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Background: Malfunctioning of the default mode network (DMN) has been consistently related to mild cognitive impairment (MCI) and Alzheimer’s disease (AD). However, evidence on differences in this network between MCI converters (MCI-c) and non-converters (MCI-nc), which could mark progression to AD, is still inconsistent. Objective: To multimodally investigate the DMN in the AD continuum. Methods: We measured gray matter (GM) volume, white matter (WM) integrity, and functional connectivity (FC) at rest in healthy elderly controls, MCI-c, MCI-nc, and AD patients, matched on sociodemographic variables. Results: Significant differences between AD patients and controls were found in the structure of most of the regions of the DMN. MCI-c only differed from MCI-nc in GM volume of the left parahippocampus and bilateral hippocampi and middle frontal gyri, as well as in WM integrity of the parahippocampal cingulum connecting the left hippocampus and precuneus. We found significant correlations between integrity in some of those regions and global neuropsychological status, as well as an excellent discrimination ability between converters and non-converters for the sum of GM volume of left parahippocampus, bilateral hippocampi, and middle frontal gyri, and WM integrity of left parahippocampal cingulum. However, we found no significant differences in FC. Conclusion: These results further support the relationship between abnormalities in the DMN and AD, and suggest that structural measures could be more accurate than resting-state estimates as markers of conversion from MCI to AD.

A low number of individuals show an atypical brain control of language functions that differs from the typical lateralization in the left cerebral hemisphere. In these cases, the neural distribution of other cognitive functions is not fully understood. Although there is a bias towards a mirrored brain organization consistent with the Causal hypothesis, some individuals are found to be exceptions to this rule. However, no study has focused on what happens to the homologous language areas in the right frontal inferior cortex. Using an fMRI-adapted stop-signal task in a healthy non right-handed sample (50 typically lateralized and 36 atypically lateralized for language production), our results show that atypical lateralization is associated with a mirrored brain organization of the inhibitory control network in the left hemisphere: inferior frontal cortex, presupplementary motor area, and subthalamic nucleus. However, the individual analyses revealed a large number of cases with a noteworthy overlap in the inferior frontal gyrus, which shared both inhibitory and language functions. Further analyses showed that atypical lateralization was associated with stronger functional and structural interhemispheric connectivity.Importantly, we did not find task performance differences as a function of lateralization, but there was an association between atypical dominance in the inferior frontal cortex and higher scores on schizotypy and autistic spectrum traits, as well as worse performance on a reading accuracy test. Together, these results partially support the Causal hypothesis of hemispheric specialization and provide further evidence of the link between atypical hemispheric lateralization and increased interhemispheric transfer through the corpus callosum.

Background and purpose Previous investigations show that bilinguals exhibit the first symptoms of dementia 4-5 years later than monolinguals. Therefore, bilingualism has been proposed as a cognitive reserve mechanism. Recent studies have advanced towards an understanding of the brain mechanisms underlying bilingualism's protection against dementia, but none of them deals with white matter (WM) diffusion. Methods In this study, the topic was investigated by measuring WM integrity in a sample of 35 bilinguals and 53 passive bilinguals with mild cognitive impairment. Results No significant differences were found between the groups in cognitive level, education, age or sex. However, bilinguals showed higher mean diffusivity in the fornix, but higher fractional anisotropy, lower mean diffusivity, axial diffusivity and radial diffusivity in the parahippocampal cingulum, and lower radial diffusivity in the right uncinate fasciculus. Significant correlations were also found between WM integrity in the left parahippocampal cingulum and the Boston Naming Test in passive bilinguals. Conclusions These results suggest that bilingualism contributes to a differential pattern of WM disintegration due to mild cognitive impairment in fibers related to bilingualism and memory.

Alzheimer's disease (AD) has been associated with memory impairment due to alterations in the medial temporal lobe (MTL) and the precuneus. Therefore, the goal of this study was to investigate the effects of AD on the brain networks associated with the hippocampus and precuneus during an encoding memory task. 68 mild cognitive impairment patients (MCI), 21 AD patients, and 20 healthy controls (HC) were included. Participants were instructed to memorize landscapes while undergoing fMRI scanning, followed by a recognition test. MCI were followed up clinically for 18 months to track conversion status. Independent component analysis (ICA) was performed to investigate AD effects on precuneus and MTL networks during memory encoding. Behavioral analyses indicate that HC had a better performance than MCI converters (MCIc) and AD. ICA showed that MCIc had significantly higher activation in the MTL-associated network than MCI non converters (MCIn) and AD, including bilateral hippocampus, parahippocampus, and fusiform gyrus. Furthermore, the precuneus-associated network fitted the default mode network, showing a negative correlation with behavioral performance. These findings indicate that the hyperactivation of the hippocampal network displayed by MCIc has potential discrimination capacity to distinguish them of MCIn, and could be interpreted as a compensatory mechanism.

