Dynamic time course of typical childhood absence seizures: EEG, behavior, and functional magnetic resonance imaging.

Absence seizures are 5-10 s episodes of impaired consciousness accompanied by 3-4 Hz generalized spike-and-wave discharge on electroencephalography (EEG). The time course of functional magnetic resonance imaging (fMRI) changes in absence seizures in relation to EEG and behavior is not known. We acquired simultaneous EEG-fMRI in 88 typical childhood absence seizures from nine pediatric patients. We investigated behavior concurrently using a continuous performance task or simpler repetitive tapping task. EEG time-frequency analysis revealed abrupt onset and end of 3-4 Hz spike-wave discharges with a mean duration of 6.6 s. Behavioral analysis also showed rapid onset and end of deficits associated with electrographic seizure start and end. In contrast, we observed small early fMRI increases in the orbital/medial frontal and medial/lateral parietal cortex >5 s before seizure onset, followed by profound fMRI decreases continuing >20 s after seizure end. This time course differed markedly from the hemodynamic response function (HRF) model used in conventional fMRI analysis, consisting of large increases beginning after electrical event onset, followed by small fMRI decreases. Other regions, such as the lateral frontal cortex, showed more balanced fMRI increases followed by approximately equal decreases. The thalamus showed delayed increases after seizure onset followed by small decreases, most closely resembling the HRF model. These findings reveal a complex and long-lasting sequence of fMRI changes in absence seizures, which are not detectable by conventional HRF modeling in many regions. These results may be important mechanistically for seizure initiation and termination and may also contribute to changes in EEG and behavior.

Impaired attention and network connectivity in childhood absence epilepsy.

Patients with childhood absence epilepsy (CAE) often demonstrate impaired interictal attention, even with control of their seizures. No previous study has investigated the brain networks involved in this impairment. We used the continuous performance task (CPT) of attentional vigilance and the repetitive tapping task (RTT), a control motor task, to examine interictal attention in 26 children with CAE and 22 matched healthy controls. Each subject underwent simultaneous 3T functional magnetic resonance imaging-electroencephalography (fMRI-EEG) and CPT/RTT testing. Areas of activation on fMRI during the CPT task were correlated with behavioral performance and used as seed regions for resting functional connectivity analysis. All behavioral measures reflecting inattention were significantly higher in patients. Correlation analysis revealed that impairment on all measures of inattention on the CPT task was associated with decreased medial frontal cortex (MFC) activation during CPT. In addition, analysis of resting functional connectivity revealed an overall decrease within an 'attention network' in patients relative to controls. Patients demonstrated significantly impaired connectivity between the right anterior insula/frontal operculum (In/FO) and MFC relative to controls. Our results suggest that there is impaired function in an attention network comprising anterior In/FO and MFC in patients with CAE. These findings provide an anatomical and functional basis for impaired interictal attention in CAE, which may allow the development of improved treatments targeted at these networks.

Functional MRI connectivity as a predictor of the surgical outcome of epilepsy.

PURPOSE: In planning epilepsy surgery, it is important to be able to assess the likelihood of success of surgery for each patient so that the possible risk and benefit can be properly considered. In this study, functional connectivity was investigated as a means for predicting surgical outcome from the preoperative functional magnetic resonance imaging (fMRI) of epilepsy patients. METHODS: Resting-state simultaneous electroencephalography (EEG)-fMRI data were collected from 18 patients with intractable epilepsy before surgery and from 14 healthy subjects. For each patient, EEG-spike correlated fMRI analysis was performed and an activation cluster that overlapped the most with the planned resection area for each patient was chosen as the seed for the functional connectivity analysis. After the functional connectivity maps were computed, laterality indices of functional connectivity were contrasted between patients who had seizures after surgeries (seizure-recurrence group) and those who did not have them for at least a year (seizure-free group). KEY FINDINGS: Patients in the seizure-recurrence group had less-lateralized functional connectivity than patients in the seizure-free group (t(16) = 2.3, after control subtracted and Fisher transformed, p < 0.05, two-tailed). SIGNIFICANCE: This study suggests the potential for using preoperative fMRI connectivity analysis as a predictive outcome measure. If confirmed by further research, a high laterality will be an important addition to the other predictors of better surgical outcome such as febrile seizures, mesial temporal sclerosis, tumors, abnormal MRI, and EEG/MRI concordance.

