Whole-brain white matter organization, intelligence, and educational attainment.

General cognitive ability, sometimes referred to as intelligence, is associated with educational attainment throughout childhood. Most studies that have explored the neural correlates of intelligence in childhood focus on individual brain regions. This analytical approach is designed to identify restricted sets of voxels that overlap across participants. By contrast, we explored the relationship between white matter connectome organization, intelligence, and education. In both a sample of typically-developing children (N = 63) and a sample of struggling learners (N = 139), the white matter connectome efficiency was strongly associated with intelligence and educational attainment. Further, intelligence partially mediated the relationship between connectome efficiency and educational attainment. In contrast, a canonical voxel-wise analysis failed to identify any significant relationships. The results emphasize the importance of distributed brain network properties for cognitive or educational ability in childhood. Our findings are interpreted in the context of a developmental theory, which emphasizes the interaction between different subsystems over developmental time.

Preventing intrusive memories after trauma via a brief intervention involving Tetris computer game play in the emergency department: a proof-of-concept randomized controlled trial.

After psychological trauma, recurrent intrusive visual memories may be distressing and disruptive. Preventive interventions post trauma are lacking. Here we test a behavioural intervention after real-life trauma derived from cognitive neuroscience. We hypothesized that intrusive memories would be significantly reduced in number by an intervention involving a computer game with high visuospatial demands (Tetris), via disrupting consolidation of sensory elements of trauma memory. The Tetris-based intervention (trauma memory reminder cue plus c. 20 min game play) vs attention-placebo control (written activity log for same duration) were both delivered in an emergency department within 6 h of a motor vehicle accident. The randomized controlled trial compared the impact on the number of intrusive trauma memories in the subsequent week (primary outcome). Results vindicated the efficacy of the Tetris-based intervention compared with the control condition: there were fewer intrusive memories overall, and time-series analyses showed that intrusion incidence declined more quickly. There were convergent findings on a measure of clinical post-trauma intrusion symptoms at 1 week, but not on other symptom clusters or at 1 month. Results of this proof-of-concept study suggest that a larger trial, powered to detect differences at 1 month, is warranted. Participants found the intervention easy, helpful and minimally distressing. By translating emerging neuroscientific insights and experimental research into the real world, we offer a promising new low-intensity psychiatric intervention that could prevent debilitating intrusive memories following trauma.

Differences between endogenous attention to spatial locations and sensory modalities.

Vibell et al. (J Cogn Neurosci 19:109-120, 2007) reported that endogenously attending to a sensory modality (vision or touch) modulated perceptual processing, in part, by the relative speeding-up of neural activation (i.e., as a result of prior entry). However, it was unclear whether it was the fine temporal discrimination required by the temporal-order judgment task that was used, or rather, the type of attentional modulation (spatial locations or sensory modalities) that was responsible for the shift in latencies that they observed. The present study used a similar experimental design to evaluate whether spatial attention would also yield similar latency effects suggestive of prior entry in the early visual P1 potentials. Intriguingly, while the results demonstrate similar neural latency shifts attributable to spatial attention, they started at a somewhat later stage than seen in Vibell et al.'s study. These differences are consistent with different neural mechanisms underlying attention to a specific sensory modality versus to a spatial location.

Preparatory α-band oscillations reflect spatial gating independently of predictions regarding target identity.

Preparatory modulations of cortical α-band oscillations are a reliable index of the voluntary allocation of covert spatial attention. It is currently unclear whether attentional cues containing information about a target's identity (such as its visual orientation), in addition to its location, might additionally shape preparatory α modulations. Here, we explore this question by directly comparing spatial and feature-based attention in the same visual detection task while recording brain activity using magnetoencephalography (MEG). At the behavioral level, preparatory feature-based and spatial attention cues both improved performance and did so independently of each other. Using MEG, we replicated robust α lateralization following spatial cues: in preparation for a visual target, α power decreased contralaterally and increased ipsilaterally to the attended location. Critically, however, preparatory α lateralization was not significantly modulated by predictions regarding target identity, as carried via the behaviorally effective feature-based attention cues. Furthermore, nonlateralized α power during the cue-target interval did not differentiate between uninformative cues and cues carrying feature-based predictions either. Based on these results we propose that preparatory α modulations play a role in the gating of information between spatially segregated cortical regions and are therefore particularly well suited for spatial gating of information.NEW & NOTEWORTHY The present work clarifies if and how human brain oscillations in the α-band support multiple types of anticipatory attention. Using magnetoencephalography, we show that posterior α-band oscillations are modulated by predictions regarding the spatial location of an upcoming visual target, but not by feature-based predictions regarding its identity, despite robust behavioral benefits. This provides novel insights into the functional role of preparatory α mechanisms and suggests a limited specificity with which they may operate.

