Cerebral lateralization in schizophrenia and dyslexia: neuromagnetic responses to auditory stimuli

Many studies have shown altered hemispheric asymmetry-particularly in perisylvian regions-in schizophrenia patients as well as in individuals with dyslexia. Here we explore the similarity of these findings comparing the localization of the magnetic auditory N100m to the German syllable [ba:] in schizophrenia patients, dyslexic adults, and healthy control subjects. Control subjects showed the typical finding of more anterior sources in the right than in the left perisylvian region. In contrast, both schizophrenia patients and dyslexic subjects displayed a symmetrical N100m source configuration. While in people with dyslexia the alteration appears to originate in the right hemisphere, left-hemispheric deviations might contribute to reduced asymmetry in schizophrenia patients. Our results indicate that an absence of lateralized auditory responses in the temporal lobes may reflect a common deviance present in dyslexia and schizophrenia. The nonspecific finding of reduced cerebral laterality may be accounted for by population-specific differences in the functional organization of perisylvian sites.     

Altered hemispheric asymmetry of auditory P100m in dyslexia

In various studies, deviances of hemispheric laterality in the organization of the perisylvian region in dyslexia have been suggested. Although associated with impaired language functioning, the clinical significance of atypical cerebral lateralization remains unclear. The present study examined interhemispheric source differences of magnetic responses to the German synthetic syllable [ba:] in the auditory cortex of 14 dyslexic children and 12 normally literate controls aged 8-15 years. In all subjects, two main deflections, P100m and N260m, were evident in the responses over each hemisphere. While in the control group the right P100m dipole was located more anterior than the corresponding dipole of the left hemisphere, the dyslexic group displayed a rather symmetrical source configuration between the hemispheres. This symmetry reflected a deviance in the right perisylvian region for the dyslexic subjects' P100m, which was generated approximately 1 cm more posterior than the response in controls. The deviation was also obvious relative to the source location of the later component, N260m, which did not systematically differ between the participant groups. Our results suggest that the altered hemispheric asymmetry reflects an atypical organization of the right hemisphere in children and adolescents with dyslexia.     

Reduced hemispheric asymmetry of the auditory N260m in dyslexia

Dyslexia seems to be related to a lack of planum temporale (PT) asymmetry that is accompanied by functional differences to control subjects in both left and right hemispheric temporal regions during language tasks. PT asymmetry has been found to correlate with phonological and verbal skills. In accordance, reduced asymmetry of the auditory N100m sources in dyslexic adults and P100m sources in dyslexic children has been reported. These results might also be related to an atypical PT symmetry or the recruitment of other structures than the PT for speech processing in dyslexia. In the present study we tried to replicate and extend previous findings by examining a sample of 64 dyslexic and 22 control children in the MEG. We measured cortical activity during a passive auditory oddball-paradigm and localised ERF sources evoked by the standard stimulus /ba/. Reduced hemispheric asymmetry in the localisation of the auditory N260m was revealed. While control children displayed a typical asymmetrical pattern with more anterior sources in the right hemisphere, this asymmetry was not present for the dyslexic children. Further, a correlation between N260m asymmetry and spelling test performance was found. Our results suggest that localisation of ERF components is indeed an applicative tool for investigating cortical deviances in dyslexia. A lack of source localisation asymmetry in dyslexia appears to be a robust finding across different samples of dyslexic children and adults. It appears that cortical auditory (language) processing is organised differently in dyslexic subjects than in controls. This might be the consequence of a more symmetrical PT organisation, which in turn might be the result of maturational delay.     

The caudal infrasylvian surface in dyslexia: novel magnetic resonance imaging-based findings.

OBJECTIVE: To detect anatomic abnormalities of auditory association cortex in dyslexia by measuring the area of the perisylvian region known as the caudal infrasylvian surface(s) (cIS) in dyslexic and control subjects. BACKGROUND: Several quantitative morphometric investigations of cortical areas in dyslexia have focused on the cIS, which encompasses the supratemporal plane and the inferior bank of the posterior ascending ramus of the sylvian fissure. Inconsistencies in the results of these studies may be attributable in part to the use of measurement methods that do not account fully for surface undulations of the cIS. METHODS: The authors used an MRI-based surface reconstruction technique that models the curvature of the cerebral cortex in three dimensions to obtain whole-hemisphere and regional surface area estimates. Measurements were obtained in both hemispheres of eight right-handed male dyslexic subjects and eight right-handed male control subjects. RESULTS: The cIS area of dyslexic subjects was significantly larger than that of control subjects, and this result was not attributable to a difference in whole-hemisphere surface area. Neither the dyslexic nor control subjects showed a left or right asymmetry in this region, although there was a trend toward less variance of the asymmetry scores in dyslexic subjects. CONCLUSIONS: The gross anatomic organization of this region is different in dyslexic subjects, and elucidation of the precise nature of these differences may be aided by surface modeling techniques.     

