Neural correlates of rapid auditory processing are disrupted in children with developmental dyslexia and ameliorated with training: an fMRI study.

PURPOSE: Developmental dyslexia, characterized by unexpected difficulty in reading, may involve a fundamental deficit in processing rapid acoustic stimuli. Using functional magnetic resonance imaging (fMRI) we previously reported that adults with developmental dyslexia have a disruption in neural response to rapid acoustic stimuli in left prefrontal cortex. Here we examined the neural correlates of rapid auditory processing in children. METHODS: Whole-brain fMRI was performed on twenty-two children with developmental dyslexia and twenty-three typical-reading children while they listened to nonlinguistic acoustic stimuli, with either rapid or slow transitions, designed to mimic the spectro-temporal structure of consonant-vowel-consonant speech syllables. RESULTS: Typical-reading children showed activation for rapid compared to slow transitions in left prefrontal cortex. Children with developmental dyslexia did not show any differential response in these regions to rapid versus slow transitions. After eight weeks of remediation focused primarily on rapid auditory processing, phonological and linguistic training the children with developmental dyslexia showed significant improvements in language and reading skills, and exhibited activation for rapid relative to slow transitions in left prefrontal cortex. CONCLUSION: The presence of a disruption in the neural response to rapid stimuli in children with developmental dyslexia prior to remediation, coupled with significant improvement in language and reading scores and increased brain activation after remediation, gives further support to the importance of rapid auditory processing in reading development and disorders.

Neural correlates of rapid spectrotemporal processing in musicians and nonmusicians.

Our results suggest that musical training alters the functional anatomy of rapid spectrotemporal processing, resulting in improved behavioral performance along with a more efficient functional network primarily involving traditional language regions. This finding may have important implications for improving language/reading skills, especially in children struggling with dyslexia.

Familial aggregation in specific language impairment.

A case-control family study design, in which the current language-related abilities of all biological, primary relatives (mother, father, siblings) of probands with specific language impairment (SLI) and matched controls were assessed, was used to investigate familial aggregation for language disorders. Current test data from each family member showed the rate of language impairment for mothers, fathers, sisters, and brothers of the SLI probands to be significantly higher than for members of control families. Impairment rates for fathers and mothers were approximately equal, whereas rates for brothers were significantly higher than for sisters. In SLI proband families, Language Impairment (LI) occurred in 13.0% of offspring (excluding proband) with neither parent affected, 40% of offspring with one parent affected, and 71.4% of offspring in families in which both parents were language impaired. Rates of impairment as determined in current testing were compared directly to impairment rates estimated from family-history questionnaires collected from the same families. Group data showed impairment rates estimated from the family-history questionnaires to be similar to the rates based on actual testing. Furthermore, both appeared in line with rates based primarily on questionnaire data as reported previously in the literature. However, case-by-case analyses showed poor intrasubject agreement on classification as language impaired on the basis of current testing as compared to history information.

Relations between the neural bases of dynamic auditory processing and phonological processing: evidence from fMRI.

Functional magnetic resonance imaging (fMRI) was used to examine how the brain responds to temporal compression of speech and to determine whether the same regions are also involved in phonological processes associated with reading. Recorded speech was temporally compressed to varying degrees and presented in a sentence verification task. Regions involved in phonological processing were identified in a separate scan using a rhyming judgment task with pseudowords compared to a lettercase judgment task. The left inferior frontal and left superior temporal regions (Broca's and Wernicke's areas), along with the right inferior frontal cortex, demonstrated a convex response to speech compression; their activity increased as compression increased, but then decreased when speech became incomprehensible. Other regions exhibited linear increases in activity as compression increased, including the middle frontal gyri bilaterally. The auditory cortices exhibited compression-related decreases bilaterally, primarily reflecting a decrease in activity when speech became incomprehensible. Rhyme judgments engaged two left inferior frontal gyrus regions (pars triangularis and pars opercularis), of which only the pars triangularis region exhibited significant compression-related activity. These results directly demonstrate that a subset of the left inferior frontal regions involved in phonological processing is also sensitive to transient acoustic features within the range of comprehensible speech.

Use of cognitive state predicates by language-impaired children.