Introducción: Recientes estudios sugieren que el bilingüismo es uno de los factores que contribuye a la reserva cognitiva, ya que las personas bilingües suelen manifestar los síntomas de la enfermedad de Alzheimer (EA) significativamente más tarde que los monolingües. Otros estudios han revelado que los bilingües muestran mayor atrofia e hipometabolismo comparados con los monolingües, pese a tener el mismo diagnóstico. Sin embargo, todas estas investigaciones incluyen participantes bilingües y monolingües que muestran diferencias en nivel educativo, nivel socioeconómico o estatus de inmigración. El objetivo de este trabajo es investigar las bases neurales del supuesto efecto protector del bilingüismo. Metodología: Una muestra de 68 pacientes con deterioro cognitivo leve (DCL) fue incluida en el estudio, con 26 bilingües y 42 monolingües. Se recogieron imágenes 3D de resonancia magnética a partir de las cuales se compararon los volúmenes de sustancia gris de ambos grupos. Resultados: Bilingües y monolingües no mostraron diferencias significativas en variables demográficas ni en rendimiento cognitivo en pruebas psicológicas. Sin embargo, los bilingües mostraron menor volumen de sustancia gris (mayor atrofia cerebral) que los monolingües en las siguientes áreas: precuneus izquierdo, área de Wernicke izquierda, ínsula/giro de Heschl bilateral y vermis cerebelar bilateral. Conclusión: Los bilingües, con la misma edad, nivel educativo y manifestación de síntomas de la enfermedad, muestran mayor atrofia de sustancia gris que los monolingües en áreas relevantes para la EA. Esto sugiere que el bilingüismo actúa como un factor protector de la demencia, ya que requiere mayor atrofia cerebral para llegar al mismo estado patológico. Introduction: Evidence from previous studies suggests that bilingualism is one of the factors which contributes to cognitive reserve, by showing that bilingual individuals manifest symptoms of Alzheimer’s disease (AD) significantly later than monolinguals. Other evidences revealed that bilinguals show greater amounts of atrophy or hypometabolism compared to monolinguals, despite having the same diagnosis of AD and similar symptoms. However, these previous studies included samples in which bilinguals and monolinguals showed differences in education, immigration and/or socioeconomic status. The aim of this work was to investigate the neural bases of these putative protective effects of bilingualism. Methods: A sample of 68 patients with mild cognitive impairment (MCI), 26 bilinguals and 42 monolinguals, was included in the study. Whole-brain 3-D magnetic resonance images were collected in order to compare the gray matter volume of both groups. Results: Bilinguals and monolinguals showed no significant differences in sociodemographic variables nor cognitive performance in neuropsychological testing. However, bilinguals showed less gray matter volume (more brain atrophy) than monolinguals in the following areas: left precuneus, left Wernicke’s area, bilateral insula/Heschl’s gyrus and bilateral cerebellar vermis. Conclusion: Bilinguals with the same age, level of education and manifestation of symptoms as monolinguals, show higher levels of gray matter atrophy than monolinguals in relevant areas for AD. This suggests that bilingualism acts as a protective factor against dementia, since it requires more brain atrophy in order to get to the same pathological state.

Structural and functional neuroimaging studies have shown that brain areas associated with fear and anxiety (defensive system areas) are modulated by individual differences in sensitivity to punishment (SP). However, little is known about how SP is related to brain functional connectivity and the factors that modulate this relationship. In this study, we investigated whether a simple methodological manipulation, such as performing a resting state with eyes open or eyes closed, can modulate the manifestation of individual differences in SP. To this end, we performed an exploratory fMRI resting state study in which a group of participants (n = 88) performed a resting state with eyes closed and another group (n = 56) performed a resting state with eyes open. All participants completed the Sensitivity to Punishment and Sensitivity to Reward Questionnaire. Seed-based functional connectivity analyses were performed in the amygdala, hippocampus, and periaqueductal gray (PAG). Our results showed that the relationship between SP and left amygdala-precuneus and left hippocampus-precuneus functional connectivity was modulated by eye state. Moreover, in the eyes open group, SP was negatively related to the functional connectivity between the PAG and amygdala and between the PAG and left hippocampus, and it was positively related to the functional connectivity between the amygdala and hippocampus. Together, our results may suggest underlying differences in the connectivity between anxiety-related areas based on eye state, which in turn would affect the manifestation of individual differences in SP. This work was supported by grants from Generalitat Valenciana (PROMETEO/2017/109) and Ministerio de Economía y Competitividad (PSI2016-78805-R) to C.A. Also, it was supported by a grant from Jaume I University (UJI-B2016-21) to A.B-L. Additionally, this work was supported by a pre-doctoral graduate program grant (National FPU to J.A-V, L.M-M, E.V-R and N.A) and a post-doctoral graduate program grant (Juan de la Cierva to V.C and postdoc-UJI to A.M-P and M-Á.P-G). Author E.B was funded by a post-doctoral grant from the "Generalitat Valenciana (2018 APOSTD)" and the "European Social Fund (Investing in your future)"

