A previous study showed a subjective cognitive decline (SCD) related factorial score derived from the geriatric depression scale (GDS, 30 items) to predict cognitive decline within a group of healthy elderlies in interaction with amyloid status[1]. On the other hand, several features associated with SCD (SCD plus), including subjective decline in the memory domain, concerns about cognitive decline, onset within five years and over 60 years old, and cognitive performance worse than other people, have been proposed to increase the likelihood of preclinical AD in subjects with SCD[2]. Here, we test the association between SCD plus features and GDS factorial scores in two independent cohorts from Germany and China.

Altered intrinsic connectivity within the default mode network (DMN) has been frequently observed in patients with Alzheimer's disease (AD) as well as in its at risk stages such as mild cognitive impairment (MCI) and subjective cognitive decline (SCD). Recent studies showed that DMN can be further segregated into several sub-networks. It is unclear whether the intrinsic connectivity within these sub-networks is altered in individuals with AD, MCI and SCD. T1 images and resting state fMRI images of 301 subjects (28 AD, 48 MCI, 98 SCD, and 127 healthy controls) were obtained from the German Center for Neurodegenerative Diseases Longitudinal Cognitive Impairment and Dementia (DELCODE) Study (mean age ± S.D. = 70.5 ± 5.7 years). Preprocessing of the functional MRI images was performed using SPM12 with standardized procedures including DARTEL normalization. The functional data were then decomposed into 75 independent components (ICs) using the GIFT toolbox. Meaningful ICs including sub-networks of DMN were selected via spatial correlation using an online template (Allen et al., 2011). Differences in functional connectivity strength of all ICs among the four groups were calculated using one-way ANOVA implemented in SPM12. Twenty-three meaningful ICs including three sub-networks of DMN emerged via spatial correlation. Significant gradient changes (HC > SCD > MCI > AD) in the functional connectivity were found in bilateral precuneus (pFWE=0.012) and posterior cingulate cortex (PCC) (pFWE=0.002) within the posterior DMN.

To form a coherent percept of the environment, the brain must integrate sensory signals emanating from a common source but segregate those from different sources. Temporal regularities are prominent cues for multisensory integration, particularly for speech and music perception. In line with models of predictive coding, we suggest that the brain adapts an internal model to the statistical regularities in its environment. This internal model enables cross-sensory and sensorimotor temporal predictions as a mechanism to arbitrate between integration and segregation of signals from different senses.

To form a coherent percept of the environment, the brain must integrate sensory signals emanating from a common source but segregate those from different sources. Temporal regularities are prominent cues for multisensory integration, particularly for speech and music perception. In line with models of predictive coding, we suggest that the brain adapts an internal model to the statistical regularities in its environment. This internal model enables cross-sensory and sensorimotor temporal predictions as a mechanism to arbitrate between integration and segregation of signals from different senses.