Inferring task-related networks using independent component analysis in magnetoencephalography.

A novel framework for analysing task-positive data in magnetoencephalography (MEG) is presented that can identify task-related networks. Techniques that combine beamforming, the Hilbert transform and temporal independent component analysis (ICA) have recently been applied to resting-state MEG data and have been shown to extract resting-state networks similar to those found in fMRI. Here we extend this approach in two ways. First, we systematically investigate optimisation of time-frequency windows for connectivity measurement. This is achieved by estimating the distribution of functional connectivity scores between nodes of known resting-state networks and contrasting it with a distribution of artefactual scores that are entirely due to spatial leakage caused by the inverse problem. We find that functional connectivity, both in the resting-state and during a cognitive task, is best estimated via correlations in the oscillatory envelope in the 8-20 Hz frequency range, temporally down-sampled with windows of 1-4s. Second, we combine ICA with the general linear model (GLM) to incorporate knowledge of task structure into our connectivity analysis. The combination of ICA with the GLM helps overcome problems of these techniques when used independently: namely, the interpretation and separation of interesting independent components from those that represent noise in ICA and the correction for multiple comparisons when applying the GLM. We demonstrate the approach on a 2-back working memory task and show that this novel analysis framework is able to elucidate the functional networks involved in the task beyond that which is achieved using the GLM alone. We find evidence of localised task-related activity in the area of the hippocampus, which is difficult to detect reliably using standard methods. Task-positive ICA, coupled with the GLM, has the potential to be a powerful tool in the analysis of MEG data.

Temporal order is coded temporally in the brain: early event-related potential latency shifts underlying prior entry in a cross-modal temporal order judgment task.

The speeding-up of neural processing associated with attended events (i.e., the prior-entry effect) has long been proposed as a viable mechanism by which attention can prioritize our perception and action. In the brain, this has been thought to be regulated through a sensory gating mechanism, increasing the amplitudes of early evoked potentials while leaving their latencies unaffected. However, the majority of previous research has emphasized speeded responding and has failed to emphasize fine temporal discrimination, thereby potentially lacking the sensitivity to reveal putative modulations in the timing of neural processing. In the present study, we used a cross-modal temporal order judgment task while shifting attention between the visual and tactile modalities to investigate the mechanisms underlying selective attention electrophysiologically. Our results indicate that attention can indeed speed up neural processes during visual perception, thereby providing the first electrophysiological support for the existence of prior entry.

Modulation of brain activity by selective task sets observed using event-related potentials.

We investigated the ability of subjects to shift dynamically between selective task sets, using informative trial-by-trial cues. Two tasks were used which involved non-overlapping neural systems and different hemispheric specialization. In a verbal task, subjects decided whether a letter string was a real word or a non-word. In a spatial task, subjects decided whether an angle was acute or obtuse. A behavioural experiment showed that performance improved when cues predicted the upcoming task (80% validity), compared to when neutral cues did not afford selective task sets. Event-related potentials (ERPs) revealed brain activity related to forming selective task expectations, to switching tasks, and to the modulation of target processing as a function of such expectations and switches. Activity predicting the probable task started over parietal electrodes 160 ms after cue presentation, while activity related to task switching started at frontal electrodes around 280 ms. Both types of activities developed before target onset. Target processing was significantly influenced by the validity of the cue prediction, including strong modulation of language-related potentials. These results show that it is possible to switch dynamically between task sets involving distinct neural systems, even before the appearance of an imperative target stimulus, and that the nature of the task sets can influence neural activity related to task-set reconfiguration. Selective task sets can in turn modulate the processing of target stimuli. The effects also apply to the case of foveally presented words, whose processing has often been hypothesized to be automatic and outside the influence of selective attention.

Components of attentional set-switching.