Two studies of the use of cognitive state predicates by children with specific language impairment (SLI) were conducted. Study I analysed longitudinal language samples collected from 26 children with SLI and 25 children with normal language (NL) development, aged 4;4 and 2;11, respectively, at Time I. Study II analysed samples from SLI children with more severe delays at an earlier language stage. There were 10 SLI children and 10 NL children, aged 4;11 and 2;8, respectively, matched by MLU. All cognitive state predicates were identified using both broad and narrow definitions. In Study 1, the SLI children used cognitive state predicates less frequently than their mental age peers, and with no greater frequency or variety than their younger, language peers. In Study II, children with SLI used more predicates referring to communication events, but there were no further group differences. These findings are discussed as they relate to two current psycholinguistic issues: the possible dissociation of grammar and the lexicon, and the role of language in the development of children's theory of mind.

Disrupted neural responses to phonological and orthographic processing in dyslexic children: an fMRI study.

Developmental dyslexia, characterized by difficulty in reading, has been associated with phonological and orthographic processing deficits. fMRI was performed on dyslexic and normal-reading children (8-12 years old) during phonological and orthographic tasks of rhyming and matching visually presented letter pairs. During letter rhyming, both normal and dyslexic reading children had activity in left frontal brain regions, whereas only normal-reading children had activity in left temporo-parietal cortex. During letter matching, normal-reading children showed activity throughout extrastriate cortex, especially in occipito-parietal regions, whereas dyslexic children had little activity in extrastriate cortex during this task. These results indicate dyslexia may be characterized in childhood by disruptions in the neural bases of both phonological and orthographic processes important for reading.

Disruption of the neural response to rapid acoustic stimuli in dyslexia: evidence from functional MRI.

The biological basis for developmental dyslexia remains unknown. Research has suggested that a fundamental deficit in dyslexia is the inability to process sensory input that enters the nervous system rapidly and that deficits in processing rapid acoustic information are associated with impaired reading. Functional magnetic resonance imaging (fMRI) was used to identify the brain basis of rapid acoustic processing in normal readers and to discover the status of that response in dyslexic readers. Normal readers showed left prefrontal activity in response to rapidly changing, relative to slowly changing, nonlinguistic acoustic stimuli. Dyslexic readers showed no differential left frontal response. Two dyslexic readers participated in a remediation program and showed increased activity in left prefrontal cortex after training. These fMRI results identify left prefrontal regions as normally being sensitive to rapid relative to slow acoustic stimulation, insensitive to the difference between such stimuli in dyslexic readers, and plastic enough in adulthood to develop such differential sensitivity after intensive training.

Impaired processing of complex auditory stimuli in rats with induced cerebrocortical microgyria: An animal model of developmental language disabilities.

Individuals with developmental language disabilities, including developmental dyslexia and specific language impairment (SLI), exhibit impairments in processing rapidly presented auditory stimuli. It has been hypothesized that these deficits are associated with concurrent deficits in speech perception and, in turn, impaired language development. Additionally, postmortem analyses of human dyslexic brains have revealed the presence of focal neocortical malformations such as cerebrocortical microgyria. In an initial study bridging these research domains, we found that male rats with induced microgyria were impaired in discriminating rapidly presented auditory stimuli. In order to further assess this anatomical- behavioral association, we designed two experiments using auditory-reflex modification. These studies were intended to assess whether auditory processing deficits in microgyric male rats would be seen in threshold detection of a silent gap in white noise, and in oddball detection of a two-tone stimulus of variable duration. Results showed no differences between sham and microgyric subjects on gap detection, but did show that microgyric subjects were impaired in the discrimination of two-tone stimuli presented in an oddball paradigm. This impairment was evident for stimuli with total duration of 64 msec or less, while both groups were able to discriminate stimuli with duration of 89 msec or greater. The current results further support the relationship between malformations of the cerebral cortex and deficits in rapid auditory processing. They also suggest that the parameters characterizing rapid auditory processing deficits for a specific task may be influenced by stimulus features and/or cognitive demand of that particular task.

Neurological and MRI profiles of children with developmental language impairment.

