Benign Epilepsy with Centro-temporal Spikes: Spike Triggered fMRI Shows Somato-sensory Cortex Activity

Summary:  Objective: We performed spike triggered functional MRI (fMRI) in a 12 year old girl with Benign Epilepsy with Centro-temporal Spikes (BECTS) and left-sided spikes. Our aim was to demonstrate the cerebral origin of her interictal spikes. Methods: EEG was recorded within the 3 Tesla MRI. Whole brain fMRI images were acquired, beginning 2–3 seconds after spikes. Baseline fMRI images were acquired when there were no spikes for 20 seconds. Image sets were compared with the Student's t-test. Results: Ten spike and 20 baseline brain volumes were analysed. Focal activiation was seen in the inferior left sensorimotor cortex near the face area. The anterior cingulate was more active during baseline than spikes. Conclusions: Left sided epileptiform activity in this patient with BECTS is associated with fMRI activation in the left face region of the somatosensory cortex, which would be consistent with the facial sensorimotor involvement in BECT seizures. The presence of BOLD signal change in other regions raises the possibility that the scalp recorded field of this patient with BECTs may reflect electrical change in more than one brain region.

Semantic interference in object naming : an fMRI study of the postcue naming paradigm

It is well established that the time to name target objects can be influenced by the presence of categorically related versus unrelated distractor items. A variety of paradigms have been developed to determine the level at which this semantic interference effect occurs in the speech production system. In this study, we investigated one of these tasks, the postcue naming paradigm, for the first time with fMRI. Previous behavioural studies using this paradigm have produced conflicting interpretations of the processing level at which the semantic interference effect takes place, ranging from pre- to post-lexical. Here we used fMRI with a sparse, event-related design to adjudicate between these competing explanations. We replicated the behavioural postcue naming effect for categorically related target/distractor pairs, and observed a corresponding increase in neuronal activation in the right lingual and fusiform gyri-regions previously associated with visual object processing and colour-form integration. We interpret these findings as being consistent with an account that places the semantic interference effect in the postcue paradigm at a processing level involving integration of object attributes in short-term memory.

Semantic context and visual feature effects in object naming : an fMRI study using arterial spin labeling

Previous behavioral studies reported a robust effect of increased naming latencies when objects to be named were blocked within semantic category, compared to items blocked between category. This semantic context effect has been attributed to various mechanisms including inhibition or excitation of lexico-semantic representations and incremental learning of associations between semantic features and names, and is hypothesized to increase demands on verbal self-monitoring during speech production. Objects within categories also share many visual structural features, introducing a potential confound when interpreting the level at which the context effect might occur. Consistent with previous findings, we report a significant increase in response latencies when naming categorically related objects within blocks, an effect associated with increased perfusion fMRI signal bilaterally in the hippocampus and in the left middle to posterior superior temporal cortex. No perfusion changes were observed in the middle section of the left middle temporal cortex, a region associated with retrieval of lexical-semantic information in previous object naming studies. Although a manipulation of visual feature similarity did not influence naming latencies, we observed perfusion increases in the perirhinal cortex for naming objects with similar visual features that interacted with the semantic context in which objects were named. These results provide support for the view that the semantic context effect in object naming occurs due to an incremental learning mechanism, and involves increased demands on verbal self-monitoring.

Functional neuroanatomy of auditory mismatch processing : an event-related fMRI study of duration-deviant oddballs

This study was designed to identify the neural networks underlying automatic auditory deviance detection in 10 healthy subjects using functional magnetic resonance imaging. We measured blood oxygenation level-dependent contrasts derived from the comparison of blocks of stimuli presented as a series of standard tones (50 ms duration) alone versus blocks that contained rare duration-deviant tones (100 ms) that were interspersed among a series of frequent standard tones while subjects were watching a silent movie. Possible effects of scanner noise were assessed by a “no tone” condition. In line with previous positron emission tomography and EEG source modeling studies, we found temporal lobe and prefrontal cortical activation that was associated with auditory duration mismatch processing. Data were also analyzed employing an event-related hemodynamic response model, which confirmed activation in response to duration-deviant tones bilaterally in the superior temporal gyrus and prefrontally in the right inferior and middle frontal gyri. In line with previous electrophysiological reports, mismatch activation of these brain regions was significantly correlated with age. These findings suggest a close relationship of the event-related hemodynamic response pattern with the corresponding electrophysiological activity underlying the event-related “mismatch negativity” potential, a putative measure of auditory sensory memory.

