Deficits on self ordered tasks associated with hyperostosis frontalis interna

A 74 year old patient, EW, with dorsolateral frontal cortical compression due to hyperostosis frontalis interna, in the absence of the Morgagni or Stewart-Morel syndromes, is described. In addition to conventional neuropsychological measures EW was administered one nonspatial and two spatial self ordered working memory tasks, as well as a standard measure of fluid intelligence or g. She showed impaired performance on all three self ordered working memory tasks compared with a normal control group of 10 subjects matched for age, education, sex, and IQ. By contrast, her performance on the fluid intelligence test was comparable with that of the controls. It is concluded that the compression of dorsolateral frontal cortex accompanying hyperostosis frontalis interna may produce selective cognitive impairment.

Brain activity during the encoding, retention, and retrieval of stimulus representations

Studies of delayed nonmatching-to-sample (DNMS) performance following lesions of the monkey cortex have revealed a critical circuit of brain regions involved in forming memories and retaining and retrieving stimulus representations. Using event-related functional magnetic resonance imaging (fMRI), we measured brain activity in 10 healthy human participants during performance of a trial-unique visual DNMS task using novel barcode stimuli. The event-related design enabled the identification of activity during the different phases of the task (encoding, retention, and retrieval). Several brain regions identified by monkey studies as being important for successful DNMS performance showed selective activity during the different phases, including the mediodorsal thalamic nucleus (encoding), ventrolateral prefrontal cortex (retention), and perirhinal cortex (retrieval). Regions showing sustained activity within trials included the ventromedial and dorsal prefrontal cortices and occipital cortex. The present study shows the utility of investigating performance on tasks derived from animal models to assist in the identification of brain regions involved in human recognition memory.

Auditory context effects in picture naming investigated with event-related fMRI

Naming an object entails a number of processing stages, including retrieval of a target lexical concept and encoding of its phonological word form. We investigated these stages using the picture-word interference task in an fMRI experiment. Participants named target pictures in the presence of auditorily presented semantically related, phonologically related, or unrelated distractor words or in isolation. We observed BOLD signal changes in left-hemisphere regions associated with lexical-conceptual and phonological processing, including the midto-posterior lateral temporal cortex. However, these BOLD responses manifested as signal reductions for all distractor conditions relative to naming alone. Compared with unrelated words, phonologically related distractors showed further signal reductions, whereas only the pars orbitalis of the left inferior frontal cortex showed a selective reduction in response in the semantic condition. We interpret these findings as indicating that the word forms of lexical competitors are phonologically encoded and that competition during lexical selection is reduced by phonologically related distractors. Since the extended nature of auditory presentation requires a large portion of a word to be presented before its meaning is accessed, we attribute the BOLD signal reductions observed for semantically related and unrelated words to lateral inhibition mechanisms engaged after target name selection has occurred, as has been proposed in some production models.

Memory strength effects in fMRI studies: A matter of confidence

To investigate potentially dissociable recognition memory responses in the hippocampus and perirhinal cortex, fMRI studies have often used confidence ratings as an index of memory strength. Confidence ratings, although correlated with memory strength, also reflect sources of variability, including task-irrelevant item effects and differences both within and across individuals in terms of applying decision criteria to separate weak from strong memories. We presented words one, two, or four times at study in each of two different conditions, focused and divided attention, and then conducted separate fMRI analyses of correct old responses on the basis of subjective confidence ratings or estimates from single- versus dual-process recognition memory models. Overall, the effect of focussing attention on spaced repetitions at study manifested as enhanced recognition memory performance. Confidence- versus model-based analyses revealed disparate patterns of hippocampal and perirhinal cortex activity at both study and test and both within and across hemispheres. The failure to observe equivalent patterns of activity indicates that fMRI signals associated with subjective confidence ratings reflect additional sources of variability. The results are consistent with predictions of single-process models of recognition memory.

fMRI evidence of word frequency and strength effects in recognition memory

We used event-related fMRI to investigate the neural correlates of encoding strength and word frequency effects in recognition memory. At test, participants made Old/New decisions to intermixed low (LF) and high frequency (HF) words that had been presented once or twice at study and to new, unstudied words. The Old/New effect for all hits vs. correctly rejected unstudied words was associated with differential activity in multiple cortical regions, including the anterior medial temporal lobe (MTL), hippocampus, left lateral parietal cortex and anterior left inferior prefrontal cortex (LIPC). Items repeated at study had superior hit rates (HR) compared to items presented once and were associated with reduced activity in the right anterior MTL. By contrast, other regions that had shown conventional Old/New effects did not demonstrate modulation according to memory strength. A mirror effect for word frequency was demonstrated, with the LF word HR advantage associated with increased activity in the left lateral temporal cortex. However, none of the regions that had demonstrated Old/New item retrieval effects showed modulation according to word frequency. These findings are interpreted as supporting single-process memory models proposing a unitary strength-like memory signal and models attributing the LF word HR advantage to the greater lexico-semantic context-noise associated with HF words due to their being experienced in many pre-experimental contexts.

