Impact of intellectual status on response to cognitive task training in patients with schizophrenia

Cognitive remediation is a promising rehabilitation procedure for people with schizophrenia, but very little is known about who can benefit. In the current analyses, we examined the role of pre-morbid and morbid intellectual function in predicting response to cognitive remediation in a sample of 152 patients diagnosed with schizophrenia or schizoaffective disorder. They were participants in a trial of work therapy and cognitive remediation and had been randomized to receive either Neurocognitive Enhancement Therapy with Work Therapy (NET+WT) or Work Therapy only (WT only). For the current analyses, patients were divided into three intellectual subgroups based on their pattern of premorbid and morbid deficits (preserved intelligence, compromised intelligence, and deteriorated intelligence), and their cognitive remediation outcomes were examined. Cognitive remediation response was measured in two ways: normalization of performance on a computerized training task, and pre-post neuropsychological test performance. Subjects in NET+WT showed greater improvement in cognition than those in WT only, but response differed by intellectual group. For patients in the compromised group, those in NET+WT showed a significantly higher proportion of task normalization than those in the WT only condition, but no such differences were found with the preserved and deteriorated intellectual groups. For patients in the preserved and deteriorated intellectual groups, those in the NET+WT condition showed significantly greater improvement in the analysis of pre-post neuropsychological test performance, but this difference was not found in the compromised intellectual group. These findings suggest that the compromised intellectual group, which had the lowest frequency of normal performers at intake, benefited from NET by achieving dramatic increases in normalization, but that they had difficulty in generalizing these gains to untrained tasks. Those in the preserved and deteriorated intellectual groups were more successful in generalizing their training.     

Effects of scopolamine on stimulus sensitivity and response bias in a visual vigilance task

Signal detection analysis was used to examine the effects of scopolamine on a visual vigilance task. A group of non-smokers performed the 60-min task on three separate occasions, receiving a different dose of scopolamine each time. Scopolamine significantly lowered stimulus sensitivity and prevented the rise in response bias which occurred over time in the placebo condition. In a second study methscopolamine was found to have no effect on either stimulus sensitivity or response bias, showing that peripheral cholinergic blockade was not involved in the effects of scopolamine on these measures. It is concluded (1) that in this study central cholinergic blockade disrupted vigilance performance by lowering stimulus sensitivity, and (2) that this finding provides further evidence that central cholinergic pathways are involved in the control of human information processing.     

Low doses of atropine sulfate impair retention of a well-learned spatial task

Summary Retention of a well-learned spatial task was assessed in rats 10 minutes prior to, and 10, 20, 30, 40, and 50 minutes after treatment with 3, 10 or 30 mg/kg, iv, atropine sulfate or the equivalent volume of saline, iv. There was a variable dose effect for escape latency and choice accuracy measures of spatial retention. A relatively large dose of atropine sulfate (30 mg/kg, iv) significantly impaired choice accuracy and escape latency compared with the control group. Moreover, impairment in choice accuracy was observed with smaller doses of atropine sulfate (3, 10mg/kg, iv) than have previously been shown to disrupt spatial retention.     

Abnormal brain response of chronic schizophrenia patients despite normal performance during a visual vigilance task

Deficits of attention are common among individuals with schizophrenia (SZ) and are related both to genetic liability to the disorder and to functional outcome among patients. To explore the brain systems underlying these attentional abnormalities, we compared the response of nine patients with chronic SZ or schizoaffective disorder to that of 10 matched healthy individuals performing a simple visual vigilance task during functional magnetic resonance imaging. The two groups performed equivalently on the task. When the blood oxygen level dependent (BOLD) signal during identification of a target letter among similar-looking letters was compared to the response during fixation trials, both groups showed multiple clusters of significant brain response in widespread cortical regions. Compared with healthy participants, SZ patients showed a diminished response in the inferior frontal cortex and an abnormally enhanced response in right postcentral gyrus, right medial temporal lobe and left cerebellum. The results suggest that abnormalities of functional brain response to attentional tasks can be observed among patients with SZ even when behavioral performance is unimpaired, and provide further evidence that brain systems related to attention are likely to be involved in the pathophysiology of the disorder.     

Abnormal brain response of chronic schizophrenia patients despite normal performance during a visual vigilance task

Deficits of attention are common among individuals with schizophrenia (SZ) and are related both to genetic liability to the disorder and to functional outcome among patients. To explore the brain systems underlying these attentional abnormalities, we compared the response of nine patients with chronic SZ or schizoaffective disorder to that of 10 matched healthy individuals performing a simple visual vigilance task during functional magnetic resonance imaging. The two groups performed equivalently on the task. When the blood oxygen level dependent (BOLD) signal during identification of a target letter among similar-looking letters was compared to the response during fixation trials, both groups showed multiple clusters of significant brain response in widespread cortical regions. Compared with healthy participants, SZ patients showed a diminished response in the inferior frontal cortex and an abnormally enhanced response in right postcentral gyrus, right medial temporal lobe and left cerebellum. The results suggest that abnormalities of functional brain response to attentional tasks can be observed among patients with SZ even when behavioral performance is unimpaired, and provide further evidence that brain systems related to attention are likely to be involved in the pathophysiology of the disorder.     