Children with developmental language impairment (LI) are defined partly by the absence of other identifiable neurological diagnoses. Such children are generally considered to be neurologically normal, but no systematic studies of neurological function have been reported. We obtained detailed medical histories and conducted neurological examinations for 72 children aged 5 to 14 years with LI and 82 typically developing age-matched control children. All the children took a standardized test of language, and those who were at least 8 years old and were willing to have brain MRI scans (35 children with LI and 27 control children) had scans. Analysis of developmental milestones from the medical histories revealed that children with LI were not only significantly later in speaking, but also mildly but significantly delayed in motor milestones, particularly walking. On neurological examination, abnormalities were found in 70% of the children with LI and only 22% of the control children. The most common abnormalities in the LI group included obligatory synkinesis, fine motor impairments, and hyperreflexia. The children with LI with the most abnormal neurological findings had the lowest language scores. Finally, 12 of 35 children with LI had abnormalities on their MRI scan, while none of the 27 control children had abnormal scans. Abnormal findings included ventricular enlargement (in five), central volume loss (in three), and white matter abnormalities (in four). These findings suggest that developmental LI is not an isolated finding but is indicative of more widespread nervous system dysfunction. Children with LI may need more comprehensive intervention programs than language therapy alone, depending on their other areas of dysfunction. Early identification of such problems may allow for more successful remediation.

Impaired two-tone processing at rapid rates in male rats with induced microgyria.

We previously reported that adult male rats with bilateral induced microgyria exhibit deficits in rapid auditory processing, which appear similar to auditory processing deficits seen in individuals with developmental language disabilities. The current study was designed to further elaborate that finding using an improved paradigm in which stimulus duration was uncoupled from testing experience and learning effects. Specifically, two-tone stimuli with durations of 540, 390, 332 and 249 ms were all presented within a single test session in a modified operant conditioning paradigm. Subjects were tested over a period of 12 days using this variable-stimulus format. Results confirmed microgyric male rats were impaired only in processing two-tone stimuli presented at rapid rates (i.e., 249 ms duration). Thus the current results support the previously observed link between focal malformations and deficits in rapid auditory processing.

Cortical auditory signal processing in poor readers.

Magnetoencephalographic responses recorded from auditory cortex evoked by brief and rapidly successive stimuli differed between adults with poor vs. good reading abilities in four important ways. First, the response amplitude evoked by short-duration acoustic stimuli was stronger in the post-stimulus time range of 150-200 ms in poor readers than in normal readers. Second, response amplitude to rapidly successive and brief stimuli that were identical or that differed significantly in frequency were substantially weaker in poor readers compared with controls, for interstimulus intervals of 100 or 200 ms, but not for an interstimulus interval of 500 ms. Third, this neurological deficit closely paralleled subjects' ability to distinguish between and to reconstruct the order of presentation of those stimulus sequences. Fourth, the average distributed response coherence evoked by rapidly successive stimuli was significantly weaker in the beta- and gamma-band frequency ranges (20-60 Hz) in poor readers, compared with controls. These results provide direct electrophysiological evidence supporting the hypothesis that reading disabilities are correlated with the abnormal neural representation of brief and rapidly successive sensory inputs, manifested in this study at the entry level of the cortical auditory/aural speech representational system(s).

Different origin of auditory and phonological processing problems in children with language impairment: evidence from a twin study.

This study investigated the heritability of auditory processing impairment, as assessed by Tallal's Auditory Repetition Test (ART). The sample consisted of 37 same-sex twin pairs who had previously been selected because one or both twins met criteria for language impairment (LI) and 104 same-sex twin pairs in the same age range (7 to 13 years) from the general population. These samples yielded 55 children who met criteria for LI, who were compared with 76 children whose language was normal for their age (LN group). We replicated earlier work showing that group LI is impaired relative to group LN on ART. However, there was no evidence of a heritable influence on ART scores: Correlations between twins and their co-twins were reasonably high for both MZ and DZ twins, suggesting that performance is more influenced by shared environment than genetic factors. Analyses of extreme scores gave a similar picture of nonsignificant group heritability. In contrast, a test of phonological short-term memory, the Children's Nonword Repetition Test (CNRep), gave high estimates of group heritability. In general, CNRep was a better predictor of low language test scores than ART, but ART did make a significant independent contribution in accounting for variance in a test of grammatical understanding.

Sex and hemispheric differences for rapid auditory processing in normal adults.

Previous research suggests that left hemisphere specialisation for processing speech may specifically depend on rate-specific parameters, with rapidly successive or faster changing acoustic stimuli (e.g. stop consonant-vowel syllables) processed preferentially by the left hemisphere. The current study further investigates the involvement of the left hemisphere in processing rapidly changing auditory information, and examines the effects of sex on the organisation of this function. Twenty subjects participated in an auditory discrimination task involving the target identification of a two-tone sequence presented to one ear, paired with white noise to the contralateral ear. Analyses demonstrated a right ear advantage for males only at the shorter interstimulus interval durations (mean = 20 msec) whereas no ear advantage was observed for women. These results suggest that the male brain is more lateralised for the processing of rapidly presented auditory tones, specifically at shorter stimulus durations.