fMRI evidence of word frequency and strength effects during episodic memory encoding

Word frequency (WF) and strength effects are two important phenomena associated with episodic memory. The former refers to the superior hit-rate (HR) for low (LF) compared to high frequency (HF) words in recognition memory, while the latter describes the incremental effect(s) upon HRs associated with repeating an item at study. Using the "subsequent memory" method with event-related fMRI, we tested the attention-at-encoding (AE) [M. Glanzer, J.K. Adams, The mirror effect in recognition memory: data and theory, J. Exp. Psychol.: Learn Mem. Cogn. 16 (1990) 5-16] explanation of the WF effect. In addition to investigating encoding strength, we addressed if study involves accessing prior representations of repeated items via the same mechanism as that at test [J.L. McClelland, M. Chappell, Familiarity breeds differentiation: a subjective-likelihood approach to the effects of experience in recognition memory, Psychol. Rev. 105 (1998) 724-760], entailing recollection [K.J. Malmberg, J.E. Holden, R.M. Shiffrin, Modeling the effects of repetitions, similarity, and normative word frequency on judgments of frequency and recognition memory, J. Exp. Psychol.: Learn Mem. Cogn. 30 (2004) 319-331] and whether less processing effort is entailed for encoding each repetition [M. Cary, L.M. Reder, A dual-process account of the list-length and strength-based mirror effects in recognition, J. Mem. Lang. 49 (2003) 231-248]. The increased BOLD responses observed in the left inferior prefrontal cortex (LIPC) for the WF effect provide support for an AE account. Less effort does appear to be required for encoding each repetition of an item, as reduced BOLD responses were observed in the LIPC and left lateral temporal cortex; both regions demonstrated increased responses in the conventional subsequent memory analysis. At test, a left lateral parietal BOLD response was observed for studied versus unstudied items, while only medial parietal activity was observed for repeated items at study, indicating that accessing prior representations at encoding does not necessarily occur via the same mechanism as that at test, and is unlikely to involve a conscious recall-like process such as recollection. This information may prove useful for constraining cognitive theories of episodic memory.

Negative priming in naming of categorically related objects: An fMRI study

Ignoring an object slows subsequent naming responses to it, a phenomenon known as negative priming (NP). A central issue in NP research concerns the level of representation at which the effect occurs. As object naming is typically considered to involve access to abstract semantic representations, Tipper 1985 proposed that the NP effect occurred at this level of processing, and other researchers supported this proposal by demonstrating a similar result with categorically related objects (e.g., Allport et al., 1985; Murray, 1995), an effect referred to as semantic NP. However, objects within categories share more physical or structural features than objects from different categories. Consequently, the NP effect observed with categorically related objects might occur at a structural rather than semantic level of representation. We used event related fMRI interleaving overt object naming and image acquisition to demonstrate for the first time that the semantic NP effect activates the left posterior-mid fusiform and insular-opercular cortices. Moreover, both naming latencies and left posterior-mid fusiform cortex responses were influenced by the structural similarity of prime-probe object pairings in the categorically related condition, increasing with the number of shared features. None of the cerebral regions activated in a previous fMRI study of the identity NP effect (de Zubicaray et al., 2006) showed similar activation during semantic NP, including the left anterolateral temporal cortex, a region considered critical for semantic processing. The results suggest that the identity and semantic NP effects differ with respect to their neural mechanisms, and the label "semantic NP" might be a misnomer. We conclude that the effect is most likely the result of competition between structurally similar category exemplars that determines the efficiency of object name retrieval.

Orthographic/phonological facilitation of naming responses in the picture-word task: An event-related fMRI study using overt vocal responding