A series of distinct event-related potentials (ERPs) have been recorded from the scalp of human subjects as they switch from one task to another. It is possible that task switching may depend on different mechanisms depending on whether the switch requires a change in attentional set, in other words the redirecting of attention to different aspects of a sensory stimulus, or whether it requires a change in intentional set, in others words a change in the way that responses are selected. To address this issue, the current study recorded ERPs while subjects switched between attentional sets and the results were compared with those of a previous investigation in which subjects switched between intentional sets. Subjects selected stimuli according to two conflicting attentional sets, each emphasizing one visual stimulus dimension (colour, shape). Pairs of stimuli, only one of which was to be attended, were presented for between eight and seventeen trials then either a switch or a stay cue was shown. The switch cue instructed subjects to switch from the current attentional set to the other set, while the stay cue instructed subjects to maintain the current set. Comparing ERPs time-locked to the switch and stay cues revealed neural correlates of the initiation of a task switch. Comparing the ERPs time locked to the first stimuli after either stay or switch cues identified neural correlates of the implementation of a task switch. A similar modulation over parietal electrodes was seen when subjects were switching between either attentional or intentional sets. While an intentional set switch began with a medial frontal modulation, attentional set switching began with a lateral frontal modulation. Implementing a new attentional set was associated with modulation of relatively early visual potentials, while implementing a new intentional set was associated with modulation of later response-related potentials. The results confirm that task switching consists of a number of constituent processes which may be taxed to different degrees depending on whether a task-switch paradigm requires subjects to change the way in which they select stimuli or responses.

Thalidomide and pentoxifylline block the renal effects of supernatants of macrophages activated with Crotalus durissus cascavella venom

Because thalidomide and pentoxifylline inhibit the synthesis and release of tumor necrosis factor-alpha (TNF-alpha), we determined the effect of these drugs on the renal damage induced by supernatants of macrophages activated with Crotalus durissus cascavella venom in order to identify the role of TNF-alpha in the process. Rat peritoneal macrophages were collected with RPMI medium and stimulated in vitro with C.d. cascavella venom (10 µg/ml) in the absence and presence of thalidomide (15 µM) or pentoxifylline (500 µM) for 1 h and washed and kept in culture for 2 h. Supernatant (1 ml) was tested on an isolated perfused rat kidney (N = 6 for each group). The first 30 min of each experiment were used as control. The supernatant was added to the perfusion system. All experiments lasted 120 min. The toxic effect of the preparation of venom-stimulated macrophages on renal parameters was determined. At 120 min, thalidomide (Thalid) and pentoxifylline (Ptx) inhibited (P < 0.05) the increase in perfusion pressure caused by the venom (control = 114.0 ± 1.3; venom = 137.1 ± 1.5; Thalid = 121.0 ± 2.5; Ptx = 121.4 ± 4.0 mmHg), renal vascular resistance (control = 4.5 ± 0.2; venom = 7.3 ± 0.6; Thalid = 4.5 ± 0.9; Ptx = 4.8 ± 0.6 mmHg/ml g-1 min-1), urinary flow (control = 0.23 ± 0.001; venom = 0.44 ± 0.01; Thalid = 0.22 ± 0.007; Ptx = 0.21 ± 0.009 ml g-1 min-1), glomerular filtration rate (control = 0.72 ± 0.06; venom = 1.91 ± 0.11; Thalid = 0.75 ± 0.04; Ptx = 0.77 ± 0.05 ml g-1 min-1) and the decrease in percent tubular sodium transport (control = 77.0 ± 0.9; venom = 73.9 ± 0.66; Thalid = 76.6 ± 1.1; Ptx = 81.8 ± 2.0 percent), percent tubular chloride transport (control = 77.1 ± 1.2; venom = 71.4 ± 1.1; Thalid = 77.6 ± 1.7; Ptx = 76.8 ± 1.2 percent), and percent tubular potassium transport (control = 72.7 ± 1.1; venom = 63.0 ± 1.1; Thalid = 72.6 ± 1.0; Ptx = 74.8 ± 1.0 percent), 30 min before and during the stimulation of macrophages with C.d. cascavella venom. These data suggest the participation of TNF-alpha in the renal effects induced by supernatant of macrophages activated with C.d. cascavella venom.

Thalidomide and pentoxifylline block the renal effects of supernatants of macrophages activated with Crotalus durissus cascavella venom.

