Paul S. Foster

Aceruloplasminaemia with progressive atrophy without brain iron overload: treatment with oral chelation

Background: Hereditary aceruloplasminaemia is a disorder of iron metabolism that is characterised by iron accumulation in the brain and other visceral organs. In previously reported cases, individuals with the disorder were noted to have evidence of iron accumulation in the brain. Oral chelating agents have not been used in neurological diseases of iron metabolism. Methods: A 54-year-old woman who presented with ataxia, lower extremity spasticity and chorea was evaluated for evidence of the source of neurological dysfunction. Results: Blood studies revealed no detectable ceruloplasmin. Marked iron overload was defined by a liver biopsy, which showed a variegated pattern consistent with a primary cause of iron overload. Review of MRI scans showed progressive brain atrophy without visible iron accumulation occurring over a 5-year period. The history suggested that neurodegeneration was coincident with aggressive oral iron replacement. Oral chelation improved many symptoms. Conclusions: Our findings in this patient suggest that disorders of iron transport such as aceruloplasminaemia can be a cause of neurological symptoms such as chorea and cognitive decline, as well as progressive neurodegeneration in the absence of visible iron on MRI scans. We found that oral iron chelation was effective at improving symptoms.

Effects of NREM sleep instability on cognitive processing.

OBJECTIVE Cyclic alternating pattern (CAP) A1 subtypes, characterized by high-voltage slow waves, are generated by the frontal cortex and are suspected to have a role in cognitive processing during NREM sleep. Conversely, CAP A2 and A3 subtypes are characterized by variable amounts of rapid EEG potentials arising from the parietal-occipital areas and often coincide with arousals. We tested the hypothesis that CAP subtypes differentially correlate with cognitive functions. SUBJECTS AND METHODS Eight healthy participants were recruited. Two nocturnal polysomnography studies and a series of neuropsychological tests were obtained in the subjects during the morning and afternoon of the first day and on the morning of the second day. RESULTS In agreement with our original hypothesis, we found that CAP A1 subtypes were correlated with better neuropsychological functioning the day after, for verbal fluency, working memory, and both delayed recall and recognition of words. These same neuropsychological test results were found to be negatively correlated with CAP A2 subtypes. CAP A3 subtypes were negatively correlated with the Trial Making test Parts A and B. CONCLUSIONS The results suggest that CAP A1 might be related to better cognitive functioning, whereas CAP A2 and A3 correlated with worse cognitive functioning. Further studies are needed to better understand how CAP influences cognitive performance, especially frontally-dependent functions and memory.

Effects of Donepezil on Verbal Memory After Semantic Processing in Healthy Older Adults

ObjectiveTo learn if acetylcholinesterase inhibitors alter verbal recall by improving semantic encoding in a double-blind randomized placebo-controlled trial. BackgroundCholinergic supplementation has been shown to improve delayed recall in adults with Alzheimer disease. With functional magnetic resonance imaging, elderly adults, when compared with younger participants, have reduced cortical activation with semantic processing. There have been no studies investigating the effects of cholinergic supplementation on semantic encoding in healthy elderly adults. MethodTwenty elderly participants (mean age 71.5, SD±5.2) were recruited. All underwent memory testing before and after receiving donepezil (5 mg, n=11 or 10 mg, n=1) or placebo (n=8) for 6 weeks. Memory was tested using a Levels of Processing task, where a series of words are presented serially. Subjects were either asked to count consonants in a word (superficially process) or decide if the word was “pleasant” or “unpleasant” (semantically process). ResultsAfter 6 weeks of donepezil or placebo treatment, immediate and delayed recall of superficially and semantically processed words was compared with baseline performance. Immediate and delayed recall of superficially processed words did not show significant changes in either treatment group. With semantic processing, both immediate and delayed recall performance improved in the donepezil group. ConclusionsOur results suggest that when using semantic encoding, older normal subjects may be aided by anticholinesterase treatment. However, this treatment does not improve recall of superficially encoded words.

The relationship between magnitude of cerebral activation and intensity of emotional arousal.

There is considerable knowledge concerning the cerebral localization of positive and negative emotions; however, relatively little is known about the cerebral representation of subjective emotional intensity. Indeed, few studies to date seem to have been conducted on the cerebral effects of increased emotional intensity. The purpose of the present investigation was to investigate the relationship between the intensity of cerebral activation and emotional arousal using quantitative electroencephalography (QEEG). Participants were asked to recollect an angry memory while QEEG was recorded from 19 electrode sites arranged according to the International 10/20 System. Significant positive correlations were found between subjective intensity of angry memories and changes in low beta (13-21 Hz) and high beta (21-32 Hz) magnitude (µV) at the F8, T6, and O1 electrode sites among the male participants. Additionally, a significant positive correlation between emotion intensity and changes in high beta at the T6 electrode site was found among female participants. Results are discussed in terms of implications for emotional regulation and dysfunction.