Treadmill exercise training augments brain norepinephrine response to familiar and novel stress

In a test of hypothalamic-pituitary-adrenal (HPA) cortical and hypothalamic-pituitary-gonadal (HPG) interaction during familiar and novel stress, we previously reported that treadmill exercise training led to blunted plasma adrenocorticotrophin (ACTH) response to acute treadmill running but a hyper-responsiveness of ACTH after novel immobilization. In this follow-up analysis, we examined whether those results might be plausibly explained by a similar effect of treadmill exercise training on increased levels of norepinephrine (NE) in hypothalamic and limbic brain regions which synergize to modulate the release of ACTH during stress. Ovariectomized Sprague-Dawley rats that had been exercise trained by treadmill running or remained sedentary for 6 weeks received intramuscular injections of estradiol benzoate (Eb) or sesame oil on each of 3 days prior to 15 min of familiar treadmill running or novel immobilization. Treadmill exercise training, regardless of Eb treatment or type of stress, increased NE levels in the paraventricular (PVN), arcuate, medial preoptic, and ventromedial areas of the hypothalamus and protected against depletion of NE in the locus coeruleus, amygdala, and hippocampus. We conclude that treadmill exercise training has a hyperadrenergic effect in brain areas that modulate hypothalamic regulation of ACTH release during stress that is independent of HPA-HPG interaction and novelty of the stressor. To help elucidate these findings, the effects of treadmill exercise training on A1-A2 nuclei which innervate the PVN and their relationship with the limbic and hypothalamic responses we report require study.     

Psychological response to exercise training and/or energy restriction in obese women

OBJECTIVE: The effect of 12 weeks of exercise training (five 45-minute walking sessions/week at 60% to 75% maximum heart rate) and/or moderate energy restriction (4.19 to 5.44 MJ or 1200 to 1300 kcal/day) on psychological general well-being (GWB) and profile of mood states (POMS) was studied in obese women (n = 91, age 45.6 +/- 1.1 years, body mass index 33.1 +/- 0.6 kg/m2). METHODS: Subjects were randomized to one of four groups: control (C); exercise (E); diet (D); and exercise and diet (ED). Psychological variables were measured in all subjects at three timepoints--prestudy, 3 weeks, and poststudy--and analyzed using a 4 x 3 repeated measures design. RESULTS: GWB but not POMS was improved in ED (but not E or D) relative to C poststudy, especially in four of six subscales: freedom from health concern or worry, life satisfaction; cheerful versus depressed mood; and relaxed versus tense feelings. CONCLUSION: These data demonstrate that the combination of moderate energy restriction and exercise training during a 12-week period improves psychological general well-being scores but not mood states in obese subjects.     

Cerebral lateralization of vigilance: A function of task difficulty

Functional near infrared spectroscopy (fNIRS) measures of cerebral oxygenation levels were collected from participants performing difficult and easy versions of a 12 min vigilance task and for controls who merely watched the displays without a work imperative. For the active participants, the fNIRS measurements in both vigilance tasks showed higher levels of cerebral activity than was present in the case of the no-work controls. In the easier task, greater activation was found in the right than in the left cerebral hemisphere, matching previous results indicating right hemisphere dominance for vigilance. However, for the more difficult task, this laterality difference was not found, instead activation was bilateral. Unilateral hemispheric activation in vigilance may be a result of employing relatively easy/simple tasks, not vigilance per se.     

Differential response of enzyme activities in rat diaphragm and intercostal muscles to exercise training

To determine whether respiratory muscles undergo alterations in enzyme activities of energy metabolism as a result of increased mechanical activity, adult male Wistar rats were subjected to a prolonged endurance training program. Analysis off maximal enzyme activity patterns in the diaphragm following 15 weeks of extreme training (final running duration: 210 min per day, 27 m.min-1 at 15 degrees grade, indicated significant reductions in the marker enzymes of the citric acid cycle (citrate synthase), glycolysis (pyruvate kinase, PK; lactate dehydrogenase, LDH), ketone body utilization (3-keto acid: CoA transferase) and transamination (glutamate pyruvate transaminase, GPT). No changes were found for the enzymes of glycogenolysis (phosphorylase, PHOSPH), glycolysis (glyceraldehyde phosphate dehydrogenase, GAPDH), glucose phosphorylation (hexokinase, HK) and beta-oxidation (3-hydroxyacyl: CoA dehydrogenase, HAD) following training. In contrast, in the external intercostal muscle, increases in the range of 57-77% were noted for the enzymes CS and HAD, whereas in the internal intercostal muscles no training induced alteration was evident for these enzymes. For both the intercostal muscles, a consistent trend was noted towards a reduction in all of the glycolytic enzymes investigated, however, significantly lower values were recorded for only PK and LDH in the internal intercostals. GPT was increased in the internal intercostal muscles. These findings indicate that the response pattern observed in the enzyme activities studied following training are to some degree specific to the respiratory muscle investigated.     