The neural correlates of justified and unjustified killing: An fMRI study

Despite moral prohibitions on hurting other humans, some social contexts allow for harmful actions such as the killing of others. One example is warfare, where killing enemy soldiers is seen as morally justified. Yet, the neural underpinnings distinguishing between justified and unjustified killing are largely unknown. To improve understanding of the neural processes involved in justified and unjustified killing, participants had to imagine being the perpetrator whilst watching “first-person perspective” animated videos where they shot enemy soldiers (‘justified violence’) and innocent civilians (‘unjustified violence’). When participants imagined themselves shooting civilians compared to soldiers, greater activation was found in the lateral orbitofrontal cortex (OFC). Regression analysis revealed that the more guilt participants felt about shooting civilians, the greater the response in the lateral OFC. Effective connectivity analyses further revealed an increased coupling between lateral OFC and the tempoparietal junction (TPJ) when shooting civilians. The results show that the neural mechanisms typically implicated with harming others, such as the OFC, become less active when the violence against a particular group is seen as justified. This study therefore provides unique insight into how normal individuals can become aggressors in specific situations.

Quantifying the heritability of task-related brain activation and performance during the N-back working memory task: A twin fMRI study

Working memory-related brain activation has been widely studied, and impaired activation patterns have been reported for several psychiatric disorders. We investigated whether variation in N-back working memory brain activation is genetically influenced in 60 pairs of twins, (29 monozygotic (MZ), 31 dizygotic (DZ); mean age 24.4 ± 1.7S.D.). Task-related brain response (BOLD percent signal difference of 2 minus 0-back) was measured in three regions of interest. Although statistical power was low due to the small sample size, for middle frontal gyrus, angular gyrus, and supramarginal gyrus, the MZ correlations were, in general, approximately twice those of the DZ pairs, with non-significant heritability estimates (14-30%) in the low-moderate range. Task performance was strongly influenced by genes (57-73%) and highly correlated with cognitive ability (0.44-0.55). This study, which will be expanded over the next 3 years, provides the first support that individual variation in working memory-related brain activation is to some extent influenced by genes.

Neural correlates of semantic priming for ambiguous words: An event-related fMRI study

We investigated the neural correlates of semantic priming by using event-related fMRI to record blood oxygen level dependent (BOLD) responses while participants performed speeded lexical decisions (word/nonword) on visually presented related versus unrelated prime-target pairs. A long stimulus onset asynchrony of 1000 ms was employed, which allowed for increased controlled processing and selective frequency-based ambiguity priming. Conditions included an ambiguous word prime (e.g. bank) and a target related to its dominant (e.g. money) or subordinate meaning (e.g. river). Compared to an unrelated condition, primed dominant targets were associated with increased activity in the LIFG, the right anterior cingulate and superior temporal gyrus, suggesting postlexical semantic integrative mechanisms, while increased right supramarginal activity for the unrelated condition was consistent with expectancy based priming. Subordinate targets were not primed and were associated with reduced activity primarily in occipitotemporal regions associated with word recognition, which may be consistent with frequency-based meaning suppression. These findings provide new insights into the neural substrates of semantic priming and the functional-anatomic correlates of lexical ambiguity suppression mechanisms.

Dopaminergic neuromodulation of semantic processing: A 4-T fMRI study with levodopa

There is emerging evidence that alterations in dopaminergic transmission can influence semantic processing, yet the neural mechanisms involved are unknown. The influence of levodopa (L-DOPA) on semantic priming was investigated in healthy individuals (n=20) using event-related functional magnetic resonance imaging with a randomized, double-blind crossover design. Critical prime-target pairs consisted of a lexical ambiguity prime and 1) a target related to the dominant meaning of the prime (e.g., bank-money), 2) a target related to the subordinate meaning (e.g., fence-sword), or 3) an unrelated target (e.g., ball-desk). Behavioral data showed that both dominant and subordinate meanings were primed on placebo. In contrast, there was preserved priming of dominant meanings and no significant priming of subordinate meanings on L-DOPA, the latter associated with decreased anterior cingulate and dorsal prefrontal cortex activity. Dominant meaning activation on L-DOPA was associated with increased activity in the left rolandic operculum and left middle temporal gyrus. These findings suggest that L-DOPA enhances frequency-based semantic focus via prefrontal and temporal modulation of automatic semantic priming and through engagement of anterior cingulate mechanisms supporting attentional/controlled priming.

