Subvocal articulatory rehearsal during verbal working memory in multiple sclerosis

This study was designed to examine verbal working memory (VWM) components among multiple sclerosis (MS) patients and determine the influence of information processing speed. Of two frequently studied VWM sub-components, subvocal rehearsal was expected to be more affected by MS than short-term memory buffering. Furthermore, worse subvocal rehearsal was predicted to be specifically related to slower cognitive processing. Fifteen MS patients were administered a neuropsychological battery assessing VWM, processing speed, mood, fatigue, and disability. Participants performed a 2-Back VWM task with modified nested conditions designed to increase subvocal rehearsal (via inter-stimulus interval) and short-term memory buffering demands (via phonological similarity). Performance during these 2-Back conditions did not significantly differ and both exhibited strong positive correlations with disability. However, only scores on the subvocal rehearsal 2-Back were significantly related to performance on the remaining test battery, including processing speed and depressive symptoms. Findings suggest that performance during increased subvocal rehearsal demands is specifically influenced by cognitive processing speed and depressive symptoms.     

Alternative applications of cyclosporin A to improve kidney allograft survival

This study applies cyclosporin A as a donor pretreatment prior to organ harvesting or as a graft pretreatment during preservation of canine kidney allografts by hypothermic pulsatile perfusion or hypothermic storage. All recipients except those in Group IX received minimal immunosuppression with azathioprine after transplantation (5 to 2.5 mg. per kg. per day). No significant differences in survival (X +/- SD) were observed between the 3 control groups which were either 1) flushed with untreated Ringer's lactate solution and immediately transplanted (Group I, no. = 8, 14 +/- 3.33 days), 2) preserved by hypothermic pulsatile perfusion for 24 hours (Group II, no. = 7, 12.0 +/- 8.92 days), or 3) hypothermically stored for 24 hours (Group III, no. = 7 13.1 +/- 11.6 days). A trend towards improved survival was seen in the 2 groups of animals that received kidneys that had been graft pretreated with cyclosporin A (12.5 mg.) during 24 hours preservation by either hypothermic pulsatile perfusion (Group IV, no. = 10, 17.4 +/- 13.32 days, p less than .25) or hypothermic storage (Group V, no. = 6, 8 +/- 12.75 days, p less than .25). Survival of recipients in Groups VI (no. = 6) and VII (no. = 9) who received kidneys whose donors had been pretreated with 25 and 50 mg. per kg. respectively was dependent on the dosage of cyclosporin A used. Donor pretreatment at 50 mg. per kg. was deleterious to kidney function (Group VI, 2.16 +/- 1.47 days, p less than 0.0005). Donor pretreatment with 25 mg. per kg. did not significantly improve survival over control groups (15.66 +/- 12.9 days). Recipients in Groups VIII (no. = 10) and IX (no. = 6) were transplanted with kidneys from cyclosporin A pretreated donors (15 mg. per kg.). These kidneys also received cyclosporin A graft pretreatment (10 mg.) during 24 hours of hypothermic storage. The only difference between Groups VIII and IX was that the animals in Group IX received minimal amounts of cyclosporin A (5 mg. per kg. per day) after transplantation. Combined donor and graft pretreatment yielded improved kidney allograft survival (Group VIII, 21.7 +/- 13.36 days, p greater than .10, Group IX, 20.83 +/- 14.2 days, p greater than .10). However, there was no significant difference observed as a result of the different immunosuppressive protocols used in Groups VIII and IX. These results indicate a trend towards improved renal allograft survival under certain conditions, after donor and graft pretreatment with cyclosporin A.     

Administration of insulin-like growth factor-I improves fatigue resistance of skeletal muscles from dystrophic mdx mice

Muscle fatigue occurs in many neuromuscular diseases, including the muscular dystrophies, and it contributes to a loss of functional capacity and reduced quality of life for affected patients. An improvement in fatigue resistance has been observed in diaphragm muscles of mdx mice following insulin-like growth factor-I (IGF-I) administration. Whether similar treatment can improve locomotor muscle function in mdx mice is not known. We examined the efficacy of IGF-I administration (1 mg/kg daily s.c. for 8 weeks) on structural, metabolic, and functional properties of extensor digitorum longus (EDL) and soleus muscles of mdx mice, and tested the hypothesis that IGF-I treatment would improve function in these muscles. After treatment, muscles were more resistant to fatigue during repeated maximal contractions than muscles from untreated mice, an improvement associated with increased muscle fiber succinate dehydrogenase activity in the absence of changes in cellular (single-fiber) contractile activation characteristics. The findings have important clinical implications, not just for the dystrophinopathies, but for all neuromuscular pathologies where fatigue of locomotor muscles limits functional capacity and decreases quality of life.     