Anxiety and depression severity are related to right but not left onset Parkinson's disease duration

Depression and anxiety have both been associated with relative left frontal hypoactivation and the motor symptoms of Parkinsons disease typically begin in a lateral or asymmetrical fashion. Hence, PD patients with right hemibody onset may experience heightened depression and anxiety. However, research is mixed regarding whether right or left hemibody onset PD is associated with elevated levels of depression and anxiety. This literature, though, has not considered the potential moderating variable of disease duration. We hypothesized that disease duration would be positively correlated with measures of depression and anxiety in right but not left hemibody onset PD patients. The results indicated that scores on the Geriatric Depression Scale, Beck Depression Inventory-II, and the State Trait Anxiety Scale - State correlated positively with disease duration, but only in the right hemibody onset group of PD patients. Thus, right hemibody onset PD is associated with more severe depressive and anxiety symptoms, but only when disease duration is considered.

Creativity in Parkinson's disease as a function of right versus left hemibody onset.

OBJECTIVE Creativity is heavily dependent on divergent thinking and divergent thinking appears to be strongly dependent on fontal lobe function. Since patients with Parkinsons disease (PD) often have evidence of frontal lobe dysfunction we wanted to learn if these patients have a reduction of creativity, as well as learning if the side of onset (right versus left) influences the type (verbal versus visuospatial) of decrement in creativity. DESIGN Participants of this study were patients with right (RHO) or left (LHO) onset PD as well as matched controls. All subjects were given the Abbreviated Torrance Test of Creative Thinking for Adults (ATTA), a widely used test to assess creativity that examines Fluency, Originality, Flexibility and Elaboration. Subjects were also assessed with the Controlled Word Association Test (COWAT). RESULTS/CONCLUSIONS When compared to controls the patients with RHO, but not LHO, had a decrease of verbal creative fluency. Patients with PD often have a decrease on the COWAT, but performance on the COWAT did not differ between the RHO and the LHO patients. This suggests that patients with PD who have RHO have a decrease in verbal creativity and this decrement does not appear to be related to decreased fluency.

Magnitude of cerebral asymmetry at rest: Covariation with baseline cardiovascular activity

The cerebral regulation of cardiovascular functioning varies along both a lateral and a longitudinal axis. The parasympathetic and sympathetic nervous systems are lateralized to the left and right cerebral hemispheres, respectively. Further, the frontal lobes are known to be inhibitory in nature, whereas the temporal lobes are excitatory. However, no systematic investigation has been conducted to determine the nature and strength of the relationship between the left and right frontal and temporal lobes in regulating cardiovascular activity. The present investigation sought to examine these relationships by testing the hypothesis that negative correlations would be found between baseline heart rate and blood pressure and asymmetry of alpha magnitude across the frontal lobes. Further, positive correlations were hypothesized to exist across the temporal lobes. A total of 20 women were asked to relax with their eyes closed while heart rate and blood pressure as well as quantitative electroencephalography data were obtained. The results indicated that, as hypothesized, significant negative correlations existed across the frontal lobes and significant positive correlations existed across the temporal lobes. The results provide further support for a division of responsibility between the left and right frontal and temporal lobes in the regulation of heart rate and blood pressure.

Emotional Influences on Spatial Attention

The relationships between the anterior-posterior and left-right regions of the brain have been characterized as mutually inhibitory. Whereas the left hemisphere attends to right proximal hemispace and is associated with positive emotions, the right hemisphere attends to left distal hemispace and is associated with negative emotions. Because of the excitatory and inhibitory influences between the left and right frontal and posterior regions of the brain, the expression of emotion will result in an ipsilateral attentional bias. Given these functional systems, we hypothesized that positive emotions would be associated with a bias for left distal hemispace and negative emotions would be associated with a bias for right proximal hemispace. We tested these hypotheses by having 138 undergraduate students place emotionally labeled pegs on a large board. Our results indicated that the positively labeled pegs were placed in left distal hemispace and the relative placement of negatively labeled pegs was rightward and proximally. Whereas numerous research investigations have examined how attention is biased for emotional stimuli, ours is the first investigation to provide evidence that emotions can bias attentional allocation.

What’s inside the art? The influence of frontotemporal dementia in art production

We evaluated the productions of an artist with frontotemporal lobar degeneration from before dementia onset until she was fully symptomatic. We noted an improvement of technique that might be related to sparing and disinhibition of the right posterior neocortex. There was a reduction of closure (completeness of the painting), possibly induced by impersistence and a decrease in evocative impact that might be explained by frontal and anterotemporal-limbic dysfunction.

Cerebral moderation of cardiovascular functioning: A functional cerebral systems perspective

OBJECTIVE Interhemispheric and intrahemispheric balance models may be integrated to gain an increased understanding of how cerebral systems are involved in the regulation of heart rate and blood pressure. We sought to examine the relationship between left and right frontal and posterior activity and resting heart rate and blood pressure. Based on this integration, we predicted that lateral (left minus right hemisphere) and longitudinal (frontal minus posterior regions) asymmetry in cerebral activity would be related to resting measures of heart rate and blood pressure. METHODS Resting heart rate, blood pressure, and EEG (low and high beta) were obtained in a sample of 42 men. Physiological measures were obtained during an eyes closed resting period. RESULTS Our results provided partial support, finding significant correlations between resting heart rate and not only frontal lobe lateral asymmetry but also frontal-parietal asymmetry. CONCLUSIONS These results provide support for the relative differential associations of the left and right frontal and parietal lobes and cardiovascular activity. SIGNIFICANCE Previous research has not examined cerebral control of cardiovascular functioning from a functional cerebral systems perspective. The results are discussed as they relate to research on aggression and hostility.