Because thalidomide and pentoxifylline inhibit the synthesis and release of tumor necrosis factor-alpha (TNF-alpha), we determined the effect of these drugs on the renal damage induced by supernatants of macrophages activated with Crotalus durissus cascavella venom in order to identify the role of TNF-alpha in the process. Rat peritoneal macrophages were collected with RPMI medium and stimulated in vitro with C.d. cascavella venom (10 micro g/ml) in the absence and presence of thalidomide (15 micro M) or pentoxifylline (500 micro M) for 1 h and washed and kept in culture for 2 h. Supernatant (1 ml) was tested on an isolated perfused rat kidney (N = 6 for each group). The first 30 min of each experiment were used as control. The supernatant was added to the perfusion system. All experiments lasted 120 min. The toxic effect of the preparation of venom-stimulated macrophages on renal parameters was determined. At 120 min, thalidomide (Thalid) and pentoxifylline (Ptx) inhibited (P < 0.05) the increase in perfusion pressure caused by the venom (control = 114.0 +/- 1.3; venom = 137.1 +/- 1.5; Thalid = 121.0 +/- 2.5; Ptx = 121.4 +/- 4.0 mmHg), renal vascular resistance (control = 4.5 +/- 0.2; venom = 7.3 +/- 0.6; Thalid = 4.5 +/- 0.9; Ptx = 4.8 +/- 0.6 mmHg/ml g-1 min-1), urinary flow (control = 0.23 +/- 0.001; venom = 0.44 +/- 0.01; Thalid = 0.22 +/- 0.007; Ptx = 0.21 +/- 0.009 ml g-1 min-1), glomerular filtration rate (control = 0.72 +/- 0.06; venom = 1.91 +/- 0.11; Thalid = 0.75 +/- 0.04; Ptx = 0.77 +/- 0.05 ml g-1 min-1) and the decrease in percent tubular sodium transport (control = 77.0 +/- 0.9; venom = 73.9 +/- 0.66; Thalid = 76.6 +/- 1.1; Ptx = 81.8 +/- 2.0%), percent tubular chloride transport (control = 77.1 +/- 1.2; venom = 71.4 +/- 1.1; Thalid = 77.6 +/- 1.7; Ptx = 76.8 +/- 1.2%), and percent tubular potassium transport (control = 72.7 +/- 1.1; venom = 63.0 +/- 1.1; Thalid = 72.6 +/- 1.0; Ptx = 74.8 +/- 1.0%), 30 min before and during the stimulation of macrophages with C.d. cascavella venom. These data suggest the participation of TNF-alpha in the renal effects induced by supernatant of macrophages activated with C.d. cascavella venom.

Microcystin-LR promote intestinal secretion of water and electrolytes in rats.

We showed previously that exposure to microcystin-LR causes renal toxic effects in isolated perfused rat kidney, and that inflammatory mediators from supernatants of macrophages stimulated by microcystin-LR are involved in this process. The aim of this research was to examine water and electrolytes secretion in vivo, induced by microcystin-LR and supernatant of macrophages stimulated for this toxin (SUP.MphiS + MCLR), using perfused rat ileal segment and ligated intestinal loop models. We found microcystin-LR at 1 microg/ml (0.09 +/- 0.003* vs. control 0.07 +/- 0.001 g of secretion/2 cm of loop; P < 0.05*) and the SUP.MphiS + MCLR after 18 h postinoculation (0.10 +/- 0.003 vs. control 0.03 +/- 0.002 g/cm) caused intestinal secretion. In addition, microcystin-LR caused significant sodium secretion (-2.18 +/- 0.72* vs. control 2.18 +/- 0.50 microEq g(-1) min(-1)), potassium (-0.26 +/- 0.04* vs. control 0.32 +/- 0.03 microEq g(-1) min(-1)), chloride (MCLR = -3.29 +/- 1.93* vs. control 0.88 +/- 1.25 microEq g(-1) min(-1)) and water (-0.012 +/- 0.004* vs. control 0.002 +/- 0.002 ml g(-1) min(-1)). We also demonstrated SUP.MphiS + MCLR to induce intestinal secretion of electrolytes (sodium, potassium, chloride) and water. These findings suggested that microcystin-LR and lamina propria macrophages-derived mediators are able to induce intestinal secretion in vivo, probably via inhibition of protein phosphatase.

Orienting attention to locations in perceptual versus mental representations.

Extensive clinical and imaging research has characterized the neural networks mediating the adaptive distribution of spatial attention. In everyday behavior, the distribution of attention is guided not only by extrapersonal targets but also by mental representations of their spatial layout. We used event-related functional magnetic resonance imaging to identify the neural system involved in directing attention to locations in arrays held as mental representations, and to compare it with the system for directing spatial attention to locations in the external world. We found that these two crucial aspects of spatial cognition are subserved by extensively overlapping networks. However, we also found that a region of right parietal cortex selectively participated in orienting attention to the extrapersonal space, whereas several frontal lobe regions selectively participated in orienting attention within on-line mental representations.