Simultaneous EEG, fMRI, and behavior in typical childhood absence seizures.

PURPOSE: Absence seizures cause transient impairment of consciousness. Typical absence seizures occur in children, and are accompanied by 3-4-Hz spike-wave discharges (SWDs) on electroencephalography (EEG). Prior EEG-functional magnetic resonance imaging (fMRI) studies of SWDs have shown a network of cortical and subcortical changes during these electrical events. However, fMRI during typical childhood absence seizures with confirmed impaired consciousness has not been previously investigated. METHODS: We performed EEG-fMRI with simultaneous behavioral testing in 37 children with typical childhood absence epilepsy (CAE). Attentional vigilance was evaluated by a continuous performance task (CPT), and simpler motor performance was evaluated by a repetitive tapping task (RTT). RESULTS: SWD episodes were obtained during fMRI scanning from 9 patients among the 37 studied. fMRI signal increases during SWDs were observed in the thalamus, frontal cortex, primary visual, auditory, somatosensory, and motor cortex, and fMRI decreases were seen in the lateral and medial parietal cortex, cingulate gyrus, and basal ganglia. Omission error rate (missed targets) with SWDs during fMRI was 81% on CPT and 39% on RTT. For those seizure epochs during which CPT performance was impaired, fMRI changes were seen in cortical and subcortical structures typically involved in SWDs, whereas minimal changes were observed for the few epochs during which performance was spared. DISCUSSION: These findings suggest that typical absence seizures involve a network of cortical-subcortical areas necessary for normal attention and primary information processing. Identification of this network may improve understanding of cognitive impairments in CAE, and may help guide development of new therapies for this disorder.

Comparator and non-comparator mechanisms of change detection in the context of speech--an ERP study.

Automatic change detection reflects a cognitive memory-based comparison mechanism as well as a sensorial non-comparator mechanism based on differential states of refractoriness. The purpose of this study was to examine whether the comparator mechanism of the mismatch negativity component (MMN) is differentially affected by the lexical status of the deviant. Event-related potential (ERP) data was collected during an "oddball" paradigm designed to elicit the MMN from 15 healthy subjects that were involved in a counting task. Topography pattern analysis and source estimation were utilized to examine the deviance (deviants vs. standards), cognitive (deviants vs. control counterparts) and refractoriness (standards vs. control counterparts) effects elicited by standard-deviant pairs ("deh-day"; "day-deh"; "teh-tay") embedded within "oddball" blocks. Our results showed that when the change was salient regardless of lexical status (i.e., the /e:/ to /eI/ transition) the response tapped the comparator based-mechanism of the MMN which was located in the cuneus/posterior cingulate, reflected sensitivity to the novelty of the auditory object, appeared in the P2 latency range and mainly involved topography modulations. In contrast, when the novelty was low (i.e., the /eI/ to /e:/ transition) an acoustic change complex was elicited which involved strength modulations over the P1/N1 range and implicated the middle temporal gyrus. This result pattern also resembled the one displayed by the non-comparator mechanism. These findings suggest spatially and temporally distinct brain activities of comparator mechanisms of change detection in the context of speech.

An EEG (electroencephalogram) recording system with carbon wire electrodes for simultaneous EEG-fMRI (functional magnetic resonance imaging) recording.

Simultaneous EEG-fMRI (Electroencephalography-functional Magnetic Resonance Imaging) recording provides a means for acquiring high temporal resolution electrophysiological data and high spatial resolution metabolic data of the brain in the same experimental runs. Carbon wire electrodes (not metallic EEG electrodes with carbon wire leads) are suitable for simultaneous EEG-fMRI recording, because they cause less RF (radio-frequency) heating and susceptibility artifacts than metallic electrodes. These characteristics are especially desirable for recording the EEG in high field MRI scanners. Carbon wire electrodes are also comfortable to wear during long recording sessions. However, carbon electrodes have high electrode-electrolyte potentials compared to widely used Ag/AgCl (silver/silver chloride) electrodes, which may cause slow voltage drifts. This paper introduces a prototype EEG recording system with carbon wire electrodes and a circuit that suppresses the slow voltage drift. The system was tested for the voltage drift, RF heating, susceptibility artifact, and impedance, and was also evaluated in a simultaneous ERP (event-related potential)-fMRI experiment.

