[Clinical features and predictors of early neurological deterioration in acute isolated pontine infarction].

Objective: To investigate the clinical and imaging characteristics of early neurological deterioration (END) in acute isolated pontine infarction (AIPI) and analyze the predictive factors of END. Methods: Patients with AIPI who were confirmed by magnetic resonance imaging (MRI) in Zhengzhou University People's Hospital from January 2020 to December 2021were collected and divided into END group and non-END group (NEND group). General data and imaging characteristics of the patients were compared between the two groups, the neurological function of patients was evaluated by using the modified Rankin scale (mRS) at 1 and 3 months after stroke. Multivariate binary logistic regression model was used to analyze the risk factors of END after isolated pontine infarction, and the receiver operating characteristic curve(ROC) curve was drawn. Z-test was used to compare the area under the curve to determine the best predictor of END. Results: A total of 113 patients with AIPI were enrolled, including 72 males and 41 females, aged (62±11) years, with 40 cases in the END group and 73 cases in the NEND group. The incidence of END in AIPI was 35.4% (40/113). The National Institutes of Health Stroke Scale (NIHSS) score in the END group (5.15±1.88) was higher than that in the NEND group (4.10±1.63), and the infarcts size in the END group [(2.15±0.39) mm2] was larger than that in the NEND group [(1.61±0.46) mm2] (P=0.002 and P<0.001, respectively). Multivariate binary logistic regression analysis showed that NIHSS score on admission (OR=1.393, 95%CI: 1.017-1.909, P=0.039), infarct size (OR=11.539, 95%CI: 3.574-37.255, P<0.001) were associated with END. Comparing the area of ROC curve, infarct size [area under curve (AUC)=0.787, with a sensitivity of 0.750 and specificity of 0.545] and NIHSS score on admission (AUC=0.688, with a sensitivity of 0.700 and specificity of 0.589) showed no significant difference in the value of predicting END (P=0.056). Conclusion: Patients with AIPI had higher NIHSS score and larger infarct size on admission, and both of them exhibit good predictive performance for END.

Evidence for functional specialization of hippocampal subfields detected by MR subfield volumetry on high resolution images at 4 T.

Animal studies suggest an involvement of CA3 and dentate gyrus (CA3&DG) in memory encoding and early retrieval and an involvement of CA1 in late retrieval, consolidation and recognition. The aim of this study was to test if similar associations could be found between hippocampal subfield volumes measured in vivo using a manual parcellation scheme and selected scores of the California Verbal Learning Test II (CVLTII): total immediate free recall discriminability (IFRD), short free recall discriminability (SFRD), and delayed recall discriminability (DRD). 50 elderly subjects (25 controls and 25 cognitively impaired subjects) had CVLTII and high resolution hippocampal MRI at 4T. Entorhinal cortex, subiculum, CA1, CA1-CA2 transition zone, and CA3&DG were manually marked on five slices in the anterior hippocampal body on the MRI. Pearson correlations followed by stepwise regression analysis were used to test for associations between subfield volumes and CVLTII. IFRD and SFRD, which are measures of encoding/early retrieval, were associated with CA3&DG, and DRD, which measures consolidation/late retrieval, with CA1. These preliminary findings demonstrate that subfield volumetry has the potential to study non invasively subfield specific memory functions.

Boston biorepository, recruitment and integrative network (BBRAIN): A resource for the Gulf War Illness scientific community.

AIMS: Gulf War Illness (GWI), a chronic debilitating disorder characterized by fatigue, joint pain, cognitive, gastrointestinal, respiratory, and skin problems, is currently diagnosed by self-reported symptoms. The Boston Biorepository, Recruitment, and Integrative Network (BBRAIN) is the collaborative effort of expert Gulf War Illness (GWI) researchers who are creating objective diagnostic and pathobiological markers and recommend common data elements for GWI research. MAIN METHODS: BBRAIN is recruiting 300 GWI cases and 200 GW veteran controls for the prospective study. Key data and biological samples from prior GWI studies are being merged and combined into retrospective datasets. They will be made available for data mining by the BBRAIN network and the GWI research community. Prospective questionnaire data include general health and chronic symptoms, demographics, measures of pain, fatigue, medical conditions, deployment and exposure histories. Available repository biospecimens include blood, plasma, serum, saliva, stool, urine, human induced pluripotent stem cells and cerebrospinal fluid. KEY FINDINGS: To date, multiple datasets have been merged and combined from 15 participating study sites. These data and samples have been collated and an online request form for repository requests as well as recommended common data elements have been created. Data and biospecimen sample requests are reviewed by the BBRAIN steering committee members for approval as they are received. SIGNIFICANCE: The BBRAIN repository network serves as a much needed resource for GWI researchers to utilize for identification and validation of objective diagnostic and pathobiological markers of the illness.