Effects of Thalassophryne nattereri fish venom in isolated perfused rat kidney.

Thalassophryne nattereri, popularly known as Niquim, is a venomous fish responsible for many accidents in fishermen in the Northeast of Brazil. The effects of T. nattereri venom on renal physiology has not been tested. Isolated kidneys from Wistar rats of 240-280 g weight were perfused with Krebs-Henseleit solution containing 6g% of previously dialyzed bovine serum albumin. The effects of Niquim venom were studied on the perfusion pressure (PP), renal vascular resistance (RVR), urinary flow (UF), glomerular filtration rate (GFR), percent of sodium tubular transport (%TNa(+)), percent of potassium tubular transport (%TK(+)) and percent of chloride tubular transport (%TCl(-)). The venom of T. nattereri (0.3, 1.0, and 3.0 microg/ml) was always added to the system 30 minutes after the beginning of each experiment (n=6). All experiments were preceded by 30 minutes internal control period and an external control group, where kidneys were perfused with only Krebs-Henseleit solution. All three doses tested promoted increases in PP and RVR. The first two doses also increased GFR and UF. The higher dose promoted decreases in GFR, UF, %TNa(+), %TK(+), %TCl(-). In the treated groups we observed hyalin casts inside all tubules and proteinaceous material in the urinary space. We conclude that the effects resulted from niquim venom agents that promoted a direct effect in kidney cells causing the release of vasoactive factors.

Brain potentials associated with conscious aftereffects induced by unseen stimuli in a blindsight subject.

The study is of brain activity in a blindsight subject (D.B.), who reports conscious visual afterimages of stimuli of which he is unaware when they are presented. This contrast offered a unique opportunity to study event-related potential recordings of conscious versus unconscious visual phenomena generated by the very same stimulus in the identical locus of the visual field. The behavioral results confirmed the reliability of the difference in the subject's report for inducing stimuli versus their aftereffects. The rationale of the event-related potential analysis was to subtract "on" signals from "off" signals, the latter associated with the onset of conscious events and the former for events that remained unconscious. Because there are inherent differences in on and off potentials, the subtractive resultants for the blind hemifield were compared with the same subtractions for the good hemifield when the subject was aware both of the stimuli and their afterimages. A differential pattern in subtractive resultants emerged with a strong anterior left frontal focus for the blind field and a posterior focus for the intact field. The results are compared with other studies suggesting an anterior focus for conscious visual events.

The posterior cingulate and medial prefrontal cortex mediate the anticipatory allocation of spatial attention.

The purpose of this study was to identify brain regions underlying internally generated anticipatory biases toward locations where significant events are expected to occur. Subjects fixated centrally and responded to peripheral targets preceded by a spatially valid (predictive), invalid (misleading), or neutral central cue while undergoing fMRI scanning. In some validly cued trials, reaction time was significantly shorter than in trials with neutral cues, indicating that the cue had successfully induced a spatial redistribution of motivational valence, manifested as expectancy. The largest cue benefits led to selectively greater activations within the posterior cingulate and medial prefrontal cortex. These two areas thus appear to establish a neural interface between attention and motivation. An inverse relationship to cue benefit was seen in the parietal cortex, suggesting that spatial expectancy may entail the inhibition of attention-related areas to reduce distractibility by events at irrelevant locations.

Renal effects of supernatant from rat peritoneal macrophages activated by microcystin-LR: role protein mediators.

We have demonstrated previously that microcystin-LR promoted some renal alterations using the isolated perfused rat kidney preparation. However, these effects were not proved to be direct or indirect. The aim of the current work is to examine the renal effects promoted by supernatants from rat macrophages stimulated with microcystin-LR and the role of inflammatory mediators. Peritoneal macrophages were collected previously and were incubated for 1h in fresh medium (control) and in medium containing microcystin-LR. Dexamethasone, quinacrine, thalidomide and cycloheximide were administered 30 min before microcystin-LR. Supernatants of macrophages stimulated with or without pharmacological inhibitors were added on the perfused rat kidney model. The infusion of macrophages supernatants stimulated by microcystin-LR caused significant increases in renal vascular resistance (C: 4.93+/-0.33 vs T: 5.15+/-0.21), glomerular filtration rate (C: 0.559+/-0.008 vs T: 0.978+/-0.15) and urinary flow (C: 0.16+/-0.01 vs T: 0.23+/-0.03). Cycloheximide, quinacrine and dexamethasone blocked these effects and thalidomide blocked renal vascular resistance. Macrophages stimulated by microcystin-LR release mediators capable of promoting nephotoxicity in isolated perfused rat kidney. Phospholipase A(2), TNF-alpha and other protein mediators appear to be involved on its renal toxic mechanism.

