Ruminative reflection is associated with anticorrelations between the orbitofrontal cortex and the default mode network in depression: implications for repetitive transcranial magnetic stimulation.

Patients with depression who ruminate repeatedly focus on depressive thoughts; however, there are two cognitive subtypes of rumination, reflection and brooding, each associated with different prognoses. Reflection involves problem-solving and is associated with positive outcomes, whereas brooding involves passive, negative, comparison with other people and is associated with poor outcomes. Rumination has also been related to atypical functional hyperconnectivity between the default mode network and subgenual prefrontal cortex. Repetitive pulse transcranial magnetic stimulation of the prefrontal cortex has been shown to alter functional connectivity, suggesting that the abnormal connectivity associated with rumination could potentially be altered. This study examined potential repetitive pulse transcranial magnetic stimulation prefrontal cortical targets that could modulate one or both of these rumination subtypes. Forty-three patients who took part in a trial of repetitive pulse transcranial magnetic stimulation completed the Rumination Response Scale questionnaire and resting-state functional magnetic resonance imaging. Seed to voxel functional connectivity analyses identified an anticorrelation between the left lateral orbitofrontal cortex (-44, 26, -8; k = 172) with the default mode network-subgenual region in relation to higher levels of reflection. Parallel analyses were not significant for brooding or the RRS total score. These findings extend previous studies of rumination and identify a potential mechanistic model for symptom-based neuromodulation of rumination.

Identifying cardiovascular risk factors that impact cerebrovascular reactivity: An ASL MRI study.

BACKGROUND: To maintain cerebral blood flow (CBF), cerebral blood vessels dilate and contract in response to blood supply through cerebrovascular reactivity (CR). PURPOSE: Cardiovascular (CV) disease is associated with increased stroke risk, but which risk factors specifically impact CR is unknown. STUDY TYPE: Prospective longitudinal. SUBJECTS: Fifty-three subjects undergoing carotid endarterectomy or stenting. FIELD STRENGTH/SEQUENCE: 3T, 3D pseudo-continuous arterial spin labeling (PCASL) ASL, and T1 3D fast spoiled gradient echo (FSPGR). ASSESSMENT: We evaluated group differences in CBF changes for multiple cardiovascular risk factors in patients undergoing carotid revascularization surgery. STATISTICAL TESTS: PRE (baseline), POST (48-hour postop), and 6MO (6 months postop) whole-brain CBF measurements, as 129 CBF maps from 53 subjects were modeled as within-subject analysis of variance (ANOVA). To identify CV risk factors associated with CBF change, the CBF change from PRE to POST, POST to 6MO, and PRE to 6MO were modeled as multiple linear regression with each CV risk factor as an independent variable. Statistical models were performed controlling for age on a voxel-by-voxel basis using SPM8. Significant clusters were reported if familywise error (FWE)-corrected cluster-level was P < 0.05, while the voxel-level significance threshold was set for P < 0.001. RESULTS: The entire group showed significant (cluster-level P < 0.001) CBF increase from PRE to POST, decrease from POST to 6MO, and no significant difference (all voxels with P > 0.001) from PRE to 6MO. Of multiple CV risk factors evaluated, only elevated systolic blood pressure (SBP, P = 0.001), chronic renal insufficiency (CRI, P = 0.026), and history of prior stroke (CVA, P < 0.001) predicted lower increases in CBF PRE to POST. Over POST to 6MO, obesity predicted lower (P > 0.001) and cholesterol greater CBF decrease (P > 0.001). DATA CONCLUSION: The CV risk factors of higher SBP, CRI, CVA, BMI, and cholesterol may indicate altered CR, and may warrant different stroke risk mitigation and special consideration for CBF change evaluation. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2020;51:734-747.

Convergence Analysis of Micro-Lesions (CAML): An approach to mapping of diffuse lesions from carotid revascularization.