Abnormal auditory cortical activation in dyslexia 100 msec after speech onset

Reading difficulties are associated with problems in processing and manipulating speech sounds. Dyslexic individuals seem to have, for instance, difficulties in perceiving the length and identity of consonants. Using magnetoencephalography (MEG), we characterized the spatio-temporal pattern of auditory cortical activation in dyslexia evoked by three types of natural bisyllabic pseudowords (/ata/, /atta/, and /a a/), complex nonspeech sound pairs (corresponding to /atta/ and /a a/) and simple 1-kHz tones. The most robust difference between dyslexic and non-reading-impaired adults was seen in the left supratemporal auditory cortex 100 msec after the onset of the vowel /a/. This N100m response was abnormally strong in dyslexic individuals. For the complex nonspeech sounds and tone, the N100m response amplitudes were similar in dyslexic and nonimpaired individuals. The responses evoked by syllable /ta/ of the pseudoword /atta/ also showed modest latency differences between the two subject groups. The responses evoked by the corresponding nonspeech sounds did not differ between the two subject groups. Further, when the initial formant transition, that is, the consonant, was removed from the syllable /ta/, the N100m latency was normal in dyslexic individuals. Thus, it appears that dyslexia is reflected as abnormal activation of the auditory cortex already 100 msec after speech onset, manifested as abnormal response strengths for natural speech and as delays for speech sounds containing rapid frequency transition. These differences between the dyslexic and nonimpaired individuals also imply that the N100m response codes stimulus-specific features likely to be critical for speech perception. Which features of speech (or nonspeech stimuli) are critical in eliciting the abnormally strong N100m response in dyslexic individuals should be resolved in future studies.     

Developmental evaluation of atypical auditory sampling in dyslexia: Functional and structural evidence

Whether phonological deficits in developmental dyslexia are associated with impaired neural sampling of auditory information at either syllabic‐ or phonemic‐rates is still under debate. In addition, whereas neuroanatomical alterations in auditory regions have been documented in dyslexic readers, whether and how these structural anomalies are linked to auditory sampling and reading deficits remains poorly understood. In this study, we measured auditory neural synchronization at different frequencies corresponding to relevant phonological spectral components of speech in children and adults with and without dyslexia, using magnetoencephalography. Furthermore, structural MRI was used to estimate cortical thickness of the auditory cortex of participants. Dyslexics showed atypical brain synchronization at both syllabic (slow) and phonemic (fast) rates. Interestingly, while a left hemispheric asymmetry in cortical thickness was functionally related to a stronger left hemispheric lateralization of neural synchronization to stimuli presented at the phonemic rate in skilled readers, the same anatomical index in dyslexics was related to a stronger right hemispheric dominance for neural synchronization to syllabic‐rate auditory stimuli. These data suggest that the acoustic sampling deficit in development dyslexia might be linked to an atypical specialization of the auditory cortex to both low and high frequency amplitude modulations. Hum Brain Mapp 36:4986–5002, 2015. © 2015 Wiley Periodicals, Inc.     

Interhemispheric sensorimotor integration in pointing movements: a study on dyslexic adults

In addition to reading disorders, numerous deficits have been found to be associated with dyslexia, suggesting that various neurological factors might be involved in its etiology. In the present study, we focused on three of the deficits which have been thought to accompany and to a certain extent, to explain dyslexia: an abnormal pattern of hemispheric asymmetry, abnormal hemispheric communication, and abnormal motor control. The aim of the present study was to determine whether adults with reading difficulties perform differently from control subjects in a visuo-manual pointing task, in which the subject was required to point with the right or the left hand to targets appearing to the right or left of a central fixation point. A total of 14 dyslexic adults and 14 control adults participated in this experiment. Motor control was assessed based on the time taken to perform the pointing task, hemispheric asymmetry in terms of the inter-hand differences in the reaction and movement times, and hemispheric communication based on the interhemispheric transfer time under crossed conditions, where the hand and the target were not on the same side.The results showed that neither hemispheric asymmetry nor interhemispheric transfer differed between dyslexic and control adults. However, the dyslexics were significantly slower when performing the pointing task. These results are in agreement with the hypothesis that dyslexia may involve a mild motor deficit.     

Asymmetry of voice onset time-processing in adult developmental dyslexics.