Individual differences in EEG theta and alpha dynamics during working memory correlate with fMRI responses across subjects.

OBJECTIVE: Theta and alpha range EEG oscillations are commonly induced in cognitive tasks, but their possible relationship to the BOLD signal of fMRI is not well understood, and individual variability is high. We explored individual differences in EEG reactivity to determine whether it is positively or negatively correlated with BOLD across subjects. METHODS: A Sternberg working memory task with 2, 4, or 6 digits was administered to 18 subjects in separate fMRI and EEG sessions. Memory load-dependent theta and alpha reactivity was quantified and used as a regressor to reveal brain areas exhibiting EEG-fMRI correlation across subjects. RESULTS: Theta increases localized to medial prefrontal cortex, and correlated negatively with BOLD in that region and in other "default mode" areas. Alpha modulation localized to parietal-occipital midline cortex and also correlated negatively with BOLD. CONCLUSIONS: Individual tendencies to exhibit memory load-dependent oscillations are associated with negative BOLD responses in certain brain regions. SIGNIFICANCE: Positive BOLD responses and increased EEG oscillations do not necessarily arise in the same regions. Negative BOLD responses may also relate to cognitive activity, as traditionally indexed by increased EEG power in the theta band.

Origin of the radio frequency pulse artifact in simultaneous EEG-fMRI recording: rectification at the carbon-metal interface.

Simultaneous electroencephalograph-functional magnetic resonance imaging (EEG-fMRI) recording has become an important tool for investigating spatiotemporal properties of brain events, such as epilepsy, evoked brain responses, and changes in brain rhythms. Reduction of noise in EEG signals during fMRI recording is crucial for acquiring high-quality EEG-fMRI data. The main source of the noise includes the gradient artifact, the radio frequency (RF) pulse artifact, and the cardiac pulse artifact. Since the RF pulse artifact is relatively small in amplitude, little attention has been paid to this artifact, and its origin is not well understood. However, the amplitude of the RF pulse artifact fluctuates randomly even if a very high EEG sampling rate is used, making it more salient than the gradient artifact after postprocessing for noise removal. In this paper, we investigate the cause of the RF pulse artifact in EEG systems that use carbon wires.

Metonymy as Referential Dependency: Psycholinguistic and Neurolinguistic Arguments for a Unified Linguistic Treatment.

We examine metonymy at psycho- and neurolinguistic levels, seeking to adjudicate between two possible processing implementations (one- vs. two-mechanism). We compare highly conventionalized systematic metonymy (producer-for-product: "All freshmen read O'Connell") to lesser-conventionalized circumstantial metonymy ("[a waitress says to another:] 'Table 2 asked for more coffee."'). Whereas these two metonymy types differ in terms of contextual demands, they each reveal a similar dependency between the named and intended conceptual entities (e.g., Jackendoff, 1997; Nunberg, 1979, 1995). We reason that if each metonymy yields a distinct processing time course and substantially non-overlapping preferential localization pattern, it would not only support a two-mechanism view (one lexical, one pragmatic) but would suggest that conventionalization acts as a linguistic categorizer. By contrast, a similar behavior in time course and localization would support a one-mechanism view and the inference that conventionalization acts instead as a modulator of contextual felicitousness, and that differences in interpretation introduced by conventionalization are of degree, not of kind. Results from three paradigms: self-paced reading (SPR), event-related potentials (ERP), and functional magnetic resonance imaging (fMRI), reveal the following: no main effect by condition (metonymy vs. matched literal control) for either metonymy type immediately after the metonymy trigger, and a main effect for only the Circumstantial metonymy one word post-trigger (SPR); a N400 effect across metonymy types and a late positivity for Circumstantial metonymy (ERP); and a highly overlapping activation connecting the left ventrolateral prefrontal cortex and the left dorsolateral prefrontal cortex (fMRI). Altogether, the pattern observed does not reach the threshold required to justify a two-mechanism system. Instead, the pattern is more naturally (and conservatively) understood as resulting from the implementation of a generalized referential dependency mechanism, modulated by degree of context dependence/conventionalization, thus supporting architectures of language whereby "lexical" and "pragmatic" meaning relations are encoded along a cline of contextual underspecification.

