Baseline long-term potentiation-like cortical plasticity is associated with longitudinal cortical thinning in healthy adults and in adults with bipolar disorder type II.

The precise neurobiological processes underlying cerebral cortical thinning in aging and psychiatric illnesses remain undetermined, yet aging- and synaptic dysfunction-related loss of synapses are potentially important mechanisms. We used long-term potentiation-like plasticity of the visual evoked potential as an index of synaptic function in the cortex and hypothesized that plasticity at baseline would be negatively associated with future cortical thinning in healthy adults and in adults with bipolar disorder type II. Thirty-two healthy adults and 15 adults with bipolar disorder type II underwent electroencephalography-based measurement of visual evoked potential plasticity and 3T magnetic resonance imaging of the brain at baseline and a follow-up brain scan on average 2.3 years later. The relationships between visual evoked potential plasticity at baseline and longitudinal cortical thickness changes were examined using Freesurfer and the Permutation Analysis of Linear Models tool. The analyses showed a negative association between the plasticity of the N1 visual evoked potential amplitude at baseline and thinning rate in the medial and lateral parietal and medial occipital cortices in healthy adults and in the right medial occipital cortex in the total sample of healthy adults and adults with bipolar disorder type II, indicating greater thinning over time in subjects with less N1 plasticity (pFWER < .05). Although preliminary, the results indicate an association between visual evoked potential plasticity and the future rate of cortical thinning in healthy adults and in bipolar disorder type II, supporting the hypothesis that cortical thinning might be related to synaptic dysfunction.

Long term potentiation-like neural plasticity and performance-based memory function.

OBJECTIVE: Experience-dependent modulation of the visual evoked potential (VEP) has emerged as a promising non-invasive proxy for assaying long term potentiation (LTP)-like plasticity in the cerebral cortex. LTP is considered the principal candidate mechanism underlying learning and memory. There is, however, a paucity of evidence exploring associations between LTP-like plasticity and performance-based learning and memory. The present study aimed to explore the relationship between VEP-plasticity and higher-order learning and memory in healthy adults. METHOD: Visual and verbal learning and memory was assessed using the Aggie Figures Learning Test (AFLT) and the Rey Auditory Verbal Learning Test (RAVLT). The study included 111 healthy adults (61.1% females; mean age 37.6 years, range 17-71) who underwent a VEP paradigm employing visual high-frequency stimulation to induce a change in visual evoked responses recorded by scalp EEG. In addition, a more comprehensive neuropsychological assessment was administered. RESULTS: Several significant moderate age-corrected positive correlations were found between modulation of the later VEP components (N1 and P1-N1 peak-to-peak) and both visual and verbal learning and memory performance. Further, there were significant differences in learning and memory performance between participants showing a higher degree of modulation (>1 SD above mean) compared to participants showing a lower degree of modulation. No significant associations were found between VEP-plasticity and other neurocognitive domains. CONCLUSIONS: The current results suggest that LTP-like plasticity indexed by VEP modulation reflect processes specific to learning and memory. Future research is needed to further delineate the complex relationship between neural plasticity and learning and memory, specifically concerning possible clinical implications in populations with deficits in learning and memory function.

Genetic control of variability in subcortical and intracranial volumes.

Sensitivity to external demands is essential for adaptation to dynamic environments, but comes at the cost of increased risk of adverse outcomes when facing poor environmental conditions. Here, we apply a novel methodology to perform genome-wide association analysis of mean and variance in ten key brain features (accumbens, amygdala, caudate, hippocampus, pallidum, putamen, thalamus, intracranial volume, cortical surface area, and cortical thickness), integrating genetic and neuroanatomical data from a large lifespan sample (n = 25,575 individuals; 8-89 years, mean age 51.9 years). We identify genetic loci associated with phenotypic variability in thalamus volume and cortical thickness. The variance-controlling loci involved genes with a documented role in brain and mental health and were not associated with the mean anatomical volumes. This proof-of-principle of the hypothesis of a genetic regulation of brain volume variability contributes to establishing the genetic basis of phenotypic variance (i.e., heritability), allows identifying different degrees of brain robustness across individuals, and opens new research avenues in the search for mechanisms controlling brain and mental health.

