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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.

BACKGROUND: The efficacy of repetitive transcranial magnetic stimulation (rTMS) for depression may vary depending on the subregion stimulated within the dorsolateral prefrontal cortex (DLPFC). Clinical TMS typically uses scalp-based landmarks for DLPFC targeting, rather than individualized MRI guidance. OBJECTIVE: In rTMS patients, determine the brain systems targeted by multiple DLPFC stimulation rules by computing several surrogate measures: underlying brain targets labeled with connectivity-based atlases, subgenual cingulate anticorrelation strength, and functionally connected networks. METHODS: Forty-nine patients in a randomized controlled trial of rTMS therapy for treatment resistant major depression underwent structural and functional MRI. DLPFC rules were applied virtually using MR-image guidance. Underlying cortical regions were labeled, and connectivity with the subgenual cingulate and whole-brain computed. RESULTS: Scalp-targeting rules applied post hoc to these MRIs that adjusted for head size, including Beam F3, were comparably precise, successful in directly targeting classical DLPFC and frontal networks, and anticorrelated with the subgenual cingulate. In contrast, all rules involving fixed distances introduced variability in regions and networks targeted. The 5cm rule targeted a transitional DLPFC region with a different connectivity profile from the adjusted rules. Seed-based connectivity analyses identified multiple regions, such as posterior cingulate and inferior parietal lobe, that warrant further study in order to understand their potential contribution to clinical response. CONCLUSION: EEG-based rules consistently targeted DLPFC brain regions with resting-state fMRI features known to be associated with depression response. These results provide a bridge from lab to clinic by enabling clinicians to relate scalp-targeting rules to functionally connected brain systems.

Visual field defects can arise from any part of visual system commencing from retina to brain. It is important to identify the structure from where they arise. Structure is obtained by different imaging devices (disc photos, OCT, HRT) and direct viewing and function obtained by visual field machines (Humphry Visual Field analyser or Octopus). Critical structure function correlation is done to make this information useful for clinical purpose. Automated computerized perimetry has added a third dimension to visual field defects by recognition of depth translating into degree of severity of visual field defect. This chapter is devoted to analysing site of lesion or anatomical correlation, reliability of data available for detection of structure or function, their correlation with each other and if discrepancy/inability to detect a possible defect, what are the other methods to reach to goal of detection. Limitations of available tools have also been integrated in-between the sentences.

BackgroundPrecise targeting of brain functional networks is believed critical for treatment efficacy of rTMS (repetitive pulse transcranial magnetic stimulation) in treatment resistant major depression.ObjectiveTo use imaging data from a "failed" clinical trial of rTMS in Veterans to test whether treatment response was associated with rTMS coil location in active but not sham stimulation, and compare fMRI functional connectivity between those stimulation locations.MethodsAn imaging substudy of 49 Veterans (mean age, 56 years; range, 27-78 years; 39 male) from a randomized, sham-controlled, double-blinded clinical trial of rTMS treatment, grouping participants by clinical response, followed by group comparisons of treatment locations identified by individualized fiducial markers on structural MRI and resting state fMRI derived networks.ResultsThe average stimulation location for responders versus nonresponders differed in the active but not in the sham condition (P=.02). The average responder location derived from the active condition showed significant negative functional connectivity with the subgenual cingulate (P&nbsp

To maintain cerebral blood flow (CBF), cerebral blood vessels dilate and contract in response to blood supply through cerebrovascular reactivity (CR).Cardiovascular (CV) disease is associated with increased stroke risk, but which risk factors specifically impact CR is unknown.Prospective longitudinal.Fifty-three subjects undergoing carotid endarterectomy or stenting.3T, 3D pseudo-continuous arterial spin labeling (PCASL) ASL, and TWe evaluated group differences in CBF changes for multiple cardiovascular risk factors in patients undergoing carotid revascularization surgery.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.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).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.1 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2020;51:734-747.

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 mm 3 . 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 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 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.

Sex differences in procedural skill learning have not been well characterized. Skill learning is an important area to explore in clinical settings that involve rehabilitation and deficit remediation, especially for returning Veterans that have a range of co-morbid conditions (traumatic brain injury, posttraumatic stress disorder, and depression) and possess impairments in multiple domains. Sixty-five (55 males, 10 females) Veterans completed two procedural learning tasks and answered self-report questionnaires. Participants’ performance and total learning slope were analyzed to determine sex differences in learning. Our results revealed sex differences in both tasks demonstrating females tend to perform better than males with a large effect size for these mean differences. While females performed better on the procedural learning tasks compared to males, their rate of learning was equivalent. Skill learning is an important requisite for rehabilitation, as skill learning is necessary to perform daily activities in new settings. Ultimately, these results provide insight into skill learning in Veterans with a range of co-morbid conditions and provide support for further investigation of sex differences in procedural learning.

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).

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.

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.

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/wa 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/wa stimuli, and vice versa. For the ART contrast, the same procedure was implemented using the /ba/ and /ba/wa 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.

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.

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.

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.

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.