Impaired consciousness in patients with absence seizures investigated by functional MRI, EEG, and behavioural measures: a cross-sectional study.

BACKGROUND: The neural underpinnings of impaired consciousness and of the variable severity of behavioural deficits from one absence seizure to the next are not well understood. We aimed to measure functional MRI (fMRI) and electroencephalography (EEG) changes in absence seizures with impaired task performance compared with seizures in which performance was spared. METHODS: In this cross-sectional study done at the Yale School of Medicine, CT, USA, we recruited patients from 59 paediatric neurology practices in the USA. We did simultaneous EEG, fMRI, and behavioural testing in patients aged 6-19 years with childhood or juvenile absence epilepsy, and with an EEG with typical 3-4 Hz bilateral spike-wave discharges and normal background. The main outcomes were fMRI and EEG amplitudes in seizures with impaired versus spared behavioural responses analysed by t test. We also examined the timing of fMRI and EEG changes in seizures with impaired behavioural responses compared with seizures with spared responses. FINDINGS: 93 patients were enrolled between Jan 1, 2005, and Sept 1, 2013; we recorded 1032 seizures in 39 patients. fMRI changes during seizures occurred sequentially in three functional brain networks. In the default mode network, fMRI amplitude was 0·57% (SD 0·26) for seizures with impaired and 0·40% (0·16) for seizures with spared behavioural responses (mean difference 0·17%, 95% CI 0·11-0·23; p<0·0001). In the task-positive network, fMRI amplitude was 0·53% (SD 0·29) for seizures with impaired and 0·39% (0·15) for seizures with spared behavioral responses (mean difference 0·14%, 95% CI 0·08-0·21; p<0·0001). In the sensorimotor-thalamic network, fMRI amplitude was 0·41% (0·25) for seizures with impaired and 0·34% (0·14) for seizures with spared behavioural responses (mean difference 0·07%, 95% CI 0·01-0·13; p=0·02). Mean fractional EEG power in the frontal leads was 50·4 (SD 15·2) for seizures with impaired and 24·8 (6·5) for seizures with spared behavioural responses (mean difference 25·6, 95% CI 21·0-30·3); middle leads 35·4 (6·5) for seizures with impaired, 13·3 (3·4) for seizures with spared behavioural responses (mean difference 22·1, 95% CI 20·0-24·1); posterior leads 41·6 (5·3) for seizures with impaired, 24·6 (8·6) for seizures with spared behavioural responses (mean difference 17·0, 95% CI 14·4-19·7); p<0·0001 for all comparisons. Mean seizure duration was longer for seizures with impaired behaviour at 7·9 s (SD 6·6), compared with 3·8 s (3·0) for seizures with spared behaviour (mean difference 4·1 s, 95% CI 3·0-5·3; p<0·0001). However, larger amplitude fMRI and EEG signals occurred at the outset or even preceding seizures with behavioural impairment. INTERPRETATION: Impaired consciousness in absence seizures is related to the intensity of physiological changes in established networks affecting widespread regions of the brain. Increased EEG and fMRI amplitude occurs at the onset of seizures associated with behavioural impairment. These finding suggest that a vulnerable state might exist at the initiation of some absence seizures leading them to have more severe physiological changes and altered consciousness than other absence seizures. FUNDING: National Institutes of Health, National Institute of Neurological Disorders and Stroke, National Center for Advancing Translational Science, the Loughridge Williams Foundation, and the Betsy and Jonathan Blattmachr Family.

Removal of time-varying gradient artifacts from EEG data acquired during continuous fMRI.