Age differences in vigilance as a function of health-related physical fitness and task demands

The influence of health-related physical fitness on age differences in vigilance as a function of the level of task complexity was examined in a group of 24 younger women aged 21-30 years (M = 24.04, S.D. = 2.51), and 23 older women aged between 61 and 83 years (M = 68.70, S.D. = 6.38). In the high event rate vigilance task, task demands were manipulated by degrading stimuli by 10, 20, and 30%. Age variation in performance was found in respect to time-on-task and level of stimulus degradation. As predicted, physical fitness moderated that age variance. It is concluded that physical fitness has greater influence on age differences in vigilance in situations placing high demands on attentional resources. The theoretical implications of the findings are discussed with emphasis upon the possible mediating role of the frontal cortex.     

Arousal and auditory vigilance in individuals with aphasia during a linguistic and nonlinguistic task

Background: Attentional deficits have been observed in individuals with aphasia. Attention, specifically vigilance, is believed to be related to arousal. However, our understanding of arousal and its impact on vigilance performance in individuals with aphasia is very limited. Aims: The purpose of the current study was to investigate whether there is nonoptimal arousal in individuals with aphasia that would affect auditory processing of linguistic and nonlinguistic stimuli. Additionally, this study explored whether there was generalised, nonoptimal arousal and impaired vigilance or deficits specific to linguistic processing. Methods & Procedures: A total of 20 males (10 with left‐hemisphere stroke and aphasia and 10 nonbrain‐damaged controls) participated in this study. Physiologic arousal indexed by cardiovascular and neuroendocrine measures and vigilance performance was compared between the two groups during linguistic and nonlinguistic vigilance tasks. Outcomes & Results: Results indicated that arousal levels and vigilance performance differed between the two groups. However, within groups arousal and vigilance did not differ between the linguistic and nonlinguistic tasks. Conclusions: The present findings suggest that individuals with aphasia have decreased overall vigilance and nonoptimal arousal regardless of the linguistic or nonlinguistic nature of the stimuli.     

Think differently: a brain orienting response to task novelty

Cognitive flexibility hinges on a readiness to direct attention to novel events, and on an ability to change one's mental set to find new solutions for old problems. Human event-related potential (ERP) studies have described a brain 'orienting' response to discrete novel events, marked by a frontally distributed positive potential peaking 300-400 ms post-stimulus (P3a). This brain potential has been typically related to bottom-up processing of novel non-targets under a fixed task-set (i.e., press a button to coloured targets), but had never been related to top-down attention control in dual-task paradigms. In this study, 27 subjects had their ERPs measured while they performed a version of the Wisconsin card sorting test (WCST), a dual-task paradigm where the same feedback cue signalled unpredictable shifts to a new task set (i.e., from 'sort by colour' to 'sort by shape'). Feedback cues that directed a shift in the subject's mental set to a new task-set elicited frontally distributed P3a activity, thus suggesting a role of the P3a response system in task-set shifting. Feedback cues also evoked a longer latency positive potential (350-600 ms; P3b), that was larger the more task rules were held in memory. In line with current models of prefrontal function in the executive control of attention, this P3a/P3b response system appears to reflect the co-ordinated action of prefrontal and posterior association cortices during the switching and updating of task sets in working memory.     

Impact of resistance exercise training on interleukin-6 and JAK/STAT in young men

The JAK/STAT signaling pathway is essential for myogenic regeneration and is regulated by a diverse range of ligands, including interleukin-6 (IL-6) and platelet-derived growth factor-BB (PDGF-BB). Our aim was to evaluate the responsiveness of IL-6 and PDGF-BB to intense exercise, along with STAT3 activation, before and after 12 weeks of resistance training. In young men, IL-6 and PDGF-BB protein concentrations were quantified in biopsied muscle and increased at 3 h post-exercise (17.5-fold and 3-fold, respectively). The response was unaltered by 12 weeks of training. Similarly, STAT3 phosphorylation was elevated post-exercise (12.5-fold), irrespective of training status, as was the expression of downstream targets c-MYC (8-fold), c-FOS (4.5-fold), and SOCS3 (2.3-fold). Thus, intense exercise transiently increases IL-6 and PDGF-BB proteins, and STAT3 phosphorylation is increased. These responses are preserved after intense exercise. This suggests they are not modified by training and may be an essential component of the adaptive responses to intense exercise.     

