Mapping cognitive and emotional networks in neurosurgical patients using resting-state functional magnetic resonance imaging.

Neurosurgery has been at the forefront of a paradigm shift from a localizationist perspective to a network-based approach to brain mapping. Over the last 2 decades, we have seen dramatic improvements in the way we can image the human brain and noninvasively estimate the location of critical functional networks. In certain patients with brain tumors and epilepsy, intraoperative electrical stimulation has revealed direct links between these networks and their function. The focus of these techniques has rightfully been identification and preservation of so-called "eloquent" brain functions (i.e., motor and language), but there is building momentum for more extensive mapping of cognitive and emotional networks. In addition, there is growing interest in mapping these functions in patients with a broad range of neurosurgical diseases. Resting-state functional MRI (rs-fMRI) is a noninvasive imaging modality that is able to measure spontaneous low-frequency blood oxygen level-dependent signal fluctuations at rest to infer neuronal activity. Rs-fMRI may be able to map cognitive and emotional networks for individual patients. In this review, the authors give an overview of the rs-fMRI technique and associated cognitive and emotional resting-state networks, discuss the potential applications of rs-fMRI, and propose future directions for the mapping of cognition and emotion in neurosurgical patients.

Specifying a Causal Role for Angular Gyrus in Autobiographical Memory.

Considerable recent evidence indicates that angular gyrus dysfunction in humans does not result in amnesia, but does impair a number of aspects of episodic memory. Patients with parietal lobe lesions have been reported to exhibit a deficit when freely recalling autobiographical events from their pasts, but can remember details of the events when recall is cued by specific questions. In apparent contradiction, inhibitory brain stimulation targeting angular gyrus in healthy volunteers has been found to have no effect on free recall or cued recall of word pairs. The present study sought to resolve this inconsistency by testing free and cued recall of both autobiographical memories and word-pair memories in the same healthy male and female human participants following continuous theta burst stimulation (cTBS) of angular gyrus and a vertex control location. Angular gyrus cTBS resulted in a selective reduction in the free recall, but not cued recall, of autobiographical memories, whereas free and cued recall of word-pair memories were unaffected. Additionally, participants reported fewer autobiographical episodes as being experienced from a first-person perspective following angular gyrus cTBS. The findings add to a growing body of evidence that a function of angular gyrus within the network of brain regions responsible for episodic recollection is to integrate memory features within an egocentric framework into the kind of first-person perspective representation that enables the subjective experience of remembering events from our personal pasts.SIGNIFICANCE STATEMENT In seeking to understand the role played by the angular gyrus region of parietal cortex in human memory, interpreting the often conflicting findings from neuroimaging and neuropsychology studies has been hampered by differences in anatomical specificity and localization between methods. In the present study, we address these limitations using continuous theta burst stimulation in healthy volunteers to disrupt function of angular gyrus and a vertex control region. With this method, we adjudicate between two competing theories of parietal lobe function, finding evidence that is inconsistent with an attentional role for angular gyrus in memory, supporting instead an account in terms of integrating memory features within an egocentric framework into a first-person perspective representation that enables the subjective experience of remembering.

Boxing injury epidemiology in the Great Britain team: a 5-year surveillance study of medically diagnosed injury incidence and outcome.

OBJECTIVES: There has been no comprehensive injury report of elite-level amateur boxers in competition and training. We reviewed injuries in training and competition in the Great Britain (GB) amateur boxing squad between 2005 and 2009. METHODS: Longitudinal, prospective injury surveillance over 5 years of the GB boxing squad from 2005 to 2009. 66 boxers passed through the squad. The location, region affected, description, and the duration of each injury were recorded by the team doctor and team physiotherapist. We recorded whether the injury occurred during competition or training, and also whether it was a new or a recurrent injury. The injury rate during competition was calculated as the number of injuries per 1000 h. RESULTS: More injuries affected the hand than any other body location. This was the case overall, in training and competition individually, and for both new and recurrent injuries. More injuries occurred during training than during competition, and most injuries were new rather than recurrent. Total injury rate during competition was 828 per 1000 h and hand injury rate in competition was 302 injuries per 1000 h. Hand injury rate in competition was significantly higher than at the other locations. The incidence of concussion is comparatively low. CONCLUSIONS: Injury prevention should aim to protect the hands and wrists of elite amateur boxers.