Carotid revascularization (endarterectomy, stenting) prevents stroke; however, procedure-related embolization is common and results in small brain lesions easily identified by diffusion weighted magnetic resonance imaging (DWI). A crucial barrier to understanding the clinical significance of these lesions has been the lack of a statistical approach to identify vulnerable brain areas. The problem is that the lesions are small, numerous, and non-overlapping. Here we address this problem with a new method, the Convergence Analysis of Micro-Lesions (CAML) technique, an extension of the Anatomic Likelihood Analysis (ALE). The method combines manual lesion tracing, constraints based on known lesion patterns, and convergence analysis to represent regions vulnerable to lesions as probabilistic brain atlases. Two studies were conducted over the course of 12 years in an active, vascular surgery clinic. An analysis in an initial group of 126 patients at 1.5 T MRI was cross-validated in a second group of 80 patients at 3T MRI. In CAML, lesions were manually defined and center points identified. Brains were aligned according to side of surgery since this factor powerfully determines lesion distribution. A convergence based analysis, was performed on each of these groups. Results indicated the most consistent region of vulnerability was in motor and premotor cortex regions. Smaller regions common to both groups included the dorsolateral prefrontal cortex and medial parietal regions. Vulnerability of motor cortex is consistent with previous work showing changes in hand dexterity associated with these procedures. The consistency of CAML also demonstrates the feasibility of this new approach to characterize small, diffuse, non-overlapping lesions in patients with multifocal pathologies.

Volume of subclinical embolic infarct correlates to long-term cognitive changes after carotid revascularization.

OBJECTIVE: Carotid intervention is safe and effective in stroke prevention in appropriately selected patients. Despite minimal neurologic complications, procedure-related subclinical microemboli are common and their cognitive effects are largely unknown. In this prospective longitudinal study, we sought to determine long-term cognitive effects of embolic infarcts. METHODS: The study recruited 119 patients including 46% symptomatic patients who underwent carotid revascularization. Neuropsychological testing was administered preoperatively and at 1 month, 6 months, and 12 months postoperatively. Rey Auditory Verbal Learning Test (RAVLT) was the primary cognitive measure with parallel forms to avoid practice effect. All patients also received 3T brain magnetic resonance imaging with a diffusion-weighted imaging (DWI) sequence preoperatively and within 48 hours postoperatively to identify procedure-related new embolic lesions. Each DWI lesion was manually traced and input into a neuroimaging program to define volume. Embolic infarct volumes were correlated with cognitive measures. Regression models were used to identify relationships between infarct volumes and cognitive measures. RESULTS: A total of 587 DWI lesions were identified on 3T magnetic resonance imaging in 81.7% of carotid artery stenting (CAS) and 36.4% of carotid endarterectomy patients with a total volume of 29,327 mm3. Among them, 54 DWI lesions were found in carotid endarterectomy patients and 533 in the CAS patients. Four patients had transient postoperative neurologic symptoms and one had a stroke. CAS was an independent predictor of embolic infarction (odds ratio, 6.6 [2.1-20.4]; P < .01) and infarct volume (P = .004). Diabetes and contralateral carotid severe stenosis or occlusion had a trend of positive association with infarct volume, whereas systolic blood pressure ≥140 mm Hg had a negative association (P = .1, .09, and .1, respectively). There was a trend of improved RAVLT scores overall after carotid revascularization. Significantly higher infarct volumes were observed among those with RAVLT decline. Within the CAS cohort, infarct volume was negatively correlated with short- and long-term RAVLT changes (P < .05). CONCLUSIONS: Cognitive assessment of procedure-related subclinical microemboli is challenging. Volumes of embolic infarct correlate with long-term cognitive changes, suggesting that microembolization should be considered a surrogate measure for carotid disease management.

Cortical Auditory Evoked Potentials to Evaluate Cochlear Implant Candidacy in an Ear With Long-standing Hearing Loss: A Case Report.

OBJECTIVES: We describe a novel use of cortical auditory evoked potentials in the preoperative workup to determine ear candidacy for cochlear implantation. METHODS: A 71-year-old male was evaluated who had a long-deafened right ear, had never worn a hearing aid in that ear, and relied heavily on use of a left-sided hearing aid. Electroencephalographic testing was performed using free field auditory stimulation of each ear independently with pure tones at 1000 and 2000 Hz at approximately 10 dB above pure-tone thresholds for each frequency and for each ear. RESULTS: Mature cortical potentials were identified through auditory stimulation of the long-deafened ear. The patient underwent successful implantation of that ear. He experienced progressively improving aided pure-tone thresholds and binaural speech recognition benefit (AzBio score of 74%). CONCLUSIONS: Findings suggest that use of cortical auditory evoked potentials may serve a preoperative role in ear selection prior to cochlear implantation.

Acoustic Cue Weighting by Adults with Cochlear Implants: A Mismatch Negativity Study.