Cardiovascular and electrodermal adjustments during a vigilance task in patients with borderline and established hypertension

We studied cardiovascular and noncardiovascular sympathetic nervous system (SNS) responses to a vigilance task in patients with borderline (BT) or established hypertension (HT). Twelve patients in each group and twelve normotensive controls (NT) were subjected to a signalled reaction-time (RT) task which included the presentation of a noxious 110 dB white noise contingent upon RT-performance at the end of a 30 sec foreperiod. During this foreperiod recordings were made of: systolic and diastolic blood pressures, heart rate, skin- and muscle-blood flows. Skin and muscle vascular resistances were calculated from mean blood pressure and regional blood flows. Skin conductance level, fluctuations and responses were recorded as noncardiovascular SNS-responses. Compared to NT both HT and BT had higher resting blood pressures, heart rate, skin- and muscle-vascular resistances. BT showed higher resting skin conductance levels than HT and NT who were not different from one another. During stimulation HT and BT evidenced pressor hyperreactivity compared to NT. The electrodermal effects did not parallel the cardiovascular ones. Skin conductance and cardiovascular variables were more closely related in NT than HT or BT. The presence of cardiovascular hyperreactivity together with the absence of noncardiovascular hyperreactivity in HT indicates heightened SNS-activity specific to the cardiovascular system and not part of generalized SNS-arousal. The similarity between HT and BT is consistent with the notion that the differences between BT and HT are quantitative rather than qualitative.     

Impact of a Menninger training experience

In light of her experience working with victims of severe physical and psychological trauma, the author comments on the benefits of her training in psychodynamic psychology. She highlights in particular the value of understanding the complexity of diagnosis and the importance of psychodynamically informed thinking in all treatment approaches.     

Somatosensory cell response to an auditory cue in a haptic memory task

Neurons in the monkey's anterior parietal cortex (Brodmann's areas 3a, 3b, 1, and 2) have been reported to retain information from a visual cue that has been associated with a tactile stimulus in a haptic memory task. This cross-modal transfer indicates that neurons in somatosensory cortex can respond to non-tactile stimuli if they are associated with tactile information needed for performance of the task. We hypothesized that neurons in somatosensory cortex would be activated by other non-tactile stimuli signaling the haptic movements--of arm and hand--that the task required. We found such cells in anterior parietal areas. They reacted with short-latency activity changes to an auditory signal (a click) that prompted those movements. Further, some of those cells changed their discharge in temporal correlation with the movements themselves, with the touch of the test objects, and with the short-term memory of those objects for subsequent tactile discrimination. These findings suggest that cells in the somatosensory cortex participate in the behavioral integration of auditory stimuli with other sensory stimuli and with motor acts that are associated with those stimuli.     

Hand response differences in a self-face identification task

Evidence has indicated that the right frontal cortex is preferentially involved in self-face recognition. To test this further, we employed a face identification task and examined hand response differences (N=10). Pictures of famous faces were combined with pictures of the participants' faces (self) and their co-workers' faces (familiar). These images were presented as a 'movie' in which one face transformed into another. Under the first instruction set, the movies began with either the participant's face or a co-worker's face, and the sequences gradually morphed into a famous face. When told to stop the movie when the face in the sequence became famous, a significantly later 'frame' was identified when the movies were composed of self-faces and the participants responded with their left hand. When the movies started with the famous faces and participants had to stop the movie when it became their own or their familiar co-worker's image (Instruction set 2), a significantly earlier frame was identified in the 'Self: Left hand' condition. The data suggest that participants are inclined to identify images as their own when the right hemisphere is preferentially accessed.     

The effects of continuous and partial reward on the vigilance task performance of adults with attentional deficits: a pilot investigation

The effects of reward schedule (100% and 30%) and extinction on attention (reaction time to auditory stimuli) and frustration levels (pressure exerted on a response key) of 15 adults with attentional disorders and 21 normal adults were examined using a continuous performance task. We predicted, that adults with attentional deficits would (a) perform similar to comparisons when rewarded on a continuous schedule, (b) exhibit higher levels of frustration when that continuous schedule was moved to an extinction schedule, and (c) experience more frustration than comparisons when rewarded on a partial schedule. Overall, adults with attentional deficits were slower to respond and their responses were more variable than typical comparisons across trials, similar to what is observed for children. Continuous reward resulted in poorer performance earlier in the reward phase and continued throughout an extinction phase. The frustration levels of adults with attentional deficits did not differ from comparisons across schedule conditions. Results are discussed in terms of the role of arousal in mediating responding to various schedules of reward.