Cognition is often affected in a variety of neuropsychiatric, neurological, and neurodevelopmental disorders. The neural discriminative response, reflected in mismatch negativity (MMN) and its ...magnetoencephalographic equivalent (MMNm), has been used as a tool to study a variety of disorders involving auditory cognition. MMN/MMNm is an involuntary brain response to auditory change or, more generally, to pattern regularity violation. For a number of disorders, MMN/MMNm amplitude to sound deviance has been shown to be attenuated or the peak-latency of the component prolonged compared to controls. This general finding suggests that while not serving as a specific marker to any particular disorder, MMN may be useful for understanding factors of cognition in various disorders, and has potential to serve as an indicator of risk. This review presents a brief history of the MMN, followed by a description of how MMN has been used to index auditory processing capability in a range of neuropsychiatric, neurological, and neurodevelopmental disorders. Finally, we suggest future directions for research to further enhance our understanding of the neural substrate of deviance detection that could lead to improvements in the use of MMN as a clinical tool.
The theory of statistical learning has been influential in providing a framework for how humans learn to segment patterns of regularities from continuous sensory inputs, such as speech and music. ...This form of learning is based on statistical cues and is thought to underlie the ability to learn to segment patterns of regularities from continuous sensory inputs, such as the transition probabilities in speech and music. However, the connection between statistical learning and brain measurements is not well understood. Here we focus on ERPs in the context of tone sequences that contain statistically cohesive melodic patterns. We hypothesized that implicit learning of statistical regularities would influence what was held in auditory working memory. We predicted that a wrong note occurring within a cohesive pattern (within-pattern deviant) would lead to a significantly larger brain signal than a wrong note occurring between cohesive patterns (between-pattern deviant), even though both deviant types were equally likely to occur with respect to the global tone sequence. We discuss this prediction within a simple Markov model framework that learns the transition probability regularities within the tone sequence. Results show that signal strength was stronger when cohesive patterns were violated and demonstrate that the transitional probability of the sequence influences the memory basis for melodic patterns. Our results thus characterize how informational units are stored in auditory memory trace for deviance detection and provide new evidence about how the brain organizes sequential sound input that is useful for perception.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The goal of this review article is to redefine what the mismatch negativity (MMN) component of event-related potentials reflects in auditory scene analysis, and to provide an overview of how the MMN ...serves as a valuable tool in Cognitive Neuroscience research. In doing so, some of the old beliefs (five common ‘myths’) about MMN will be dispelled, such as the notion that MMN is a simple feature discriminator and that attention itself modulates MMN elicitation. A revised description of what MMN truly reflects will be provided, which includes a principal focus onto the highly context-dependent nature of MMN elicitation and new terminology to discuss MMN and attention. This revised framework will help clarify what has been a long line of seemingly contradictory results from studies in which behavioral ability to hear differences between sounds and passive elicitation of MMN have been inconsistent. Understanding what MMN is will also benefit clinical research efforts by providing a new picture of how to design appropriate paradigms suited to various clinical populations.
Processing the wealth of sensory information from the surrounding environment is a vital human function with the potential to develop learning, advance social interactions, and promote safety and ...well-being.
To elucidate underlying processes governing these activities we measured neurophysiological responses to patterned stimulus sequences during a sound categorization task to evaluate attention effects on implicit learning, sound categorization, and speech perception. Using a unique experimental design, we uncoupled conceptual categorical effects from stimulus-specific effects by presenting categorical stimulus tokens that did not physically repeat.
We found effects of implicit learning, categorical habituation, and a speech perception bias when the sounds were attended, and the listeners performed a categorization task (task-relevant). In contrast, there was no evidence of a speech perception bias, implicit learning of the structured sound sequence, or repetition suppression to repeated within-category sounds (no categorical habituation) when participants passively listened to the sounds and watched a silent closed-captioned video (task-irrelevant). No indication of category perception was demonstrated in the scalp-recorded brain components when participants were watching a movie and had no task with the sounds.
These results demonstrate that attention is required to maintain category identification and expectations induced by a structured sequence when the conceptual information must be extracted from stimuli that are acoustically distinct. Taken together, these striking attention effects support the theoretical view that top-down control is required to initiate expectations for higher level cognitive processing.
Background We assessed the impact of preoperative Staphylococcus aureus screening and targeted decolonization on the incidence of postoperative methicillin-resistant S aureus (MRSA) colonization, ...intensive care unit MRSA transmission, and surgical site infections in cardiac surgery patients. Methods We reviewed medical records for all adult patients during two periods: preintervention (January 2007 to April 2010) and intervention (January 2011 to December 2014). In the intervention period, we performed nasal screening for methicillin-sensitive S aureus and MRSA using polymerase chain reaction within 30 days of the operation. Colonized patients received intranasal mupirocin twice daily and chlorhexidine baths daily for 5 days; patients colonized with MRSA also received prophylactic vancomycin plus cefazolin with contact isolation precautions. Nasal surveillance for MRSA was performed on intensive care unit admission and weekly thereafter. Multivariable logistic regression models were constructed to determine risk factors for postoperative MRSA colonization, and surgical site infections and the impact of our screening program was assessed in these models. Poisson regression was used to assess MRSA transmission. Results Comparing 2,826 preintervention and 4,038 intervention patients, cases differed in age, diabetes mellitus, preoperative infection, preoperative length of stay, and bypass time (all p ≤ 0.03). Intervention patients had risk-adjusted reductions in MRSA colonization (odds ratio 0.53, 95% confidence interval CI: 0.37 to 0.76, p < 0.001), transmission (incidence rate ratio 0.29, 95% CI: 0.13 to 0.65, p = 0.002), and surgical site infections (odds ratio 0.58, 95% CI: 0.40 to 0.86, p = 0.007). Increased duration of preoperative decolonization therapy was associated with decreased postoperative MRSA colonization (odds ratio 0.73, 95% CI: 0.53 to 1.00, p = 0.05). Conclusions Preoperative S aureus screening with targeted decolonization was associated with reduced MRSA colonization, transmission, and surgical site infections. Duration of preoperative therapy correlated with decreased frequency of postoperative MRSA colonization.