OBJECTIVES: Formant rise time (FRT) and amplitude rise time (ART) are acoustic cues that inform phonetic identity. FRT represents the rate of transition of the formant(s) to a steady state, while ART represents the rate at which the sound reaches its peak amplitude. Normal-hearing (NH) native English speakers weight FRT more than ART during the perceptual labeling of the /ba/-/wa/ contrast. This weighting strategy is reflected neurophysiologically in the magnitude of the mismatch negativity (MMN)-MMN is larger during the FRT than the ART distinction. The present study examined the neurophysiological basis of acoustic cue weighting in adult cochlear implant (CI) listeners using the MMN design. It was hypothesized that individuals with CIs who weight ART more in behavioral labeling (ART users) would show larger MMNs during the ART than the FRT contrast, and the opposite would be seen for FRT users. DESIGN: Electroencephalography was recorded while 20 adults with CIs listened passively to combinations of 3 synthetic speech stimuli: a /ba/ with /ba/-like FRT and ART; a /wa/ with /wa/-like FRT and ART; and a /ba/ stimulus with /ba/-like FRT and /wa/-like ART. The MMN response was elicited during the FRT contrast by having participants passively listen to a train of /wa/ stimuli interrupted occasionally by /ba/ stimuli, and vice versa. For the ART contrast, the same procedure was implemented using the /ba/ and /ba/ stimuli. RESULTS: Both ART and FRT users with CIs elicited MMNs that were equal in magnitudes during FRT and ART contrasts, with the exception that FRT users exhibited MMNs for ART and FRT contrasts that were temporally segregated. That is, their MMNs occurred significantly earlier during the ART contrast (~100 msec following sound onset) than during the FRT contrast (~200 msec). In contrast, the MMNs for ART users of both contrasts occurred later and were not significantly separable in time (~230 msec). Interestingly, this temporal segregation observed in FRT users is consistent with the MMN behavior in NH listeners. CONCLUSIONS: Results suggest that listeners with CIs who learn to classify phonemes based on formant dynamics, consistent with NH listeners, develop a strategy similar to NH listeners, in which the organization of the amplitude and spectral representations of phonemes in auditory memory are temporally segregated.

Putative mechanisms mediating tolerance for audiovisual stimulus onset asynchrony.

Audiovisual (AV) speech perception is robust to temporal asynchronies between visual and auditory stimuli. We investigated the neural mechanisms that facilitate tolerance for audiovisual stimulus onset asynchrony (AVOA) with EEG. Individuals were presented with AV words that were asynchronous in onsets of voice and mouth movement and judged whether they were synchronous or not. Behaviorally, individuals tolerated (perceived as synchronous) longer AVOAs when mouth movement preceded the speech (V-A) stimuli than when the speech preceded mouth movement (A-V). Neurophysiologically, the P1-N1-P2 auditory evoked potentials (AEPs), time-locked to sound onsets and known to arise in and surrounding the primary auditory cortex (PAC), were smaller for the in-sync than the out-of-sync percepts. Spectral power of oscillatory activity in the beta band (14-30 Hz) following the AEPs was larger during the in-sync than out-of-sync perception for both A-V and V-A conditions. However, alpha power (8-14 Hz), also following AEPs, was larger for the in-sync than out-of-sync percepts only in the V-A condition. These results demonstrate that AVOA tolerance is enhanced by inhibiting low-level auditory activity (e.g., AEPs representing generators in and surrounding PAC) that code for acoustic onsets. By reducing sensitivity to acoustic onsets, visual-to-auditory onset mapping is weakened, allowing for greater AVOA tolerance. In contrast, beta and alpha results suggest the involvement of higher-level neural processes that may code for language cues (phonetic, lexical), selective attention, and binding of AV percepts, allowing for wider neural windows of temporal integration, i.e., greater AVOA tolerance.

Visual context due to speech-reading suppresses the auditory response to acoustic interruptions in speech.

Speech reading enhances auditory perception in noise. One means by which this perceptual facilitation comes about is through information from visual networks reinforcing the encoding of the congruent speech signal by ignoring interfering acoustic signals. We tested this hypothesis neurophysiologically by acquiring EEG while individuals listened to words with a fixed portion of each word replaced by white noise. Congruent (meaningful) or incongruent (reversed frames) mouth movements accompanied the words. Individuals judged whether they heard the words as continuous (illusion) or interrupted (illusion failure) through the noise. We hypothesized that congruent, as opposed to incongruent, mouth movements should further enhance illusory perception by suppressing the auditory cortex's response to interruption onsets and offsets. Indeed, we found that the N1 auditory evoked potential (AEP) to noise onsets and offsets was reduced when individuals experienced the illusion during congruent, but not incongruent, audiovisual streams. This N1 inhibitory effect was most prominent at noise offsets, suggesting that visual influences on auditory perception are instigated to a greater extent during noisy periods. These findings suggest that visual context due to speech-reading disengages (inhibits) neural processes associated with interfering sounds (e.g., noisy interruptions) during speech perception.

