Quantitative validation of immunofluorescence and lectin staining using reduced CLARITY acrylamide formulations.

The CLARITY technique enables three-dimensional visualization of fluorescent-labeled biomolecules in clarified intact brain samples, affording a unique view of molecular neuroanatomy and neurocircuitry. It is therefore, essential to find the ideal combination for clearing tissue and detecting the fluorescent-labeled signal. This method requires the formation of a formaldehyde-acrylamide fixative-generated hydrogel mesh through which cellular lipid is removed with sodium dodecyl sulfate. Several laboratories have used differential acrylamide and detergent concentrations to achieve better tissue clearing and antibody penetration, but the potential effects upon fluorescent signal retention is largely unknown. In an effort to optimize CLARITY processing procedures we performed quantitative parvalbumin immunofluorescence and lectin-based vasculature staining using either 4 or 8% sodium dodecyl sulfate detergent in combination with different acrylamide formulas in mouse brain slices. Using both confocal and CLARITY-optimized lightsheet microscope-acquired images, we demonstrate that 2% acrylamide monomer combined with 0.0125% bis-acrylamide and cleared with 4% sodium dodecyl sulfate generally provides the most optimal signal visualization amongst various hydrogel monomer concentrations, lipid removal times, and detergent concentrations.

Greenhouse gases emission from soils under major crops in Northwest India.

Quantification of greenhouse gases (GHGs) emissions from agriculture is necessary to prepare the national inventories and to develop the mitigation strategies. Field experiments were conducted during 2008-2010 at the experimental farm of the Indian Agricultural Research Institute, New Delhi, India to quantify nitrous oxide (N2O), methane (CH4), and carbon dioxide (CO2) emissions from soils under cereals, pulses, millets, and oilseed crops. Total cumulative N2O emissions were significantly different (P>0.05) among the crop types. Emission of N2O as percentage of applied N was the highest in pulses (0.67%) followed by oilseeds (0.55%), millets (0.43%) and cereals (0.40%). The emission increased with increasing rate of N application (r(2)=0.74, P<0.05). The cumulative flux of CH4 from the rice crop was 28.64±4.40 kg ha(-1), while the mean seasonal integrated flux of CO2 from soils ranged from 3058±236 to 3616±157 kg CO2 ha(-1) under different crops. The global warming potential (GWP) of crops varied between 3053 kg CO2 eq. ha(-1) (pigeon pea) and 3968 kg CO2 eq. ha(-1) (wheat). The carbon equivalent emission (CEE) was least in pigeon pea (833 kg C ha(-1)) and largest in wheat (1042 kg C ha(-1)). The GWP per unit of economic yield was the highest in pulses and the lowest in cereal crops. The uncertainties in emission values varied from 4.6 to 22.0%. These emission values will be useful in updating the GHGs emission inventory of Indian agriculture.

The effect of a single aerobic training session on cognitive flexibility in late middle-aged adults.

Research has shown that aerobic exercise enhances cognitive function, specifically executive functions. This study examines the effect of acute aerobic exercise on cognitive flexibility - an executive function - in late middle-aged individuals. Fourteen men and 45 women aged 50 - 64, were randomly assigned to moderate exercise (60 % of heart rate reserve), moderately-intense (70 % of heart rate reserve) exercise, and movie-watching control groups after a maximal exercise test. Prior to and following the exercise or control sessions participants performed two cognitive tasks: the Alternate Uses assessing cognitive flexibility and the Digit Span Forward subtest from the Wechsler Adult Intelligence Scale - Revised assessing attention span. Results indicated significant improvement in Alternate Uses in the exercise groups but not in the control group. No group differences were indicated on the Digit Span. These results provide partial support for the benefit of acute aerobic exercise on cognitive flexibility.

The neural correlates of understanding the other's distress: a positron emission tomography investigation of accurate empathy.

The purpose of the present study was to assess the relationship between brain metabolism and empathic response. Six right-handed healthy volunteers were scanned with PET and fluorodeoxyglucose twice: during an interview about neutral story themes and during an empathic response eliciting interview about a story of a character in distress. Metabolic values in the medial and superior frontal gyrus, occipitotemporal cortices, thalamus and the cerebellum were higher during empathic response than during the neutral theme interview. Furthermore, the subjects' empathy scores were positively correlated with metabolism in the medial aspects of the superior frontal gyrus. Our results suggest that empathy consists of both affective and cognitive components and hence may involve cortices that mediate simulation of emotional processing and mental state attribution.

The neuroanatomical basis of understanding sarcasm and its relationship to social cognition.