In the picture-word interference task, naming responses are facilitated when a distractor word is orthographically and phonologically related to the depicted object as compared to an unrelated word. We used event-related functional magnetic resonance imaging (fMRI) to investigate the cerebral hemodynamic responses associated with this priming effect. Serial (or independent-stage) and interactive models of word production that explicitly account for picture-word interference effects assume that the locus of the effect is at the level of retrieving phonological codes, a role attributed recently to the left posterior superior temporal cortex (Wernicke's area). This assumption was tested by randomly presenting participants with trials from orthographically related and unrelated distractor conditions and acquiring image volumes coincident with the estimated peak hemodynamic response for each trial. Overt naming responses occurred in the absence of scanner noise, allowing reaction time data to be recorded. Analysis of this data confirmed the priming effect. Analysis of the fMRI data revealed blood oxygen level-dependent signal decreases in Wernicke's area and the right anterior temporal cortex, whereas signal increases were observed in the anterior cingulate, the right orbitomedial prefrontal, somatosensory, and inferior parietal cortices, and the occipital lobe. The results are interpreted as supporting the locus for the facilitation effect as assumed by both classes of theoretical model of word production. In addition, our results raise the possibilities that, counterintuitively, picture-word interference might be increased by the presentation of orthographically related distractors, due to competition introduced by activation of phonologically related word forms, and that this competition requires inhibitory processes to be resolved. The priming effect is therefore viewed as being sufficient to offset the increased interference. We conclude that information from functional imaging studies might be useful for constraining theoretical models of word production.

Pre-experimental familiarization increases hippocampal activity for both targets and lures in recognition memory: An fMRI study

In the present study, items pre-exposed in a familiarization series were included in a list discrimination task to manipulate memory strength. At test, participants were required to discriminate strong targets and strong lures from weak targets and new lures. This resulted in a concordant pattern of increased "old" responses to strong targets and lures. Model estimates attributed this pattern to either equivalent increases in memory strength across the two types of items (unequal variance signal detection model) or equivalent increases in both familiarity and recollection (dual process signal detection [DPSD] model). Hippocampal activity associated with strong targets and lures showed equivalent increases compared with missed items. This remained the case when analyses were restricted to high-confidence responses considered by the DPSD model to reflect predominantly recollection. A similar pattern of activity was observed in parahippocampal cortex for high-confidence responses. The present results are incompatible with "noncriterial" or "false" recollection being reflected solely in inflated DPSD familiarity estimates and support a positive correlation between hippocampal activity and memory strength irrespective of the accuracy of list discrimination, consistent with the unequal variance signal detection model account.

Independent distractor frequency and age-of-acquisition dffects in picture-word interference: FMRI evidence for post-lexical and lexical accounts according to distractor type

In two fMRI experiments, participants named pictures with superimposed distractors that were high or low in frequency or varied in terms of age of acquisition. Pictures superimposed with low-frequency words were named more slowly than those superimposed with high-frequency words, and late-acquired words interfered with picture naming to a greater extent than early-acquired words. The distractor frequency effect (Experiment 1) was associated with increased activity in left premotor and posterior superior temporal cortices, consistent with the operation of an articulatory response buffer and verbal selfmonitoring system. Conversely, the distractor age-of-acquisition effect (Experiment 2) was associated with increased activity in the left middle and posterior middle temporal cortex, consistent with the operation of lexical level processes such as lemma and phonological word form retrieval. The spatially dissociated patterns of activity across the two experiments indicate that distractor effects in picture-word interference may occur at lexical or postlexical levels of processing in speech production.

The semantic interference effect in the picture-word paradigm: An event-related fMRI study employing overt responses

We used event-related functional magnetic resonance imaging (fMRI) to investigate neural responses associated with the semantic interference (SI) effect in the picture-word task. Independent stage models of word production assume that the locus of the SI effect is at the conceptual processing level (Levelt et al. [1999]: Behav Brain Sci 22:1-75), whereas interactive models postulate that it occurs at phonological retrieval (Starreveld and La Heij [1996]: J Exp Psychol Learn Mem Cogn 22:896-918). In both types of model resolution of the SI effect occurs as a result of competitive, spreading activation without the involvement of inhibitory links. These assumptions were tested by randomly presenting participants with trials from semantically-related and lexical control distractor conditions and acquiring image volumes coincident with the estimated peak hemodynamic response for each trial. Overt vocalization of picture names occurred in the absence of scanner noise, allowing reaction time (RT) data to be collected. Analysis of the RT data confirmed the SI effect. Regions showing differential hemodynamic responses during the SI effect included the left mid section of the middle temporal gyrus, left posterior superior temporal gyrus, left anterior cingulate cortex, and bilateral orbitomedial prefrontal cortex. Additional responses were observed in the frontal eye fields, left inferior parietal lobule, and right anterior temporal and occipital cortex. The results are interpreted as indirectly supporting interactive models that allow spreading activation between both conceptual processing and phonological retrieval levels of word production. In addition, the data confirm that selective attention/response suppression has a role in resolving the SI effect similar to the way in which Stroop interference is resolved. We conclude that neuroimaging studies can provide information about the neuroanatomical organization of the lexical system that may prove useful for constraining theoretical models of word production.

