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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.

Background: Working memory (WM) deficits are common in multiple sclerosis (MS) patients. Computerized cognitive training may enhance WM capabilities but its efficacy in MS patients has not been sufficiently explored. Methods: This study examines the effects of n-back training on cognitive performance and functional connectivity (FC) in 29 MS patients and 29 healthy controls (HC). Baseline (S1) performance on 2- and 3-back tasks and FC within the fronto-parietal network were assessed before randomly splitting the sample into four subgroups: trained MS (MSt, n = 15), trained HC (HCt, n = 14), untrained MS (MSu, n = 14), and untrained HC (HCu, n = 15). The trained subgroups underwent adaptive n-back training (60 min/day; 4 days) and n-back task performance and FC were reassessed in a second session (S2). Results: As revealed by mixed two-way ANOVAs, trained participants (MSt and HCt) exhibited a significant increase in the number of correct responses and significantly reduced reaction times in S2. These performance improvements were accompanied by an increase in FC in the fronto-parietal pathways and statistically significant correlations between both effects were found. Conclusions: Computerised WM training results in behavioural and neuroplasticity positive effects that may be useful when trying to prevent or attenuate cognitive decline in MS patients.

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)"

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.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The present study aimed to investigate altered grey matter (GM) and functional connectivity (FC) in deep subcortical areas, like the thalamus and basal ganglia, and their relationship with cognitive impairment in multiple sclerosis (MS). Thirty-six patients were neuropsychologically assessed, classified as cognitive preserved (CP) and cognitive impairment (CI), and were compared with 18 healthy controls (HC). GM atrophy and FC were observed in 10 predefined functional areas of the thalamus and in six of basal ganglia. GM atrophy was prominent in the basal ganglia in CI patients compared to CP MS patients. Increased FC was observed between the right caudate and the bilateral orbitofrontal cortex in CI vs. CP patients. The discriminant and correlation analyses revealed that the enhanced FC observed between the right caudate and the orbitofrontal cortex was closely associated with cognitive impairment in MS patients. In conclusion, reduced GM volume and enhanced fronto-basal ganglia connectivity are related to cognition in MS patients.

Sex differences in 116 local gray matter volumes (GMVOL) were assessed in 444 males and 444 females without correcting for total intracranial volume (TIV) or after adjusting the data with the scaling, proportions, power-corrected proportions (PCP), and residuals methods. The results confirmed that only the residuals and PCP methods completely eliminate TIV-variation and result in sex-differences that are “small” (∣d∣ $$\approx $$ ≈ 93%) than scaling and proportions adjusted-data $$( \approx $$ ( ≈ 68%) or raw data ($$\approx $$ ≈ 45%). The replicated effects were meta-analyzed together and confirmed that, when TIV-variation is adequately controlled, volumetric sex differences become “small” (∣d∣ VOL features in predicting individuals’ sex with 12 different machine learning classifiers. Sex could be reliably predicted (> 80%) when using raw local GMVOL, but also when using scaling or proportions adjusted-data or TIV as a single predictor. Conversely, after properly controlling TIV variation with the PCP and residuals’ methods, prediction accuracy dropped to $$\approx $$ ≈ 60%. It is concluded that gross morphological differences account for most of the univariate and multivariate sex differences in GMVOL

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)".

Background/Objective. To explore the effectiveness of a specific working memory (WM) training program in MS patients and healthy controls (HC). Method. 29 MS patients and 29 matched HC were enrolled in the study. MS and HC were randomly split into two groups: nontraining groups (15HC/14 MS) and training groups (14 HC/15 MS). Training groups underwent adaptive n-back training (60 min/day; 4 days). Functional magnetic resonance imaging (fMRI) was used to monitor brain activity during n-back performance (conditions: 0-back, 2-back, and 3-back) at 3 time points: (1) baseline, (2) post-training (+7days), and (3) follow-up (+35days). Results. In post-training and follow-up fMRI sessions, trained groups (HC and MS patients) exhibited significant reaction time (RT) reductions and increases in Correct Responses (CRs) during 2-back and 3-back performance. This improvement of task performance was accompanied by a decrease in brain activation in the WM frontoparietal network. The two effects were significantly correlated. Conclusions. After WM training, both cognitively preserved MS patients and HC participants showed task performance improvement made possible by neuroplastic processes that enhanced neural efficiency.

La Esclerosis Múltiple (EM) es una enfermedad en la que la memoria de trabajo (MT) se encuentra comúnmente afectada. Estudiar la eficacia de un programa de entrenamiento en MT en pacientes de EM. 29 pacientes de EM Remitente-Recurrente fueron seleccionados para el estudio: 15 realizaron el entrenamiento en MT y 14 fueron seleccionados como grupo control. Todos los participantes fueron valorados a nivel neuropsicológico y se adquirieron imágenes de Resonancia Magnética funcional (RMf) durante la realización de la tarea 2 y 3-back (basal y post tratamiento-7 días). Los pacientes entrenados mejoraron su ejecución en 2 y 3-back (p