The authors explored the neurobiology of sarcasm and the cognitive processes underlying it by examining the performance of participants with focal lesions on tasks that required understanding of sarcasm and social cognition. Participants with prefrontal damage (n=25) showed impaired performance on the sarcasm task, whereas participants with posterior damage (n=16) and healthy controls (n=17) performed the same task without difficulty. Within the prefrontal group, right ventromedial lesions were associated with the most profound deficit in comprehending sarcasm. In addition, although the prefrontal damage was associated with deficits in theory of mind and right hemisphere damage was associated with deficits in identifying emotions, these 2 abilities were related to the ability to understand sarcasm. This suggests that the right frontal lobe mediates understanding of sarcasm by integrating affective processing with perspective taking.

Impaired "affective theory of mind" is associated with right ventromedial prefrontal damage.

OBJECTIVE: To examine the hypothesis that patients with ventromedial (VM) frontal lesions are impaired in the affective rather than cognitive facets of theory of mind (ToM). BACKGROUND: Prefrontal brain damage may result in impaired social behavior, especially when the damage involves the orbitofrontal/VM prefrontal cortex (PFC). It has been previously suggested that deficits in ToM may account for such aberrant behavior. However, inconsistent results have been reported, and different regions within the frontal cortex have been associated with ToM impairment. METHOD: The performance of 26 patients with localized lesions in the PFC was compared with responses of 13 patients with posterior lesions and 13 normal control subjects. Three ToM tasks differing in the level of emotional processing involved were used: second-order false belief task, understanding ironic utterances, and identifying social faux pas. RESULTS AND CONCLUSIONS: The results indicated that patients with VM (but not dorsolateral) prefrontal lesions were significantly impaired in irony and faux pas but not in second-order false belief as compared with patients with posterior lesions and normal control subjects. Lesions in the right VM area were associated with the most severe ToM deficit. These results are discussed in terms of the cognitive and affective facets of "mind-reading" processes mediated by the VM cortex.

Impairment in cognitive and affective empathy in patients with brain lesions: anatomical and cognitive correlates.

The present study was designed to examine the degree of impairment in cognitive and affective empathy among patients with focal brain lesions, and the contribution of specific cognitive abilities (such as cognitive flexibility and processing of emotional information), to empathy. The cognitive and affective empathic response of patients with localized prefrontal lesions (n=36) was compared to responses of patients with parietal lesions (n=15) and healthy control subjects (n=19). Results indicate that patients with prefrontal lesions (especially those with lesions involving the orbitoprefrontal and medial regions) were significantly impaired in both cognitive and affective empathy as compared to parietal patients and healthy controls. When the damage was restricted to the prefrontal cortex, either left- or right-hemisphere lesions resulted in impaired empathy. However, when the lesion involved the right hemisphere, patients with parietal lesions were also impaired. The pattern of relationships between cognitive performance and empathy suggested dissociation between the cognitive correlates of affective and cognitive empathy.

Novelty seeking and harm avoidance in Parkinson's disease: effects of asymmetric dopamine deficiency.

OBJECTIVES: Although changes in novelty seeking and harm avoidance have been reported among patients with Parkinson's disease (PD), the findings regarding the neurochemical correlates of such changes are inconsistent. This study was designed to examine the hypothesis that different patterns of motor and neurochemical asymmetry in PD may have contributed to the conflicting results. METHODS: Forty PD patients (divided into two groups according to initial asymmetry in dopamine deficit: left hemisphere, n = 22; right hemisphere, n = 18) and 17 age matched healthy controls completed the Tridimensional Personality Questionnaire (Cloninger, 1987). RESULTS: Only patients with greater dopamine loss in the left hemisphere showed reduced novelty seeking, whereas only patients with reduced dopamine in the right hemisphere reported higher harm avoidance than matched healthy controls. Novelty seeking was not associated with disease duration, current motor symptoms, or medication, whereas harm avoidance was significantly correlated only with the severity of bradykinesia and depression. CONCLUSIONS: Approach and avoidance reflect different patterns of dopaminergic asymmetry. Whereas reduced novelty seeking reflects deficit in the mesolimbic branch of ascending dopamine transmission in the left hemisphere, increased harm avoidance is associated with greater dopamine loss in the right striatum.

Cognitive performance following endarterectomy in asymptomatic severe carotid stenosis.

Cognition and the effects of carotid endarterectomy (CEA) were evaluated in 22 non-demented subjects with vascular risk factors (VRF) and asymptomatic severe carotid artery stenosis (ASCAS), 14 volunteers with VRF but without stenosis, and 24 healthy controls (HC) without VRF. Non-demented subjects with VRF, with or without carotid stenosis scored inferior to HC. It is concluded that carotid stenosis is not a primary cause of cognitive deterioration and CEA does not improve cognition in patients with ASCAS.

Characterization of empathy deficits following prefrontal brain damage: the role of the right ventromedial prefrontal cortex.