OBJECTIVE: Recording low amplitude electroencephalography (EEG) signals in the face of large gradient artifacts generated by changing functional magnetic resonance imaging (fMRI) magnetic fields continues to be a challenge. We present a new method of removing gradient artifacts with time-varying waveforms, and evaluate it in continuous (non-interleaved) simultaneous EEG-fMRI experiments. METHODS: The current method consists of an analog filter, an EEG-fMRI timing error correction algorithm, and a temporal principal component analysis based gradient noise removal algorithm. We conducted a phantom experiment and a visual oddball experiment to evaluate the method. RESULTS: The results from the phantom experiment showed that the current method reduced the number of averaged samples required to obtain high correlation between injected and recovered signals, compared to a conventional average waveform subtraction method with adaptive noise cancelling. For the oddball experiment, the results obtained from the two methods were very similar, except that the current method resulted in a higher P300 amplitude when the number of averaged trials was small. CONCLUSIONS: The current method enabled us to obtain high quality EEGs in continuous simultaneous EEG-fMRI experiments. SIGNIFICANCE: Continuous simultaneous EEG-fMRI acquisition enables efficient use of data acquisition time and better monitoring of rare EEG events.

2D Magnetic resonance electrical property tomography based on B1(-) field mapping.

Magnetic Resonance Electrical Property Tomography (MREPT) is a method to visualize electrical conductivity and permittivity distributions in the object. Traditional MREPT relies on either the radio frequency (RF) transmit field (B(+)1) mapping, or using a transmit/receive RF coil, to compute tissue's electrical conductivity and permittivity. This paper introduces an alternative approach based on the reconstructed receive field (B(-)1) By solving a system of homogeneous equations consisting of the signal ratios from multi-channel receive coils, the receive field distribution with both magnitude and phase can be computed. Similar to (B(+)1) based MREPT method, the conductivity and permittivity in the imaging object can be calculated from the (B(-)1) field. We demonstrated the feasibility to image electrical property contrasts through computer simulated studies and phantom experiments. Although this study focuses on the 2D reconstruction, the presented method can be extended to full 3D. This method can be applied to regular MR imaging collected with multi-channel receive coils, and therefore, tissue anomaly based on electrical properties can potentially be revealed with a higher imaging quality, providing useful information for clinical diagnosis.

Altered functional connectivity in seizure onset zones revealed by fMRI intrinsic connectivity.

OBJECTIVE: The purpose of this study was to investigate functional connectivity (FC) changes in epileptogenic networks in intractable partial epilepsy obtained from resting-state fMRI by using intrinsic connectivity contrast (ICC), a voxel-based network measure of degree that reflects the number of connections to each voxel. METHODS: We measured differences between intrahemispheric- and interhemispheric-ICC (ICCintra-inter) that could reveal localized connectivity abnormalities in epileptogenic zones while more global network changes would be eliminated when subtracting these values. The ICCintra-inter map was compared with the seizure onset zone (SOZ) based on intracranial EEG (icEEG) recordings in 29 patients with at least 1 year of postsurgical follow-up. Two independent reviewers blindly interpreted the icEEG and fMRI data, and the concordance rates were compared for various clinical factors. RESULTS: Concordance between the icEEG SOZ and ICCintra-inter map was observed in 72.4% (21/29) of the patients, which was higher in patients with good surgical outcome, especially in those patients with temporal lobe epilepsy (TLE) or lateral temporal seizure localization. Concordance was also better in the extratemporal lobe epilepsy than the TLE group. In 85.7% (18/21) of the cases, the ICCintra-inter values were negative in the SOZ, indicating decreased FC within the epileptic hemisphere relative to between hemispheres. CONCLUSIONS: Assessing alterations in FC using fMRI-ICC map can help localize the SOZ, which has potential as a noninvasive presurgical diagnostic tool to improve surgical outcome. In addition, the method reveals that, in focal epilepsy, both intrahemispheric- and interhemispheric-FC may be altered, in the presence of both regional as well as global network abnormalities.

A feasibility study of magnetic resonance driven electrical impedance tomography using a phantom.