A perfusion fMRI investigation of thematic and categorical context effects in the spoken production of object names

The context in which objects are presented influences the speed at which they are named. We employed the blocked cyclic naming paradigm and perfusion functional magnetic resonance imaging (fMRI) to investigate the mechanisms responsible for interference effects reported for thematicallyand categorically related compared to unrelated contexts. Naming objects in categorically homogeneous contexts induced a significant interference effect that accumulated from the second cycle onwards. This interference effect was associated with significant perfusion signal decreases in left middle and posterior lateral temporal cortex and the hippocampus. By contrast, thematically homogeneous contexts facilitated naming latencies significantly in the first cycle and did not differ from heterogeneous contexts thereafter, nor were they associated with any perfusion signal changes compared to heterogeneous contexts. These results are interpreted as being consistent with an account in which the interference effect both originates and has its locus at the lexical level, with an incremental learning mechanism adapting the activation levels of target lexical representations following access. We discuss the implications of these findings for accounts that assume thematic relations can be active lexical competitors or assume mandatory involvement of top-down control mechanisms in interference effects during naming.

Top-down influences on lexical selection during spoken word production: A 4T fMRI investigation of refractory effects in picture naming

Spoken word production is assumed to involve stages of processing in which activation spreads through layers of units comprising lexical-conceptual knowledge and their corresponding phonological word forms. Using high-field (4T) functional magnetic resonance imagine (fMRI), we assessed whether the relationship between these stages is strictly serial or involves cascaded-interactive processing, and whether central (decision/control) processing mechanisms are involved in lexical selection. Participants performed the competitor priming paradigm in which distractor words, named from a definition and semantically related to a subsequently presented target picture, slow picture-naming latency compared to that with unrelated words. The paradigm intersperses two trials between the definition and the picture to be named, temporally separating activation in the word perception and production networks. Priming semantic competitors of target picture names significantly increased activation in the left posterior temporal cortex, and to a lesser extent the left middle temporal cortex, consistent with the predictions of cascaded-interactive models of lexical access. In addition, extensive activation was detected in the anterior cingulate and pars orbitalis of the inferior frontal gyrus. The findings indicate that lexical selection during competitor priming is biased by top-down mechanisms to reverse associations between primed distractor words and target pictures to select words that meet the current goal of speech.

Support for an auto-associative model of spoken cued recall: Evidence from fMRI

Cued recall and item recognition are considered the standard episodic memory retrieval tasks. However, only the neural correlates of the latter have been studied in detail with fMRI. Using an event-related fMRI experimental design that permits spoken responses, we tested hypotheses from an auto-associative model of cued recall and item recognition [Chappell, M., & Humphreys, M. S. (1994). An auto-associative neural network for sparse representations: Analysis and application to models of recognition and cued recall. Psychological Review, 101, 103-128]. In brief, the model assumes that cues elicit a network of phonological short term memory (STM) and semantic long term memory (LTM) representations distributed throughout the neocortex as patterns of sparse activations. This information is transferred to the hippocampus which converges upon the item closest to a stored pattern and outputs a response. Word pairs were learned from a study list, with one member of the pair serving as the cue at test. Unstudied words were also intermingled at test in order to provide an analogue of yes/no recognition tasks. Compared to incorrectly rejected studied items (misses) and correctly rejected (CR) unstudied items, correctly recalled items (hits) elicited increased responses in the left hippocampus and neocortical regions including the left inferior prefrontal cortex (LIPC), left mid lateral temporal cortex and inferior parietal cortex, consistent with predictions from the model. This network was very similar to that observed in yes/no recognition studies, supporting proposals that cued recall and item recognition involve common rather than separate mechanisms.

Perfusion fMRI evidence for priming of shared feature-to-lexical connections during cumulative semantic interference in spoken word production

The speed at which target pictures are named increases monotonically as a function of prior retrieval of other exemplars of the same semantic category and is unaffected by the number of intervening items. This cumulative semantic interference effect is generally attributed to three mechanisms: shared feature activation, priming and lexical-level selection. However, at least two additional mechanisms have been proposed: (1) a 'booster' to amplify lexical-level activation and (2) retrieval-induced forgetting (RIF). In a perfusion functional Magnetic Resonance Imaging (fMRI) experiment, we tested hypotheses concerning the involvement of all five mechanisms. Our results demonstrate that the cumulative interference effect is associated with perfusion signal changes in the left perirhinal and middle temporal cortices that increase monotonically according to the ordinal position of exemplars being named. The left inferior frontal gyrus (LIFG) also showed significant perfusion signal changes across ordinal presentations; however, these responses did not conform to a monotonically increasing function. None of the cerebral regions linked with RIF in prior neuroimaging and modelling studies showed significant effects. This might be due to methodological differences between the RIF paradigm and continuous naming as the latter does not involve practicing particular information. We interpret the results as indicating priming of shared features and lexical-level selection mechanisms contribute to the cumulative interference effect, while adding noise to a booster mechanism could account for the pattern of responses observed in the LIFG.