Dysregulation of arousal and amygdala-prefrontal systems in paranoid schizophrenia

OBJECTIVE: The authors investigated impaired differentiation of limbic-prefrontal systems by autonomic arousal in schizophrenia. It was predicted that paranoid patients would be distinguished by a disjunction of hyperarousal but reduced amygdala and medial prefrontal activity relative to both healthy comparison subjects and patients with nonparanoid schizophrenia. METHOD: Pictures depicting facial expressions of fear were presented to 27 schizophrenia patients (13 paranoid, 14 nonparanoid) and 22 matched healthy comparison subjects in an implicit perception task to evoke limbic activity. Simultaneous functional magnetic resonance imaging and skin conductance arousal recordings were acquired during presentation of faces expressing fear or neutral emotion. Responses to fear stimuli were further examined by contrasting those that were associated with a skin conductance response ("with arousal") and those that were not ("without arousal"). RESULTS: In the comparison subjects, arousal dissociated amygdala/medial prefrontal ("visceral") networks and hippocampus/lateral prefrontal ("context") networks for fear perception. Excessive arousal responses were elicited in the schizophrenia subjects, but there was an associated reduction in amygdala/medial prefrontal activity. This disjunction was pronounced in paranoid patients relative to both healthy subjects and nonparanoid patients. Paranoid patients also showed a relatively greater prefrontal deficit for "without-arousal" responses. CONCLUSIONS: This is the first study to reveal a functional disconnection in autonomic and central systems for processing threat-related signals in patients with paranoid schizophrenia. Paranoid cognition may reflect an internally generated cycle of misattribution regarding incoming fear signals due to a breakdown in the regulation of these systems.     

Functional differences among those high and low on a trait measure of psychopathy.

BACKGROUND: It has been established that individuals who score high on measures of psychopathy demonstrate difficulty when performing tasks requiring the interpretation of other's emotional states. The aim of this study was to elucidate the relation of emotion and cognition to individual differences on a standard psychopathy personality inventory (PPI) among a nonpsychiatric population. METHODS: Twenty participants completed the PPI. Following survey completion, a mean split of their scores on the emotional-interpersonal factor was performed, and participants were placed into a high or low group. Functional magnetic resonance imaging data were collected while participants performed a recognition task that required attention be given to either the affect or identity of target stimuli. RESULTS: No significant behavioral differences were found. In response to the affect recognition task, significant differences between high- and low-scoring subjects were observed in several subregions of the frontal cortex, as well as the amygdala. No significant differences were found between the groups in response to the identity recognition condition. CONCLUSIONS: Results indicate that participants scoring high on the PPI, although not behaviorally distinct, demonstrate a significantly different pattern of neural activity (as measured by blood oxygen level-dependent contrast)in response to tasks that require affective processing. The results suggest a unique neural signature associated with personality differences in a nonpsychiatric population.     

Language-association cortex asymmetry in autism and specific language impairment

Language deficits are among the core impairments of autism. We previously reported asymmetry reversal of frontal language cortex in boys with autism. Specific language impairment (SLI) and autism share similar language deficits and may share genetic links. This study evaluated asymmetry of frontal language cortex in a new, independent sample of right-handed boys, including a new sample of boys with autism and a group of boys with SLI. The boys with autism were divided into those with language impairment (ALI) and those with normal language ability (ALN). Subjects (right-handed, aged 6.2-13.4 years) included 22 boys with autism (16 ALI and 6 ALN), 9 boys with a history of or present SLI, and 11 normal controls. MRI brain scans were segmented into grey and white matter; then the cerebral cortex was parcellated into 48 gyral-based divisions per hemisphere. Group differences in volumetric asymmetry were predicted a priori in language-related regions in inferior lateral frontal (Broca's area) and posterior superior temporal cortex. Language impaired boys with autism and SLI both had significant reversal of asymmetry in frontal language-related cortex; larger on the right side in both groups of language impaired boys and larger on the left in both unimpaired language groups, strengthening a phenotypic link between ALI and SLI. Thus, we replicated the observation of reversed asymmetry in frontal language cortex reported previously in an independent autism sample, and observed similar reversal in boys with SLI, further strengthening a phenotypic link between SLI and a subgroup of autism. Linguistically unimpaired boys with autism had similar asymmetry compared with the control group, suggesting that Broca's area asymmetry reversal is related more to language impairment than specifically to autism diagnosis.