Propofol attenuates low-frequency fluctuations of resting-state fMRI BOLD signal in the anterior frontal cortex upon loss of consciousness.

Recent studies indicate that spontaneous low-frequency fluctuations (LFFs) of resting-state functional magnetic resonance imaging (rs-fMRI) blood oxygen level-dependent (BOLD) signals are driven by the slow (<0.1Hz) modulation of ongoing neuronal activity synchronized locally and across remote brain regions. How regional LFFs of the BOLD fMRI signal are altered during anesthetic-induced alteration of consciousness is not well understood. Using rs-fMRI in 15 healthy participants, we show that during administration of propofol to achieve loss of behavioral responsiveness indexing unconsciousness, the fractional amplitude of LFF (fALFF index) was reduced in comparison to wakeful baseline in the anterior frontal regions, temporal pole, hippocampus, parahippocampal gyrus, and amygdala. Such changes were absent in large areas of the motor, parietal, and sensory cortices. During light sedation characterized by the preservation of overt responsiveness and therefore consciousness, fALFF was reduced in the subcortical areas, temporal pole, medial orbital frontal cortex, cingulate cortex, and cerebellum. Between light sedation and deep sedation, fALFF was reduced primarily in the medial and dorsolateral frontal areas. The preferential reduction of LFFs in the anterior frontal regions is consistent with frontal to sensory-motor cortical disconnection and may contribute to the suppression of consciousness during general anesthesia.

Disrupted small world topology and modular organisation of functional networks in late-life depression with and without amnestic mild cognitive impairment.

BACKGROUND: The topological architecture of the whole-brain functional networks in those with and without late-life depression (LLD) and amnestic mild cognitive impairment (aMCI) are unknown. AIMS: To investigate the differences in the small-world measures and the modular community structure of the functional networks between patients with LLD and aMCI when occurring alone or in combination and cognitively healthy non-depressed controls. METHODS: 79 elderly participants (LLD (n=23), aMCI (n=18), comorbid LLD and aMCI (n=13), and controls (n=25)) completed neuropsychiatric assessments. Graph theoretical methods were employed on resting-state functional connectivity MRI data. RESULTS: LLD and aMCI comorbidity was associated with the greatest disruptions in functional integration measures (decreased global efficiency and increased path length); both LLD groups showed abnormal functional segregation (reduced local efficiency). The modular network organisation was most variable in the comorbid group, followed by patients with LLD-only. Decreased mean global, local and nodal efficiency metrics were associated with greater depressive symptom severity but not memory performance. CONCLUSIONS: Considering the whole brain as a complex network may provide unique insights on the neurobiological underpinnings of LLD with and without cognitive impairment.

Intrinsic functional connectivity of the brain swallowing network during subliminal esophageal acid stimulation.

BACKGROUND: Intrinsic synchronous fluctuations of the functional magnetic resonance imaging signal are indicative of the underlying 'functional connectivity' (FC) and serve as a technique to study dynamics of the neuronal networks of the human brain. Earlier studies have characterized the functional connectivity of a distributed network of brain regions involved in swallowing, called brain swallowing network (BSN). The potential modulatory effect of esophageal afferent signals on the BSN, however, has not been systematically studied. METHODS: Fourteen healthy volunteers underwent steady state functional magnetic resonance imaging across three conditions: (i) transnasal catheter placed in the esophagus without infusion; (ii) buffer solution infused at 1 mL/min; and (iii) acidic solution infused at 1 mL/min. Data were preprocessed according to the standard FC analysis pipeline. We determined the correlation coefficient values of pairs of brain regions involved in swallowing and calculated average group FC matrices across conditions. Effects of subliminal esophageal acidification and nasopharyngeal intubation were determined. KEY RESULTS: Subliminal esophageal acid stimulation augmented the overall FC of the right anterior insula and specifically the FC to the left inferior parietal lobule. Conscious stimulation by nasopharyngeal intubation reduced the overall FC of the right posterior insula, particularly the FC to the right prefrontal operculum. CONCLUSIONS & INFERENCES: The FC of BSN is amenable to modulation by sensory input. The modulatory effect of sensory pharyngoesophageal stimulation on BSN is mainly mediated through changes in the FC of the insula. The alteration induced by subliminal visceral esophageal acid stimulation is in different insular connections compared with that of conscious somatic pharyngeal stimulation.

The co-existence of geriatric depression and amnestic mild cognitive impairment detrimentally affect gray matter volumes: voxel-based morphometry study.