Brain activations during visual search: contributions of search efficiency versus feature binding.

We investigated the involvement of the parietal cortex in binding features during visual search using functional magnetic resonance imaging. We tested 10 subjects in four visual search tasks across which we independently manipulated (1) the requirement to integrate different types of features in a stimulus (feature or conjunction search) and (2) the degree of search efficiency (efficient or inefficient). We identified brain areas that were common to all conditions of visual search and areas that were sensitive to the factors of efficiency and feature binding. Visual search engaged an extensive network of parietal, frontal, and occipital areas. The factor of efficiency exerted a strong influence on parietal activations along the intraparietal sulcus and in the superior parietal lobule. These regions showed a main effect of efficiency and showed a simple effect when inefficient conditions were compared directly with efficient pop-out conditions in the absence of feature binding. Furthermore, a correlation analysis supported a tight correspondence between posterior parietal activation and the slope of reaction-time search functions. Conversely, feature binding during efficient pop-out search was not sufficient to modulate the parietal cortex. The results confirm the important role of the parietal cortex in visual search, but suggest that feature binding is not a requirement to engage its contribution.

Components of switching intentional set.

Despite the intuition that we can shift cognitive set on instruction, some behavioral studies have suggested that set shifting might only be accomplished once we engage in performance of the new task. It is possible that set switching consists of more than one component cognitive process and that the component processes might segregated in time. We recorded event-related potentials (ERPs) during two set-switching tasks to test whether different component processes were responsible for (i) set initiation and reconfiguration when presented with the instruction to switch, and (ii) the implementation of the new set once subjects engaged in performing the new task. The response switching (RS) task required shifts of intentional set; subjects selected between responses according to one of two conflicting intentional sets. The results demonstrated the existence of more than one constituent process. Some of the processes were linked to the initiation and reconfiguration of the set prior to actual performance of the new task. Other processes were time locked to performance of new task items. Set initiation started with modulation of medial frontal ERPs and was followed by modulation over parietal electrodes. Implementation of intentional set was associated with modulation of response-related ERPs.

Filtering of distractors during visual search studied by positron emission tomography.

We investigated the sensitivity of brain areas to the presence of filtering operations during overt visual search in crowded displays. Task conditions involved either visual search or predetermined simple eye movements for the detection of target digits. Furthermore, visual displays either contained letter foils that required filtering or contained only target digits. Brain imaging using positron emission tomography showed extensive overlap between areas involved in overt visual search and eye movements. Selective filtering of foils affected visual processing in ventral areas associated with object recognition and in primary visual cortex.

The response of left temporal cortex to sentences.

The meaning of a sentence differs from the sum of the meanings of its constituents. Left anterior temporal cortex responds to sentences more strongly than to unconnected words. We hypothesized that the anterior temporal response to sentences is due to this difference in meaning (compositional semantics). Using positron emission tomography (PET), we studied four experimental conditions (2 x 2 factorial design): In one condition, subjects read normal sentences. In a second condition, they read grammatically correct sentences containing numerous semantic violations (semantically random sentences). In a third condition, we scrambled the word order within the normal sentences, and, in a fourth condition, the word order was scrambled within the semantically random sentences. The left anterior temporal pole responded strongly to sentences compared to scrambled versions of sentences. A similar although weaker response occurred in the left anterior superior temporal sulcus and the left posterior middle temporal gyrus. A subset of voxels within the left anterior temporal pole responded more to semantically random sentences and their scrambled versions than to normal sentences and the corresponding scrambled versions (main effect of semantic randomness). Finally, the grammatical and the semantic factor interacted in a subset of voxels within the anterior temporal pole: Activity was higher when subjects read normal sentences compared to their scrambled versions but not for semantically random sentences compared to their corresponding scrambled versions. The effects of grammar and meaning and, most importantly, the interaction between grammatical and semantic factors are compatible with the hypothesis that the left anterior temporal pole contributes to the composition of sentence meaning.