Impaired empathic response has been described in patients following brain injury, suggesting that empathy may be a fundamental aspect of the social behavior disturbed by brain damage. However, the neuroanatomical basis of impaired empathy has not been studied in detail. The empathic response of patients with localized lesions in the prefrontal cortex (n = 25) was compared to responses of patients with posterior (n = 17) and healthy control subjects (n = 19). To examine the cognitive processes that underlie the empathic ability, the relationships between empathy scores and the performance on tasks that assess processes of cognitive flexibility, affect recognition, and theory of mind (TOM) were also examined. Patients with prefrontal lesions, particularly when their damage included the ventromedial prefrontal cortex, were significantly impaired in empathy as compared to patients with posterior lesions and healthy controls. However, among patients with posterior lesions, those with damage to the right hemisphere were impaired, whereas those with left posterior lesions displayed empathy levels similar to healthy controls. Seven of nine patients with the most profound empathy deficit had a right ventromedial lesion. A differential pattern regarding the relationships between empathy and cognitive performance was also found: Whereas among patients with dorsolateral prefrontal damage empathy was related to cognitive flexibility but not to TOM and affect recognition, empathy scores in patients with ventromedial lesions were related to TOM but not to cognitive flexibility. Our findings suggest that prefrontal structures play an important part in a network mediating the empathic response and specifically that the right ventromedial cortex has a unique role in integrating cognition and affect to produce the empathic response.

Empathy deficits in Asperger syndrome: a cognitive profile.

Although lack of empathy has been considered a central characteristic of Asperger syndrome, quantitative and qualitative assessments of empathy in this syndrome are lacking. We present two cases of adolescents with Asperger syndrome who show extreme deficits on measures of both cognitive and affective empathy. Analysis of their performance on tasks assessing cognitive and affective processing did not reveal significant impairment in executive functions, nor in their ability to recognize emotions or the ability to create a mental representation of another person's knowledge. However, both patients were unable to integrate the emotional content with mental representations and deduce the other person's emotional state. These results suggest that impaired empathy in individuals with Asperger syndrome may be due to impaired integration of the cognitive and affective facets of the other person's mental state.

Preliminary analyses of Hebrew verbal fluency measures.

Hebrew language versions of phonemic and semantic fluency were administered to samples of normal control participants and individuals who had been hospitalized for 24 hr following a head injury. For the control sample, verbal fluency tasks were normally distributed and significantly correlated with education. The head injury sample's word generation was significantly lesser than that of the control's and not at all related to educational attainment. The findings provide evidence for the use of Hebrew fluency measures for clinical assessment and the need for collection of normative data across education levels.

Creating interpretation guidelines for the Hebrew trail making test.

The Hebrew language version of the Trail Making Test (TMT; Army Individual Test Battery, 1944) was administered to a group of normal control participants as well as a sample of outpatients approximately 1 year following a head injury. A ratio of TMT-B to TMT-A performance was computed in an effort to establish usable cutting scores for the Hebrew TMT. A ratio of 2.26 was observed to result in 63% sensitivity and 77% specificity for the sample, with positive predictive power of 71% and negative predictive power of 70%. A more stringent cutoff of 3.09 reduced sensitivity (22%) and negative predictive power (44%). In contrast, specificity (97%) and positive predictive power (86%) were greatly improved once the speed of TMT-A performance was also considered. The more conservative cutoff is considered appropriate when a finding is indicative of pathological performance.

Behavioral differences between white matter lacunar dementia and Alzheimer's disease: a comparison on the neuropsychiatric inventory.

BACKGROUND AND PURPOSE: Behavioral abnormalities account for much of the morbidity of vascular dementia (VaD) and Alzheimer's disease (AD). The goals of the study were to compare the behavioral changes in patients with VaD associated with ischemic white matter subcortical changes and lacunar infarctions (VaD-WSI) to those in patients with AD. METHODS: Thirty outpatients with VaD and multiple lacunar infarctions in the periventricular white matter and 30 AD patients, matched for age and severity of dementia, were enrolled in this prospective study. The behavioral abnormalities of these patients were assessed by interviewing their caregivers with the Neuropsychiatric Inventory. RESULTS: A similar spectrum of noncognitive behavioral changes was found in AD and WSI patients. In VaD-WSI, the severity of delusions, hallucinations, aggression, irritability, aberrant motor behavior, nighttime behavior and appetite changes was correlated with cognitive decline, whereas depression, apathy, anxiety and euphoria were unrelated to the severity of dementia. In AD, none of the behavioral changes correlated with the severity of dementia. CONCLUSION: Behavioral changes are frequent in VaD-WSI and are present regardless of the severity of the cognitive decline. It is therefore important to assess behavioral as well as cognitive changes at early stages of the illness, to ensure appropriate treatment.