The Apolipoprotein (APOE)-e4 allele is associated with an increased risk of developing Alzheimer's disease (AD). Although the entorhinal cortex is one of the first brain areas to show AD pathology, other parts of the medial temporal lobe such as the hippocampus are relatively early affected as well [1]. The hippocampal dentate gyrus (DG), which has been linked to pattern separation, may be particularly vulnerable [2, 3]. However, it is unknown if young APOE-e4 carriers show subtle pattern separation deficits and activity alternations in the hippocampal subfields. A preliminary study of 26 healthy volunteers (13 heterozygous APOE-e4 carriers, and 13 APOE-e3 homozygotes) performed a pattern separation paradigm using repeated, similar lures and novel foil items while being scanned in a 7T Siemens MRI scanner. We manipulated 4 levels of difficulty for similar lures (lures 1–4). For each subject, t-statistics were extracted in the hippocampal subfields using SPM12. We tested for group differences (APOE-e4 carriers vs. non-carriers) in novelty and pattern separation effects. Using representational similarity analysis (RSA), we investigated the correlation between first and second presentation of trials in each condition. We hypothesized that lower correlations reflect more distinct items representations, i.e. pattern separation. Behaviourally, we found that APOE-e4 carriers as compared to non-carriers were less accurate in pattern separation of the most difficult lure1 items and were more likely to incorrectly label those lures as repeated items (Fig. 1A). In the fMRI data, we found a stronger novelty effect (first > repeat) in right DG of the APOE-e4 carriers as compared to non-carriers (Fig. 1Bi). We did not find any group differences for brain activity related to pattern separation (lure1 > repeat) (Fig. 1Bii). No significant differences in RSA patterns were found, due to the small sample size (Fig. 1C). Our analyses with a small group of participants reveal possible differences between APOE-e4 carriers and non-carriers in pattern separation in the DG and in other hippocampal subfields. References: 1. Yassa, M.A., et al., Neuroimage, 2010. 51(3): p. 1242–52. 2. Baker, S., et al., Curr Biol, 2016. 26(19): p. 2629–2634. 3. Berron, D., et al., J Neurosci, 2016. 36(29): p. 7569–79. A. Barplots representing mean proportion of responses for lure items as “old same” for APOE-ε4 carriers and APOE-ε4 non-carriers. B.i. Barplots representing mean t-statistics of novelty effect (i.e. first > repeat) in right dentate gyrus for APOE-ε4 carriers and APOE-ε4 non-carriers. B.ii. Barplots representing mean t-statistics of pattern separation effect (i.e. lure1 > repeat) in right dentate gyrus for APOE-ε4 carriers and APOE-ε4 non-carriers. C. Representational similarity analysis: barplots representing mean correlation between first and second presentation of items for each condition in right dentate gyrus for APOE-ε4 carriers and APOE-ε4 non-carriers. Individual subject's values are indicated as small coloured plots. The asterisks indicate significance of direct comparisons (i.e. APOE-ε4 carriers > non-carriers) at *p<0.05 uncorrected.

Deep brain stimulation (DBS) has been proposed to ameliorate memory dysfunction in patients with Alzheimer’s disease (AD). In this study, we investigated the changes in electroencephalography (EEG) resting-state oscillatory power and phase synchronization after one year of DBS of the nucleus basalis of Meynert (NBM) in AD patients.

Using functional magnetic resonance imaging, we found that when bilinguals named pictures or read words aloud, in their native or nonnative language, activation was higher relative to monolinguals in 5 left hemisphere regions: dorsal precentral gyrus, pars triangularis, pars opercularis, superior temporal gyrus, and planum temporale. We further demonstrate that these areas are sensitive to increasing demands on speech production in monolinguals. This suggests that the advantage of being bilingual comes at the expense of increased work in brain areas that support monolingual word processing. By comparing the effect of bilingualism across a range of tasks, we argue that activation is higher in bilinguals compared with monolinguals because word retrieval is more demanding; articulation of each word is less rehearsed; and speech output needs careful monitoring to avoid errors when competition for word selection occurs between, as well as within, language.

Several perisylvian brain regions show preferential activation for spoken language above and beyond other complex sounds. These "speech-selective" effects might be driven by regions' intrinsic biases for processing the acoustical or informational properties of speech. Alternatively, such speech selectivity might emerge through extensive experience in perceiving and producing speech sounds. This functional magnetic resonance imaging (fMRI) study disambiguated such audiomotor expertise from speech selectivity by comparing activation for listening to speech and music in female professional violinists and actors. Audiomotor expertise effects were identified in several right and left superior temporal regions that responded to speech in all participants and music in violinists more than actresses. Regions associated with the acoustic/information content of speech were identified along the entire length of the superior temporal sulci bilaterally where activation was greater for speech than music in all participants. Finally, an effect of performing arts training was identified in bilateral premotor regions commonly activated by finger and mouth movements as well as in right hemisphere "language regions." These results distinguish the seemingly speech-specific neural responses that can be abolished and even reversed by long-term audiomotor experience.