Evidence for ongoing brain injury in human immunodeficiency virus-positive patients treated with antiretroviral therapy.

Treatment with antiretroviral therapy (ART) has greatly reduced the incidence of dementia. The goal of this longitudinal study was to determine if there are ongoing macrostructural brain changes in human immunodeficiency virus-positive (HIV + ) individuals treated with ART. To quantify brain structure, three-dimensional T1-weighted magnetic resonance imaging (MRI) scans were performed at baseline and again after 24 months in 39 HIV+ patients on ART and 30 HIV- controls. Longitudinal changes in brain volume were measured using tissue segmentation within regions of interest and deformation morphometry. Measured by tissue segmentation, HIV+ patients on ART had significantly (all P<.05) greater rates of white matter volume loss than HIV- control individuals. Compared with controls, the subgroup of HIV+ individuals on ART with viral suppression also had significantly greater rates of white matter volume loss. Deformation morphometry confirmed these results with more specific spatial localization. Deformation morphometry also detected greater rates of gray matter and white matter loss in the subgroup of HIV+ individuals with detectable viral loads. These results provide evidence of ongoing brain volume loss in HIV+ individuals on stable ART, possibly suggesting ongoing cerebral injury. The presence of continuing injury raises the possibility that HIV+ individuals-even in the presence of viral suppression in the periphery-are at greater risk for future cognitive impairments and dementia and possibly faster cognitive decline. Therefore, HIV+ individuals on ART should be monitored for cognitive decline, and treatments that reduce ongoing neurological injury should be considered.

Attribute-based neural substrates in temporal cortex for perceiving and knowing about objects.

The cognitive and neural mechanisms underlying category-specific knowledge remain controversial. Here we report that, across multiple tasks (viewing, delayed match to sample, naming), pictures of animals and tools were associated with highly consistent, category-related patterns of activation in ventral (fusiform gyrus) and lateral (superior and middle temporal gyri) regions of the posterior temporal lobes. In addition, similar patterns of category-related activity occurred when subjects read the names of, and answered questions about, animals and tools. These findings suggest that semantic object information is represented in distributed networks that include sites for storing information about specific object attributes such as form (ventral temporal cortex) and motion (lateral temporal cortex).

Semantic memory and the brain: structure and processes.

Recent functional brain imaging studies suggest that object concepts may be represented, in part, by distributed networks of discrete cortical regions that parallel the organization of sensory and motor systems. In addition, different regions of the left lateral prefrontal cortex, and perhaps anterior temporal cortex, may have distinct roles in retrieving, maintaining and selecting semantic information.

Age-related prefrontal alterations during auditory memory.

Event-related potentials were recorded from young and elderly subjects while they performed a modified auditory Sternberg memory task. Aging was associated with a decrease in frontal activation, suggesting that prefrontal alterations may be central to age-related impairments in auditory working memory. Young subjects showed significant serial position effects electrophysiologically, while elderly subjects showed no recency effects for P3 latency and no serial position effects for N4 and SFN amplitude. This finding, in combination with increased false alarm rates in the elderly, suggest that the two group of subjects employed different cortico-limbic circuits to perform the task.

Prefrontal and posterior cortical activation during auditory working memory.

The present study investigated brain mechanisms underlying auditory memory. In a modified Sternberg memory scanning task, 11 subjects indicated whether a probe sound was part of a previously presented 4-item memory set by a button press. Behaviorally, subjects responded fastest and most accurately to probes that matched the last memory set items and slowest and least accurately to negative probes and to positive probes to the first two memory set items. Electrophysiologically, probes to the last memory set items elicited the largest amplitude and earliest latency P3 components while other probes elicited smaller amplitude, prolonged P3s as well as a negativity around 400 ms. These results suggest that subjects utilized a trace strength/self-terminating search model to perform the memory scanning task. Subjects only generated the P3 component during the matching phase of the auditory memory task while a sustained frontal negativity was elicited during both the encoding and matching phase. Taken together these findings provide evidence of differential activation of distributed neural activity during non-linguistic auditory memory.

Human prefrontal lesions increase distractibility to irrelevant sensory inputs.

