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Supplemental Materials to the manuscript - "Learning a new class of multisensory associations: High-density electrophysiological mapping of the temporal course of audio-visual object processing" by Tiziana Vercillo, Edward G. Freedman, Joshua B. Ewen, Sophie Molholm and John J. Foxe

Additional file 2: d-prime values by group and condition.

Supplemental Materials to the manuscript - "Learning a new class of multisensory associations: High-density electrophysiological mapping of the temporal course of audio-visual object processing" by Tiziana Vercillo, Edward G. Freedman, Joshua B. Ewen, Sophie Molholm and John J. Foxe

Additional file 5: Topographic representation of the instantaneous amplitude of evoked response to each of SM, UM and IM in the unattended and attended tasks for NT and ASD participants at 50-ms intervals between 100 and 400ms post-stimulus onset.

Additional file 4: Grand average visual evoked potentials at bilateral parieto-occipital sites (PO7 and PO8) obtained in A) younger participants (age 6-10) and B) older participants (age 11-16) to UM (orange), SM (purple), and IM (blue) collapsed across groups and tasks. C) Difference waveform of the evoked potential to UM minus SM in younger (dotted line) and older (solid line) participants.

Additional file 7: EEG–phenotype correlations-Vineland Socialization Subscales.

Additional file 8: EEG–phenotype correlations (additional Vineland subscales).

Additional file 1: Interpolated channels and accepted trials.

Contains fulltext : 200963.pdf (Publisher’s version ) (Closed access) Objective: Although lower brain volume has been routinely observed in individuals with substance dependence compared with nondependent control subjects, the brain regions exhibiting lower volume have not been consistent across studies. In addition, it is not clear whether a common set of regions are involved in substance dependence regardless of the substance used or whether some brain volume effects are substance specific. Resolution of these issues may contribute to the identification of clinically relevant imaging biomarkers. Using pooled data from 14 countries, the authors sought to identify general and substance-specific associations between dependence and regional brain volumes. Method: Brain structure was examined in a mega-analysis of previously published data pooled from 23 laboratories, including 3,240 individuals, 2,140 of whom had substance dependence on one of five substances: alcohol, nicotine, cocaine, methamphetamine, or cannabis. Subcortical volume and cortical thickness in regions defined by FreeSurfer were compared with nondependent control subjects when all sampled substance categories were combined, as well as separately, while controlling for age, sex, imaging site, and total intracranial volume. Because of extensive associations with alcohol dependence, a secondary contrast was also performed for dependence on all substances except alcohol. An optimized split-half strategy was used to assess the reliability of the findings. Results: Lower volume or thickness was observed in many brain regions in individuals with substance dependence. The greatest effects were associated with alcohol use disorder. A set of affected regions related to dependence in general, regardless of the substance, included the insula and the medial orbitofrontal cortex. Furthermore, a support vector machine multivariate classification of regional brain volumes successfully classified individuals with substance dependence on alcohol or nicotine relative to nondependent control subjects. Conclusions: The results indicate that dependence on a range of different substances shares a common neural substrate and that differential patterns of regional volume could serve as useful biomarkers of dependence on alcohol and nicotine. 10 p.

Additional file 2: Supplementary Figure 2. Correlation matrix of clinical scores and Similarity Index (SI). Gray scale colors code for Pearson rho. Uncorrected P values are given for each correlation.

Additional file 1: Supplementary Figure 1. Pearson correlations for test-retest pairs. Results are shown for all behavioral (red) and evoked sensory (blue) ERP measures used in the study. Rho and p values for show significant correlations for all but high-order EEG measures. NC: No-Cue.