Language learning impairments: integrating basic science, technology, and remediation.

One of the fundamental goals of the modern field of neuroscience is to understand how neuronal activity gives rise to higher cortical function. However, to bridge the gap between neurobiology and behavior, we must understand higher cortical functions at the behavioral level at least as well as we have come to understand neurobiological processes at the cellular and molecular levels. This is certainly the case in the study of speech processing, where critical studies of behavioral dysfunction have provided key insights into the basic neurobiological mechanisms relevant to speech perception and production. Much of this progress derives from a detailed analysis of the sensory, perceptual, cognitive, and motor abilities of children who fail to acquire speech, language, and reading skills normally within the context of otherwise normal development. Current research now shows that a dysfunction in normal phonological processing, which is critical to the development of oral and written language, may derive, at least in part, from difficulties in perceiving and producing basic sensory-motor information in rapid succession--within tens of ms (see Tallal et al. 1993a for a review). There is now substantial evidence supporting the hypothesis that basic temporal integration processes play a fundamental role in establishing neural representations for the units of speech (phonemes), which must be segmented from the (continuous) speech stream and combined to form words, in order for the normal development of oral and written language to proceed. Results from magnetic resonance imaging (MRI) and positron emission tomography (PET) studies, as well as studies of behavioral performance in normal and language impaired children and adults, will be reviewed to support the view that the integration of rapidly changing successive acoustic events plays a primary role in phonological development and disorders. Finally, remediation studies based on this research, coupled with neuroplasticity research, will be presented.

Language learning impairment: integrating research and remediation.

Timing cues present in the acoustic waveform of speech provide critical information for the recognition and segmentation of the ongoing speech signal. Research has demonstrated that deficient temporal perception rates, that have been shown to specifically disrupt acoustic processing of speech, are related to specific language-based learning impairments (LLI). Temporal processing deficits correlate highly with the phonological discrimination and processing deficits of these children. Electrophysiological single cell mapping studies of sensory cortex in brains of primates have shown that neural circuitry can be remapped after specific, temporally cohesive training regimens, demonstrating the dynamic plasticity of the brain. Recently, we combined these two lines of research in a series of studies that addressed whether the temporal processing deficits seen in LLIs can be significantly modified through adaptive training aimed at reducing temporal integration thresholds. Simultaneously, we developed a computer algorithm that expanded and enhanced the brief, rapidly changing acoustic segments within ongoing speech and used this to provide intensive speech and language training exercises to these children. Results to date from two independent laboratory experiments, as well as a large national clinical efficacy trial, demonstrate that dramatic improvements in temporal integration thresholds, together with speech and language comprehension abilities of LLI children, results from training with these new computer-based training procedures.

Speech modifications algorithms used for training language learning-impaired children.

In this paper, the details of processing algorithms used in a training program with language learning-impaired children (LLI's) are described. The training program utilized computer games, speech/language training exercises, books-on-tape and educational CD-ROM's. Speech tracks in these materials were processed using these algorithms. During a four week training period, recognition of both processed and normal speech in these children continually increased to near age-appropriate levels. We conclude that this form of processed speech is subject to profound perceptual learning effects and exhibits widespread generalization to normal speech. This form of learning and generalization contributes to the rehabilitation of temporal processing deficits and language comprehension in this subject population.

Look who's talking: a prospective study of familial transmission of language impairments.

Language impairments have been hypothesized to have a genetic component. Previous studies of the familial aggregation of language impairments have relied on a retrospective approach based on parental/self-reported history of language development. This study examined familial aggregation prospectively, by investigating language acquisition and cognitive development in the younger siblings and offspring of individuals with well-defined language impairments. It was predicted that children with a positive family history for language impairments would be more likely to show delays in language acquisition than would age- and gender-matched controls. Similar delays were not expected in nonlinguistic domains, such as conceptual, gestural, or general cognitive development. Ten children with a positive family history and 10 age- and gender-matched controls were tested. Analyses of linguistic and cognitive assessments at 16 to 26 months confirmed the predictions. Children with a family history of language impairments had lower receptive and expressive language scores than controls, with 50% of them scoring at least 1.5 SD below the mean for their age. At the same time, performance on a number of tasks that did not rely on language abilities did not differ as a function of family history. These results indicate that children with a positive family history for language impairments are at risk for language delay; the results also support a familial component to language impairments.