Direct brain recordings suggest a causal subsequent-memory effect.

Endogenous variation in brain state and stimulus-specific evoked activity can both contribute to successful encoding. Previous studies, however, have not clearly distinguished among these components. We address this question by analysing intracranial EEG recorded from epilepsy patients as they studied and subsequently recalled lists of words. We first trained classifiers to predict recall of either single items or entire lists and found that both classifiers exhibited similar performance. We found that list-level classifier output-a biomarker of successful encoding-tracked item presentation and recall events, despite having no information about the trial structure. Across widespread brain regions, decreased low- and increased high-frequency activity (HFA) marked successful encoding of both items and lists. We found regional differences in the hippocampus and prefrontal cortex, where in the hippocampus HFA correlated more strongly with item recall, whereas, in the prefrontal cortex, HFA correlated more strongly with list performance. Despite subtle differences in item- and list-level features, the similarity in overall classification performance, spectral signatures of successful recall and fluctuations of spectral activity across the encoding period argue for a shared endogenous process that causally impacts the brain's ability to learn new information.

Contribution of left supramarginal and angular gyri to episodic memory encoding: An intracranial EEG study.

The role of the left ventral lateral parietal cortex (VPC) in episodic memory is hypothesized to include bottom-up attentional orienting to recalled items, according to the dual-attention model (Cabeza et al., 2008). However, its role in memory encoding could be further clarified, with studies showing both positive and negative subsequent memory effects (SMEs). Furthermore, few studies have compared the relative contributions of sub-regions in this functionally heterogeneous area, specifically the anterior VPC (supramarginal gyrus/BA40) and the posterior VPC (angular gyrus/BA39), on a within-subject basis. To elucidate the role of the VPC in episodic encoding, we compared SMEs in the intracranial EEG across multiple frequency bands in the supramarginal gyrus (SmG) and angular gyrus (AnG), as twenty-four epilepsy patients with indwelling electrodes performed a free recall task. We found a significant SME of decreased theta power and increased high gamma power in the VPC overall, and specifically in the SmG. Furthermore, SmG exhibited significantly greater spectral tilt SME from 0.5 to 1.6 s post-stimulus, in which power spectra slope differences between recalled and unrecalled words were greater than in the AnG (p = 0.04). These results affirm the contribution of VPC to episodic memory encoding, and suggest an anterior-posterior dissociation within VPC with respect to its electrophysiological underpinnings.

Sequence Variation Associated with SLC12A5 Gene Expression Is Linked to Brain Structure and Function in Healthy Adults.

A single-nucleotide polymorphism in the promoter region of the Matrix Metalloproteinase-9 (MMP9) gene, rs3918242, has been shown to affect MMP9 expression in macrophages and was associated with schizophrenia by two independent groups. However, rs3918242's effects on MMP9 expression were not replicable in cell lines or brain tissue. Additionally, publically available data indicate that rs3918242 genotype is related not to MMP9 expression, but rather to expression of SLC12A5, a nearby gene coding for a K+/Cl- cotransporter, whose expression has also been related to schizophrenia. Here, we studied brain structure and function in healthy participants stratified by rs3918242 genotype using structural MRI (N = 298), functional MRI during an N-back working memory task (N = 554), and magnetoencephalography (MEG) during the same task (N = 190). We found rs3918242 was associated with gray matter volume (GMV) in the insula and dorsolateral prefrontal cortex bilaterally, closely replicated in discovery and replication samples; and with inferior parietal lobule (IPL) GMV when the samples were meta-analytically combined. Additionally, using both fMRI and MEG, rs3918242 was associated with right IPL working memory-related activation, replicated in two cohorts and across imaging modalities. These convergent results provide further impetus for examinations of the relationship of SLC12A5 with brain structure and function in neuropsychiatric disease.

High-gamma and beta bursts in the Left Supramarginal Gyrus can accurately differentiate verbal memory states and performance.

The left supramarginal gyrus (LSMG) may mediate attention to memory, and gauge memory state and performance. We performed a secondary analysis of 142 verbal delayed free recall experiments, in patients with medically-refractory epilepsy with electrode contacts implanted in the LSMG. In 14 of 142 experiments (in 14 of 113 patients), the cross-validated convolutional neural networks (CNNs) that used 1-dimensional(1-D) pairs of convolved high-gamma and beta tensors, derived from the LSMG recordings, could label recalled words with an area under the receiver operating curve (AUROC) of greater than 60% [range: 60-90%]. These 14 patients were distinguished by: 1) higher amplitudes of high-gamma bursts; 2) distinct electrode placement within the LSMG; and 3) superior performance compared with a CNN that used a 1-D tensor of the broadband recordings in the LSMG. In a pilot study of 7 of these patients, we also cross-validated CNNs using paired 1-D convolved high-gamma and beta tensors, from the LSMG, to: a) distinguish word encoding epochs from free recall epochs [AUC 0.6-1]; and distinguish better performance from poor performance during delayed free recall [AUC 0.5-0.86]. These experiments show that bursts of high-gamma and beta generated in the LSMG are biomarkers of verbal memory state and performance.

Spatiotemporal Alterations in Working Memory-Related Beta Band Neuromagnetic Activity of Patients With Schizophrenia On and Off Antipsychotic Medication: Investigation With MEG.

BACKGROUND AND HYPOTHESIS: We used the uniquely high combined spatial and temporal resolution of magnetoencephalography to characterize working memory (WM)-related modulation of beta band activity in neuroleptic-free patients with schizophrenia in comparison to a large sample of performance-matched healthy controls. We also tested for effects of antipsychotic medication on identified differences in these same patients. STUDY DESIGN: Inpatients with schizophrenia (n = 21) or psychotic disorder not otherwise specified (n = 4) completed N-back and control tasks during magnetoencephalography while on placebo and during antipsychotic medication treatment, in a blinded, randomized, counterbalanced manner. Healthy, performance-matched controls (N = 100) completed the same tasks. WM-related neural activation was estimated as beta band (14-30 Hz) desynchronization throughout the brain in successive 400 ms time windows. Voxel-wise statistical comparisons were performed between controls and patients while off-medication at each time window. Significant clusters resulting from this between-groups analysis were then used as regions-of-interest, the activations of which were compared between on- and off-medication conditions in patients. STUDY RESULTS: Controls showed beta-band desynchronization (activation) of a fronto-parietal network immediately preceding correct button press responses-the time associated with WM updating and task execution. Altered activation in medication-free patients occurred largely during this time, in prefrontal, parietal, and visual cortices. Medication altered patients' neural responses such that the activation time courses in these regions-of-interest more closely resembled those of controls. CONCLUSIONS: These findings demonstrate that WM-related beta band alterations in schizophrenia are time-specific and associated with neural systems targeted by antipsychotic medications. Future studies may investigate this association by examining its potential neurochemical basis.