Population-based neuroimaging reveals traces of childbirth in the maternal brain.

Maternal brain adaptations have been found across pregnancy and postpartum, but little is known about the long-term effects of parity on the maternal brain. Using neuroimaging and machine learning, we investigated structural brain characteristics in 12,021 middle-aged women from the UK Biobank, demonstrating that parous women showed less evidence of brain aging compared to their nulliparous peers. The relationship between childbirths and a "younger-looking" brain could not be explained by common genetic variation or relevant confounders. Although prospective longitudinal studies are needed, the results suggest that parity may involve neural changes that could influence women's brain aging later in life.

Do visual and auditory stimulus-specific response modulation reflect different mechanisms of neocortical plasticity?

Stimulus response modulation (SRM) of sensory evoked potentials represents a promising method as a non-invasive index of long-term potentiation (LTP)-like synaptic plasticity in the human sensory cortices. As of today, however, no consensus exists regarding which experimental parameters elicit the most robust SRM response. The aim of the current study was twofold; firstly, we aimed to replicate former studies demonstrating visual SRM in healthy adults. Second, we integrated visual and auditory stimuli within the same SRM recording session to assay potential cross-modal associations. Such an association between modalities would strengthen the assumption that the SRM effect reflects common mechanisms underlying synaptic plasticity rather than reflecting modality-specific phenomena. A replication of previous findings showing robust potentiation of the visual evoked potential was evident, supporting the majority of previous work using similar paradigms, lending further support to the notion that high-frequent visual stimulation is a viable probe into LTP-like synaptic plasticity in the human visual cortex. The auditory evoked potentials (AEPs) did not, however, fully replicate previous work, though a significant increase of temporally later AEP components was found. In contrast to our hypothesis, there were no significant within-subject cross-modality correlations between the visual and auditory SRM. This lack of significant association might suggest that auditory and visual SRM depend on different mechanisms, and that further SRM studies on non-invasive LTP-like synaptic plasticity should focus on optimizing paradigms within the visual modality.

A history of previous childbirths is linked to women's white matter brain age in midlife and older age.

Maternal brain adaptations occur in response to pregnancy, but little is known about how parity impacts white matter and white matter ageing trajectories later in life. Utilising global and regional brain age prediction based on multi-shell diffusion-weighted imaging data, we investigated the association between previous childbirths and white matter brain age in 8,895 women in the UK Biobank cohort (age range = 54-81 years). The results showed that number of previous childbirths was negatively associated with white matter brain age, potentially indicating a protective effect of parity on white matter later in life. Both global white matter and grey matter brain age estimates showed unique contributions to the association with previous childbirths, suggesting partly independent processes. Corpus callosum contributed uniquely to the global white matter association with previous childbirths, and showed a stronger relationship relative to several other tracts. While our findings demonstrate a link between reproductive history and brain white matter characteristics later in life, longitudinal studies are required to establish causality and determine how parity may influence women's white matter trajectories across the lifespan.

Replicating extensive brain structural heterogeneity in individuals with schizophrenia and bipolar disorder.

Identifying brain processes involved in the risk and development of mental disorders is a major aim. We recently reported substantial interindividual heterogeneity in brain structural aberrations among patients with schizophrenia and bipolar disorder. Estimating the normative range of voxel-based morphometry (VBM) data among healthy individuals using a Gaussian process regression (GPR) enables us to map individual deviations from the healthy range in unseen datasets. Here, we aim to replicate our previous results in two independent samples of patients with schizophrenia (n1 = 94; n2 = 105), bipolar disorder (n1 = 116; n2 = 61), and healthy individuals (n1 = 400; n2 = 312). In line with previous findings with exception of the cerebellum our results revealed robust group level differences between patients and healthy individuals, yet only a small proportion of patients with schizophrenia or bipolar disorder exhibited extreme negative deviations from normality in the same brain regions. These direct replications support that group level-differences in brain structure disguise considerable individual differences in brain aberrations, with important implications for the interpretation and generalization of group-level brain imaging findings to the individual with a mental disorder.