Imaging the electrical properties of human tissue may aid in cancer diagnoses or monitoring organ function. Traditionally, the electrical properties are revealed with electrical impedance tomography, where currents are injected into human tissue and voltages are measured on the surface. This paper focuses on a method of measuring the electrical properties using a magnetic resonance (MR) scanner without current injection. In magnetic resonance driven electrical impedance tomography (MRDEIT), the MR phenomenon is used to induce currents in the body and the complex permittivity map is inversely computed from the difference between the modeled electric field and the actual surface electrode measurements. Computer simulations indicate that with noise level under 20%, the contrast is visually discernible in the reconstruction image. A phantom experiment is demonstrated and this supports results from computer simulation studies. The noise level in electrode measurements is evaluated to be approximately 7.8% from repeated experiments, confirming the potential to reconstruct conductivity contrast using MRDEIT. With further improvements in hardware and image reconstruction, MRDEIT may provide an additional contrast mechanism reflecting the electrical properties of human tissue, which may ultimately be used to diagnose a cancer or assist in electroencephalography.

Magnetic resonance driven electrical impedance tomography: a simulation study.

Magnetic resonance electrical impedance tomography (MREIT) is a method for reconstructing a three-dimensional image of the conductivity distribution in a target volume using magnetic resonance (MR). In MREIT, currents are applied to the volume through surface electrodes and their effects on the MR induced magnetic fields are analyzed to produce the conductance image. However, current injection through surface electrodes poses technical problems such as the limitation on the safely applicable currents. In this paper, we present a new method called magnetic resonance driven electrical impedance tomography (MRDEIT), where the magnetic resonance in each voxel is used as the applied magnetic field source, and the resultant electromagnetic field is measured through surface electrodes or radio-frequency (RF) detectors placed near the surface. Because the applied magnetic field is at the RF frequency and eddy currents are the integral components in the method, a vector wave equation for the electric field is used as the basis of the analysis instead of a quasi-static approximation. Using computer simulations, it is shown that complex permittivity images can be reconstructed using MRDEIT, but that improvements in signal detection are necessary for detecting moderate complex permittivity changes.

Dissociation between the activity of the right middle frontal gyrus and the middle temporal gyrus in processing semantic priming.

The aim of this event-related functional magnetic resonance imaging (fMRI) study was to test whether the right middle frontal gyrus (MFG) and middle temporal gyrus (MTG) would show differential sensitivity to the effect of prime-target association strength on repetition priming. In the experimental condition (RP), the target occurred after repetitive presentation of the prime within an oddball design. In the control condition (CTR), the target followed a single presentation of the prime with equal probability of the target as in RP. To manipulate semantic overlap between the prime and the target both conditions (RP and CTR) employed either the onomatopoeia "oink" as the prime and the referent "pig" as the target (OP) or vice-versa (PO) since semantic overlap was previously shown to be greater in OP. The results showed that the left MTG was sensitive to release of adaptation while both the right MTG and MFG were sensitive to sequence regularity extraction and its verification. However, dissociated activity between OP and PO was revealed in RP only in the right MFG. Specifically, target "pig" (OP) and the physically equivalent target in CTR elicited comparable deactivations whereas target "oink" (PO) elicited less inhibited response in RP than in CTR. This interaction in the right MFG was explained by integrating these effects into a competition model between perceptual and conceptual effects in priming processing.

Social network theory applied to resting-state fMRI connectivity data in the identification of epilepsy networks with iterative feature selection.

Epilepsy is a brain disorder usually associated with abnormal cortical and/or subcortical functional networks. Exploration of the abnormal network properties and localization of the brain regions involved in human epilepsy networks are critical for both the understanding of the epilepsy networks and planning therapeutic strategies. Currently, most localization of seizure networks come from ictal EEG observations. Functional MRI provides high spatial resolution together with more complete anatomical coverage compared with EEG and may have advantages if it can be used to identify the network(s) associated with seizure onset and propagation. Epilepsy networks are believed to be present with detectable abnormal signatures even during the interictal state. In this study, epilepsy networks were investigated using resting-state fMRI acquired with the subjects in the interictal state. We tested the hypothesis that social network theory applied to resting-state fMRI data could reveal abnormal network properties at the group level. Using network data as input to a classification algorithm allowed separation of medial temporal lobe epilepsy (MTLE) patients from normal control subjects indicating the potential value of such network analyses in epilepsy. Five local network properties obtained from 36 anatomically defined ROIs were input as features to the classifier. An iterative feature selection strategy based on the classification efficiency that can avoid 'over-fitting' is proposed to further improve the classification accuracy. An average sensitivity of 77.2% and specificity of 83.86% were achieved via 'leave one out' cross validation. This finding of significantly abnormal network properties in group level data confirmed our initial hypothesis and provides motivation for further investigation of the epilepsy process at the network level.