Impact of diet on mortality from stroke: results from the U.S. multiethnic cohort study.

OBJECTIVES: Stroke is the fourth leading cause of death in the United States and stroke mortality rates vary by ethnicity. The purpose of this study was to examine the associations between food group consumption and risk of death from stroke among 5 ethnic groups in the United States. METHODS: The Multiethnic Cohort includes >215,000 participants, the majority of whom are African American, Native Hawaiian, Japanese American, Latino, and Caucasian men and women recruited by mail survey in Hawaii and Los Angeles in 1993-1996. Deaths from stroke were identified by linkage to the state death files and the U.S. National Death Index. Diet was assessed using a validated food frequency questionnaire. Associations were examined using multivariable Cox proportional hazards models, stratified by ethnicity and gender. RESULTS: A total of 860 deaths from stroke were identified among the cohort participants. Vegetable intake was associated with a significant reduction in risk for fatal stroke among African American women (relative risk [RR]=0.60; 95% CI: 0.36-0.99). Among Japanese American women only, high fruit intake was significantly associated with a risk reduction for stroke mortality (RR=0.43; 95% confidence interval [CI]: 0.22-0.85), whereas meat intake increased risk (RR=2.36; 95% CI: 1.31-4.26). Among men, a significant reduction in stroke mortality was observed among Native Hawaiians (RR=0.26; 95% CI: 0.07-0.95). After pooling the data for the ethnic groups, the findings support an elevated risk for high meat intake among women overall (RR=1.56; 95% CI: 1.12-2.16); no significant effects of dietary intake on risk for fatal stroke were observed among men. CONCLUSIONS: Although some variations were observed for the associations between diet and stroke mortality among ethnic groups, the findings suggest that these differences are not substantial and may be due to dietary intake of specific food subgroups. Additional investigations including dietary subgroups and nutrients sources are needed to clarify these findings.

Adherence to the USDA dietary recommendations for fruit and vegetable intake and risk of fatal stroke among ethnic groups: a prospective cohort study.

BACKGROUND: Stroke is the fourth leading cause of death in the U.S. and stroke mortality rates differ substantially by ethnic group. The impact of adherence to the USDA dietary guidelines on risk for fatal stroke among different ethnic groups has not previously been examined. METHODS: A prospective cohort design was used to examine associations between adherence with dietary recommendations for fruit and vegetable intake and risk for stroke mortality among 174,888 men and women representing five ethnic groups; African American, Native Hawaiian, Japanese American, Latino, and Caucasian. Dietary intake was assessed using a mailed quantitative food frequency questionnaire. Associations were examined using Cox proportional hazards models. RESULTS: There was no evidence that ethnicity modified associations between fruit and vegetable intake and stroke mortality. When data for different ethnicities were combined, a reduced risk for fatal stroke was observed among women who were adherent with the USDA dietary recommendations for vegetable intake, although this result did not reach statistical significance (RR = 0.84, 95% CI = 0.68-1.04). No associations were observed among men. CONCLUSIONS: The results of this study do not provide evidence that dietary intake of fruits and vegetables differentially impacts risk for stroke mortality among different ethnic groups.

ICU management of aneurysmal subarachnoid hemorrhage.

INTRODUCTION: Aneurysmal subarachnoid hemorrhage (SAH) has very high morbidity and mortality rates. Optimal intensive care unit (ICU) management requires knowledge of the potential complications that occur in this patient population. METHODS: Review of the ICU management of SAH. Level of evidence for specific recommendations is provided. RESULTS: Grading scales utilizing clinical factors and brain imaging studies can help in determining prognosis and are reviewed. Misdiagnosis of SAH is fairly common so the clinical symptoms and signs of SAH are summarized. The ICU management of SAH is discussed beginning with a focus on avoiding aneurysm re-rupture and securing the aneurysm, followed by a review of the neurologic and medical complications that may occur after the aneurysm is secured. Detailed treatment strategies and areas of current and future research are reviewed. CONCLUSIONS: The ICU management of the patient with SAH can be particularly challenging and requires an awareness of all potential neurologic and medical complications and their urgent treatments.

The effect of a neurocritical care service without a dedicated neuro-ICU on quality of care in intracerebral hemorrhage.