Previous neuroimaging studies have suggested that developmental dyslexia has a different neural basis in Chinese and English populations because of known differences in the processing demands of the Chinese and English writing systems. Here, using functional magnetic resonance imaging, we provide the first direct statistically based investigation into how the effect of dyslexia on brain activation is influenced by the Chinese and English writing systems. Brain activation for semantic decisions on written words was compared in English dyslexics, Chinese dyslexics, English normal readers and Chinese normal readers, while controlling for all other experimental parameters. By investigating the effects of dyslexia and language in one study, we show common activation in Chinese and English dyslexics despite different activation in Chinese versus English normal readers. The effect of dyslexia in both languages was observed as less than normal activation in the left angular gyrus and in left middle frontal, posterior temporal and occipitotemporal regions. Differences in Chinese and English normal reading were observed as increased activation for Chinese relative to English in the left inferior frontal sulcus; and increased activation for English relative to Chinese in the left posterior superior temporal sulcus. These cultural differences were not observed in dyslexics who activated both left inferior frontal sulcus and left posterior superior temporal sulcus, consistent with the use of culturally independent strategies when reading is less efficient. By dissociating the effect of dyslexia from differences in Chinese and English normal reading, our results reconcile brain activation results with a substantial body of behavioural studies showing commonalities in the cognitive manifestation of dyslexia in Chinese and English populations. They also demonstrate the influence of cognitive ability and learning environment on a common neural system for reading.

Neuropsychological and functional imaging studies have associated the conceptual processing of numbers with bilateral parietal regions (including intraparietal sulcus). However, the processes driving these effects remain unclear because both left and right posterior parietal regions are activated by many other conceptual, perceptual, attention, and response-selection processes. To dissociate parietal activation that is number-selective from parietal activation related to other stimulus or response-selection processes, we used fMRI to compare numbers and object names during exactly the same conceptual and perceptual tasks while factoring out activations correlating with response times. We found that right parietal activation was higher for conceptual decisions on numbers relative to the same tasks on object names, even when response time effects were fully factored out. In contrast, left parietal activation for numbers was equally involved in conceptual processing of object names. We suggest that left parietal activation for numbers reflects a range of processes, including the retrieval of learnt facts that are also involved in conceptual decisions on object names. In contrast, number selectivity in right parietal cortex reflects processes that are more involved in conceptual decisions on numbers than object names. Our results generate a new set of hypotheses that have implications for the design of future behavioral and functional imaging studies of patients with left and right parietal damage.

Cognitive models of reading predict that high frequency regular words can be read in more than one way. We investigated this hypothesis using functional MRI and covariance analysis in 43 healthy skilled readers. Our results dissociated two sets of regions that were differentially engaged across subjects who were reading the same familiar words. Some subjects showed more activation in left inferior frontal and anterior occipito-temporal regions while other subjects showed more activation in right inferior parietal and left posterior occipito-temporal regions. To explore the behavioural correlates of these systems, we measured the difference between reading speed for irregularly spelled words relative to pseudowords outside the scanner in fifteen of our subjects and correlated this measure with fMRI activation for reading familiar words. The faster the lexical reading the greater the activation in left posterior occipito-temporal and right inferior parietal regions. Conversely, the slower the lexical reading the greater the activation in left anterior occipito-temporal and left ventral inferior frontal regions. Thus, the double dissociation in irregular and pseudoword reading behaviour predicted the double dissociation in neuronal activation for reading familiar words. We discuss the implications of these results which may be important for understanding how reading is learnt in childhood or re-learnt following brain damage in adulthood.

A recurrent question concerning the neural organization of language processing in bilinguals concerns the extent to which different languages engage brain regions involved in language processing. This question continues to result in new publications and fresh debate because activation topography can be influenced by task demands and language experience. In this presentation, we will review our own work as well as work by other functional imaging laboratories concerning the role of prior language experience on brain activation topography and magnitude.

Several lines of evidence suggest the importance of phonological working memory (PWM) in language acquisition. We investigated the neural correlates of PWM in young adults who were under compelling social pressure to be bilingual. Equal bilinguals had high proficiency in English and Chinese as measured by a standardized examination, whereas unequal bilinguals were proficient in English but not Chinese. Both groups were matched on several measures of nonverbal intelligence and working memory. In-scanner behavioral results did not show between-group differences. Of the regions showing load-dependent increments in activation, the left insula showed greater activation in equal bilinguals. Unequal bilinguals showed greater task-related deactivation in the anterior medial frontal region and greater anterior cingulate activation. Although unequal bilinguals kept apace with equal bilinguals in the simple PWM task, the differential cortical activations suggest that more optimal engagement of PWM in the latter may correlate with better second-language attainment.