Neurobehavioral consequences of closed head injury in the elderly.

The assessment of neurobehavioural outcome after head injury in older patients (> 60 year old) has met with difficultives, due to the obstacles in finding subjects who would constitute an appropriate control group. In the present study, survivors of closed head injury (CHI) of this age group were compared to two control groups: (1) orthopaedic patients (OP) who were injured in similar circumstances but did not sustain head injury and (2) healthy, age-matched volunteers (HC). Compared with HC, CHI and OP were impaired on word fluency, memory and reasoning. No differences were found between CHI and the OP. These results may indicate that, rather than resulting only from the head injury brought about by falling, the cognitive decline may predate the injury and increase the risk of accidents in old age.

Psychiatric symptoms, atypical dementia, and left visual field inattention in corticobasal ganglionic degeneration.

We longitudinally examined the neuropsychological and psychiatric characteristics of an adult male with pathologically confirmed corticobasal ganglionic degeneration (CBGD). The patient was seen on an inpatient and outpatient basis by members of the Departments of Neurology and Radiology of the University of Miami School of Medicine. Longitudinal neuropsychological testing revealed a lateralized cortical-subcortical dementia and left visual field inattention consistent with neurological and postmortem neuropathological findings of greater right hemisphere dysfunction. Symptoms of depression and obsessive-compulsive symptomatology were also documented. Our findings are consistent with prior reports indicating that CBGD is characterized by lateralized cerebral dysfunction and suggest that a detailed neuropsychological examination is a useful procedure to assist in the differential diagnosis of this movement disorder.

Side of onset of motor symptoms influences cognition in Parkinson's disease.

Studies attempting to relate cognitive impairment to asymmetry of motor symptoms in Parkinson's disease (PD) have found contradictory results. We examined 88 patients with unilateral onset of idiopathic PD who underwent a comprehensive neuropsychological assessment, including language, visuospatial abilities, abstraction and reasoning, attention and mental tracking, set shifting, and memory. Patients whose motor signs began on the left side of the body consistently performed more poorly on the battery of cognitive measures than did patients with right-side onset. Significant differences were found on immediate and delayed verbal recall, word retrieval, semantic verbal fluency, visuospatial analysis, abstract reasoning, attention span, and mental tracking. These differences could not be attributed to differences in the overall severity of motor symptoms at the time of cognitive assessment, or the current pattern of motor asymmetry. This finding suggests that damage to right-hemisphere dopamine systems plays a disproportionately greater role in PD-related cognitive decline than a presumably comparable left-hemisphere dopamine depletion.

Differential effects of aging on two verbal fluency tasks.

The effect of age on verbal fluency was studied in 84 healthy volunteers, ages 45 to 91 years, who performed letter-fluency and semantic-fluency tasks. Older subjects (75 to 91 yr.) performed as well as younger (50 to 64 yr.) on letter fluency but did significantly worse on semantic category fluency. This pattern is similar to that observed in Alzheimer-type dementia.

Cognitive impairments in Parkinson's disease.

The clinical neuropsychologic profiles of patients with Parkinson's disease and patients with SDAT show both overlap and dissociation. Speech, language, and certain memory skills are examples of dissociable differences, especially in the early stages of the disease. Furthermore the presence of depression, evidence of cognitive slowing, and absence of aphasia in patients with Parkinson's disease suggest prominent subcortical involvement. It is probably premature to categorize all of the cognitive changes in patients with Parkinson's disease as subcortical, however. Some skills, such as visuospatial and executive functions, are impaired in both disorders, and although the etiologic bases for task failure may differ for each, this issue remains open-ended. Another problem is that often the evidence for or against the cortical/subcortical distinction is insufficient and in some cases based on a single measure thought to be representative of a given cognitive domain. Most importantly there are few comparative studies that provide unequivocal support for making a cortical/subcortical distinction. Failure to equate for level of cognitive impairment or functional disability between dementias and strict adherence to cross-sectional study designs further compromise efforts to characterize each syndrome precisely. Whitehouse suggested that a prospective study of several different dementias studied in parallel, examining a wide range of cognitive skills, is required before the cortical/subcortical classification scheme can be validated. A critical component is an autopsy program to confirm diagnoses and provide clinicopathologic correlation. It is possible that the diverse nature of the cognitive impairment in patients with Parkinson's disease is not a methodologic artifact but reflects multiple disease subtypes. Ross, Mahler, and Cummings proposed three dementia syndromes in patients with Parkinson's disease: one that is relatively mild and meets the criteria for subcortical dementia, a second that is more severe and shows a wider range of cognitive impairment but is still neuropathologically distinct from SDAT, and a third severe dementia with both subcortical and cortical involvement that may reflect basal ganglia and Alzheimer-type pathology.