BACKGROUND: Introduction of neurocritical care services to dedicated neuro-ICUs is associated with improved quality of care. The impact of a neurocritical care service without a dedicated neuro-ICU has not been studied. METHODS: We retrospectively identified all patients admitted to our institution with intracerebral hemorrhage (ICH) in two 12-month periods: immediately before the arrival of the first neurointensivist ("before") and after the neurocritical care service was established ("after"). There was no nursing team, ICU housestaff/physician extender team, or physical unit dedicated to the care of patients with critical neurologic illness during either period. Using an uncontrolled before-after design, we compared clinical outcomes and performance on quality metrics between groups. RESULTS: We included 74 patients with primary supratentorial ICH. Mortality, length of stay (LOS), proportion of patients with modified Rankin Score 0-3, and destination on discharge did not differ between groups when adjusted for confounders. Time to first two consecutive systolic blood pressure (SBP) measurements <180 mmHg was shorter in the "after" cohort (mean 4.5 vs. 3.2 h, p = 0.001). Area under the curve measurement for change in SBP from baseline over the first 24 h after ED arrival demonstrated greater, sustained SBP reduction in the "after" cohort (mean -187.9 vs. -720.9, p = 0.04). A higher proportion of patients were fed without passing a dysphagia screen in the "before" group (45 vs. 0%, p < 0.001). CONCLUSIONS: Introduction of a neurocritical service without a neuro-ICU at our institution was associated with a trend toward longer ICU LOS and improvement in some key metrics of quality of care for patients with ICH.

Impact of methamphetamine on regional metabolism and cerebral blood flow after traumatic brain injury.

BACKGROUND: Substance abuse is a frequent comorbid condition among patients with traumatic brain injury (TBI), but little is known about its potential additive or interactive effects on tissue injury or recovery from TBI. This study aims to evaluate changes in regional metabolism and cerebral perfusion in subjects who used methamphetamine (METH) prior to sustaining a TBI. We hypothesized that METH use would decrease pericontusional cerebral perfusion and markers of neuronal metabolism, in TBI patients compared to those without METH use. METHODS: This is a single center prospective observational study. Adults with moderate and severe TBI were included. MRI scanning was performed on a 3 Tesla scanner. MP-RAGE and FLAIR sequences as well as Metabolite spectra of NAA and lactate in pericontusional and contralateral voxels identified on the MP-RAGE scans. A spiral-based FAIR sequence was used for the acquisition of cerebral blood flow (CBF) maps. Regional CBF images were analyzed using ImageJ open source software. Pericontusional and contralateral CBF, NAA, and lactate were assessed in the entire cohort and in the METH and non-METH groups. RESULTS: Seventeen subjects completed the MR studies. Analysis of entire cohort: pericontusional NAA concentrations (5.81 ± 2.0 mM/kg) were 12% lower compared to the contralateral NAA (6.98 ± 1.2 mM/kg; p = 0.03). Lactate concentrations and CBF were not significantly different between the two regions; however, regional CBF was equally reduced in the two regions. Subgroup analysis: 41% of subjects tested positive for METH. The mean age, Glasgow Coma Scale, and time to scan did not differ between groups. The two subject groups also had similar regional NAA and lactate. Pericontusional CBF was 60% lower in the METH users than the non-users, p = 0.04; contralateral CBF did not differ between the groups. CONCLUSION: This small study demonstrates that tissue metabolism is regionally heterogeneous after TBI and pericontusional perfusion was significantly reduced in the METH subgroup.

Postpartum trifecta: simultaneous eclamptic intracerebral hemorrhage, PRES, and herniation due to intracranial hypotension.

BACKGROUND: In the postpartum patient, sudden depression of consciousness may be caused by a number of etiologies and can result in serious consequences. Rapid, accurate diagnosis allows for specific treatments that optimize outcome, but diagnosis can be challenging in this population. We present a case of postpartum herniation due to intracranial hypotension in a patient with eclampsia, posterior reversible encephalopathy syndrome (PRES), and intracerebral hemorrhage (ICH). METHODS: Case report. RESULTS: A 26-year-old woman developed headache on postpartum day (PD) 1 after cesarean section with epidural anesthesia. Over the next 3 days, she developed progressively worsening headache and hypertension. On PD 5, she had a generalized seizure, leading to endotracheal intubation, propofol infusion, and transfer to our institution. By PD 6, she opened her eyes to voice, followed commands, moved all extremities, and had briskly reactive 4 mm pupils. MRI showed L parasagittal ICH with minimal mass effect, edema consistent with PRES, and brain descent with obliteration of the basal cisterns and tonsillar herniation. Later on PD 6, after diuresis for pulmonary edema, she became unresponsive with a dilated and nonreactive left pupil. She was laid flat for transport to CT, with improvement in arousal and pupil reactivity within 5 min. Intravascular volume was repleted with normal saline and albumin, and she was placed in the Trendelenburg position. Over the subsequent 8 h, she developed a dilated and nonreactive left pupil whenever her head was raised to horizontal. Her head position was gradually successfully raised over 48 h without need for a lumbar epidural blood patch. She was discharged home on PD 13 with only mild left arm dysmetria. CONCLUSIONS: Intracranial hypotension may coexist with other potential causes of cerebral herniation in the postpartum period. Establishing this diagnosis is crucial because its treatment is opposite that of other causes of herniation.