Neurological patients with focal lesions in either the dorsolateral prefrontal cortex, temporal-parietal junction or the posterior hippocampus, and control subjects, were tested on a task requiring short-term retention of environmental sounds. Subjects had to indicate whether initial and subsequent test sounds were identical in two conditions. The initial and test sounds were separated by either a silent period varying from 4 to 12.6 s (no-distractor condition) or a series of irrelevant tones (distractor condition). Prefrontal patients were significantly impaired by distractors at all delays, hippocampal patients were impaired only at longer delays, while temporal-parietal patients performed similar to controls. The findings suggest that dorsolateral prefrontal cortex is crucial for gating of distracting information during delay tasks.

Are face-responsive regions selective only for faces?

To examine the specificity of face-responsive regions for face processing, we used fMRI to measure the response of the fusiform gyrus and the superior temporal sulcus (STS) to pictures of human faces, animals, faceless animals, and houses. Results indicate that faces, animals, and faceless animals all elicited greater activity than houses, and had identical peaks of activation in the lateral fusiform gyrus, bilaterally, and in the right posterior STS. Moreover, within the lateral fusiform gyrus the responses to faces, animals and faceless animals were all greater than the responses to these stimuli in the medial aspect of the fusiform gyrus, a region that responds more strongly to other objects (e.g. houses). These findings suggest that the neural representation of animals in the fusiform gyrus and the posterior STS relies strongly on the same neural substrates that represent faces.

Lyme disease in Taiwan: primary isolation of Borrelia burgdorferi-like spirochetes from rodents in the Taiwan area.

To investigate the prevalence of Lyme disease infection in Taiwan, we conducted a zoonotic survey for spirochetal infection in the small mammals. Ear tissues of trapped rodents collected from various localities in Taiwan were incubated into BSK-H culture medium and examined for the evidence of spirochetal infection by dark-field microscopy. Spirochetes cultured from six species of wild and peridomestic rodents and seven isolates, designated TWKM 1-7, were purified by serial dilution and membrane filtration. Infection was detected in 16.6% (53 of 320) of captured rodents and the highest infection rate (36.4%) was observed in the brown country rat (Rattus losea, Swinhoe). Higher infection rates based on the geographic distribution were observed in the eastern localities and on Kimmen Island. Reactivity with Borrelia burgdorferi-specific monoclonal antibodies and Western blot analysis indicated that these Taiwan isolates were closely related to the causative agent of Lyme disease, B. burgdorferi sensu lato. These results provide the first evidence of the existence of Lyme disease spirochetes in the Taiwan area.

Prefrontal cortex regulates inhibition and excitation in distributed neural networks.

Prefrontal cortex provides both inhibitory and excitatory input to distributed neural circuits required to support performance in diverse tasks. Neurological patients with prefrontal damage are impaired in their ability to inhibit task-irrelevant information during behavioral tasks requiring performance over a delay. The observed enhancements of primary auditory and somatosensory cortical responses to task-irrelevant distractors suggest that prefrontal damage disrupts inhibitory modulation of inputs to primary sensory cortex, perhaps through abnormalities in a prefrontal-thalamic sensory gating system. Failure to suppress irrelevant sensory information results in increased neural noise, contributing to the deficits in decision making routinely observed in these patients. In addition to a critical role in inhibitory control of sensory flow to primary cortical regions, and tertiary prefrontal cortex also exerts excitatory input to activity in multiple sub-regions of secondary association cortex. Unilateral prefrontal damage results in multi-modal decreases in neural activity in posterior association cortex in the hemisphere ipsilateral to damage. This excitatory modulation is necessary to sustain neural activity during working memory. Thus, prefrontal cortex is able to sculpt behavior through parallel inhibitory and excitatory regulation of neural activity in distributed neural networks.

Prediction of conversion from mild cognitive impairment to Alzheimer disease based on bayesian data mining with ensemble learning.

Prediction of disease progress is of great importance to Alzheimer disease (AD) researchers and clinicians. Previous attempts at constructing predictive models have been hindered by undersampling, and restriction to linear associations among variables, among other problems. To address these problems, we propose a novel Bayesian data-mining method called Bayesian Outcome Prediction with Ensemble Learning (BOPEL). BOPEL uses a Bayesian-network representation with boosting, to allow the detection of nonlinear multivariate associations, and incorporates resampling-based feature selection to prevent over-fitting caused by undersampling. We demonstrate the use of this approach in predicting conversion to AD in individuals with mild cognitive impairment (MCI), based on structural magnetic-resonance and magnetic-resonance- spectroscopy data. This study includes 26 subjects with amnestic MCI: the converter group (n = 8) met MCI criteria at baseline, but converted to AD within five years, whereas the non-converter group (n = 18) met MCI criteria at baseline and at follow-up. We found that BOPEL accurately differentiates MCI converters from non-converters, based on the baseline volumes of the left hippocampus, the banks of the right superior temporal sulcus, the right entorhinal cortex, the left lingual gyrus, and the rostral aspect of the left middle frontal gyrus. Prediction accuracy was 0.81, sensitivity was 0.63 and specificity was 0.89. We validated the generated predictive model with an independent data set constructed from the Alzheimer Disease Neuroimaging Initiative database, and again found high predictive accuracy (0.75).