Cerebral regions associated with verbal response initiation, suppression and strategy use

Cerebral activation associated with performance on a novel task involving two conditions was investigated with functional magnetic resonance imaging (fMRI). In the response initiation condition, subjects nominated the general superordinate category to which each of a series of exemplars (concrete nouns) belonged. In the response suppression condition, subjects were required to nominate a general superordinate category to which each exemplar did not belong, with the instruction that they were not to nominate the same category response twice in a row. Both conditions produced distinct patterns of activation relative to an articulation control condition employing identical stimuli. When initiation and suppression conditions were directly compared, response suppression produced activation in the right frontal pole, orbital frontal cortex and anterior cingulate, left dorsolateral prefrontal cortex and posterior cingulate, and bilaterally in the precuneus, visual association cortex and cerebellum. Response latencies were significantly longer in the suppression condition. Two broadly-defined strategies associated with the correct production of words during the suppression condition were a self-ordered selection from among the superordinate categories identified during the first section of the task and the generation of novel category responses. The neuroanatomical correlates of response initiation, suppression and strategy use are discussed, as are the respective roles of response suppression and strategy generation.

Development of brain structural connectivity between ages 12 and 30: A 4-Tesla diffusion imaging study in 439 adolescents and adults

Understanding how the brain matures in healthy individuals is critical for evaluating deviations from normal development in psychiatric and neurodevelopmental disorders. The brain's anatomical networks are profoundly re-modeled between childhood and adulthood, and diffusion tractography offers unprecedented power to reconstruct these networks and neural pathways in vivo. Here we tracked changes in structural connectivity and network efficiency in 439 right-handed individuals aged 12 to 30 (211 female/126 male adults, mean age=23.6, SD=2.19; 31 female/24 male 12 year olds, mean age=12.3, SD=0.18; and 25 female/22 male 16 year olds, mean age=16.2, SD=0.37). All participants were scanned with high angular resolution diffusion imaging (HARDI) at 4 T. After we performed whole brain tractography, 70 cortical gyral-based regions of interest were extracted from each participant's co-registered anatomical scans. The proportion of fiber connections between all pairs of cortical regions, or nodes, was found to create symmetric fiber density matrices, reflecting the structural brain network. From those 70 × 70 matrices we computed graph theory metrics characterizing structural connectivity. Several key global and nodal metrics changed across development, showing increased network integration, with some connections pruned and others strengthened. The increases and decreases in fiber density, however, were not distributed proportionally across the brain. The frontal cortex had a disproportionate number of decreases in fiber density while the temporal cortex had a disproportionate number of increases in fiber density. This large-scale analysis of the developing structural connectome offers a foundation to develop statistical criteria for aberrant brain connectivity as the human brain matures.

Development of insula connectivity between ages 12 and 30 revealed by high angular resolution diffusion imaging

The insula, hidden deep within the Sylvian fissures, has proven difficult to study from a connectivity perspective. Most of our current information on the anatomical connectivity of the insula comes from studies of nonhuman primates and post mortem human dissections. To date, only two neuroimaging studies have successfully examined the connectivity of the insula. Here we examine how the connectivity of the insula develops between ages 12 and 30, in 307 young adolescent and adult subjects scanned with 4-Tesla high angular resolution diffusion imaging (HARDI). The density of fiber connections between the insula and the frontal and parietal cortex decreased with age, but the connection density between the insula and the temporal cortex generally increased with age. This trajectory is in line with well-known patterns of cortical development in these regions. In addition, males and females showed different developmental trajectories for the connection between the left insula and the left precentral gyrus. The insula plays many different roles, some of them affected in neuropsychiatric disorders; this information on the insula's connectivity may help efforts to elucidate mechanisms of brain disorders in which it is implicated.

Sex differences in the human connectome: 4-Tesla high angular resolution diffusion imaging (HARDI) tractography in 234 young adult twins

Cortical connectivity is associated with cognitive and behavioral traits that are thought to vary between sexes. Using high-angular resolution diffusion imaging at 4 Tesla, we scanned 234 young adult twins and siblings (mean age: 23.4 2.0 SD years) with 94 diffusion-encoding directions. We applied a novel Hough transform method to extract fiber tracts throughout the entire brain, based on fields of constant solid angle orientation distribution functions (ODFs). Cortical surfaces were generated from each subject's 3D T1-weighted structural MRI scan, and tracts were aligned to the anatomy. Network analysis revealed the proportions of fibers interconnecting 5 key subregions of the frontal cortex, including connections between hemispheres. We found significant sex differences (147 women/87 men) in the proportions of fibers connecting contralateral superior frontal cortices. Interhemispheric connectivity was greater in women, in line with long-standing theories of hemispheric specialization. These findings may be relevant for ongoing studies of the human connectome.