Neuropsychiatric symptoms (NPS) are common in Alzheimer's disease (AD)-associated neurodegeneration. However, NPS lack a consistent relationship with AD pathology. It is unknown whether any common neural circuits can link these clinically disparate while mechanistically similar features with AD pathology. Here, we explored the neural circuits of NPS in AD-associated neurodegeneration using multivariate pattern analysis (MVPA) of resting-state functional MRI data. Data from 98 subjects (70 amnestic mild cognitive impairment and 28AD subjects) were obtained. The top 10 regions differentiating symptom presence across NPS were identified, which were mostly the fronto-limbic regions (medial prefrontal cortex, caudate, etc.). These 10 regions' functional connectivity classified symptomatic subjects across individual NPS at 69.46-81.27%, and predicted multiple NPS (indexed by Neuropsychiatric Symptom Questionnaire-Inventory) and AD pathology (indexed by baseline and change of beta-amyloid/pTau ratio) all above 70%. Our findings suggest a fronto-limbic dominated neural circuit that links multiple NPS and AD pathology. With further examination of the structural and pathological changes within the circuit, the circuit may shed light on linking behavioral disturbances with AD-associated neurodegeneration.

Hemispheric asymmetry is a cardinal feature of human brain organization. Altered brain asymmetry has also been linked to some cognitive and neuropsychiatric disorders. Here the ENIGMA consortium presents the largest ever analysis of cerebral cortical asymmetry and its variability across individuals. Cortical thickness and surface area were assessed in MRI scans of 17,141 healthy individuals from 99 datasets worldwide. Results revealed widespread asymmetries at both hemispheric and regional levels, with a generally thicker cortex but smaller surface area in the left hemisphere relative to the right. Regionally, asymmetries of cortical thickness and/or surface area were found in the inferior frontal gyrus, transverse temporal gyrus, parahippocampal gyrus, and entorhinal cortex. These regions are involved in lateralized functions, including language and visuospatial processing. In addition to population-level asymmetries, variability in brain asymmetry was related to sex, age, and brain size (indexed by intracranial volume). Interestingly, we did not find significant associations between asymmetries and handedness. Finally, with two independent pedigree datasets (N = 1,443 and 1,113, respectively), we found several asymmetries showing modest but highly reliable heritability. The structural asymmetries identified, and their variabilities and heritability provide a reference resource for future studies on the genetic basis of brain asymmetry and altered laterality in cognitive, neurological, and psychiatric disorders.Significance StatementLeft-right asymmetry is a key feature of the human brain's structure and function. It remains unclear which cortical regions are asymmetrical on average in the population, and how biological factors such as age, sex and genetic variation affect these asymmetries. Here we describe by far the largest ever study of cerebral cortical brain asymmetry, based on data from 17,141 participants. We found a global anterior-posterior 'torque' pattern in cortical thickness, together with various regional asymmetries at the population level, which have not been previously described, as well as effects of age, sex, and heritability estimates. From these data, we have created an on-line resource that will serve future studies of human brain anatomy in health and disease.

While navigating complex environments the brain must continuously adapt to both external demands such as fluctuating sensory inputs, as well as internal demands, such as engagement in a cognitively demanding task. Previous studies have demonstrated changes in behavior and gait with increased sensory and cognitive load, but the underlying cortical mechanisms remain largely unknown. Here, in a Mobile Brain/Body Imaging (MoBI) approach sixteen young adults walked on a treadmill with high-density EEG while 3D motion capture tracked kinematics of the head and feet. Visual load was manipulated with the presentation of optic flow with and without continuous mediolateral perturbations. The effects of cognitive load were assessed by the performance of a Go/No-Go task on half of the blocks. During increased sensory load, participants walked with shorter and wider strides, which may indicate a more restrained pattern of gait. Interestingly, cognitive task engagement attenuated these effects of sensory load on gait. Using an Independent Component Analysis and dipole-fitting approach, we found that cautious gait was accompanied by neuro-oscillatory modulations localized to frontal (supplementary motor area, anterior cingulate cortex) and parietal (inferior parietal lobule, precuneus) areas. Our results show suppression in alpha/mu (8-12Hz) and beta (13-30Hz) rhythms, suggesting enhanced activation of these regions with unreliable sensory inputs. These findings provide insight into the neural correlates of gait adaptation, and may be particularly relevant to older adults who are less able to adjust to ongoing cognitive and sensory demands while walking.