Brain scans from 21,297 individuals reveal the genetic architecture of hippocampal subfield volumes.

The hippocampus is a heterogeneous structure, comprising histologically distinguishable subfields. These subfields are differentially involved in memory consolidation, spatial navigation and pattern separation, complex functions often impaired in individuals with brain disorders characterized by reduced hippocampal volume, including Alzheimer's disease (AD) and schizophrenia. Given the structural and functional heterogeneity of the hippocampal formation, we sought to characterize the subfields' genetic architecture. T1-weighted brain scans (n = 21,297, 16 cohorts) were processed with the hippocampal subfields algorithm in FreeSurfer v6.0. We ran a genome-wide association analysis on each subfield, co-varying for whole hippocampal volume. We further calculated the single-nucleotide polymorphism (SNP)-based heritability of 12 subfields, as well as their genetic correlation with each other, with other structural brain features and with AD and schizophrenia. All outcome measures were corrected for age, sex and intracranial volume. We found 15 unique genome-wide significant loci across six subfields, of which eight had not been previously linked to the hippocampus. Top SNPs were mapped to genes associated with neuronal differentiation, locomotor behaviour, schizophrenia and AD. The volumes of all the subfields were estimated to be heritable (h2 from 0.14 to 0.27, all p < 1 × 10-16) and clustered together based on their genetic correlations compared with other structural brain features. There was also evidence of genetic overlap of subicular subfield volumes with schizophrenia. We conclude that hippocampal subfields have partly distinct genetic determinants associated with specific biological processes and traits. Taking into account this specificity may increase our understanding of hippocampal neurobiology and associated pathologies.

Experience-dependent modulation of the visual evoked potential: Testing effect sizes, retention over time, and associations with age in 415 healthy individuals.

Experience-dependent modulation of the visual evoked potential (VEP) is a promising proxy measure of synaptic plasticity in the cerebral cortex. However, existing studies are limited by small to moderate sample sizes as well as by considerable variability in how VEP modulation is quantified. In the present study, we used a large sample (n = 415) of healthy volunteers to compare different quantifications of VEP modulation with regards to effect sizes and retention of the modulation effect over time. We observed significant modulation for VEP components C1 (Cohen's d = 0.53), P1 (d = 0.66), N1 (d=-0.27), N1b (d=-0.66), but not P2 (d = 0.08), and in three clusters of total power modulation, 2-4 min after 2 Hz prolonged visual stimulation. For components N1 (d=-0.21) and N1b (d=-0.38), as well for the total power clusters, this effect was retained after 54-56 min, by which time also the P2 component had gained modulation (d = 0.54). Moderate to high correlations (0.39≤ρ≤0.69) between modulation at different postintervention blocks revealed a relatively high temporal stability in the modulation effect for each VEP component. However, different VEP components also showed markedly different temporal retention patterns. Finally, participant age correlated negatively with C1 (χ2=30.4), and positively with P1 modulation (χ2=13.4), whereas P2 modulation was larger for female participants (χ2=15.4). There were no effects of either age or sex on N1 and N1b potentiation. These results provide strong support for VEP modulation, and especially N1b modulation, as a robust measure of synaptic plasticity, but underscore the need to differentiate between components, and to control for demographic confounders.

Alterations in Schizophrenia-Associated Genes Can Lead to Increased Power in Delta Oscillations.