Decompressive laparotomy for refractory intracranial hypertension after traumatic brain injury.

BACKGROUND: Intracranial hypertension is a crucial modifiable risk factor for poor outcome after traumatic brain injury (TBI). Limited evidence suggests that decompressive laparotomy may be an effective treatment for refractory ICH in patients who have elevated intra-abdominal pressure. METHODS: Case report. RESULTS: We present a multi-trauma patient who sustained severe TBI in a motor vehicle collision. Intracranial pressure (ICP) was initially medically managed but became refractory to standard therapies. Emergent decompressive laparotomy performed in the surgical intensive care unit for abdominal compartment syndrome concomitantly improved the patient's ICP. CONCLUSIONS: Elevated intra-abdominal pressure can exacerbate intracranial hypertension in patients with TBI. Recognition of this condition and treatment with decompressive laparotomy may be useful in patients with intracranial hypertension refractory to optimal medical therapy.

Asymmetric posterior reversible encephalopathy syndrome complicating hemodynamic augmentation for subarachnoid hemorrhage-associated cerebral vasospasm.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is a rare complication of hemodynamic augmentation for subarachnoid hemorrhage (SAH)-associated vasospasm. The roles of hyperperfusion and hypoperfusion in the genesis of PRES remain uncertain. METHODS: Case report. RESULTS: We admitted a 35-year-old woman with Hunt & Hess grade II SAH secondary to rupture of a right middle cerebral artery (MCA) aneurysm. This was surgically clipped. Beginning on hospital day 3, she developed recurrent symptomatic vasospasm of the right MCA despite hemodynamic augmentation to a MAP as high as 130 mmHg and endovascular therapy. On hospital day 7, after 36 h of sustained MAP 120-130 mmHg, her level of arousal progressively declined, culminating in stupor and two generalized tonic-clonic seizures. MRI showed widespread, yet markedly asymmetric changes consistent with PRES largely sparing the right MCA territory. After the MAP was decreased to 85-100 mmHg, she had no further seizures. 2 days later she was fully alert with mild left hemiparesis. CONCLUSIONS: PRES is a rare complication of hemodynamic augmentation that should be considered in the differential diagnosis of delayed neurological decline in patients with aneurysmal SAH-associated cerebral vasospasm. The markedly asymmetric distribution of PRES lesions with sparing of the territory affected by vasospasm supports the hypothesis that hyperperfusion underlies the pathophysiology of this disorder.

Intensive versus conventional insulin therapy in critically ill neurologic patients.

BACKGROUND: Previous studies of glycemic control in non-neurologic ICU patients have shown conflicting results. The purpose was to investigate whether intensive insulin therapy (IIT) to keep blood glucose levels from 80 to 110 mg/dl or conventional treatment to keep levels less than 151 mg/dl was associated with a reduction of mortality and improved functional outcome in critically ill neurologic patients. METHODS: Within 24 h of ICU admission, mechanically ventilated adult neurologic patients were enrolled after written informed consent and randomized to intensive or conventional control of blood glucose levels with insulin. Primary outcome measure was death within 3 months. Secondary outcome measures included 90-day modified Rankin scale (mRS) score, ICU, and hospital LOS. RESULTS: 81 patients were enrolled. The proportion of deaths was higher among IIT patients but this was not statistically significant (36 vs. 25%, P = 0.34). When good versus poor outcome at 3 months was dichotomized to mRS score 0-2 versus 3-6, respectively, there was no difference in outcome between the two groups (76.2 vs. 75% had a poor 3-month outcome, P = 1.0). There was also no difference in ICU or hospital LOS. Hypoglycemia (<60 mg/dl) and severe hypoglycemia (<40 mg/dl) were more common in the intensive arm (48 vs. 11%, P = 0.0006; and 4 vs. 0%, P = 0.5, respectively). CONCLUSION: There was no benefit to IIT in this small critically ill neurologic population. This is the first glycemic control study to specifically examine both critically ill stroke and traumatic brain injury (TBI) patients and functional outcome. Given these results, IIT cannot be recommended over conventional control.

