Proton magnetic resonance spectroscopy measurements of glutamate and GABA are important in neuropsychiatric research. Some study designs require simultaneous measurement of both metabolites. GABA measurement requires specialized pulse sequences, the most common approach being J-difference spectral editing with MEGA-PRESS. This method enables two different strategies for concurrently measuring glutamate - from either off-resonance or difference spectra. However, it is uncertain how either strategy compares to conventional glutamate measurements. Here we compared these approaches in 49 subjects (28 healthy volunteers and 21 first-episode psychosis patients), in whom both PRESS (TE 80) and MEGA-PRESS (TE 68) spectra were obtained from dorsolateral prefrontal cortex. Glutamate and glx estimates from MEGA-PRESS difference and off-resonance spectra were compared to glutamate and glx estimates from PRESS spectra using correlational analyses. In healthy volunteers, correlations between PRESS and MEGA-PRESS off-resonance values were r ≥ 0.88 and were significantly higher than correlations between PRESS and MEGA-PRESS difference spectrum values (r ≤ 0.36). Patients showed a similar pattern. Lower correlations with difference spectrum values may reflect a disproportionate impact of field instabilities on co-edited glutamate signals. The results suggest that MEGA-PRESS off-resonance spectra can substitute for separately-acquired PRESS spectra in studies requiring simultaneous glutamate and GABA measurements.

The efficacy of cognitive training is controversial, and research progress in the field requires an understanding of factors that promote transfer of training gains and their relationship to changes in brain activity. One such factor may be adaptive task difficulty, as adaptivity is predicted to facilitate more efficient processing by creating a prolonged mismatch between the supply of, and the demand upon, neural resources. To test this hypothesis, we measured behavioral and neural plasticity in fMRI sessions before and after 10 sessions of working memory updating (WMU) training, in which the difficulty of practiced tasks either adaptively increased in response to performance or was fixed. Adaptive training resulted in transfer to an untrained episodic memory task and activation decreases in striatum and hippocampus on a trained WMU task, and the amount of training task improvement was associated with near transfer to other WMU tasks and with hippocampal activation changes on both near and far transfer tasks. These findings suggest that cognitive training programs should incorporate adaptive task difficulty to broaden transfer of training gains and maximize efficiency of task-related brain activity.

Background

The degree to which individuals with autism spectrum disorder (ASD) evidence impairments in episodic memory relative to their typically developing (TD) counterparts remains unclear. According to a prominent view, ASD is associated with deficits in encoding associations between items and recollecting precise context details. Here, we evaluated behavioral and neural evidence for this impaired relational binding hypothesis using a task involving relational encoding and recollection during functional magnetic resonance imaging.

Methods

Adolescents and young adults (n_ASD = 47, n_TD = 60) performed the Relational and Item-Specific Encoding task during functional magnetic resonance imaging, including item and associative recognition testing. We modeled functional recruitment within the medial temporal lobes (MTLs), and connectivity between MTL and the posterior medial (PM) network thought to underlie relational memory. The impaired relational binding model would predict a behavioral deficit driven by aberrant recruitment and connectivity of MTL and the PM network.

Results

The ASD and TD groups showed indistinguishable item and associative recognition performance. During relational encoding, the ASD group demonstrated increased hippocampal recruitment, and decreased connectivity between MTL and PM regions relative to the TD group. Within ASD, hippocampal recruitment and MTL-PM connectivity were inversely correlated.

Conclusions

The lack of a behavioral deficit in ASD does not support the impaired relational binding hypothesis. Instead, the current data suggest that increased recruitment of the hippocampus compensates for decreased MTL-PM connectivity to support preserved episodic memory in ASD. These findings suggest a compensatory neurodevelopmental mechanism that may support preserved cognitive domains in ASD: local hyperrecruitment may offset connectivity aberrations in individuals with ASD relative to TD subjects.

Episodic memory is known to rely on the hippocampus, but how the hippocampus organizes different episodes to permit their subsequent retrieval remains controversial. One major area of debate hinges on a discrepancy between two hypothesized roles of the hippocampus: differentiating between similar events to reduce interference and assigning similar representations to events that share overlapping items and contextual information. Here, we used multivariate analyses of activity patterns measured with fMRI to characterize how the hippocampus distinguishes between memories based on similarity at the level of items and/or context. Hippocampal activity patterns discriminated between events that shared either item or context information but generalized across events that shared similar item-context associations. The current findings provide evidence that, whereas the hippocampus can reduce mnemonic interference by separating events that generalize along a single attribute dimension, overlapping hippocampal codes may support memory for events with overlapping item-context relations. This lends new insights into the way the hippocampus may balance multiple mnemonic operations in adaptively guiding behavior.