Biphasic hemodynamic responses influence deactivation and may mask activation in block-design fMRI paradigms.

A previous block-design fMRI study revealed deactivation in the hippocampus in the transverse patterning task, specifically designed, on the basis of lesion literature, to engage hippocampal information processing. In the current study, a mixed block/event-related design was used to determine the temporal nature of the signal change leading to the seemingly paradoxical deactivation. All positive activations in the hippocampal-dependent condition, relative to a closely matched control task, were seen to result from positive BOLD transients in the typical 4-7 s poststimulus time range. However, most deactivations, including in the hippocampus and in other "default mode" regions commonly deactivated in cognitive tasks, were attributable to enhanced negative transient signals in a later time range, 10-12 s. This late hemodynamic transient was most pronounced in medial prefrontal cortex. In some regions, the hippocampal-dependent condition enhanced both the early positive and late negative transients to approximately the same degree, resulting in no significant signal change when block analysis is used, despite very different event-related responses. These results imply that delayed negative transients can play a role in determining the presence and sign of brain activation in block-design studies, in which case an event-related analysis can be more sensitive than a block analysis, even if the different conditions occur within blocks. In this case, default mode deactivations are timelocked to stimulus presentation as much as positive activations are, but in a later time range, suggesting a specific role of negative transient signals in task performance.

Sensory and cognitive mechanisms of change detection in the context of speech.

The aim of this study was to dissociate the contributions of memory-based (cognitive) and adaptation-based (sensory) mechanisms underlying deviance detection in the context of natural speech. Twenty healthy right-handed native speakers of English participated in an event-related design scan in which natural speech stimuli, /de:/ ("deh") and /deI/ ("day"); (/te:/ ("teh") and /teI/ ("tay") served as standards and deviants within functional magnetic resonance imaging event-related "oddball" paradigm designed to elicit the mismatch negativity component. Thus, "oddball" blocks could involve either a word deviant ("day") resulting in a "word advantage" effect, or a non-word deviant ("deh" or "tay"). We utilized an experimental protocol controlling for refractoriness similar to that used previously when deviance detection was studied in the context of tones. Results showed that the cognitive and sensory mechanisms of deviance detection were located in the anterior and posterior auditory cortices, respectively, as was previously found in the context of tones. The cognitive effect, that was most robust for the word deviant, diminished in the "oddball" condition. In addition, the results indicated that the lexical status of the speech stimulus interacts with acoustic factors exerting a top-down modulation of the extent to which novel sounds gain access to the subject's awareness through memory-based processes. Thus, the more salient the deviant stimulus is the more likely it is to be released from the effects of adaptation exerted by the posterior auditory cortex.

On the emergence of rules in neural networks.

A simple associationist neural network learns to factor abstract rules (i.e., grammars) from sequences of arbitrary input symbols by inventing abstract representations that accommodate unseen symbol sets as well as unseen but similar grammars. The neural network is shown to have the ability to transfer grammatical knowledge to both new symbol vocabularies and new grammars. Analysis of the state-space shows that the network learns generalized abstract structures of the input and is not simply memorizing the input strings. These representations are context sensitive, hierarchical, and based on the state variable of the finite-state machines that the neural network has learned. Generalization to new symbol sets or grammars arises from the spatial nature of the internal representations used by the network, allowing new symbol sets to be encoded close to symbol sets that have already been learned in the hidden unit space of the network. The results are counter to the arguments that learning algorithms based on weight adaptation after each exemplar presentation (such as the long term potentiation found in the mammalian nervous system) cannot in principle extract symbolic knowledge from positive examples as prescribed by prevailing human linguistic theory and evolutionary psychology.