Brain atrophy associated with baseline and longitudinal measures of cognition.

The overall goal was to identify patterns of brain atrophy associated with cognitive impairment and future cognitive decline in non-demented elders. Seventy-one participants were studied with structural MRI and neuropsychological testing at baseline and 1-year follow-up. Deformation-based morphometry was used to examine the relationship between regional baseline brain tissue volume with baseline and longitudinal measures of delayed verbal memory, semantic memory, and executive function. Smaller right hippocampal and entorhinal cortex (ERC) volumes at baseline were associated with worse delayed verbal memory performance at baseline while smaller left ERC volume was associated with greater longitudinal decline. Smaller left superior temporal cortex at baseline was associated with worse semantic memory at baseline, while smaller left temporal white and gray matter volumes were associated with greater semantic memory decline. Increased CSF and smaller frontal lobe volumes were associated with impaired executive function at baseline and greater longitudinal executive decline. These findings suggest that baseline volumes of prefrontal and temporal regions may underlie continuing cognitive decline due to aging, pathology, or both in non-demented elderly individuals.

Evidence of neurodegeneration in brains of older adults who do not yet fulfill MCI criteria.

We sought to determine whether there are structural and metabolic changes in the brains of older adults with cognitive complaints yet who do not meet MCI criteria (i.e., preMCI). We compared the volumes of regional lobar gray matter (GM) and medial temporal lobe structures, including the hippocampus, entorhinal cortex (ERC), fusiform and parahippocampal gyri, and metabolite ratios from the posterior cingulate in individuals who had a Clinical Demetia Rating (CDR) of 0.5, but who did not meet MCI criteria (preMCI, N=17), patients with mild cognitive impairment (MCI, N=13), and cognitively normal controls (N=18). Controls had more ERC, fusiform, and frontal gray matter volume than preMCI and MCI subjects and greater parahippocampal volume and more posterior cingulate N-acetylaspartate (NAA)/myoinosotil (mI) than MCI. There were no significant differences between MCI and preMCI subjects on any of these measures. These findings suggest there are neurodegenerative changes in the brains of older adults who have cognitive complaints severe enough to qualify for CDR=0.5 yet show no deficits on formal neuropsychological testing. The results further support the hypothesis that detection of individuals with very mild forms of Alzheimer's disease (AD) may be facilitated by use of the CDR, which emphasizes changes in cognition over time within individuals rather than comparison with group norms.

Reduced medial temporal lobe N-acetylaspartate in cognitively impaired but nondemented patients.

BACKGROUND: N-acetylaspartate (NAA) in the medial temporal lobe (MTL) and parietal lobe gray matter (GM) is diminished in Alzheimer disease (AD). Because NAA is considered a marker of neuronal integrity, reduced medial temporal and parietal lobe NAA could be an early indication of dementia-related pathology in elderly individuals. OBJECTIVES: 1) To determine whether cognitively impaired but nondemented (CIND) elderly individuals exhibit a similar pattern of reduced medial temporal and parietal lobe NAA as AD patients. 2) To compare regional NAA patterns, hippocampal and neocortical gray matter (GM) volumes in CIND patients who remained cognitively stable and those who became demented over 3.6 years of follow-up. 3) To examine the relationship between memory performance, medial temporal lobe NAA, and hippocampal volume. METHODS: Seventeen CIND, 24 AD, and 24 cognitively normal subjects were studied using MRSI and MRI. RESULTS: Relative to controls, CIND patients had reduced MTL NAA (19 to 21%, p = 0.005), hippocampal (11 to 14%, p < or = 0.04), and neocortical GM (5%, p = 0.05) volumes. CIND patients who later became demented had less MTL NAA (26%, p = 0.01), hippocampal (17 to 23%, p < or = 0.05), and neocortical GM (13%, p = 0.02) volumes than controls, but there were no significant differences between stable CIND patients and controls. MTL NAA in combination with hippocampal volume improved discrimination of CIND and controls over hippocampal volume alone. In AD and CIND patients, decreased MTL NAA correlated significantly with impaired memory performance. CONCLUSION: Reduced medial temporal lobe N-acetylaspartate, together with reduced hippocampal and neocortical gray matter volumes, may be early indications of dementia-related pathology in subjects at high risk for developing dementia.