Neurophysiology of spectrotemporal cue organization of spoken language in auditory memory.

Listeners assign different weights to spectral dynamics, such as formant rise time (FRT), and temporal dynamics, such as amplitude rise time (ART), during phonetic judgments. We examined the neurophysiological basis of FRT and ART weighting in the /ba/-/wa/ contrast. Electroencephalography was recorded for thirteen adult English speakers during a mismatch negativity (MMN) design using synthetic stimuli: a /ba/ with /ba/-like FRT and ART; a /wa/ with /wa/-like FRT and ART; and a /ba/(wa) with /ba/-like FRT and /wa/-like ART. We hypothesized that because of stronger reliance on FRT, subjects would encode a stronger memory trace and exhibit larger MMN during the FRT than the ART contrast. Results supported this hypothesis. The effect was most robust in the later portion of MMN. Findings suggest that MMN is generated by multiple sources, differentially reflecting acoustic change detection (earlier MMN, bottom-up process) and perceptual weighting of ART and FRT (later MMN, top-down process).

Cardiovascular effects of anti-diabetic medications in type 2 diabetes mellitus.

Over the past several years, there have been a significant number of new agents developed for the treatment of type 2 diabetes. Our goal in this article is to review the cardiovascular effects (risks and benefits) of these oral and non-insulin injectable agents. We review six major categories of diabetic therapies: biguanides, sulfonylureas, alpha-glucosidase inhibitors, thiazolidinediones, GLP-1 agonists, and DPP-IV inhibitors. In order to achieve a personalized regimen that aims for optimal outcomes, we must take into consideration each drug's side effects, patients' cardiovascular risk factors, and their individual health profile.

Neural restoration of degraded audiovisual speech.

When speech is interrupted by noise, listeners often perceptually "fill-in" the degraded signal, giving an illusion of continuity and improving intelligibility. This phenomenon involves a neural process in which the auditory cortex (AC) response to onsets and offsets of acoustic interruptions is suppressed. Since meaningful visual cues behaviorally enhance this illusory filling-in, we hypothesized that during the illusion, lip movements congruent with acoustic speech should elicit a weaker AC response to interruptions relative to static (no movements) or incongruent visual speech. AC response to interruptions was measured as the power and inter-trial phase consistency of the auditory evoked theta band (4-8 Hz) activity of the electroencephalogram (EEG) and the N1 and P2 auditory evoked potentials (AEPs). A reduction in the N1 and P2 amplitudes and in theta phase-consistency reflected the perceptual illusion at the onset and/or offset of interruptions regardless of visual condition. These results suggest that the brain engages filling-in mechanisms throughout the interruption, which repairs degraded speech lasting up to ~250 ms following the onset of the degradation. Behaviorally, participants perceived speech continuity over longer interruptions for congruent compared to incongruent or static audiovisual streams. However, this specific behavioral profile was not mirrored in the neural markers of interest. We conclude that lip-reading enhances illusory perception of degraded speech not by altering the quality of the AC response, but by delaying it during degradations so that longer interruptions can be tolerated.

In vivo enhancement of natural killer cell activity through tea fortified with Ayurvedic herbs.

The effect of a tea fortified with five herbs selected from Indian traditional medicine (Ayurveda) for their putative immunoenhancing effect (Withania somnifera, Glycyrrhzia glabra, Zingiber officinale, Ocimum sanctum and Elettaria cardamomum) on innate immunity was investigated. Ex vivo natural killer (NK) cell activity was assessed after consumption of fortified tea compared with regular tea in two independent double-blind intervention studies. Both studies were conducted in India with healthy volunteers (age >or= 55 years) selected for a relatively low baseline NK cell activity and a history of recurrent coughs and colds. In a pilot study conducted with 32 volunteers, the consumption of Natural Care tea significantly improved the NK cell activity of the volunteers in comparison with a population consuming regular tea. These results were validated in an independent crossover study with 110 volunteers. Data from these two studies indicate that regular consumption of the tea fortified with Ayurvedic herbs enhanced NK cell activity, which is an important aspect of the (early) innate immune response to infections.