Illness versus substance use effects on the frontal white matter in early phase schizophrenia: A 4Tesla (1)H-MRS study.

OBJECTIVE: Young adults with early phase schizophrenia often report a past or current pattern of illicit substance use and/or alcohol misuse. Still, little is known about the cumulative and separate effects of each stressor on white matter tissue, at this vulnerable period of brain development. METHODS: Participants involved 24 healthy controls with a past or current history of sustained illicit drug use and/or alcohol misuse (users), 23 healthy controls without such history (normative data), and 27 users with early phase schizophrenia. (1)H-MRS data were acquired from a large frontal volume encompassing 95% of white matter, using a 4Tesla scanner (LASER sequence, TR/TE 3200/46ms). RESULTS: Reduced levels of choline-containing compounds (Cho) were specific to the effect of illness (Cohen's d=0.68), with 22% of the variance in Cho levels accounted for by duration of illness. Reduced levels of myoInositol (d=1.10) and creatine plus phosphocreatine (d=1.07) were specific to the effects of illness plus substance use. Effect of substance use on its own was revealed by reductions in levels of glutamate plus glutamine (d=0.83) in control users relative to normative data. CONCLUSIONS: The specific effect of illness on white matter might indicate a decreased synthesis of membrane phospholipids or alternatively, reduced membrane cellular density. In terms of limitations, this study did not include patients without a lifetime history of substance use (non-users), and the specific effect of each substance used could not be studied separately.

TypingSuite: integrated software for presenting stimuli, and collecting and analyzing typing data.

Research into typing patterns has broad applications in both psycholinguistics and biometrics (i.e., improving security of computer access via each user's unique typing patterns). We present a new software package, TypingSuite, which can be used for presenting visual and auditory stimuli, collecting typing data, and summarizing and analyzing the data. TypingSuite is a Java-based software package that is platform-independent and open-source. To validate TypingSuite as a beneficial tool for researchers who are interested in keystroke dynamics, two studies were conducted. First, a behavioural experiment based on single word typing was conducted that replicated two well-known findings in typing research, namely the lexicality and frequency effects. The results confirmed that words are typed faster than pseudowords and that high frequency words are typed faster than low frequency words. Second, in regard to biometrics, it was also shown that typing data from the same user are more similar than data from different users. Because TypingSuite allows its users to easily implement an experiment and to collect and analyze data within a single software package, it holds promise for being a valuable educational and research tool in language-related sciences such as psycholinguistics and natural language processing.

Impact of stimulus similarity between the probe and the irrelevant items during a card-playing deception detection task: the "irrelevants" are not irrelevant.

Event-related brain potential paradigms for the detection of concealed information commonly involve presenting probes embedded within a series of irrelevant items. This study investigated the impact of similarity of the irrelevant items with the probe. For the task, a card was shown followed by the sequential presentation of six "test" cards, one of which was the same as the initial card (the probe) along with five "irrelevant" cards that varied in terms of similarity with the probe. Participants either identified or denied recognition of the probe. The results show that P300 amplitude is modulated by stimulus similarity and highlight the importance of the irrelevant items on deception detection rates.

Changes in N400 topography following intensive speech language therapy for individuals with aphasia.

Our goal was to characterize the effects of intensive aphasia therapy on the N400, an electrophysiological index of lexical-semantic processing. Immediately before and after 4 weeks of intensive speech-language therapy, people with aphasia performed a task in which they had to determine whether spoken words were a 'match' or a 'mismatch' to pictures of objects. Pre-therapy, people with aphasia exhibited an N400 mismatch effect that started over right hemisphere electrodes. Post-therapy, gains were seen in clinical measures of language ability, and the onset of the N400 was left-lateralized. No changes in the scalp distribution of the N400 were observed in healthy controls tested twice over the same 4 week interval. Since the distribution of the N400 after aphasia therapy differed from that of healthy controls, we conclude that it reflects the engagement of compensatory neural mechanisms for language processing rather than a return to a "normal" pattern of brain activation.

Profiling brain function: spatiotemporal characterization of normal and abnormal visual activation.

OBJECTIVE: In clinical neuroscience, the utility of evoked and event-related potentials (EPs and ERPs) resides in the temporal information they provide. However, it is largely unknown whether valuable diagnostic information resides within the corresponding spatial patterns. To determine this, the first step involves testing whether "normal" versus "abnormal" EPs/ERPs can be differentiated based on spatial patterns. In the current study, we present a method that characterizes similarities across individual source maps, called the profile algorithm. The profile algorithm was evaluated in terms of its ability to detect spatial activation differences in myopic individuals with corrected and uncorrected vision. This experiment represents a critical test of the method before applying it to the assessment of perceptual/cognitive functions. METHODS: Visual-evoked potentials (VEPs) were recorded from healthy subjects using checkerboard stimulation. The N75 and P100 were examined in individuals with corrected (20/20) and uncorrected vision (20/40 or worse). RESULTS AND CONCLUSION: N75 and P100 amplitudes and latencies were modulated by vision condition. The profile algorithm differentiated successfully between corrected and uncorrected vision. Its discriminatory power outperformed a more traditional method based on ERP peak amplitude. Subsequent correlations revealed significant relationships between visual impairment and both the components and the spatial activation. Overall, the findings suggested that VEP spatial patterns were sensitive to manipulations of visual acuity. SIGNIFICANCE: The findings demonstrate that EP/ERP spatial activation can be evaluated at the individual level and compared against normative data. Ultimately, the method may provide a valuable tool for assessing individual spatial activation changes in perceptual/cognitive functions.

