Identification of biomarkers for cognitive dysfunction in schizophrenia is a priority for psychiatry research. Functional imaging studies suggest that intrinsic "resting state" hippocampal ...hyperactivity is a characteristic feature of schizophrenia. The relationships between this phenotype and symptoms of the illness, however, are largely unexplored. The authors examined resting hippocampal activity in schizophrenia patients and healthy comparison subjects and analyzed the relationship between intrinsic hippocampal activity and cognitive function in patients as measured by the MATRICS Consensus Cognitive Battery (MCCB).
Twenty-eight schizophrenia patients and 28 age-matched healthy comparison subjects underwent functional "resting state" 3-T MR scanning. Hippocampal activity was extracted by group independent component analysis. Correlation analyses were used to examine the relationship between hippocampal activity and MCCB composite and domain scores in patients, as well as between hippocampal activity and positive and negative symptoms.
Greater activity of the right hippocampus at rest was observed in patients relative to comparison subjects. In patients, a significant negative correlation was observed between right hippocampal activity and composite MCCB T-score. The correlation was driven by the MCCB domains of attention/vigilance, working memory, and visual learning. Hippocampal activity was positively correlated with negative symptoms. MCCB scores were inversely correlated with negative symptoms.
These findings suggest that greater intrinsic hippocampal activity is a characteristic feature of schizophrenia that is broadly associated with cognitive dysfunction, and they support hippocampal activity as a candidate biomarker for therapeutic development.
Rationale
The default mode network (DMN), one of several resting-state networks (RSN) in the brain, is thought to be involved in self-referential thought, awareness, and episodic memories. Nicotine ...improves cognitive performance, in part by improving attention. Nicotinic agonists have been shown to decrease activity in regions within DMN and increase activity in regions involved in visual attention during effortful processing of external stimuli. It is unknown if these pharmacological effects also occur in the absence of effortful processing.
Objectives
This study aims to determine if nicotine suppresses activity in default mode and enhances activity in extra-striate RSNs in the absence of an external visual task.
Methods
Within-subject, single-blinded, counterbalanced study of 19 non-smoking subjects who had resting functional MRI scans after 7 mg nicotine or placebo patch. Group independent component analysis was performed. The DMN component was identified by spatial correlation with a reference DMN mask. A visual attention component was identified by spatial correlation with an extra-striate mask. Analyses were conducted using statistical parametric mapping.
Results
Nicotine was associated with decreased activity in regions within the DMN and increased activity in extra-striate regions.
Conclusions
Suppression of DMN and enhancement of extra-striate resting-state activity in the absence of visual stimuli or effortful processing suggest that nicotine's cognitive effects may involve a shift in activity from networks that process internal to those that process external information. This is a potential mechanism by which cholinergic agonists may have a beneficial effect in diseases associated with altered resting-state activity.
Compact optically-pumped magnetometers (OPMs) are now commercially available with noise floors reaching 10 fT/Hz
. However, to be used effectively for magnetoencephalography (MEG), dense arrays of ...these sensors are required to operate as an integrated turn-key system. In this study, we present the HEDscan, a 128-sensor OPM MEG system by FieldLine Medical, and evaluate its sensor performance with regard to bandwidth, linearity, and crosstalk. We report results from cross-validation studies with conventional cryogenic MEG, the Magnes 3,600 WH Biomagnetometer by 4-D Neuroimaging. Our results show high signal amplitudes captured by the OPM-MEG system during a standard auditory paradigm, where short tones at 1000 Hz were presented to the left ear of six healthy adult volunteers. We validate these findings through an event-related beamformer analysis, which is in line with existing literature results.