OBJECTIVE: The human auditory cortex codes speech temporally according to sequential acoustico-phonetic cues like the voice onset time (VOT). This coding is predominantly left-lateralized in normal readers. We examined VOT-processing asymmetries in adults with a history of developmental dyslexia (DD-history+). METHODS: Auditory-evoked potentials (AEPs) to voiced (/ba/) and voiceless (/pa/) speech stimuli were recorded from 10 DD-history+ adults and 8 controls. Source modelling of the "release component" (RC: approximately 240 ms; time-locked to voiced consonantal release and considered reflective of VOT-processing) was conducted to explore VOT asymmetries. RESULTS: Controls demonstrated L>R RC source probe amplitude asymmetry in the auditory cortex. DD-history+ subjects with little persistent reading deficit (n=5) demonstrated normal temporal coding but rightward asymmetry. DD-history+ subjects with severe persistent deficits (n=5) exhibited numerous supplemental AEP components (notably left hemispheric) and inconsistent asymmetry (leftward or alternating). CONCLUSIONS: These preliminary findings suggest that DD-history+ adults process auditory speech cues differently than adults without previous DD. The nature of this processing may relate to the severity of persistent reading deficits. SIGNIFICANCE: Previous dyslexics with little persistent deficit can exhibit atypical functional asymmetry with normal auditory temporal coding. Source modelling represents an effective, non-invasive means of exploring processing asymmetries in clinical populations.     

Multi‐parameter machine learning approach to the neuroanatomical basis of developmental dyslexia

Despite decades of research, the anatomical abnormalities associated with developmental dyslexia are still not fully described. Studies have focused on between‐group comparisons in which different neuroanatomical measures were generally explored in isolation, disregarding potential interactions between regions and measures. Here, for the first time a multivariate classification approach was used to investigate grey matter disruptions in children with dyslexia in a large (N = 236) multisite sample. A variety of cortical morphological features, including volumetric (volume, thickness and area) and geometric (folding index and mean curvature) measures were taken into account and generalizability of classification was assessed with both 10‐fold and leave‐one‐out cross validation (LOOCV) techniques. Classification into control vs. dyslexic subjects achieved above chance accuracy (AUC = 0.66 and ACC = 0.65 in the case of 10‐fold CV, and AUC = 0.65 and ACC = 0.64 using LOOCV) after principled feature selection. Features that discriminated between dyslexic and control children were exclusively situated in the left hemisphere including superior and middle temporal gyri, subparietal sulcus and prefrontal areas. They were related to geometric properties of the cortex, with generally higher mean curvature and a greater folding index characterizing the dyslexic group. Our results support the hypothesis that an atypical curvature pattern with extra folds in left hemispheric perisylvian regions characterizes dyslexia. Hum Brain Mapp 38:900–908, 2017. © 2016 Wiley Periodicals, Inc.     

Side of the stimulated ear influences the hemispheric balance in coding tonal stimuli

OBJECTIVE: To evaluate whether the side of stimulated ear affects the hemispheric asymmetry of auditory evoked cortical activations. METHODS: Using a whole-head neuromagnetometer, we recorded neuromagnetic approximately 100 ms responses (N100m) in 21 healthy right-handers to 100 ms 1 kHz tones delivered alternatively to left and right ear. RESULTS: Although the peak latencies of N100m were shorter in contralateral than in ipsilateral hemisphere, the difference was significant only for the left ear stimulation. Based on the relative N100m amplitudes across hemispheres, the laterality evaluation showed a rightward predominance of N100m activation to tone stimuli, but the lateralization toward the right hemisphere was more apparent by the left than by the right ear stimulation (laterality index: -0.27 versus -0.10, p=0.008). Within the right hemisphere, the N100m was 2-4 mm more posterior for left ear than for right ear stimulation. CONCLUSIONS: The hemispheric asymmetry in auditory processing depends on the side of the stimulated ear. The more anterior localization of right N100m responses to ipsilateral than to contralateral ear stimulation suggests that there might be differential neuronal populations in the right hemisphere for processing spatially different auditory inputs.     

Normal planum temporale asymmetry in dyslexics with a magnocellular pathway deficit

Developmental dyslexia has been associated with both abnormal hemispheric symmetry of the planum temporale (PT) and a deficit in the magnocellular visual pathway. We examined the relationship between these two abnormalities. Using sagittal magnetic resonance images and three methods, we measured the PT in dyslexic subjects with a documented magnocellular deficit and controls. Dyslexic subjects did not deviate from normal leftward PT asymmetry, but both groups became less left-lateralized with methods that excluded sulcul tissue. Results suggest that dyslexic subjects with a magnocellular deficit do not always have abnormal symmetry of the PT. PT symmetry may instead be related to a different subtype of dyslexia. In addition, PT asymmetry in any subject group depends on the measurement method.     

