with a sentence (vs list) reading advantage, and to assess the contribution of language and reading functions that might influence this context effect.Methods & Procedures: Five fluent, aphasic patients read the same 100 words (nouns, verbs, adjectives, and function words) in lists and in sentences. Patients were selected to have relatively intact sentence production ability, which has been argued to be an important element when sentence reading is superior to list reading.Outcomes & Results: Only two of the five patients showed a significant advantage for reading words in sentences, and additional analyses were carried out in an attempt to distinguish the reading patterns of the patients who showed the effect from the patterns of those who did not. The context effect exhibited by the two patients did not appear to be related to semantic influences, or to a cumulative build-up of contextual cues across words in sentences. Rather, the one finding that distinguished the two patients with significantly better reading of words in sentences compared to lists from the other patients was improved sensitivity in sentences to target words' grammatical class.Conclusions: The results indicate that good sentence production abilities are not a strong predictor that sentence reading will be enhanced relative to list reading. We propose that the sentence context effects in the two patients arose from their ability to extract information from sentences about targets' grammatical class, an ability that was not apparently shared by the other patients. Knowledge of grammatical class was argued to improve patients' reading by combining with other influences (e.g., orthographic structure, imageability) to substantially reduce the number of candidate word responses. Further specification of the source of these effects will help to identify patients who are most likely to benefit from sentence- and text-level reading treatments.     

Dissociation between reading and written spelling in two Italian children: Dyslexia without dysgraphia?

The reading and writing to dictation skills of two mentally retarded Italian boys were tested. In both cases, written spelling was greatly superior to reading, despite the fact that visual acuity was within normal limits and simple visual matching tasks were performed well. Phenotypically, these developmental cases are analogous to cases of acquired alexia without agraphia.     

Pattern of brain atrophy in elderly patients with depression revealed by voxel-based morphometry

In this study, we explored to what extent brain abnormalities can be identified in specific brain structures of patients suffering from late onset depression. We examined the structural difference in regional gray and white matter volume between 14 community-dwelling patients suffering from geriatric depression and 20 age-matched non-depressed normal subjects by voxel-based morphometry (VBM) based on magnetic resonance imaging. All subjects also underwent an extensive neuropsychological assessment. Compared with control subjects, patients with depression were impaired in measures of verbal and visual memory, construction, executive ability, and information-processing speed. VBM of gray matter revealed a significant decrease of volume in the right rostral hippocampus, in the right amygdala and in the medial orbito-frontal cortex (gyrus rectus) bilaterally. In the correlation analysis of gray matter volume with the score of the geriatric depression scale, we observed a negative correlation with the medial orbito-frontal cortex (gyrus rectus) bilaterally. There were no differences in white matter volumes between patients with depression and healthy control subjects. The most important limitation of this study was sample size. A larger sample size may have improved detection of changes not reaching significance. Furthermore, our results may not be generalizable across depression severity or to hospitalized patients. The findings are consistent with our hypothesis that depression in the elderly is associated with local gray matter dysfunction.     

Bee but not be: oral reading of single words in aphasia and alexia.

Three studies are reported of the oral reading ability of language-impaired patients. Part of speech and picturability are shown to contribute to a word's readability. In addition, words whose referents can be easily manipulated (operative nouns) prove easier to read than matched words whose referents are relatively figurative.Comparisons of reading and naming ability were drawn between aphasic patients and patients clinically diagnosed as alexic. These comparisons suggest that for most aphasics reading and naming are mediated by separated mechanisms, with the ability to read being relatively spared; that alexics without agraphia achieve most success with short words, irrespective of part of speech; that alexics with agraphia achieve most success with picturable nouns, even when these contain more letters. In alexia with agraphia, reading and naming occur at a comparable level and may be mediated by identical or similar cognitive mechanisms.     

Seeing words in context: the interaction of lexical and sentence level information during reading

The ERP experiment reported here addresses some outstanding questions regarding word processing in sentential contexts: (1) Does only the 'message-level' representation (the representation of sentence meaning combining lexico-semantic and syntactic constraints) affect the processing of the incoming word [J. Exp. Psychol.: Learn. Mem. Cogn. 20 (1994) 92]? (2) Is lexically specified semantic relatedness between multiple words the primary factor instead [J. Exp. Psychol.: Learn. Mem. Cogn. 15 (1989) 791]? (3) Alternatively, do word and sentence level information interact during sentence comprehension? Volunteers read sentences (e.g. Dutch sentences resembling The javelin was by the athletes...) in which the (passive) syntactic structure and the semantic content of the lexical items together created a strong expectation of a specific final word (e.g., thrown), but also sentences in which the syntactic structure was changed from passive to active (e.g. Dutch sentences resembling The javelin has the athletes...), which altered the message level constraint substantially and strongly reduced the expectation of any particular completion. Half of the sentences ended in a final word with a good lexico-semantic fit relative to the preceding content words (e.g. thrown, fitting well with the preceding javelin and athletes). This creates very plausible sentences in the strong constraint context but semantically anomalous ones in the weakly constraining context (e.g., The javelin has the athletes thrown). In the other half the final word had a poor lexico-semantic fit (e.g., summarized that does not fit at all with javelin and athletes). Good lexico-semantic fit endings showed no difference in N400 amplitude in the strong and weak message-level constraint sentences, despite the fact that the latter were semantically anomalous. This result suggests that lexico-semantic fit can be more important for word processing than the meaning of the sentence as determined by the syntactic structure, at least initially. These conditions did differ, however, in the region of the P600 where the anomalous weak constraint version was much more positive, a pattern usually seen with ungrammatical sentences. The processing of poor lexico-semantic fit words showed a quite different pattern; in both strong and weak constraint sentences they elicited a substantial N400 effect, but N400-amplitude was significantly more negative following strong constraint contexts, even though both sentence contexts were equivalently anomalous. Taken together, these findings provide evidence for the importance of both message-level and lexico-semantic information during sentence comprehension. The implications for theories of sentence interpretation are discussed and an extension of the message-based hypothesis will be proposed.     