Slow wave activity (SWA) during sleep is associated with synaptic regulation and memory processing functions. Each cycle of non-rapid-eye-movement (NREM) sleep demonstrates a waxing and waning amount ...of SWA during the transitions between stages N2 and N3 sleep, and the deeper N3 sleep is associated with an increased density of SWA. Further, SWA is an amalgam of different types of slow waves, each identifiable by their temporal coupling to spindle subtypes with distinct physiological features. The objectives of this study were to better understand the neurobiological properties that distinguish different slow wave and spindle subtypes, and to examine the composition of SWA across cycles of NREM sleep. We further sought to explore changes in the composition of NREM cycles that occur among aging adults. To address these goals, we analyzed subsets of data from two well-characterized cohorts of healthy adults: (1) The DREAMS Subjects Database (
n
= 20), and (2) The Cleveland Family Study (
n
= 60). Our analyses indicate that slow wave/spindle coupled events can be characterized as frontal vs. central in their relative distribution between electroencephalography (EEG) channels. The frontal predominant slow waves are identifiable by their coupling to late-fast spindles and occur more frequently during stage N3 sleep. Conversely, the central-associated slow waves are identified by coupling to early-fast spindles and favor occurrence during stage N2 sleep. Together, both types of slow wave/spindle coupled events form the composite of SWA, and their relative contribution to the SWA rises and falls across cycles of NREM sleep in accordance with depth of sleep. Exploratory analyses indicated that older adults produce a different composition of SWA, with a shift toward the N3, frontal subtype, which becomes increasingly predominant during cycles of NREM sleep. Overall, these data demonstrate that subtypes of slow wave/spindle events have distinct cortical propagation patterns and differ in their distribution across lighter vs. deeper NREM sleep. Future efforts to understand how slow wave sleep and slow wave/spindle coupling impact memory performance and neurological disease may benefit from examining the composition of SWA to avoid potential confounds that may occur when comparing dissimilar neurophysiological events.
Connectivity within the human connectome occurs between multiple neuronal systems-at small to very large spatial scales. Independent component analysis (ICA) is potentially a powerful tool to ...facilitate multi-scale analyses. However, ICA has yet to be fully evaluated at very low (10 or fewer) and ultra-high dimensionalities (200 or greater). The current investigation used data from the Human Connectome Project (HCP) to determine the following: (1) if larger networks, or meta-networks, are present at low dimensionality, (2) if nuisance sources increase with dimensionality, and (3) if ICA is prone to overfitting. Using bootstrap ICA, results suggested that, at very low dimensionality, ICA spatial maps consisted of Visual/Attention and Default/Control meta-networks. At fewer than 10 components, well-known networks such as the Somatomotor Network were absent from results. At high dimensionality, nuisance sources were present even in denoised high-quality data but were identifiable by correlation with tissue probability maps. Artifactual overfitting occurred to a minor degree at high dimensionalities. Basic summary statistics on spatial maps (maximum cluster size, maximum component weight, and average weight outside of maximum cluster) quickly and easily separated artifacts from gray matter sources. Lastly, by using weighted averages of bootstrap stability, even ultra-high dimensional ICA resulted in highly reproducible spatial maps. These results demonstrate how ICA can be applied in multi-scale analyses, reliably and accurately reproducing the hierarchy of meta-networks, large-scale networks, and subnetworks, thereby characterizing cortical connectivity across multiple spatial scales.
Reductions in gamma band phase synchrony and evoked power have been reported in schizophrenic subjects in response to auditory stimuli. These results have been observed in the EEG at one or two ...electrode sites. We wished to extend these results using magnetic field data to estimate the responses at the neural generators themselves in each hemisphere. Whole head magnetoencephalographic (MEG) recordings were used to estimate the phase and amplitude behavior of sources in primary auditory cortex in both hemispheres of schizophrenic and comparison subjects. Both ipsi- and contralateral cases were evaluated using a driving (40 Hz modulated 1 kHz carrier) and a non-driving (1 kHz tone) stimulus. We used source space projection (SSP) to collapse the magnetic field data into estimates of the time course of source strengths in individual trials. Complex wavelet based time–frequency decomposition was used to compute inter-trial phase locking factor (PLF), and mean evoked and induced amplitude for each cortical generator. Schizophrenic subjects showed reduced SSP PLF and evoked source strength for contralateral generators responding to the driving stimulus in both hemispheres. For the pure tone stimulus, only the left hemisphere PLF's in the transient window were reduced. In contrast, subjects with schizophrenia exhibited higher induced 40 Hz power to both stimulus types, consistent with the reduced PLF findings. The method of SSP combined with wavelet based complex demodulation produces a significant improvement in signal-to-noise ratio, and directly estimates the activity of the cortical generators responsible for gamma band auditory MEG evoked fields. Schizophrenic subjects exhibit significant impairment of generation and phase locking of this activity in auditory cortex, suggesting an impairment of GABA-ergic inhibitory interneuronal modulation of pyramidal cell activity.