Positron emission tomographic studies during serial word-reading by normal and dyslexic adults

Positron-emission tomography (PET) was used to study regional cerebral metabolic activity during oral reading in right-handed adult males with, and without a childhood and family history of developmental dyslexia. Significant group differences in normalized regional metabolic values were revealed in prefrontal cortex and in the lingual (inferior) region of the occipital lobe. Lingual values were bilaterally higher for dyslexic than normal readers. In contrast to the asymmetry observed in prefrontal and lingual regions in nondyslexic subjects during reading, the dyslexic pattern was more symmetric. These results demonstrate that individuals who suffered from familial developmental dyslexia as children, activate different brain regions during reading as adults, as compared to individuals without such childhood history.     

Reduced auditory M100 asymmetry in schizophrenia and dyslexia: applying a developmental instability approach to assess atypical brain asymmetry

Although atypical structural and functional superior temporal gyrus (STG) asymmetries are frequently observed in patients with schizophrenia and individuals with dyslexia, their significance is unclear. One possibility is that atypical asymmetries reflect a general risk factor that can be seen across multiple neurodevelopmental conditions--a risk factor whose origins are best understood in the context of Developmental Instability (DI) theory. DI measures (minor physical anomalies (MPAs) and fluctuating asymmetries (FAs)) reflect perturbation of the genetic plan. The present study sought to assess whether the presence of peripheral indices of DI predicts anomalous functional auditory cortex asymmetry in schizophrenia patients and dyslexia subjects. The location of the auditory M100 response was used as a measure of functional STG asymmetry, as it has been reported that in controls (but not in subjects with schizophrenia or dyslexia) the M100 source location in the right hemisphere is shifted anterior to that seen for the left hemisphere. Whole-brain auditory evoked magnetic field data were successfully recorded from 14 male schizophrenia patients, 21 male subjects with dyslexia, and 16 normal male control subjects. MPA and FA measures were also obtained. Replicating previous studies, both schizophrenia and dyslexia groups showed less M100 asymmetry than did controls. Schizophrenia and dyslexia subjects also had higher MPA scores than normal controls. Although neither total MPA nor FA measures predicted M100 asymmetry, analyses on individual MPA items revealed a relationship between high palate and M100 asymmetry. Findings suggest that M100 positional asymmetry is not a diagnostically specific feature in several neurodevelopmental conditions. Continued research examining DI and brain asymmetry relationships is warranted.     

Planum temporale asymmetry and ear advantage in dichotic listening in Developmental Dyslexia and Attention-Deficit/Hyperactivity Disorder (ADHD).

The planum temporale is clearly involved in language processing, for it serves as the auditory association cortex. Research has consistently demonstrated that 60 to 70% of the population has leftward asymmetry of the planum temporale. Research has also suggested that dyslexic individuals tend to have either rightward asymmetry or symmetrical plana. Moreover, many studies have found a relationship between the presence of dyslexia and/or language impairment and deficits in the normal right ear advantage found in dichotic listening paradigms. In this context, this study examined the relationship between planum temporale asymmetry and ear preference in dichotic listening performance in children with Developmental Dyslexia and Attention-Deficit/Hyperactivity Disorder (ADHD). Subjects included 19 children with dyslexia (10 of whom had a comorbid diagnosis of ADHD), 23 children with ADHD, and 12 diagnosed normal control children. Dichotic listening data were not collected for 8 of the 12 normal control children and for 3 of the 23 ADHD children. Results revealed no significant difference between ADHD and dyslexic subjects in regard to ear advantage on the free recall dichotic listening task. In addition, although the directed dichotic listening tasks were not related to degree of planum asymmetry, as predicted, results indicated that subjects who consistently displayed an atypical left ear advantage tended to have larger right bank lengths than those who consistently displayed a typical right ear advantage. These findings support the notion that some individuals with dyslexia or language deficits tend to have a larger right planum temporale and that performance on dichotic listening tasks may reflect this relatively unusual pattern.     

Reduced laterality of the source locations for generators of the auditory steady-state field in schizophrenia.