Although most functional neuroimaging studies examine task effects, interest intensifies in the "default" resting brain. Resting conditions show consistent regional activity, yet oxygen extraction fraction constancy across regions. We compared resting cerebral metabolic rates of glucose (CMRgl) measured with 18F-labeled 2-fluoro-2-deoxy-D-glucose to cerebral blood flow (CBF) 15O-H2O measures, using the same positron emission tomography scanner in 2 samples (n = 60 and 30) of healthy right-handed adults. Region to whole-brain ratios were calculated for 35 standard regions of interest, and compared between CBF and CMRgl to determine perfusion relative to metabolism. Primary visual and auditory areas showed coupling between CBF and CMRgl, limbic and subcortical regions--basal ganglia, thalamus and posterior fossa structures--were hyperperfused, whereas association cortices were hypoperfused. Hyperperfusion was higher in left than right hemisphere for most cortical and subcallosal limbic regions, but symmetric in cingulate, basal ganglia and somatomotor regions. Hyperperfused regions are perhaps those where activation is anticipated at short notice, whereas downstream cortical modulatory regions have longer "lead times" for deployment. The novel observation of systematic uncoupling of CBF and CMRgl may help elucidate the potential biological significance of the "default" resting state. Whether greater left hemispheric hyperperfusion reflects lateral dominance needs further examination.

Episodic memory is associated with the encoding and retrieval of context information and with a subjective sense of reexperiencing past events. The neural correlates of episodic retrieval have been extensively studied using fMRI, leading to the identification of a "general recollection network" including medial temporal, parietal, and prefrontal regions. However, in these studies, it is difficult to disentangle the effects of context retrieval from recollection. In this study, we used fMRI to determine the extent to which the recruitment of regions in the recollection network is contingent on context reinstatement. Participants were scanned during a cued recognition test for target words from encoded sentences. Studied target words were preceded by either a cue word studied in the same sentence (thus congruent with encoding context) or a cue word studied in a different sentence (thus incongruent with encoding context). Converging fMRI results from independently defined ROIs and whole-brain analysis showed regional specificity in the recollection network. Activity in hippocampus and parahippocampal cortex was specifically increased during successful retrieval following congruent context cues, whereas parietal and prefrontal components of the general recollection network were associated with confident retrieval irrespective of contextual congruency. Our findings implicate medial temporal regions in the retrieval of semantic context, contributing to, but dissociable from, recollective experience.

In recent years, the boundaries of psychopathology as defined by diagnostic categories have been criticized as inadequately 'carving nature at its joints' with respect to the neurobiology of major mental disorders. In 2010 the NIMH launched the Research Domain Criteria (RDoC) framework for understanding mental illnesses as brain circuit disorders that extend beyond DSM-defined diagnoses. In the present study we focus on cognitive dysfunction, a core feature of schizophrenia (SZ) and bipolar disorder (BPD), and use functional magnetic resonance imaging (fMRI) during a cognitive control (CC) task in recent onset patients to test the hypothesis that at a behavioral and underlying neural circuitry level these deficits exist on a continuum (as opposed to showing categorical differences) across the two disorders. In total, 53 healthy controls, 24 recent (<1 y) onset patients with BPD Type I with psychotic features, and 70 recent onset patients with SZ performed the AX-Continuous Performance Task while undergoing event-related fMRI at 1.5 T. In addition to behavior task-associated response was examined in frontoparietal regions-of-interest. In an a priori contrast-based analysis, significant deficits across patient groups (vs controls) were observed on CC-associated performance as well as frontoparietal response. These analyses further revealed a continuum of deficits in which BPD showed intermediate levels of CC relative to controls and SZ. Poor CC was associated with poverty and disorganization symptoms across patient groups. These results support the hypothesis that CC dysfunction in BPD and SZ reflects a continuum of deficits that cuts across traditional, DSM-based classification. Implications for the neurobiology of these diseases are discussed.

Background

Motivational impairment associated with deficits in processing the anticipation of future reward is hypothesized to be a cardinal feature of schizophrenia spectrum disorders (SZ). Evidence from short-term follow-up (6-week post-treatment) studies suggests that these deficits may improve or be reversed with treatment, although longer-term outcomes are unknown. Here we examined the one-year trajectory of functional activation in brain circuitry associated with reward anticipation in people with recent onset SZ who participated in coordinated specialty care (CSC) treatment, hypothesizing normalization of brain response mirroring previous short-term findings in first-episode individuals.