Automatic syllabification in English: a comparison of different algorithms.

Automatic syllabification of words is challenging, not least because the syllable is not easy to define precisely. Consequently, no accepted standard algorithm for automatic syllabification exists. There are two broad approaches: rule-based and data-driven. The rule-based method effectively embodies some theoretical position regarding the syllable, whereas the data-driven paradigm tries to infer "new" syllabifications from examples assumed to be correctly syllabified already. This article compares the performance of several variants of the two basic approaches. Given the problems of definition, it is difficult to determine a correct syllabification in all cases and so to establish the quality of the "gold standard" corpus used either to evaluate quantitatively the output of an automatic algorithm or as the example-set on which data-driven methods crucially depend. Thus, we look for consensus in the entries in multiple lexical databases of pre-syllabified words. In this work, we have used two independent lexicons, and extracted from them the same 18,016 words with their corresponding (possibly different) syllabifications. We have also created a third lexicon corresponding to the 13,594 words that share the same syllabifications in these two sources. As well as two rule-based approaches (Hammond's and Fisher's implementation of Kahn's), three data-driven techniques are evaluated: a look-up procedure, an exemplar-based generalization technique, and syllabification by analogy (SbA). The results on the three databases show consistent and robust patterns. First, the data-driven techniques outperform the rule-based systems in word and juncture accuracies by a very significant margin but require training data and are slower. Second, syllabification in the pronunciation domain is easier than in the spelling domain. Finally, best results are consistently obtained with SbA.

ERP assessment of functional status in the temporal lobe: examining spatiotemporal correlates of object recognition.

We have previously used functional magnetic resonance imaging to assess specific anterolateral temporal regions involved in object recognition, providing a novel technique for evaluating functional status in temporal lobe epilepsy (i.e., a site directed approach). However, a method that combines high temporal resolution with spatial mapping is needed to isolate the specific processes associated with these regions (i.e., a process specific approach). In the current study, we evaluated the cognitive processes associated with object recognition and their relationship to the temporal lobe using high-density event-related potentials (ERPs). N300 and late positive component (LPC) responses were examined using a word-picture matching task, with three factors: congruity (match/mismatch), level of abstraction (basic/superordinate), and object category (natural/artificial). The N300 and LPC were analyzed in terms of their temporal characteristics as well as their spatial characteristics through source analysis. The results showed that the N300 primarily indexed processing of congruity and level of abstraction, whereas the LPC primarily indexed processing of object category. In agreement with previous functional imaging studies, N300 and LPC source analysis results confirmed temporal lobe involvement in object recognition. Importantly, LPC object category differences were detected in the anterior temporal lobe. Individual subject analyses revealed that these anterior temporal lobe differences were reliable--with greater activity for natural objects in 84% of subjects. The findings are discussed in terms of clinical applications that use spatiotemporal ERP differences to evaluate functional status of the temporal lobes.

Correlating digit span performance and event-related potentials to assess working memory.

Event-related brain potentials (ERPs) were recorded during a computerized and modified version of the Digit Span Backwards (DB) task from the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III). The modified DB version (ERP-DB task) was divided into two sections of 2, 4, 6 and 8 digits in length (Group 1) and 3, 5 and 7 digits in length (Group 2). Each trial had a study phase and a test phase. For the study phase, a series of digits was presented sequentially and aurally to 20 participants (10 for each group). For the test phase, a second series of digits was also presented sequentially and aurally that either corresponded to the reverse order of the digits in the study phase (correct condition) or had one digit in the sequence replaced by an incorrect digit (incorrect condition). The traditional DB task of the WAIS-III was also administered for comparison purposes. A prolonged positive slow wave (PSW) peaking between 450 and 750 ms was elicited to incorrect condition trials. For each participant, a derived measure was calculated from the ERP differentiation between correct and incorrect conditions. The derived measure was defined as the mean of the t-values obtained from the correct and incorrect waveform comparison, within the temporal interval that encompassed this component. The strongest statistical correlations between the derived measure and the traditional DB test scores were found at the Pz site (Group 1: r=0.79; Group 2: r=0.59). This statistical approach shows that it is possible to adequately relate an individual's performance on a traditional measure of working memory and ERP patterns. Overall, we believe that this kind of ERP approach holds promise as a technique for assessing quantitatively non-communicative patients.

Assessment of working memory abilities using an event-related brain potential (ERP)-compatible digit span backward task.