Asymmetric prefrontal cortex activation in relation to markers of overeating in obese humans.

Dietary restraint is heavily influenced by affect, which has been independently related to asymmetrical activation in the prefrontal cortex (prefrontal asymmetry) in electroencephalograph (EEG) studies. In normal weight individuals, dietary restraint has been related to prefrontal asymmetry; however, this relationship was not mediated by affect. This study was designed to test the hypotheses that, in an overweight and obese sample, dietary restraint as well as binge eating, disinhibition, hunger, and appetitive responsivity would be related to prefrontal asymmetry independent of affect at the time of assessment. Resting EEG recordings and self-report measures of overeating and affect were collected in 28 overweight and obese adults. Linear regression analyses were used to predict prefrontal asymmetry from appetitive measures while controlling for affect. Cognitive restraint and binge eating were not associated with prefrontal asymmetry. However, disinhibition, hunger, and appetitive responsivity predicted left-, greater than right-, sided prefrontal cortex activation independent of affect. Findings in this study add to a growing literature implicating the prefrontal cortex in the cognitive control of dietary intake. Further research to specify the precise role of prefrontal asymmetry in the motivation toward, and cessation of, feeding in obese individuals is encouraged.

Serum Apolipoprotein E and Other Inflammatory Markers Can Identify Non-Responding Patients to a Dendritic Cell Vaccine.

BACKGROUND: Despite the majority of patients do not gain any benefit from dendritic cells (DC) vaccines, this approach has occasionally given rise to dramatic responses in melanoma. Biomarkers are crucial to identify which patients are more likely to respond. We looked for correlations between pre- or post- vaccination biomarkers and clinical outcomes to DC therapy in a cohort of patients with stage IV melanoma receiving a vaccine with autologous ex-vivo expanded DCs pulsed with allogeneic tumor cell lysate. METHODS: Serial serum samples were collected at baseline, week 4 and 12 and they were analyzed for a panel of different inflammatory markers using cytometric bead array technology and ELISA. RESULTS: Twenty-one patients were evaluable for response. Patients were separated into responders and non-responders based on clinical benefit. Responders were defined as patients who achieved a complete response, partial response or stable disease the latter lasting for at least 6 months. Responders (N = 9) showed a significantly longer Progression-free Survival (PFS; HR 0.23; 95% CI 0.08-062; P < .001) and Overall Survival (OS; HR 0.22; 95% CI 0.08-0.59; P < .001). The clinical non-responder phenotype correlated with an elevated pre-vaccination level of cytokines associated with inflammation compared to clinical responders (Apolipoprotein C111; IL-12 p40; MiP1α; Stem Cell Factor and TNFα). Apolipoprotein E (ApoE) was also significantly elevated in the pre-vaccine sera of the clinically non-responding group and in addition it was found to correlate with outcomes. Patients with increased levels of ApoE had a significantly shorter PFS (HR 3.02; 95% CI 1.09-8.35; P = .015) and OS (HR 2.40; 95% CI 0.9-6.3; P = .034). CONCLUSION: Our findings support the notion that treating the inflammatory background may have an impact on clinical outcome for patients receiving immunotherapy. A larger study is needed to confirm the significance of ApoE as a predictive biomarker for response to DC vaccines.

The origins of insight in resting-state brain activity.

People can solve problems in more than one way. Two general strategies involve (A) methodical, conscious, search of problem-state transformations, and (B) sudden insight, with abrupt emergence of the solution into consciousness. This study elucidated the influence of initial resting brain-state on subjects' subsequent strategy choices. High-density electroencephalograms (EEGs) were recorded from subjects at rest who were subsequently directed to solve a series of anagrams. Subjects were divided into two groups based on the proportion of anagram solutions derived with self-reported insight versus search. Reaction time and accuracy results were consistent with different cognitive problem-solving strategies used for solving anagrams with versus without insight. Spectral analyses yielded group differences in resting-state EEG supporting hypotheses concerning insight-related attentional diffusion and right-lateralized hemispheric asymmetry. These results reveal a relationship between resting-state brain activity and problem-solving strategy, and, more generally, a dependence of event-related neural computations on the preceding resting state.