Conceptual processing in music as revealed by N400 effects on words and musical targets

The cognitive processing of concepts, that is, abstract general ideas, has been mostly studied with language. However, other domains, such as music, can also convey concepts. Koelsch et al. [Koelsch, S., Kasper, E., Sammler, D., Schulze, K., Gunter, T., & Friederici, A. D. Music, language and meaning: Brain signatures of semantic processing. Nature Neuroscience, 7, 302-307, 2004] showed that 10 sec of music can influence the semantic processing of words. However, the length of the musical excerpts did not allow the authors to study the effect of words on musical targets. In this study, we decided to replicate Koelsch et al. findings using 1-sec musical excerpts (Experiment 1). This allowed us to study the reverse influence, namely, of a linguistic context on conceptual processing of musical excerpts (Experiment 2). In both experiments, we recorded behavioral and electrophysiological responses while participants were presented 50 related and 50 unrelated pairs (context/target). Experiments 1 and 2 showed a larger N400 component of the event-related brain potentials to targets following a conceptually unrelated compared to a related context. The presence of an N400 effect with musical targets suggests that music may convey concepts. The relevance of these results for the comprehension of music as a structured set of conceptual units and for the domain specificity of the mechanisms underlying N400 effects are discussed.     

Neuroimaging studies of word and pseudoword reading: consistencies,inconsistencies, and limitations

Several functional neuroimaging studies have compared words and pseudowords to test different cognitive models of reading. There are difficulties with this approach, however, because cognitive models do not make clear-cut predictions at the neural level. Therefore, results can only be interpreted on the basis of prior knowledge of cognitive anatomy. Furthermore, studies comparing words and pseudowords have produced inconsistent results. The inconsistencies could reflect false-positive results due to the low statistical thresholds applied or confounds from nonlexical aspects of the stimuli. Alternatively, they may reflect true effects that are inconsistent across subjects; dependent on experimental parameters such as stimulus rate or duration; or not replicated across studies because of insufficient statistical power. In this fMRI study, we investigate consistent and inconsistent differences between word and pseudoword reading in 20 subjects, and distinguish between effects associated with increases and decreases in activity relative to fixation. In addition, the interaction of word type with stimulus duration is explored. We find that words and pseudowords activate the same set of regions relative to fixation, and within this system, there is greater activation for pseudowords than words in the left frontal operculum, left posterior inferior temporal gyrus, and the right cerebellum. The only effects of words relative to pseudowords consistent over subjects are due to decreases in activity for pseudowords relative to fixation; and there are no significant interactions between word type and stimulus duration. Finally, we observe inconsistent but highly significant effects of word type at the individual subject level. These results (i) illustrate that pseudowords place increased demands on areas that have previously been linked to lexical retrieval, and (ii) highlight the importance of including one or more baselines to qualify word type effects. Furthermore, (iii) they suggest that inconsistencies observed in the previous literature may result from effects arising from a small number of subjects only.     

Functional neuroanatomy of English word reading in early bilingual and monolingual adults

Skilled reading is important in daily life. While the understanding of the neurofunctional organization of this uniquely human skill has advanced significantly, it does not take into consideration the common bilingual experiences around the world. To examine the role of early bilingualism on the neural substrates supporting English word processing, we compared brain activity, as well as functional connectivity, in Spanish‐English early bilingual adults (N = 25) and English monolingual adults (N = 33) during single‐word processing. Activation analysis revealed no significant differences between the two groups. A seed‐to‐voxel analysis using eight a priori selected seed‐regions (placed in regions known to be involved in reading) revealed relatively stronger functional connectivity in bilinguals between two sets of regions: left superior temporal gyrus seed positively with left lingual gyrus and left middle frontal gyrus seed negatively with left anterior cingulate cortex. Together these results suggest that an early Spanish‐English bilingual experience does not modulate local brain activity for English word reading. It does, however, have some influence on the functional intercommunication between brain regions during reading, specifically in two regions associated with reading, which are functionally connected to those inside and outside of the reading network. We conclude that brain regions involved in processing English words are not that different in Spanish‐English early bilingual adults relative to monolingual adult users of English.