The fine task of stereoscopic depth discrimination in human subjects requires a functional binocular system. Behavioral investigations show that relatively small binocular abnormalities can diminish stereoscopic acuity. Clinical evaluations are consistent with this observation. Neurons in visual cortex represent the first stage of processing of the binocular system. Cells at this level are generally acutely sensitive to differences in relative depth. However, an apparent paradox in previous work demonstrates that tuning for binocular disparities remains relatively constant even when large contrast differences are imposed between left and right eye stimuli. This implies a range of neural binocular function that is at odds with behavioral findings. To explore this inconsistency, we have conducted psychophysical tests by which human subjects view vertical sinusoidal gratings drifting in opposite directions to left and right eyes. If the opposite drifting gratings are integrated in visual cortex, as wave theory and neurophysiological data predict, the subjects should perceive a fused stationary grating that is counter-phasing in place. However, this behavioral combination may not occur if there are differences in contrast and therefore signal strength between left and right eye stimuli. As expected for the control condition, our results show fused counter-phase perception for equal inter-ocular grating contrasts. Our experimental tests show a striking retention of counter-phase perception even for relatively large differences in inter-ocular contrast. This finding demonstrates that binocular integration, although relatively coarse, can occur during substantial differences in left and right eye signal strength.

Neuronal activity plays an important role in the development and structural-functional maintenance of the brain as well as in its life-long plastic response to changes in sensory stimulation. We characterized the impact of unilateral 15° laser lesions in the temporal lower visual field of the retina, on visually-driven neuronal activity in the afferent visual pathway of adult mice using in situ hybridization for the activity reporter gene zif268. In the first days post lesion, we detected a discrete zone of reduced zif268 expression in the contralateral hemisphere, spanning the border between the monocular segment of the primary visual cortex (V1) with extrastriate visual area V2M. We could not detect a clear lesion projection zone (LPZ) in areas lateral to V1 whereas medial to V2M, areas RSA and RSG showed decreased zif268 levels over their full extent. All affected areas displayed a return to normal zif268 levels, and this faster in higher order visual areas than in V1. The lesion did however induce a permanent LPZ in the retinorecipient layers of the superior colliculus. We identified a retinotopy-based intrinsic capacity of adult mouse visual cortex to recover from restricted vision loss, with recovery speed reflecting the areal cortical magnification factor. Our observations predict incomplete visual field representations for areas lateral to V1 versus lack of retinotopic organization for areas medial to V2M. The validation of this mouse model paves the way for future interrogations of cortical region- and cell-type specific contributions to functional recovery, up to microcircuit level. ispartof: European Journal of Neuroscience vol:44 issue:5 pages:2165-2175 ispartof: location:France status: published