Structural and functional neuroimaging studies have shown that brain areas associated with fear and anxiety (defensive system areas) are modulated by individual differences in sensitivity to punishment (SP). However, little is known about how SP is related to brain functional connectivity and the factors that modulate this relationship. In this study, we investigated whether a simple methodological manipulation, such as performing a resting state with eyes open or eyes closed, can modulate the manifestation of individual differences in SP. To this end, we performed an exploratory fMRI resting state study in which a group of participants (n = 88) performed a resting state with eyes closed and another group (n = 56) performed a resting state with eyes open. All participants completed the Sensitivity to Punishment and Sensitivity to Reward Questionnaire. Seed-based functional connectivity analyses were performed in the amygdala, hippocampus, and periaqueductal gray (PAG). Our results showed that the relationship between SP and left amygdala-precuneus and left hippocampus-precuneus functional connectivity was modulated by eye state. Moreover, in the eyes open group, SP was negatively related to the functional connectivity between the PAG and amygdala and between the PAG and left hippocampus, and it was positively related to the functional connectivity between the amygdala and hippocampus. Together, our results may suggest underlying differences in the connectivity between anxiety-related areas based on eye state, which in turn would affect the manifestation of individual differences in SP.

The adhesio interthalamica (AI) is a small midline brain structure that connects the left and right thalamus. According to in vivo data, between 2.3–22.3% of the general population lack the AI, and the question of whether this absence is more prevalent in males than in females is a matter of debate. Despite the existence of these demographic figures, it remains unclear how this distinctive feature affects healthy people, or what specific anatomic profile is related to the presence or absence of the AI. The aim of this study was to investigate whole brain gray matter (GM) volumetric differences depending on the presence or absence of the AI. A total of 240 healthy adult volunteers completed one MRI scanning session. After the AI assessment, the data from 110 participants were included in the final sample, of which 12.9% of the participants (n = 31) presented complete AI absence vs. 32.9% of participants (n = 79) who presented complete AI presence. Then, whole-brain group comparison analysis revealed that the absent AI brain, compared to the present AI brain, was associated with lower GM volume in the premotor cortex, inferior frontal gyrus, and anterior temporal cortex. Interestingly, neuroscience research has linked emotional and cognitive control brain processing to the latter two regions. The importance of these findings lies in providing a neuroanatomical profile for the absent AI brain in healthy human adults.

Background Evidence from previous studies suggests that bilingualism contributes to cognitive reserve because bilinguals manifest the first symptoms of Alzheimer’s disease (AD) up to 5 years later than monolinguals. Other cross-sectional studies demonstrate that bilinguals show greater amounts of brain atrophy and hypometabolism than monolinguals, despite sharing the same diagnosis and suffering from the same symptoms. However, these studies may be biased by possible pre-existing between-group differences. Methods In this study, we used global parenchymal measures of atrophy and cognitive tests to investigate the protective effect of bilingualism against dementia cross-sectionally and prospectively, using a sample of bilinguals and monolinguals in the same clinical stage and matched on sociodemographic variables. Results Our results suggest that the two groups did not differ in their cognitive status at baseline, but bilinguals had less parenchymal volume than monolinguals, especially in areas related to brain atrophy in dementia. In addition, a longitudinal prospective analysis revealed that monolinguals lost more parenchyma and had more cognitive decline than bilinguals in a mean follow-up period of 7 months. Conclusion These results provide the first prospective evidence that bilingualism may act as a neuroprotective factor against dementia and could be considered a factor in cognitive reserve.

Working memory training causes functional adaptations in the brain, which include changes in activation and functional connectivity that remain stable over time. Few studies have investigated gray matter (GM) changes after working memory training, and they have produced heterogeneous results without clarifying the stable effects of training. The present study was designed to test for sustained and transient anatomic changes after only 200 min of working memory training. The voxel-based morphometry technique was used in order to investigate the GM changes produced by a brief single n-back training, immediately and 5 weeks after finishing it. The sample was composed by 59 human participants who underwent MRI scanning and were assigned to either a training group or a passive control group. Results showed sustained GM volume enlargement in the right superior parietal cortex and a transient GM decrease in the right putamen. The brain adaptation in the right superior parietal cortex was stronger in individuals who showed greater improvements in performance. The results provide further evidence that a brief working memory training is able to produce brain plasticity in structures related to the trained task. This work was supported by grants from Universitat Jaume I (P1•1B2013-63) and Ministerio de Economia y Competitividad (PSI2013-47504-R and PSI2016-78805-R). Authors J. Adrián-Ventura, E. Villar-Rodriguez, L. Marin-Marin and N. Aguirre were supported by a pre-doctoral graduate program grant (National FPU to J.A-V, L.M-M, E.V-R and N.A). In addition, this work was supported by a post-doctoral graduate program grant to V. Costumero, M-Á. Palomar-García and A. Miró-Padilla (Juan de la Cierva to V.C and postdoc-UJI to M-Á.P-G and A.M.P). Author E. Bueichekú was funded by a postdoctoral grant from the "Generalitat Valenciana (2018 APOSTD)" and the "European Social Fund (Investing in your future)".