Biomedical subjects

W Einar Mencl

Publications and source records attributed to W Einar Mencl.

17 recordsLinked to original sources

PubMed2006

A comparison of functional MRI and magnetoencephalography for receptive language mapping.

We compared functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) for the mapping of receptive language function. Participants performed the same language task in the two different imaging environments. MEG activation profiles showed prominent bilateral activity in superior temporal gyrus and left-lateralized activity in middle temporal gyrus. fMRI activation profiles revealed bilateral activity in prefrontal, superior temporal, middle temporal, and visual areas. Laterality quotients derived from the two modalities showed poor agreement between the two methods for commonly active regions of interest. Locations of peak activity also varied considerably within participants between the two methods.

Adult↗

PubMed2006

C957T polymorphism of the dopamine D2 receptor gene modulates the effect of nicotine on working memory performance and cortical processing efficiency.

RATIONALE: In both animals and humans, nicotine produces behavioral effects that vary across individuals. Studies examining the role of genetic variability in modulating individual response to nicotine in humans have increased, with recent work showing that genetic variation at the dopamine D2 receptor (DRD2) predicts response to pharmacotherapy for tobacco dependence. OBJECTIVES: To determine whether a polymorphism of the DRD2 gene, C957T, that alters DRD2 binding availability in humans modifies the effects of nicotine on verbal working memory performance and on processing efficiency of brain regions that support verbal working memory. MATERIALS AND METHODS: Working memory and brain function were assessed in 36 adult subjects (15,957T allele carriers and 21,957C homozygotes), each of whom was studied twice, once after placement of a placebo patch and once after placement of a nicotine patch. Brain function was assessed using functional magnetic resonance imaging while the subjects performed a verbal working memory task. RESULTS: During performance of a task with high verbal working memory load, nicotine administration worsened performance accuracy and reduced the processing efficiency of brain regions that support phonological rehearsal during verbal working memory in carriers of the 957T allele. CONCLUSIONS: These findings are consistent with the notion that genetic variation in DRD2 contributes to individual variation in a range of behavioral and brain responses to nicotine in humans.

Adult↗

PubMed2006

Functional correlates of verbal memory deficits emerging during nicotine withdrawal in abstinent adolescent cannabis users.

BACKGROUND: Cannabis remains the most widely used illicit substance by adolescents and is typically consumed by this population in the context of ongoing tobacco use. Human studies have shown that both cannabis and tobacco exert effects on cognitive function; however, little is known about possible interacting effects of these drugs on brain function and cognition during adolescent development. METHODS: Verbal learning and memory were assessed in 20 adolescent users of tobacco and cannabis and 25 adolescent tobacco users with minimal history of cannabis use. Functional magnetic resonance imaging was used to examine brain function and functional connectivity while a subset of these subjects performed a verbal working memory task. RESULTS: Delayed recall of verbal stimuli deteriorated during nicotine withdrawal among cannabis users but not among comparison subjects. During high verbal working memory load, nicotine withdrawal selectively increased task-related activation of posterior cortical regions and was associated with disruption of frontoparietal connectivity in adolescent cannabis users relative to comparison subjects. CONCLUSIONS: These observations suggest that cannabis use during adolescent development may disrupt neurocircuitry supporting verbal memory formation and that deficits associated with disruption of these neurocircuits are unmasked during nicotine withdrawal.

Adolescent↗

PubMed2006

Differentiation of speech and nonspeech processing within primary auditory cortex.

Primary auditory cortex (PAC), located in Heschl's gyrus (HG), is the earliest cortical level at which sounds are processed. Standard theories of speech perception assume that signal components are given a representation in PAC which are then matched to speech templates in auditory association cortex. An alternative holds that speech activates a specialized system in cortex that does not use the primitives of PAC. Functional magnetic resonance imaging revealed different brain activation patterns in listening to speech and nonspeech sounds across different levels of complexity. Sensitivity to speech was observed in association cortex, as expected. Further, activation in HG increased with increasing levels of complexity with added fundamentals for both nonspeech and speech stimuli, but only for nonspeech when separate sources (release bursts/fricative noises or their nonspeech analogs) were added. These results are consistent with the existence of a specialized speech system which bypasses more typical processes at the earliest cortical level.

