Ethan G. Brown

Auditory Cortical Plasticity Drives Training-Induced Cognitive Changes in Schizophrenia

Schizophrenia is characterized by dysfunction in basic auditory processing, as well as higher-order operations of verbal learning and executive functions. We investigated whether targeted cognitive training of auditory processing improves neural responses to speech stimuli, and how these changes relate to higher-order cognitive functions. Patients with schizophrenia performed an auditory syllable identification task during magnetoencephalography before and after 50 hours of either targeted cognitive training or a computer games control. Healthy comparison subjects were assessed at baseline and after a 10 week no-contact interval. Prior to training, patients (N = 34) showed reduced M100 response in primary auditory cortex relative to healthy participants (N = 13). At reassessment, only the targeted cognitive training patient group (N = 18) exhibited increased M100 responses. Additionally, this group showed increased induced high gamma band activity within left dorsolateral prefrontal cortex immediately after stimulus presentation, and later in bilateral temporal cortices. Training-related changes in neural activity correlated with changes in executive function scores but not verbal learning and memory. These data suggest that computerized cognitive training that targets auditory and verbal learning operations enhances both sensory responses in auditory cortex as well as engagement of prefrontal regions, as indexed during an auditory processing task with low demands on working memory. This neural circuit enhancement is in turn associated with better executive function but not verbal memory.

The Contribution of the Corpus Callosum to Language Lateralization.

The development of hemispheric lateralization for language is poorly understood. In one hypothesis, early asymmetric gene expression assigns language to the left hemisphere. In an alternate view, language is represented a priori in both hemispheres and lateralization emerges via cross-hemispheric communication through the corpus callosum. To address this second hypothesis, we capitalized on the high temporal and spatial resolution of magnetoencephalographic imaging to measure cortical activity during language processing, speech preparation, and speech execution in 25 participants with agenesis of the corpus callosum (AgCC) and 21 matched neurotypical individuals. In contrast to strongly lateralized left hemisphere activations for language in neurotypical controls, participants with complete or partial AgCC exhibited bilateral hemispheric activations in both auditory or visually driven language tasks, with complete AgCC participants showing significantly more right hemisphere activations than controls or than individuals with partial AgCC. In AgCC individuals, language laterality positively correlated with verbal IQ. These findings suggest that the corpus callosum helps to drive language lateralization. SIGNIFICANCE STATEMENT The role that corpus callosum development has on the hemispheric specialization of language is poorly understood. Here, we used magnetoencephalographic imaging during linguistic tests (verb generation, picture naming) to test for hemispheric dominance in patients with agenesis of the corpus callosum (AgCC) and found reduced laterality (i.e., greater likelihood of bilaterality or right hemisphere dominance) in this cohort compared with controls, especially in patients with complete agenesis. Laterality was positively correlated with behavioral measures of verbal intelligence. These findings provide support for the hypothesis that the callosum aids in functional specialization throughout neural development and that the loss of this mechanism correlates with impairments in verbal performance.

Confirmed case of levamisole-associated multifocal inflammatory leukoencephalopathy in a cocaine user

Levamisole is a common adulterant in cocaine and has previously been associated with a variety of serious complications including multifocal inflammatory leukoencephalopathy (MIL). There have been several reports of MIL in patients taking cocaine and, though suspected, the presence of levamisole was not confirmed. We present a case of a 63-year-old woman presenting with stupor and spastic quadraparesis found to have urine positive for cocaine and levamisole. An MRI brain revealed innumerable FLAIR hyperintensities with restricted diffusion and incomplete ring-enhancement. This is the first case to confirm the presence of levamisole in a patient with MIL associated with cocaine use.

Predicting inpatient delirium: The AWOL delirium risk-stratification score in clinical practice

ABSTRACT Inpatient delirium improves with multicomponent interventions by hospital staff, though the resources needed are often limited. Risk‐stratification to predict delirium is a useful first step to help triage resources, but the performance of risk‐stratification as part of a functioning multicomponent pathway has not been assessed. We retrospectively studied the performance of a validated delirium prediction rule, the AWOL score, as a part of a multicomponent delirium care pathway in practice on a university hospital ward. We reviewed the hospitalizations of patients 50 years or older for evidence of delirium and extracted the AWOL score from nursing documentation (n = 347). The area under the receiver operating characteristic curve (AUC) was 0.83 (95% CI 0.77–0.89) for all cases and 0.73 (95% CI 0.60–0.85) when cases of prevalent delirium were removed. Involving minimal additional assessment, this nursing‐based risk stratification score performed well as part of a multicomponent delirium care pathway. HIGHLIGHTSRisk‐stratification for predicting inpatient delirium is evaluatedThe nursing‐based “AWOL” score involves minimal additional assessment timeBrief assessment of cognition and illness are essential components of the scoreThe score performed well in predicting prevalent and incident deliriumRisk‐stratification is a useful addition to a multicomponent delirium care pathway