Accurate perception of speech sound features forms the basis of language and oral communication. Cortical speech processing consists of sound identification, feature extraction, and change discrimination, all occurring within a few hundred milliseconds timescale, and leading to conscious perception of sounds in their context. When these processes do not work optimally, speech perception is hampered, which can lead to problems in academic achievement or social interaction. Therefore, in this thesis, the processing of sublexical syllables and changes if their five features (consonant, vowel, vowel duration, fundamental frequency (F0), and intensity) were compared to the processing of complex nonspeech sounds in adults and six-year-old children, using event-related potentials (ERPs). Overall, larger ERP amplitudes or stronger magnetic mismatch negativity (MMNm) sources were found for speech than nonspeech stimuli. Stronger responses in the speech than the nonspeech condition were seen in both groups for changes in consonants, vowels, vowel duration and vowel F0. This is consistent with their role in Finnish: in addition to phonemic changes, vowel duration and F0 changes co-signal vowel quantity, which differentiates word meaning. Furthermore, children, but not adults, had larger left-lateralized responses for speech than nonspeech intensity changes, which is possibly beneficial for word segmentation and learning. Moreover, children's cortical measures were associated with neurocognitive skills. The overall pattern of larger speech than nonspeech responses was associated with better reasoning skills. Furthermore, larger left than right hemisphere ERP amplitudes for speech stimuli were associated with better performance in language tasks. Finally, the early responses (P1, early differentiating negativity, EDN) were associated with phonological and prereading skills, and later responses (N2, N4, late differentiating negativity, LDN) with verbal short-term memory and naming speed. The results suggest that speech and nonspeech sounds are processed by at least partially different neural substrates in preschoolers and adults. Furthermore, intra-individual differences in ERP amplitudes between conditions and hemispheres might be a useful tool in assessing cortical auditory functioning in children without the requirement of attention or motivation to carry out tasks. Puheen piirteiden tarkka havaitseminen muodostaa puhutun kielen ymmärtämisen perustan. Puheen neuraalinen käsittely sisältää äänten tunnistamisen, piirre-erottelun sekä muutosten havaitsemisen, jotka tapahtuvat muutaman sadan millisekunnin aikana, ja johtavat tietoiseen havaintoon. Jos nämä prosessit eivät toimi tehokkaasti, puheen havaitseminen vaikeutuu, mikä johtaa yleensä vaikeuksiin oppimisessa tai sosiaalisessa vuorovaikutuksessa. Tässä väitöskirjassa selvitettiin puheen prosessoinnin hermostollista perustaa rekisteröimällä tapahtumasidonnaisia herätevasteita tavuille ja niiden viidelle piirteelle (konsonantti, vokaali, vokaalin kesto, perustaajuus (F0) ja intensiteetti) sekä niiden ei-kielellisille vastineille. Tulosten perusteella neljälle tavupiirteelle (konsonantti, vokaali, vokaalin kesto ja F0) syntyi suurempia vasteita kuin vastaaville ei-kielellisille äänenpiirteille niin aikuisten kuin lastenkin kuulojärjestelmässä. Tulos on johdonmukainen suhteessa aiempiin tuloksiin, joiden mukaan foneemien ja vokaalin keston lisäksi myös vokaalin F0 vaikuttaa suomenkielen sanojen merkitysten erotteluun, sillä vokaalin kesto ja F0 muodostavat yhdessä havainnon vokaalin kestosta. Toisin kuin aikuisilla, lapsilla havaittiin myös suurempia vasemmalle painottuneita vasteita vokaalin kuin ei-kielellisen äänen intensiteetin muutoksille, mistä on mahdollisesti hyötyä sanapainon ja siten sanarajojen havaitsemiselle ja sanojen oppimiselle. Kaikki lasten vasteet olivat yhteydessä neurokognitiivisiin taitoihin. Suuremmat vasteet tavuille tai niiden piirteille kuin ei-kielellisille vastineille olivat yhteydessä parempiin päättelytaitoihin, ja suuremmat vasteet kielellisille ärsykkeille vasemmalla kuin oikealla pään puoliskolla parempiin kielellisiin taitoihin. Lisäksi varhaiset vasteet olivat yhteydessä fonologisiin ja varhaisiin lukemisen taitoihin, kun taas myöhäisemmät vasteet olivat yhteydessä kielelliseen lyhytkestoiseen muistiin sekä nimeämisen nopeuteen. Tulosten perusteella kielellinen ja ei-kielellinen prosessointi on ainakin osittain eriytynyttä niin aikuisten kuin lastenkin kuulojärjestelmässä. Lisäksi vasteiden eroja voidaan mahdollisesti hyödyntää lasten kuulojärjestelmän toiminnan arvioinnissa silloinkin, kun lapsen toiminnanohjauksen ja tarkkaavuuden taidot eivät riitä tehtävien tekemiseen.