Acoustic Stimulation↗

PubMed2005

Visuospatial memory deficits emerging during nicotine withdrawal in adolescents with prenatal exposure to active maternal smoking.

Active maternal smoking during pregnancy elevates the risk of cognitive deficits and tobacco smoking among offspring. Preclinical work has shown that combined prenatal and adolescent exposure to nicotine produces more pronounced hippocampal changes and greater deficits in cholinergic activity upon nicotine withdrawal than does prenatal or adolescent exposure to nicotine alone. Few prior studies have examined the potential modifying effects of gestational exposure to active maternal smoking on cognitive or brain functional response to tobacco smoking or nicotine withdrawal in adolescents. We examined visuospatial and verbal memory in 35 adolescent tobacco smokers with prenatal exposure to active maternal smoking and 26 adolescent tobacco smokers with no prenatal exposure to maternal smoking who were similar in age, educational attainment, general intelligence, and baseline plasma cotinine. Subjects were studied during ad libitum smoking and after 24 h of abstinence from smoking. A subset of subjects from each group also underwent functional magnetic resonance imaging while performing a visuospatial encoding and recognition task. Adolescent tobacco smokers with prenatal exposure experienced greater nicotine withdrawal-related deficits in immediate and delayed visuospatial memory relative to adolescent smokers with no prenatal exposure. Among adolescent smokers with prenatal exposure, nicotine withdrawal was associated with increased activation of left parahippocampal gyrus during early recognition testing of visuospatial stimuli and increased activation of bilateral hippocampus during delayed recognition testing of visuospatial stimuli. These findings extend prior preclinical work and suggest that, in human adolescent tobacco smokers, prenatal exposure to active maternal smoking is associated with alterations in medial temporal lobe function and concomitant deficits in visuospatial memory.

Adolescent↗

PubMed2005

A functional magnetic resonance imaging study of the tradeoff between semantics and phonology in reading aloud.

Using functional magnetic resonance imaging, we explored the role of semantics in mediating orthographic-to-phonological processing in reading aloud, focusing on the interaction of imageability with spelling-to-sound consistency for low-frequency words. Behaviorally, high-imageable words attenuate the standard latency and accuracy disadvantage for low-frequency inconsistent words relative to their consistent counterparts. Neurobiologically, high-imageable words reduced consistency-related activation in the inferior frontal gyrus but increased posterior activation in the angular and middle temporal gyri, representing a possible neural signature of the tradeoff between semantics and phonology in reading aloud. We discuss implications for neurobiological models of reading in terms of understanding the interplay among areas associated with component processes and suggest that the results constitute an important step toward integrating neurobiological and computational models of reading.

Brain Mapping↗

PubMed2005

Behavioral and neurobiological effects of printed word repetition in lexical decision and naming.

A series of experiments studied the effects of repetition of printed words on (1) lexical decision (LD) and naming (NAM) behavior and (2) concomitant brain activation. It was hypothesized that subword phonological analysis (assembly) would decrease with increasing word familiarity and the greater decrease would occur in LD, a task that is believed to be less dependent on assembly than naming. As a behavioral marker of assembly, we utilized the regularity effect (the difference in response latency between words with regular versus irregular spelling-sound correspondences). In addition to repetition, stimulus familiarity was manipulated by word frequency and case alternation. Both experiments revealed an initial latency disadvantage for low frequency irregular words suggesting that assembly is the dominant process in both tasks when items are unfamiliar. As items become more familiar with repetition, the regularity effect disappeared in LD but persisted in NAM. Brain activation patterns for repeated words that were observed in fMRI paralleled the behavioral studies in showing greater reductions in activity under lexical decision than naming for regions previously identified as involved in assembly.