Genome-wide association studies have implicated many ion channels in schizophrenia pathophysiology. Although the functions of these channels are relatively well characterized by single-cell studies, the contributions of common variation in these channels to neurophysiological biomarkers and symptoms of schizophrenia remain elusive. Here, using computational modeling, we show that a common biomarker of schizophrenia, namely, an increase in delta-oscillation power, may be a direct consequence of altered expression or kinetics of voltage-gated ion channels or calcium transporters. Our model of a circuit of layer V pyramidal cells highlights multiple types of schizophrenia-related variants that contribute to altered dynamics in the delta-frequency band. Moreover, our model predicts that the same membrane mechanisms that increase the layer V pyramidal cell network gain and response to delta-frequency oscillations may also cause a deficit in a single-cell correlate of the prepulse inhibition, which is a behavioral biomarker highly associated with schizophrenia.

Distinguishing early and late brain aging from the Alzheimer's disease spectrum: consistent morphological patterns across independent samples.

Alzheimer's disease (AD) is a debilitating age-related neurodegenerative disorder. Accurate identification of individuals at risk is complicated as AD shares cognitive and brain features with aging. We applied linked independent component analysis (LICA) on three complementary measures of gray matter structure: cortical thickness, area and gray matter density of 137 AD, 78 mild (MCI) and 38 subjective cognitive impairment patients, and 355 healthy adults aged 18-78 years to identify dissociable multivariate morphological patterns sensitive to age and diagnosis. Using the lasso classifier, we performed group classification and prediction of cognition and age at different age ranges to assess the sensitivity and diagnostic accuracy of the LICA patterns in relation to AD, as well as early and late healthy aging. Three components showed high sensitivity to the diagnosis and cognitive status of AD, with different relationships with age: one reflected an anterior-posterior gradient in thickness and gray matter density and was uniquely related to diagnosis, whereas the other two, reflecting widespread cortical thickness and medial temporal lobe volume, respectively, also correlated significantly with age. Repeating the LICA decomposition and between-subject analysis on ADNI data, including 186 AD, 395 MCI and 220 age-matched healthy controls, revealed largely consistent brain patterns and clinical associations across samples. Classification results showed that multivariate LICA-derived brain characteristics could be used to predict AD and age with high accuracy (area under ROC curve up to 0.93 for classification of AD from controls). Comparison between classifiers based on feature ranking and feature selection suggests both common and unique feature sets implicated in AD and aging, and provides evidence of distinct age-related differences in early compared to late aging.

Generalized role for the cerebellum in encoding internal models: evidence from semantic processing.

The striking homogeneity of cerebellar microanatomy is strongly suggestive of a corresponding uniformity of function. Consequently, theoretical models of the cerebellum's role in motor control should offer important clues regarding cerebellar contributions to cognition. One such influential theory holds that the cerebellum encodes internal models, neural representations of the context-specific dynamic properties of an object, to facilitate predictive control when manipulating the object. The present study examined whether this theoretical construct can shed light on the contribution of the cerebellum to language processing. We reasoned that the cerebellum might perform a similar coordinative function when the context provided by the initial part of a sentence can be highly predictive of the end of the sentence. Using functional MRI in humans we tested two predictions derived from this hypothesis, building on previous neuroimaging studies of internal models in motor control. First, focal cerebellar activation-reflecting the operation of acquired internal models-should be enhanced when the linguistic context leads terminal words to be predictable. Second, more widespread activation should be observed when such predictions are violated, reflecting the processing of error signals that can be used to update internal models. Both predictions were confirmed, with predictability and prediction violations associated with increased blood oxygenation level-dependent signal in the posterior cerebellum (Crus I/II). Our results provide further evidence for cerebellar involvement in predictive language processing and suggest that the notion of cerebellar internal models may be extended to the language domain.

Assessing the Longitudinal Associations Between Decision-Making Processes and Attention Problems in Early Adolescence.