Method

Blood oxygen level-dependent (BOLD) response in the dorsal anterior cingulate cortex, anterior insula, and ventral striatum (VS) associated with reward anticipation during the Incentivized Control Engagement Task (ICE-T) was analyzed in a baseline sample of 49 healthy controls (HCs) and 52 demographically matched people with SZ, with follow-up data available for 35 HCs and 17 people with SZ.

Results

In agreement with our hypothesis, significant time × diagnosis interactions were observed across all regions, in which reward anticipation-associated BOLD response increased in SZ to above baseline HC levels at follow-up. Increased VS activation was associated with decreased reality distortion symptoms over the follow-up period. Baseline reward anticipation-associated BOLD response in the right anterior insula was associated with improvement in reality distortion symptoms.

Conclusions

These findings suggest that functional deficits in reward anticipation may be reversed after one year of CSC in recent onset participants with SZ, and that this improvement is associated with reduced positive symptoms in the illness.

Introduction

To further investigate manifestations of episodic memory impairments in adolescents, we examined the role of encoding on recognition of stimuli in conditions designed to emphasize their item-specific versus relational characteristics in a group of 12-18 year olds with autism spectrum disorders (ASD). We also examined how strategic learning and memory processes, verbal abilities, attention, and age were associated with recognition in this group.

Materials and method

Twenty two high functioning adolescents with ASD (mean age=15 years; SD=1.8; range=12.2-17.9), and 26 age, gender, and IQ-matched adolescents with typical development (TYP) (mean age=14.7 years; SD=1.9; range=12.3-17.8) completed the Relational and Item-Specific Encoding task (RiSE), the California Verbal Learning Test-Children's Version (CVLT-C), the Wechsler Abbreviated Scales of Intelligence, and the Connors' Parent Rating Scale-Revised. Univariate statistical analyses were performed.

Results

The ASD group showed poorer performance on strategic memory assessed by the CVLT-C. Surprisingly, on the RiSE, ASD showed poorer discriminability for objects encoded in item-specific versus relational encoding conditions and were more impaired in familiarity (after relational encoding) than in recollection. ASD also did not show the hypothesized association between item and associative recognition and CVLT-C performance found in TYP. Instead, in the ASD group recognition was associated with increased age.

Conclusions

Findings from the RiSE task demonstrated that adolescents with ASD do not always exhibit impaired memory for relational information as commonly believed. Instead, memory was worse when cognitive control demands were high, when encoding focused on specific item features, and when familiarity was used to retrieve relational information. Recognition also was better in older participants. This suggests that learning and memory deficits in adolescents with ASD, may not be due primarily to failed relational binding processes in the hippocampus but, rather to disrupted strategic memory and familiarity processes associated with the prefrontal and perirhinal cortices. These findings demonstrate the importance and utility of using well-validated cognitive neuroscience tasks and of considering the ages of participants when comparing the neural underpinnings of different memory processes in both typical and atypical populations.

Objective

Individuals with schizophrenia have disproportionate memory impairments when encoding relational versus item-specific information, and when using recollection versus familiarity during retrieval. It is unclear whether this pattern is unique to people with chronic schizophrenia, or if it occurs in individuals after a first episode of psychosis (FE), or when at clinical high-risk for psychosis (CHR).

Methods

We administered the Relational and Item-Specific Memory task (RiSE) to 22 CHR, 101 FE, and 58 typically developing (TD) participants. We examined group differences in item and relational encoding, and familiarity-based and recollection-based retrieval using parametric analysis and structural equation modeling (SEM). Longitudinal data allowed us to examine relations between baseline RiSE performance and change in clinical symptoms at 1-year follow-up in the FE group.

Results

Groups did not differ on familiarity. FE and CHR groups were equally impaired on overall recognition accuracy. Although recollection was impaired in both FE and CHR groups following relational encoding, only the FE group had impaired recollection following item encoding. SEM showed atypical relationships between familiarity and recollection, as well as familiarity and item recognition for both the FE and CHR groups. For FE individuals, better baseline recognition accuracy predicted less severe negative symptoms at 1-year follow-up.

Conclusions

Impaired relational and recollective memory may reflect neurodevelopmental abnormalities predating conversion to psychosis. These memory deficits appear related to negative symptom changes. In contrast, item specific recollection deficits appear to occur after the development of full psychosis. Familiarity appears to be a relatively preserved memory function across the psychosis spectrum.