Adolescent↗

PubMed2005

Effects of smoking and smoking abstinence on cognition in adolescent tobacco smokers.

BACKGROUND: In adult animals and humans, nicotine can produce short-term cognitive enhancement and, in some cases, neuroprotection. Recent work in animals, however, suggests that exposure to nicotine during adolescence might be neurotoxic. We tested for evidence of acute and chronic effects of tobacco smoking on cognition in adolescents who smoked tobacco daily and were compared with adolescent nonsmokers. METHODS: Verbal working memory, verbal learning and memory, selective, divided, sustained attention, mood, symptoms of nicotine withdrawal, and tobacco craving were examined in 41 adolescent daily smokers and 32 nonsmokers who were similar in age, gender, and education. Analyses were controlled for general intelligence, reading achievement, parental educational attainment, baseline affective symptoms, and lifetime exposure to alcohol and cannabis. RESULTS: In adolescent smokers, cessation of tobacco use increased tobacco craving, symptoms of nicotine withdrawal, and depressed mood. Adolescent smokers were found to have impairments in accuracy of working memory performance irrespective of recency of smoking. Performance decrements were more severe with earlier age of onset of smoking. Adolescent smokers experienced further disruption of working memory and verbal memory during smoking cessation. As a group, male smokers initiated smoking at an earlier age than female smokers and were significantly more impaired during tests of selective and divided attention than female smokers and nonsmokers. CONCLUSIONS: Adolescent daily tobacco smokers experience acute impairments of verbal memory and working memory after smoking cessation, along with chronic decrements in cognitive performance that are consistent with preclinical evidence that neurotoxic effects of nicotine are more severe when exposure to nicotine occurs at earlier periods in development.

Adolescent↗

PubMed2005

Multidimensional analyses of voicing offsets and onsets in female speakers.

This study investigates cross-speaker differences in the factors that predict voicing thresholds during abduction-adduction gestures in six normal women. Measures of baseline airflow, pulse amplitude, subglottal pressure, and fundamental frequency were made at voicing offset and onset during intervocalic /h/, produced in varying vowel environments and at different loudness levels, and subjected to relational analyses to determine which factors were most strongly related to the timing of voicing cessation or initiation. The data indicate that (a) all speakers showed differences between voicing offsets and onsets, but the degree of this effect varied across speakers; (b) loudness and vowel environment have speaker-specific effects on the likelihood of devoicing during /h/; and (c) baseline flow measures significantly predicted times of voicing offset and onset in all participants, but other variables contributing to voice timing differed across speakers. Overall, the results suggest that individual speakers have unique methods of achieving phonatory goals during running speech. These data contribute to the literature on individual differences in laryngeal function, and serve as a means of evaluating how well laryngeal models can reproduce the range of voicing behavior used by speakers during running speech tasks.

Adult↗

PubMed2004

Development of left occipitotemporal systems for skilled reading in children after a phonologically- based intervention.

BACKGROUND: A range of neurobiological investigations shows a failure of left hemisphere posterior brain systems to function properly during reading in children and adults with reading disabilities. Such evidence of a disruption in the normal reading pathways provides a neurobiological target for reading interventions. In this study, we hypothesized that the provision of an evidence-based, phonologically mediated reading intervention would improve reading fluency and the development of the fast-paced occipitotemporal systems serving skilled reading. METHODS: Functional magnetic resonance imaging was used to study the effects of a phonologically based reading intervention on brain organization and reading fluency in 77 children aged 6.1-9.4 years (49 with reading disability and 28 control subjects). Children comprised three experimental groups: experimental intervention (n = 37), community intervention (n = 12), and community control subjects (n = 28). RESULTS: Immediately after the year-long intervention, children taught with the experimental intervention had made significant gains in reading fluency and demonstrated increased activation in left hemisphere regions, including the inferior frontal gyrus and the middle temporal gyrus; 1 year after the experimental intervention had ended these children were activating bilateral inferior frontal gyri and left superior temporal and occipitotemporal regions. CONCLUSIONS: These data indicate that the nature of the remedial educational intervention is critical to successful outcomes in children with reading disabilities and that the use of an evidence-based phonologic reading intervention facilitates the development of those fast-paced neural systems that underlie skilled reading.