Cognitive functions and psychopathology develop in parallel in childhood and adolescence, but the temporal dynamics of their associations are poorly understood. The present study sought to elucidate the intertwined development of decision-making processes and attention problems using longitudinal data from late childhood (9-10 years) to mid-adolescence (11-13 years) from the Adolescent Brain Cognitive Development (ABCD) Study (n = 8918). We utilised hierarchical drift-diffusion modelling of behavioural data from the stop-signal task, parent-reported attention problems from the Child Behavior Checklist (CBCL), and multigroup univariate and bivariate latent change score models. The results showed faster drift rate was associated with lower levels of inattention at baseline, as well as a greater reduction of inattention over time. Moreover, baseline drift rate negatively predicted change in attention problems in females, and baseline attention problems negatively predicted change in drift rate. Neither response caution (decision threshold) nor encoding- and responding processes (non-decision time) were significantly associated with attention problems. There were no significant sex differences in the associations between decision-making processes and attention problems. The study supports previous findings of reduced evidence accumulation in attention problems and additionally shows that development of this aspect of decision-making plays a role in developmental changes in attention problems in youth.

Mismatch negativity and polygenic risk scores for schizophrenia and bipolar disorder.

OBJECTIVE: Auditory mismatch negativity (MMN) impairment is a candidate endophenotype in psychotic disorders, yet the genetic underpinnings remain to be clarified. Here, we examined the relationships between auditory MMN and polygenic risk scores (PRS) for individuals with psychotic disorders, including schizophrenia spectrum disorders (SSD) and bipolar disorder (BD) and in healthy controls (HC). METHODS: Genotyped and clinically well-characterized individuals with psychotic disorders (n = 102), including SSD (n = 43) and BD (n = 59), and HC (n = 397) underwent a roving MMN paradigm. In addition MMN, we measured the memory traces of the repetition positivity (RP) and the deviant negativity (DN), which is believed to reflect prediction encoding and prediction error signals, respectively. SCZ and BD PRS were computed using summary statistics from the latest genome-wide association studies. The relationships between the MMN, RP, and DN and the PRSs were assessed with linear regressions. RESULTS: We found no significant association between the SCZ or BD PRS and grand average MMN in the psychotic disorders group or in the HCs group (all p > 0.05). SCZ PRS and BD PRS were negatively associated with RP in the psychotic disorders group (ß = -0.46, t = -2.86, p = 0.005 and ß = -0.29, t = -0.21, p = 0.034, respectively). No significant associations were found between DN and PRS. CONCLUSION: These findings suggest that genetic variants associated with SCZ and BD may be associated with MMN subcomponents linked to predictive coding among patients with psychotic disorders. Larger studies are needed to confirm these findings and further elucidate the genetic underpinnings of MMN impairment in psychotic disorders.

Mapping Normative Trajectories of Cognitive Function and Its Relation to Psychopathology Symptoms and Genetic Risk in Youth.

Background: Adolescence hosts a sharp increase in the incidence of mental disorders. The prodromal phases are often characterized by cognitive deficits that predate disease onset by several years. Characterization of cognitive performance in relation to normative trajectories may have value for early risk assessment and monitoring. Methods: Youth aged 8 to 21 years (N = 6481) from the Philadelphia Neurodevelopmental Cohort were included. Performance scores from a computerized neurocognitive battery were decomposed using principal component analysis, yielding a general cognitive score. Items reflecting various aspects of psychopathology from self-report questionnaires and collateral caregiver information were decomposed using independent component analysis, providing individual domain scores. Using normative modeling and Bayesian statistics, we estimated normative trajectories of cognitive function and tested for associations between cognitive deviance and psychopathological domain scores. In addition, we tested for associations with polygenic scores for mental and behavioral disorders often involving cognition, including schizophrenia, bipolar disorder, attention-deficit/hyperactivity disorder, and Alzheimer's disease. Results: More negative normative cognitive deviations were associated with higher general psychopathology burden and domains reflecting positive and prodromal psychosis, attention problems, norm-violating behavior, and anxiety. In addition, better performance was associated with higher joint burden of depression, suicidal ideation, and negative psychosis symptoms. The analyses revealed no evidence for associations with polygenic scores. Conclusions: Our results show that cognitive performance is associated with general and specific domains of psychopathology in youth. These findings support the close links between cognition and psychopathology in youth and highlight the potential of normative modeling for early risk assessment.