Although sex differences in food intake have been observed consistently, contributing factors are not well understood. Using a cross-sectional online survey (
= 306; 151 men, 155 women), this study ...aimed to assess how sex impacts relationships between food ratings (appeal/desire to eat for high-calorie (HC) and low-calorie (LC) food images) and eating-related attitudes/behaviors, body mass index (BMI), and mood. Across participants, increased state- and trait-based hunger, disinhibition, and cravings were associated with both increased HC appeal and desire (
< 0.001). Increased state-based hunger and cravings were associated with greater LC desire (
< 0.001). Greater satiety was associated with decreased desire for both HC and LC (
< 0.001), while greater anxiety was associated with increased desire for both HC and LC (
< 0.001). Significant associations between BMI and food ratings were not observed. Women reported greater dietary restraint, trait-based hunger, disinhibition, eating disorder-related behaviors, depression, and stress compared to men, in addition to greater appeal and familiarity with LC foods (all
< 0.05). Significant effects of sex on the associations between food ratings and eating-related attitudes/behaviors, BMI, and mood were not observed, however. Findings support the importance of considering mood and eating-related attitudes/behaviors in investigations of food cue responsivity.
Cognitive impairment is a highly prevalent non-motor feature of Parkinson's disease (PD). A better understanding of the underlying pathophysiology may help in identifying therapeutic targets to ...prevent or treat dementia. This study sought to identify metabolic alterations in the prefrontal cortex (PFC), a key region for cognitive functioning that has been implicated in cognitive dysfunction in PD.
Proton Magnetic Resonance Spectroscopy was used to investigate metabolic changes in the PFC of a cohort of cognitively normal individuals without PD (CTL), as well as PD participants with either normal cognition (PD-NC), mild cognitive impairment (PD-MCI), or dementia (PDD). Ratios to Creatine (Cre) resonance were obtained for glutamate (Glu), glutamine and glutamate combined (Glx), N-acetylaspartate (NAA), myoinositol (mI), and total choline (Cho), and correlated with cognitive scores across multiple domains (executive function, learning and memory, language, attention, visuospatial function, and global cognition) administered to the PD participants only.
When individuals retain cognitive capabilities, the presence of Parkinson's disease does not create metabolic disturbances in the PFC. However, when cognitive symptoms are present, PFC Glu/Cre ratios decrease with significant differences between the PD-NC and PPD groups. In addition, Glu/Cre ratios and memory scores were marginally associated, but not after Bonferroni correction.
These preliminary findings indicate that fluctuations in prefrontal glutamate may constitute a biomarker for the progression of cognitive impairments in PD. We caution for larger MRS investigations of carefully defined PD groups.
Similar behavioral deficits are shared between individuals with autism spectrum disorders (ASD) and their first-degree relatives, such as impaired face memory, object recognition, and some language ...aspects. Functional neuroimaging studies have reported abnormalities in ASD in at least one brain area implicated in those functions, the fusiform gyrus (FG). High frequency oscillations have also been described as abnormal in ASD in a separate line of research. The present study examined whether low- and high-frequency oscillatory power, localized in part to FG and other language-related regions, differs in ASD subjects and first-degree relatives. Twelve individuals with ASD, 16 parents of children with ASD, and 35 healthy controls participated in a picture-naming task using magnetoencephalography (MEG) to assess oscillatory power and connectivity. Relative to controls, we observed reduced evoked high-gamma activity in the right superior temporal gyrus (STG) and reduced high-beta/low-gamma evoked power in the left inferior frontal gyrus (IFG) in the ASD group. Finally, reductions in phase-locked beta-band were also seen in the ASD group relative to controls, especially in the occipital lobes (OCC). First degree relatives, in contrast, exhibited higher high-gamma band power in the left STG compared with controls, as well as increased high-beta/low-gamma evoked power in the left FG. In the left hemisphere, beta- and gamma-band functional connectivity between the IFG and FG and between STG and OCC were higher in the autism group than in controls. This suggests that, contrary to what has been previously described, reduced connectivity is not observed across all scales of observation in autism. The lack of behavioral correlation for the findings warrants some caution in interpreting the relevance of such changes for language function in ASD. Our findings in parents implicates the gamma- and beta-band ranges as potential compensatory phenomena in autism relatives.
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