Child↗

PubMed2004

Nicotine effects on brain function and functional connectivity in schizophrenia.

BACKGROUND: Nicotine in tobacco smoke can improve functioning in multiple cognitive domains. High rates of smoking among schizophrenic patients may reflect an effort to remediate cognitive dysfunction. Our primary aim was to determine whether nicotine improves cognitive function by facilitating activation of brain regions mediating task performance or by facilitating functional connectivity. METHODS: Thirteen smokers with schizophrenia and 13 smokers with no mental illness were withdrawn from tobacco and underwent functional magnetic resonance imaging (fMRI) scanning twice, once after placement of a placebo patch and once after placement of a nicotine patch. During scanning, subjects performed an n-back task with two levels of working memory load and of selective attention load. RESULTS: During the most difficult (dichotic 2-back) task condition, nicotine improved performance of schizophrenic subjects and worsened performance of control subjects. Nicotine also enhanced activation of a network of regions, including anterior cingulate cortex and bilateral thalamus, and modulated thalamocortical functional connectivity to a greater degree in schizophrenic than in control subjects during dichotic 2-back task performance. CONCLUSIONS: In tasks that tax working memory and selective attention, nicotine may improve performance in schizophrenia patients by enhancing activation of and functional connectivity between brain regions that mediate task performance.

Adult↗

PubMed2004

Sentence complexity and input modality effects in sentence comprehension: an fMRI study.

Cortical regions engaged by sentence processing were mapped using functional MRI. The influence of input modality (spoken word vs. print input) and parsing difficulty (sentences containing subject-relative vs. object-relative clauses) was assessed. Auditory presentation was associated with pronounced activity at primary auditory cortex and across the superior temporal gyrus bilaterally. Printed sentences by contrast evoked major activity at several posterior sites in the left hemisphere, including the angular gyrus, supramarginal gyrus, and the fusiform gyrus in the occipitotemporal region. In addition, modality-independent regions were isolated, with greatest overlap seen in the inferior frontal gyrus (IFG). With respect to sentence complexity, object-relative sentences evoked heightened responses in comparison to subject-relative sentences at several left hemisphere sites, including IFG, the middle/superior temporal gyrus, and the angular gyrus. These sites showing modulation of activity as a function of sentence type, independent of input mode, arguably form the core of a cortical system essential to sentence parsing.

Acoustic Stimulation↗

PubMed2004

Impact of cannabis use on brain function in adolescents.

Cannabis is the most common illicit substance used by adolescents. This paper reports results of a pilot study using fMRI and a working memory task to compare brain function of adolescent cannabis users to that of two control groups, one matched for tobacco use and the other for nonsmokers.

Adolescent↗

PubMed2004

The neurobiology of adaptive learning in reading: a contrast of different training conditions.

fMRI was used to investigate the separate influences of orthographic, phonological, and semantic processing on the ability to learn new words and the cortical circuitry recruited to subsequently read those words. In a behavioral session, subjects acquired familiarity for three sets of pseudowords, attending to orthographic, phonological, or (learned) semantic features. Transfer effects were measured in an event-related fMRI session as the subjects named trained pseudowords, untrained pseudowords, and real words. Behaviorally, phonological and semantic training resulted in better learning than did orthographic training. Neurobiologically, orthographic training did not modulate activation in the main reading regions. Phonological and semantic training yielded equivalent behavioral facilitation but distinct functional activation patterns, suggesting that the learning resulting from these two training conditions was driven by different underlying processes. The findings indicate that the putative ventral visual word form area is sensitive to the phonological structure of words, with phonologically analytic processing contributing to the specialization of this region.