Reaction Time Variability in Children Is Specifically Associated With Attention Problems and Regional White Matter Microstructure.

BACKGROUND: Increased intraindividual variability (IIV) in reaction times (RTs) has been suggested as a key cognitive and behavioral marker of attention problems, but findings for other dimensions of psychopathology are less consistent. Moreover, while studies have linked IIV to brain white matter microstructure, large studies testing the robustness of these associations are needed. METHODS: We used data from the Adolescent Brain Cognitive Development (ABCD) Study baseline assessment to test the associations between IIV and psychopathology (n = 8622, age = 8.9-11.1 years) and IIV and white matter microstructure (n = 7958, age = 8.9-11.1 years). IIV was investigated using an ex-Gaussian distribution analysis of RTs in correct response go trials in the stop signal task. Psychopathology was measured by the Child Behavior Checklist and a bifactor structural equation model was performed to extract a general p factor and specific factors reflecting internalizing, externalizing, and attention problems. To investigate white matter microstructure, fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity were examined in 23 atlas-based tracts. RESULTS: Increased IIV in both short and long RTs was positively associated with the specific attention problems factor (Cohen's d = 0.13 and d = 0.15, respectively). Increased IIV in long RTs was also positively associated with radial diffusivity in the left and right corticospinal tract (both tracts, d = 0.12). CONCLUSIONS: Using a large sample and a data-driven dimensional approach to psychopathology, the results provide novel evidence for a small but specific association between IIV and attention problems in children and support previous findings on the relevance of white matter microstructure for IIV.

Mismatch negativity in schizophrenia spectrum and bipolar disorders: Group and sex differences and associations with symptom severity.

OBJECTIVE: Research increasingly implicates glutamatergic dysfunction in the pathophysiologies of psychotic disorders. Auditory mismatch negativity (MMN) is an electroencephalography (EEG) waveform linked to glutamatergic neurotransmission and is consistently attenuated in schizophrenia (SCZ). MMN consists of two subcomponents, the repetition positivity (RP) and deviant negativity (DN) possibly reflecting different neural mechanisms. However, whether MMN reduction is present across different psychotic disorders, linked to distinct symptom clusters, or related to sex remain to be clarified. METHODS: Four hundred participants including healthy controls (HCs; n = 296) and individuals with SCZ (n = 39), bipolar disorder (BD) BD typeI (n = 35), or BD type II (n = 30) underwent a roving MMN paradigm and clinical evaluation. MMN, RP and DN as well their memory traces were recorded at the FCZ electrode. Analyses of variance and linear regression models were used both transdiagnostically and within clinical groups. RESULTS: MMN was reduced in SCZ compared to BD (p = 0.006, d = 0.55) and to HCs (p < 0.001, d = 0.63). There was a significant group × sex interaction (p < 0.003) and the MMN impairment was only detected in males with SCZ. MMN amplitude correlated positively with Positive and Negative Syndrome Scale total score and negatively with Global Assessment of Functioning Scale score. The deviant negativity was impaired in males with SCZ. No group differences in memory trace indices of the MMN, DN, or RP. CONCLUSION: MMN was attenuated in SCZ and correlated with greater severity of psychotic symptoms and lower level of functioning. Our results may indicate sex-dependent differences of glutamatergic function in SCZ.

Relationship between function and structure in the visual cortex in healthy individuals and in patients with severe mental disorders.