OBJECTIVE: This study investigated the effectiveness of an ERP-compatible Digit Span Backward (ERP-DB) task to determine working memory abilities in healthy participants. METHODS: Participants were administered both the standard digit span backward and ERP-DB tasks. The ERP-DB task was divided into two sections, consisting of 2, 4, 6 and 8 (Group 1) and 3, 5, and 7 (Group 2) set sizes. A set of digits was aurally presented, followed by a second set that either corresponded to the reverse order of the first set (correct condition) or had one digit in the sequence replaced by an incorrect digit (incorrect condition). RESULTS: Two posterior positive components were found to distinguish the two conditions; an earlier positive component (P200/P300) was elicited in the correct condition, whereas a comparatively robust and prolonged positive slow wave (PSW) was elicited in the incorrect condition. Furthermore, the PSW and the difference in PSW amplitude between incorrect and correct conditions (dPSW) dissipated as working memory load increased and were related to working memory capacity. CONCLUSIONS: The PSW, dPSW and P200/P300 components were found to be associated with working memory abilities and may have the potential to act as neurophysiological markers for the assessment of working memory capacity. SIGNIFICANCE: This research lends support for the utility of the ERP-DB task as a means of assessing working memory abilities, which may have implications for testing patients with expressive communication impairments.

Impaired oral reading in two atypical dyslexics: a comparison with a computational lexical-analogy model.

A computational model of reading was developed based upon the notion that the structural relationship between orthography and phonology is of greater importance than the dimension of semantics for the reading aloud of single words. Degradation of this model successfully simulated the reading performance of two patients with atypical acquired dyslexia. The first patient CAV, studied and described in the literature by Warrington in 1981, presented with unusual concrete word dyslexia, i.e., he had a category-specific reading deficit for concrete words compared with abstract words. The second patient BG is a phonological dyslexic who, although displaying a strong concreteness effect (concrete words read better than abstract words), was able to read functors individually perfectly well, a pattern that is rarely if ever seen. The computational model was used to generate a set of words for which it was predicted that BG would show no concreteness effect. The results of BG's reading of these words were consistent with this prediction, thereby providing greater support for the validity of the model. It is concluded that a computational approach that attempts not only to reproduce the core symptoms of the major varieties of acquired dyslexia but also to simulate clinical data from specific patients has much to contribute to the understanding of cognitive deficits and to the design of effective rehabilitation strategies.

Electrophysiological assessment of language function following stroke.

OBJECTIVE: Event-related brain potentials (ERPs) were used to assess language function after stroke and demonstrate that it is possible to adapt neuropsychological tests to evaluate neurocognitive function using ERPs. Prior ERP assessment work has focused on language in both healthy individuals and case studies of aphasic neurotrauma patients. The objective of the current study was to evaluate left-hemisphere stroke patients who had varying degrees of receptive language impairment. It was hypothesized that ERPs would assess receptive language function accurately and correlate highly with the neuropsychological data. METHODS: Data were collected from 10 left-hemisphere stroke patients; all were undergoing rehabilitation at the time of testing. Each patient received a battery of neuropsychological tests including the Peabody Picture Vocabulary Test-Revised (PPVT-R; Minnesota: American Guidance Service, 1981). ERPs were recorded during a computerized PPVT-R, in which pictures are presented followed by digitized spoken words that are either congruent or incongruent with the pictures. RESULTS AND CONCLUSION: Incongruent spoken words within an individual's vocabulary level elicited well-known ERP components. One of the components (the N400) could be utilized as a marker of intact semantic processing. The ERP results were subsequently quantified and N400 derivative scores correlated highly with the neuropsychological findings. The results provided a clear demonstration of the efficacy of ERP-based assessment in a neurological patient group. SIGNIFICANCE: Language function in stroke patients can be evaluated, independent of behavior, using electrophysiological measures that correlate highly with traditional neuropsychological test scores.

Linking neurophysiological and neuropsychological measures for aphasia assessment.

OBJECTIVES: The objective of this study was to find the event-related brain potential (ERP) waveform features and parameters that maximize the correlation between the ERP components and behavioral performance on a neuropsychological test of language comprehension (PPVT-R) in order to develop an electrophysiological diagnostic technique that can be used in the assessment of aphasic patients. METHODS: ERPs were recorded during a computerized version of the Peabody Picture Vocabulary Test-Revised (PPVT-R, Form M). In the computerized version, a picture is presented followed by a congruent or incongruent spoken word. A derived measure was calculated from the ERP differentiation between congruent and incongruent words. The traditional PPVT-R (Form L) was also administered for comparison purposes. The participants included 10 left-sided stroke patients. RESULTS: The N400 was the primary component elicited to incongruent spoken words. Following optimization procedures, a statistical correlation (Pearson r=0.86) was found between the derived N400 measures and the neuropsychological test scores. Examination of the scatter plot confirmed that the relationship was linear. The derived N400 measure was defined primarily as the mean of the t-scores obtained from the incongruent and congruent waveform comparison, within the temporal interval that encompasses the N400. CONCLUSIONS: This novel quantification technique links ERPs with neuropsychological data at an unprecedented level. Given the high correlation, a regression line could reasonably be used to estimate a patient's language ability using only ERPs. However, before these findings can be accepted fully, these results need to be replicated in larger samples and across other paradigms.