Representation of manipulable man-made objects in the dorsal stream.

We used fMRI to examine the neural response in frontal and parietal cortices associated with viewing and naming pictures of different categories of objects. Because tools are commonly associated with specific hand movements, we predicted that pictures of tools, but not other categories of objects, would elicit activity in regions of the brain that store information about motor-based properties. We found that viewing and naming pictures of tools selectively activated the left ventral premotor cortex (BA 6). Single-unit recording studies in monkeys have shown that neurons in the rostral part of the ventral premotor cortex (canonical F5 neurons) respond to the visual presentation of graspable objects, even in the absence of any subsequent motor activity. Thus, the left ventral premotor region that responded selectively to tools in the current study may be the human homolog of the monkey canonical F5 area. Viewing and naming tools also selectively activated the left posterior parietal cortex (BA 40). This response is similar to the firing of monkey anterior intraparietal neurons to the visual presentation of graspable objects. In humans and monkeys, there appears to be a close link between manipulable objects and information about the actions associated with their use. The selective activation of the left posterior parietal and left ventral premotor cortices by pictures of tools suggests that the ability to recognize and identify at least one category of objects (tools) may depend on activity in specific sites of the ventral and dorsal visual processing streams.

Prefrontal deficits in attention and inhibitory control with aging.

Event-related potentials and behavioral measures were obtained from young and elderly subjects while they performed two different auditory delayed match-to-sample tasks. In each experiment, subjects had to indicate whether an initial and a subsequent test sound were identical in two different conditions: one filled with distracting tone pips and one with no distractors. Electrophysiologically, elderly subjects had reduced attention-related activity over frontal regions. In addition, the distracting stimuli elicited an enhanced primary auditory evoked response in the elderly. The percentage of perseverative errors on the Wisconsin card sorting test, a putative measure of frontal lobe function, was positively correlated with the amplitude of the primary auditory evoked response in elderly subjects. Behaviorally, elderly subjects were impaired by distractors at long but not short delays. Taken together, these results suggest that increased distractibility and impaired sustained attention with aging may be due to altered prefrontal cortex function. These data support the loss of prefrontal suppression over the primary auditory regions with aging.

Contribution of human prefrontal cortex to delay performance.

Neurological patients with focal lesions in the dorsolateral prefrontal cortex and age-matched control subjects were tested on an auditory version of the delayed-match-to-sample task employing environmental sounds. Subjects had to indicate whether a cue (s/S1) and a subsequent target sound (S2) were identical. On some trials, S1 and S2 were separated by a silent period of 5 sec. On other trials, the 5-sec delay between S1 and S2 was filled with irrelevant tone pips that served as distractors. Behaviorally, frontal patients were impaired by the presence of distractors. Electrophysiologically, patients generated enhanced primary auditory cortex-evoked responses to the tone pips, supporting a failure in inhibitory control of sensory processing after prefrontal damage. Intrahemispheric reductions of neural activity generated in the auditory association cortex and additional intrahemispheric reductions of attention-related frontal activity were also observed in the prefrontal patients. Together, these findings suggest that the dorsolateral prefrontal cortex is crucial for gating distracting information as well as maintaining distributed intrahemispheric neural activity during auditory working memory.

Cortical regions associated with perceiving, naming, and knowing about colors.

Positron emission tomography (PET) was used to investigate whether retrieving information about a specific object attribute requires reactivation of brain areas that mediate perception of that attribute. During separate PET scans, subjects passively viewed colored and equiluminant gray-scale Mondrians, named colored and achromatic objects, named the color of colored objects, and generated color names associated with achromatic objects. Color perception was associated with activations in the lingual and fusiform gyri of the occipital lobes, consistent with previous neuroimaging and human lesion studies. Retrieving information about object color (generating color names for achromatic objects relative to naming achromatic objects) activated the left inferior temporal, left frontal, and left posterior parietal cortices, replicating previous findings from this laboratory. When subjects generated color names for achromatic objects relative to the low-level baseline of viewing gray-scale Mondrians, additional activations in the left fusiform/lateral occipital region were detected. However, these activations were lateral to the occipital regions associated with color perception and identical to occipital regions activated when subjects simply named achromatic objects relative to the same low-level baseline. This suggests that the occipital activations associated with retrieving color information were due to the perception of object form rather than to the top-down influence of brain areas that mediate color perception. Taken together, these results indicate that retrieving previously acquired information about an object's typical color does not require reactivation of brain regions that subserve color perception.