While late-life depression (LLD) and amnestic mild cognitive impairment (aMCI), alone and in combination, is associated with an increased risk of incident Alzheimer's disease (AD), the neurobiological mechanisms of this link are unclear. We examined the main and interactive effects of LLD and aMCI on the gray matter (GM) volumes in 72 physically healthy participants aged 60 and older. Participants were separated into normal controls, cognitively normal depressed, non-depressed aMCI, and depressed aMCI groups. Optimized voxel-based morphometry estimated GM volumes. The main and interactive effects of LLD and aMCI, and of depressive symptoms and episodic memory deficits on the GM volumes were analyzed. While decreased GM volumes in the mood regulating circuitry structures were associated with depression, GM atrophy in regions essential for various cognitive performance were related to aMCI. LLD-aMCI interactions were associated with widespread subcortical and cortical GM volume loss of brain structures implicated in AD. The interactions between episodic memory deficits and depressive symptom severity are associated with volume loss in right inferior frontal gyrus/anterior insula and left medial frontal gyrus clusters. Our findings suggest that the co-existence of these clinical phenotypes is a potential marker for higher risk of AD.

Neural correlates of the interactive relationship between memory deficits and depressive symptoms in nondemented elderly: resting fMRI study.

Prospective studies have shown an association between depressive symptoms and cognitive impairment among older adults. However, the neural correlates of this relationship are poorly understood. Our aim was to examine whether interactive effects of memory deficits and depressive symptoms are present in the memory-associated functional networks, in nondemented elderly subjects. Fifteen subjects with amnestic mild cognitive impairment (aMCI) and 20 age-matched normal (CN) elderly subjects participated in this cross-sectional study. Resting-state functional connectivity MRI (R-fMRI) measured the hippocampal functional connectivity (HFC) alterations between the two groups. Voxelwise linear regression analysis was performed to correlate hippocampal network strength with the Rey Auditory Verbal Learning Test delayed recall and the Geriatric Depression Scale scores, after adjusting for age and group effects. Poorer memory performance was associated with decreased positively correlated HFC connectivity in the specific frontal lobe and default mode network (DMN) structures. Poorer memory performance also was associated with decreased anticorrelated HFC connectivity in the bilateral inferior parietal and right dorsolateral prefrontal cortices. In contrast, greater depressive symptom severity was associated with increased HFC connectivity in several frontal lobes and DMN regions. Depressive symptoms and memory functions had interactive effects on the HFC, in the frontal, temporal, and PCC structures. Our findings suggest that the R-fMRI technique can be used to examine the changes in functional neural networks where memory deficits and depressive symptoms coexist in the geriatric population.

Functional anatomy of predictive vergence and saccade eye movements in humans: a functional MRI investigation.

PURPOSE: The purpose of this study is to investigate the functional neural anatomy that generates vergence eye movement responses from predictive versus random symmetrical vergence step stimuli in humans and compare it to a similar saccadic task via the blood oxygenation level dependent signal from functional MRI. METHODS: Eight healthy subjects participated in fMRI scans obtained from a 3T Siemens Allegra scanner. Subjects tracked random and predictable vergent steps and then tracked random and predictable saccadic steps each within a block design. A general linear model (GLM) was used to determine significantly (p < 0.001) active regions of interest through a combination of correlation threshold and cluster extent. A paired t-test of the GLM beta weight coefficients was computed to determine significant spatial differences between the saccade and vergence data sets. RESULTS: Predictive saccadic and vergent eye movements induced many common sites of significant functional cortical activity including: the dorsolateral prefrontal cortex (DLPFC), parietal eye field (PEF), cuneus, precuneus, anterior and posterior cingulate, and the cerebellum. However, differentiation in spatial location was observed within the frontal lobe for the functional activity of the saccadic and vergent network induced while studying prediction. A paired t-test of the beta weights from the individual subjects showed that peak activity induced by predictive versus random vergent eye movements was significantly (t > 2.7, p < 0.03) more anterior within the frontal eye field (FEF) and the supplementary eye field (SEF) when compared to the functional activity from predictive saccadic eye movements. CONCLUSION: This research furthers our knowledge of which cortical sites facilitate a subject's ability to predict within the vergence and saccade networks. Using a predictive versus random visual task, saccadic and vergent eye movements induced activation in many shared cortical sites and also stimulated differentiation in the FEF and SEF.