Immediate Hemorrhagic Transformation After Intravenous Tissue-Type Plasminogen Activator Injection in 2 Cocaine Users

Cocaine use is associated with multiple neurovascular complications, including ischemic and hemorrhagic strokes. Intracerebral hemorrhage is especially prevalent in patients with acute cocaine intoxication as defined by positive urine toxin assays.1 In addition, intracerebral hemorrhage in patients with cocaine intoxication are more severe, often associated with intraventricular hemorrhage, and have a poorer prognosis than intracerebral hemorrhage from other causes.2 Still, the majority of patients with cocaine-associated strokes will present with ischemic strokes. Whether intravenous tissue-type plasminogen activator (tPA) can be safely used in patients presenting with ischemic strokes and recent cocaine use is unknown, and their risk toward hemorrhagic conversion is not fully characterized. We describe 2 cases of cocaine-associated ischemic stroke with immediate hemorrhagic transformation after intravenous tPA infusion. A 55-year-old man presented to the emergency department 20 minutes after the sudden onset of left arm weakness while using cocaine. Examination revealed left hemiparesis-hemiataxia and noncontrast head computed tomography (CT) was normal except for bilateral white matter hypointensities suggestive of leukoaraiosis and a nasal septum perforation indicative of chronic intranasal cocaine use (Figure 1). A bolus of intravenous tPA was administered for acute ischemic stroke, with a symptom onset to administration time of 45 minutes. During the intravenous tPA infusion, the systolic blood pressure remained below 170 mm Hg. Immediately after the tPA bolus infusion, a CT-angiogram and postcontrast CT were acquired (Figure 1B). While being transported to the neuro-ICU, the patient complained of new headache and right arm weakness before quickly progressing to coma requiring emergent intubation as tPA infusion completed. Review of initial studies revealed contrast extravasation in the dorsal pons during tPA infusion (Figure 1B, black arrow). A magnetic resonance imaging scan revealed multifocal infarcts and hemorrhages raising suspicion for …

The Microbiome in Neurodegenerative Disease

Purpose of ReviewTo review recent updates in our understanding of the microbiome and its relationship to neurodegenerative disease.Recent FindingsRecognition of the microbiome’s role in health and disease continues to expand. Recent techniques have focused on delineating the function and metabolism of resident organisms, which may correlate more directly with human physiology than identification of species. The role of the microbiome may be of particular importance in certain neurodegenerative diseases, including Parkinson’s disease and Alzheimer’s disease, among others.SummaryThe microbiome influences brain function and may play a role in neurodegenerative disease. Potential mechanisms include immunologic activation and promotion/attenuation of inflammation, as well as direct effects on induction and/or exacerbation of protein aggregation. The microbiome also has increasingly well-documented effects on the metabolism of therapeutic medications. Future studies will need to work through complex methodologic issues in order to identify which changes are truly disease-specific. Nevertheless, manipulation of the microbiome may soon improve our ability to treat neurodegenerative disease.

Moving Beyond Metabolic Encephalopathy: An Update on Delirium Prevention, Workup, and Management

Delirium is a condition that frequently complicates hospitalization and consists of an acute decline in orientation and attention, often accompanied by other cognitive changes. Delirium is tied to multiple detrimental outcomes both in the short and long term, including cognitive and functional decline, inpatient complications, and mortality. Postoperative, elderly medical, and critical care patients have been identified as populations at particular risk. In this review, the authors discuss current theories on pathophysiology, recommended workup, and evidence-based prevention and management of inpatient delirium. In general, instituting a system of active screening of at-risk populations and nonpharmacologic interventions for prevention and treatment seems to be the most effective method of addressing delirium. More research is needed to clarify the etiology of delirium and develop safe therapeutic options that address the underlying pathophysiology.