The transliminal brain at rest: baseline EEG, unusual experiences, and access to unconscious mental activity.

Transliminality reflects individual differences in the threshold at which unconscious processes or external stimuli enter into consciousness. Individuals high in transliminality possess characteristics such as magical ideation, belief in the paranormal, and creative personality traits, and also report the occurrence of manic/mystic experiences. The goal of the present research was to determine if resting brain activity differs for individuals high versus low in transliminality. We compared baseline EEG recordings (eyes-closed) between individuals high versus low in transliminality, assessed using The Revised Transliminality Scale of Lange et al. (2000). Identifying reliable differences at rest between high- and low-transliminality individuals would support a predisposition for transliminality-related traits. Individuals high in transliminality exhibited lower alpha, beta, and gamma power than individuals low in transliminality over left posterior association cortex and lower high alpha, low beta, and gamma power over the right superior temporal region. In contrast, when compared to individuals low in transliminality, individuals high in transliminality exhibited greater gamma power over the frontal-midline region. These results are consistent with prior research reporting reductions in left temporal/parietal activity, as well as the desynchronization of right temporal activity in schizotypy and related schizophrenia spectrum disorders. Further, differences between high- and low-transliminality groups extend existing theories linking altered hemispheric asymmetries in brain activity to a predisposition toward schizophrenia, paranormal beliefs, and unusual experiences.

The impact of substance abuse on mortality in patients with severe traumatic brain injury.

BACKGROUND: Drug and alcohol use are common in neurotrauma patients. Despite growing methamphetamine use there are few studies of the impact of methamphetamine use on outcome after traumatic brain injury (TBI). METHODS: We conducted a retrospective review of 5-years of data from a trauma database. Inclusion criteria included severe TBI and diagnosis codes indicating head injury. The entire database was analyzed and then a subset of patients with complete toxicology data were examined separately. Primary outcome was mortality. RESULTS: Four hundred eighty-three patients were included. Toxicology results were available for 52.6% of patients. Alcohol, amphetamines, and cannabis were the most commonly detected substances. Overall mortality was 50.9%. When the group with complete tox screen data were analyzed, a toxicology screen that was positive for alcohol or amphetamine was associated with decreased mortality with an odds ratio of 0.23 (CI: 0.10-0.56, p = 0.001) and 0.25 (CI: 0.08-0.79, p = 0.02), respectively. When the subset of patients for whom toxicology data were available was analyzed the amphetamine-positive group was more likely to use cannabis and less likely to use alcohol. CONCLUSIONS: We unexpectedly found alcohol and methamphetamine use to be associated with decreased mortality. Neurotoxic and possible neuroprotective mechanisms of these substances are discussed as well as possible interactions between cannabis and methamphetamine. The potential influence of psycho-social factors are also considered. Prospective studies are needed to further investigate the effects of drug and alcohol use on outcome after severe TBI.

Addressing disproportionality through undoing racism, leadership development, and community engagement.

In 2005 the Texas 79th legislature passed Senate Bill 6, which included mandates to address disproportionality. This article will describe how the Texas Department of Family Protective Services in collaboration with Casey Family Programs' Texas State Strategy systems improvement initiative is addressing disproportionality statewide through promising practices and innovations in undoing racism trainings, values-based leadership development, and community engagement strategies.

Comparative multiresolution wavelet analysis of ERP spectral bands using an ensemble of classifiers approach for early diagnosis of Alzheimer's disease.

Early diagnosis of Alzheimer's disease (AD) is becoming an increasingly important healthcare concern. Prior approaches analyzing event-related potentials (ERPs) had varying degrees of success, primarily due to smaller study cohorts, and the inherent difficulty of the problem. A new effort using multiresolution analysis of ERPs is described. Distinctions of this study include analyzing a larger cohort, comparing different wavelets and different frequency bands, using ensemble-based decisions and, most importantly, aiming the earliest possible diagnosis of the disease. Surprising yet promising outcomes indicate that ERPs in response to novel sounds of oddball paradigm may be more reliable as a biomarker than the more commonly used responses to target sounds.