BACKGROUND: Reduced hemispheric asymmetry of evoked field generators in schizophrenia in secondary auditory cortex has been replicated with mixed success. This disparity is possibly due to the complex nature of the 100-msec generators typically investigated. In this study, we evaluated a source located in primary auditory cortex, responsible for the steady-state response, to determine whether similar asymmetries were present. METHODS: Contralateral evoked fields were recorded with a 37-channel neuromagnetometer in response to 40-Hz pulse trains. Dipole models were used to localize the sources in both hemispheres of schizophrenic subjects (n = 17) and normal control subjects (n = 18). RESULTS: Control subjects were asymmetrically lateralized, with sources in the right hemisphere approximately 6 mm further anterior than those on the left. In contrast, schizophrenic subjects showed no significant difference between hemispheres. CONCLUSIONS:The findings support theories linking schizophrenia to disturbed asymmetry of temporal lobe function. The steady-state response, having a more discrete Heschl's gyrus generator location, may be better suited for evaluating auditory asymmetry.     

Cerebral brain metabolism in adult dyslexic subjects assessed with positron emission tomography during performance of an auditory task.

Ten dyslexic adults (aged 33.5 +/- 7.3 years, nine men, one woman) and 10 age-, sex- and handedness-matched control subjects (aged 33.6 +/- 5.8 years) performed an auditory syllable discrimination task during 18-fluoro-2-deoxyglucose uptake, and then underwent positron emission tomographic scans. A second normal control group performed an analogous visual discrimination task. Dyslexic subjects experienced greater difficulty and made significantly more errors in performing the auditory task. There were no differences in brain metabolic rates in lateral cortical areas (frontal, parietal, temporal, and occipital lobes). A significant difference emerged in the medial temporal lobe, with dyslexic subjects having significantly higher absolute and relative brain metabolism along an anterior-posterior gradient than normal adults. These data support the hypothesis of altered cerebral processing of auditory stimuli in patients with dyslexia.     

Loss of deep dyslexic reading ability from a second left-hemispheric lesion

It has been hypothesized that the residual reading ability in people with deep dyslexia (an acquired dyslexia in which the subjects make semantic paralexias, eg, child read as boy) utilizes right hemispheric structures. A patient who was deep dyslexic following an initial left hemispheric stroke was studied. Following a new left hemispheric stroke, he lost his residual reading ability. In this patient, deep dyslexic reading abilities were dependent on left hemispheric structures.     

Positron emission tomographic studies during serial word-reading by normal and dyslexic adults

Abstract

Positron-emission tomography (PET) was used to study regional cerebral metabolic activity during oral reading in right-handed adult males with, and without a childhood and family history of developmental dyslexia. Significant group differences in normalized regional metabolic values were revealed in prefrontal cortex and in the lingual (inferior) region of the occipital lobe. Lingual values were bilaterally higher for dyslexic than normal readers. In contrast to the asymmetry observed in prefrontal and lingual regions in nondyslexic subjects during reading, the dyslexic pattern was more symmetric. These results demonstrate that individuals who suffered from familial developmental dyslexia as children, activate different brain regions during reading as adults, as compared to individuals without such childhood history.     

Regional cerebral blood flow in severe developmental dyslexia

Regional cerebral blood flow was measured under three task conditions in 14 men with severe developmental dyslexia and their control subjects using a xenon 133 inhalation technique. No group differences in overall level or in pattern of gray matter flow were seen under relatively undemanding cognitive conditions. Despite minimal group differences in performance, the dyslexic group showed an increased hemispheric asymmetry (left greater than right) on a semantic classification task and a reduced anteroposterior difference on a line orientation task relative to controls. The exaggerated asymmetry suggests the possibility of less efficient information processing or inadequate bihemispheric integration. The reduced anteroposterior gradient may reflect a deficit in the ability of frontal systems to respond adequately to cognitive demands.     

Altered hemispheric asymmetry of auditory magnetic fields to tones and syllables in schizophrenia.

BACKGROUND: A growing body of literature suggests that schizophrenic patients often do not show the normal brain hemispheric asymmetry. We have found this for simple tones presented to the right ear in a previous study. In this study we extended this investigation to left ear stimulation and verbal stimuli. METHODS: With a whole-head neuromagnetometer, contra- and ipsilateral auditory-evoked magnetic fields in response to tones (1000 Hz) and to the syllables ("ba") delivered to the left and right ears in separate runs were compared between schizophrenic patients (n = 17) and healthy control subjects (n = 15). RESULTS: In response to tones, all control subjects showed the expected asymmetry (contralateral predominance) of the auditory-evoked magnetic N100m (dipole moment). In the patient sample asymmetry was reversed following tones presented to the left ear in 47% and following tones to the right ear in 24%. In response to syllables, the asymmetry was similar between groups. In patients compared with control subjects the N100m was located more anterior without asymmetry between hemispheres. CONCLUSIONS: Results suggest that deviation from the normal functional lateralization in schizophrenia appears in a proportion of patients at a basic stage of auditory processing, but may be compensated for at higher levels such as the processing of syllables.