Patients with late‐stage Kellgren‐Lawrence knee osteoarthritis received a single intra‐articular injection of 1, 10, or 50 million bone marrow mesenchymal stromal cells (BM‐MSCs) in a phase I/IIa ...trial to assess safety and efficacy using a broad toolset of analytical methods. Besides safety, outcomes included patient‐reported outcome measures (PROMs): Knee Injury and Osteoarthritis Outcome Score (KOOS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC); contrast‐enhanced magnetic resonance imaging (MRI) for cartilage morphology (Whole Organ MRI Scores WORMS), collagen content (T2 scores), and synovitis; and inflammation and cartilage turnover biomarkers, all over 12 months. BM‐MSCs were characterized by a panel of anti‐inflammatory markers to predict clinical efficacy. There were no serious adverse events, although four patients had minor, transient adverse events. There were significant overall improvements in KOOS pain, symptoms, quality of life, and WOMAC stiffness relative to baseline; the 50 million dose achieved clinically relevant improvements across most PROMs. WORMS and T2 scores did not change relative to baseline. However, cartilage catabolic biomarkers and MRI synovitis were significantly lower at higher doses. Pro‐inflammatory monocytes/macrophages and interleukin 12 levels decreased in the synovial fluid after MSC injection. The panel of BM‐MSC anti‐inflammatory markers was strongly predictive of PROMs over 12 months. Autologous BM‐MSCs are safe and result in significant improvements in PROMs at 12 months. Our analytical tools provide important insights into BM‐MSC dosing and BM‐MSC reduction of synovial inflammation and cartilage degradation and provide a highly predictive donor selection criterion that will be critical in translating MSC therapy for osteoarthritis. Stem Cells Translational Medicine 2019;8:746&757
Through anti‐inflammatory effects, bone‐marrow‐derived mesenchymal stromal cells decrease pain and improve function in patients with knee osteoarthritis.
The predictable rhythmic structure is important to most ecologically relevant sounds for humans, such as is found in the rhythm of speech or music. This study addressed the question of how rhythmic ...predictions are maintained in the auditory system when there are multiple perceptual interpretations occurring simultaneously and emanating from the same sound source. We recorded the electroencephalogram (EEG) while presenting participants with a tone sequence that had two different tone feature patterns, one based on the sequential rhythmic variation in tone duration and the other on sequential rhythmic variation in tone intensity. Participants were presented with the same sound sequences and were instructed to listen for the intensity pattern (ignore fluctuations in duration) and press a response key to detected pattern deviants (attend intensity pattern task); to listen to the duration pattern (ignore fluctuations in intensity) and make a button press to duration pattern deviants (attend duration pattern task), and to watch a movie and ignore the sounds presented to their ears (attend visual task). Both intensity and duration patterns occurred predictably 85% of the time, thus the key question involved evaluating how the brain treated the irrelevant feature patterns (standards and deviants) while performing an auditory or visual task. We expected that task-based feature patterns would have a more robust brain response to attended standards and deviants than the unattended feature patterns. Instead, we found that the neural entrainment to the rhythm of the standard attended patterns had similar power to the standard of the unattended feature patterns. In addition, the infrequent pattern deviants elicited the event-related brain potential called the mismatch negativity component (MMN). The MMN elicited by task-based feature pattern deviants had a similar amplitude to MMNs elicited by unattended pattern deviants that were unattended because they were not the target pattern or because the participant ignored the sounds and watched a movie. Thus, these results demonstrate that the brain tracks multiple predictions about the complexities in sound streams and can automatically track and detect deviations with respect to these predictions. This capability would be useful for switching attention rapidly among multiple objects in a busy auditory scene.
Stroke is the leading cause of serious long-term disability, significantly reducing mobility in almost half of the affected patients aged 65 years and older. There are currently no proven ...neurorestorative treatments for chronic stroke. To address the complex problem of restoring function in ischemic brain tissue, stem cell transplantation-based therapies have emerged as potential restorative therapies. Aligning with the major cell types found within the ischemic brain, stem-cell-based clinical trials for ischemic stroke have fallen under three broad cell lineages: hematopoietic, mesenchymal, and neural. In this review article, we will discuss the scientific rationale for transplanting cells from each of these lineages and provide an overview of published and ongoing trials using this framework.
Acute ischemic stroke is a devastating disease that is often complicated by hemorrhagic transformation. While significant advances have been made over the past two decades with regard to emergent ...treatment of AIS, many of the therapeutic options are limited by an increased risk of hemorrhage. Here, we sought to review the rates of hemorrhagic transformation in the major clinical trials of AIS intervention. Since the reviewed clinical trials vary significantly in terms of study design, eligibility criteria, stroke severity, and baseline demographic data, direct comparisons between the various trials is not valid. Nevertheless, this review is intended to consolidate the pertinent data on hemorrhagic transformation in order to call attention to any patterns that may warrant further investigation.
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