Adaptation, Psychological↗

PubMed2003

Preliminary evidence of hippocampal dysfunction in adolescent MDMA ("ecstasy") users: possible relationship to neurotoxic effects.

RATIONALE: 3,4-Methylenedioxymethamphetamine (MDMA or ecstasy) is a potent and selective serotonin neurotoxin whose use is growing among adolescents. Although cognitive deficits among adult MDMA users are well documented, little is known of the cognitive and brain functional sequelae of MDMA use during adolescence. OBJECTIVE: We tested for evidence of cognitive deficits and changes in brain function in a pilot sample of adolescent MDMA users, who were compared with adolescent non-users of MDMA. METHODS: Selective and divided attention and verbal working memory were examined in six adolescent MDMA users and six non-users of MDMA who were similar in age, gender, IQ, and other substance use. Brain function was assessed during performance of the working memory task using functional magnetic resonance imaging (fMRI). RESULTS: MDMA users had significantly prolonged reaction times during tests of selective and divided attention, and failed to deactivate the left hippocampus normally during high verbal working memory load. CONCLUSIONS: MDMA use in adolescence may be associated with cognitive impairments and dysfunction of inhibitory circuits within the hippocampus. Further work is urgently needed to delineate the developmental impact and long-term functional and clinical significance of MDMA use during adolescence.

Adolescent↗

PubMed2003

Neural systems for compensation and persistence: young adult outcome of childhood reading disability.

BACKGROUND: This study examined whether and how two groups of young adults who were poor readers as children (a relatively compensated group and a group with persistent reading difficulties) differed from nonimpaired readers and if there were any factors distinguishing the compensated from persistently poor readers that might account for their different outcomes. METHODS: Using functional magnetic resonance imaging, we studied three groups of young adults, ages 18.5-22.5 years, as they read pseudowords and real words: 1) persistently poor readers (PPR; n = 24); 2) accuracy improved (compensated) readers (AIR; n = 19); and 3) nonimpaired readers (NI, n = 27). RESULTS: Compensated readers, who are accurate but not fluent, demonstrate a relative underactivation in posterior neural systems for reading located in left parietotemporal and occipitotemporal regions. Persistently poor readers, who are both not fluent and less accurate, activate posterior reading systems but engage them differently from nonimpaired readers, appearing to rely more on memory-based rather than analytic word identification strategies. CONCLUSIONS: These findings of divergent neural outcomes as young adults are both new and unexpected and suggest a neural basis for reading outcomes of compensation and persistence in adults with childhood dyslexia.

Adult↗

PubMed2002

Disruption of posterior brain systems for reading in children with developmental dyslexia.

BACKGROUND: Converging evidence indicates a functional disruption in the neural systems for reading in adults with dyslexia. We examined brain activation patterns in dyslexic and nonimpaired children during pseudoword and real-word reading tasks that required phonologic analysis (i.e., tapped the problems experienced by dyslexic children in sounding out words). METHODS: We used functional magnetic resonance imaging (fMRI) to study 144 right-handed children, 70 dyslexic readers, and 74 nonimpaired readers as they read pseudowords and real words. RESULTS: Children with dyslexia demonstrated a disruption in neural systems for reading involving posterior brain regions, including parietotemporal sites and sites in the occipitotemporal area. Reading skill was positively correlated with the magnitude of activation in the left occipitotemporal region. Activation in the left and right inferior frontal gyri was greater in older compared with younger dyslexic children. CONCLUSIONS: These findings provide neurobiological evidence of an underlying disruption in the neural systems for reading in children with dyslexia and indicate that it is evident at a young age. The locus of the disruption places childhood dyslexia within the same neurobiological framework as dyslexia, and acquired alexia, occurring in adults.

Adolescent↗