Patients with schizophrenia spectrum disorders (SCZspect) and bipolar disorders (BD) show impaired function in the primary visual cortex (V1), indicated by altered visual evoked potential (VEP). While the neural substrate for altered VEP in these patients remains elusive, altered V1 structure may play a role. One previous study found a positive relationship between the amplitude of the P100 component of the VEP and V1 surface area, but not V1 thickness, in a small sample of healthy individuals. Here, we aimed to replicate these findings in a larger healthy control (HC) sample (n = 307) and to examine the same relationship in patients with SCZspect (n = 30) or BD (n = 45). We also compared the mean P100 amplitude, V1 surface area and V1 thickness between controls and patients and found no significant group differences. In HC only, we found a significant positive P100-V1 surface area association, while there were no significant P100-V1 thickness relationships in HC, SCZspect or BD. Together, our results confirm previous findings of a positive P100-V1 surface area association in HC, whereas larger patient samples are needed to further clarify the function-structure relationship in V1 in SCZspect and BD.

Auditory Cortex Thickness Is Associated With N100 Amplitude in Schizophrenia Spectrum Disorders.

Background and Hypothesis: The auditory cortex (AC) may play a central role in the pathophysiology of schizophrenia and auditory hallucinations (AH). Previous schizophrenia studies report thinner AC and impaired AC function, as indicated by decreased N100 amplitude of the auditory evoked potential. However, whether these structural and functional alterations link to AH in schizophrenia remain poorly understood. Study Design: Patients with a schizophrenia spectrum disorder (SCZspect), including patients with a lifetime experience of AH (AH+), without (AH-), and healthy controls underwent magnetic resonance imaging (39 SCZspect, 22 AH+, 17 AH-, and 146 HC) and electroencephalography (33 SCZspect, 17 AH+, 16 AH-, and 144 HC). Cortical thickness of the primary (AC1, Heschl's gyrus) and secondary (AC2, Heschl's sulcus, and the planum temporale) AC was compared between SCZspect and controls and between AH+, AH-, and controls. To examine if the association between AC thickness and N100 amplitude differed between groups, we used regression models with interaction terms. Study Results: N100 amplitude was nominally smaller in SCZspect (P = .03, d = 0.42) and in AH- (P = .020, d = 0.61), while AC2 was nominally thinner in AH+ (P = .02, d = 0.53) compared with controls. AC1 thickness was positively associated with N100 amplitude in SCZspect (t = 2.56, P = .016) and AH- (t = 3.18, P = .008), while AC2 thickness was positively associated with N100 amplitude in SCZspect (t = 2.37, P = .024) and in AH+ (t = 2.68, P = .019). Conclusions: The novel findings of positive associations between AC thickness and N100 amplitude in SCZspect, suggest that a common neural substrate may underlie AC thickness and N100 amplitude alterations.

Memory training impacts short-term changes in aging white matter: a longitudinal diffusion tensor imaging study.

A growing body of research indicates benefits of cognitive training in older adults, but the neuronal mechanisms underlying the effect of cognitive intervention remains largely unexplored. Neuroimaging methods are sensitive to subtle changes in brain structure and show potential for enhancing our understanding of both aging- and training-related neuronal plasticity. Specifically, studies using diffusion tensor imaging (DTI) suggest substantial changes in white matter (WM) in aging, but it is not known whether cognitive training might modulate these structural alterations. We used tract-based spatial statistics (TBSS) optimized for longitudinal analysis to delineate the effects of 8 weeks intensive memory training on WM microstructure. 41 participants (mean age 61 years) matched for age, sex and education were randomly assigned to an intervention or control group. All participants underwent MRI-scanning and neuropsychological assessments at the beginning and end of the study. Longitudinal analysis across groups revealed significant increase in frontal mean diffusivity (MD), indicating that DTI is sensitive to WM structural alterations over a 10-week interval. Further, group analysis demonstrated positive effects of training on the short-term changes. Participants in the training group showed a relative increase in fractional anisotropy (FA) compared with controls. Further, a significant relationship between memory improvement and change in FA was found, suggesting a possible functional significance of the reported changes. The training effect on FA seemed to be driven by a relative decrease in radial diffusivity, which might indicate a role for myelin-related processes in WM plasticity.