Calcifying Pseudoneoplasm of the Neuraxis, Cerebellum and Cognition: A Rare Opportunity to Learn More.

Calcifying pseudoneoplasms of the neuraxis (CAPNON) are rare tumours. We describe a CAPNON in the posterior fossa and its associated neuropsychological sequelae to provide further evidence for the role of cerebellum in cognitive function. We report the clinical details, imaging, pre-operative neuropsychological assessment, histological features and management of a patient with such a tumour in the posterior fossa location. Detailed pre-operative neuropsychological assessment identified a number of cognitive deficits that had the hallmarks of dysexecutive syndrome. Post-surgery, there was considerable improvement, most notably on processing speed tasks and selected executive tests. This rare case provides further evidence for the role of cerebellum in cognitive function.

Neuropsychological and Neuropsychiatric Concerns for Deep Brain Stimulation in Dystonia: Preoperative Profiles in a Deep Brain Stimulation Cohort and Postoperative Changes in Three Case Series Reports.

Cognitive deficits and psychiatric morbidities are commonly detected in dystonia. Psychiatric disturbances are of particular clinical concern as they not only contribute to poor quality of life and disease associated burden, but also exacerbate motor and cognitive symptoms. Bilateral deep brain stimulation of the globus pallidus internus improves motor symptoms in treatment-resistant dystonia, but its implications for non-motor manifestations are poorly understood. Improved prediction of cognitive and neuropsychiatric outcomes is important in deep brain stimulation (DBS) research and we aim to assess the latter through established assessment tools. We document the cognitive and neuropsychiatric profiles in 11 primary and 10 secondary dystonia patients attending our DBS clinic. We performed routine multidisciplinary assessments including a comprehensive battery of neuropsychometric tests and detailed neuropsychiatric evaluations. Post-operative assessment outcomes are reported for three patients in case series. The main cognitive deficit was on the Brixton test of spatial anticipation in primary dystonia. Background medical history included psychiatric illness in 38.1% of the patients with 76% of patients having mood abnormalities confirming elevated psychiatric morbidity in this population. Depressive illness was more prominent in primary, whereas clinically relevant histories in secondary dystonia were varied. Of the 21 patients three were able to perform on selected tests due to extensive limitations of their dystonia. No obvious alteration in intellectual functioning following DBS surgery relative to performance at the time of initial assessment was observed. The frequency of individual impairments suggests that difficulties associated with dystonia are likely to be of clinical relevance to cognitive functions in the majority of patients. In particular, current findings suggest that executive difficulties related to inductive processes and spatial learning may be a common in primary dystonias. Psychiatric disturbances demand recognition as a central aspect of dystonia as they contribute to overall disease burden, poor quality of life and exacerbated motor disabilities. The available evidence provides overwhelming suggestion that vulnerability to depression is inherent to the dystonia phenotype.

Verbal Memory Decline following DBS for Parkinson's Disease: Structural Volumetric MRI Relationships.

BACKGROUND: Parkinson's disease is a chronic degenerative movement disorder. The mainstay of treatment is medical. In certain patients Deep Brain Stimulation (DBS) may be offered. However, DBS has been associated with post-operative neuropsychology changes, especially in verbal memory. OBJECTIVES: Firstly, to determine if pre-surgical thalamic and hippocampal volumes were related to verbal memory changes following DBS. Secondly, to determine if clinical factors such as age, duration of symptoms or motor severity (UPDRS Part III score) were related to verbal memory changes. METHODS: A consecutive group of 40 patients undergoing bilateral Subthalamic Nucleus (STN)-DBS for PD were selected. Brain MRI data was acquired, pre-processed and structural volumetric data was extracted using FSL. Verbal memory test scores for pre- and post-STN-DBS surgery were recorded. Linear regression was used to investigate the relationship between score change and structural volumetric data. RESULTS: A significant relationship was demonstrated between change in List Learning test score and thalamic (left, p = 0.02) and hippocampal (left, p = 0.02 and right p = 0.03) volumes. Duration of symptoms was also associated with List Learning score change (p = 0.02 to 0.03). CONCLUSION: Verbal memory score changes appear to have a relationship to pre-surgical MRI structural volumetric data. The findings of this study provide a basis for further research into the use of pre-surgical MRI to counsel PD patients regarding post-surgical verbal memory changes.

Cognitive predictors of cognitive change following bilateral subthalamic nucleus deep brain stimulation in Parkinson's disease.

The beneficial effects of deep brain stimulation (DBS) of the subthalamic nucleus (STN) for the motor symptoms in advanced Parkinson's disease (PD) are well established. Early in PD, mild cognitive impairment is present in a proportion of patients. Hence, it can also be present in PD patients considered for DBS. The potential impact of even a modest decline post-surgically is a concern because it could result in impaired cognitive function. Therefore, attempts to determine which pre-operative cognitive measures predict post-operative cognitive change warrant further attention. We report our findings in a cohort of 30 routinely operated non-demented patients who underwent detailed neuropsychological assessments on average 7.1 months before and 9.4 months after STN DBS. We report the individual and group differences pre- and post-DBS. Stepwise regression analysis was used to analyse the best cognitive predictors of post-operative cognitive changes. We describe our data in relation to published normative data. Post-STN DBS, the immediate story recall component of verbal memory was the most affected cognitive function showing a significant decline in its group mean with a large effect size. The best predictors for this change were pre-surgical list learning and Full Scale Intelligence Quotient. These results suggest that non-demented patients, with even mild impairments in both general intellectual functions and list learning, may be at greater risk of decline in other aspects of verbal memory after STN DBS. Pre-existing mild executive dysfunction was not influenced post-operatively. These findings may help selection and consent for STN DBS.

Mechanisms of responsibility assignment during redundant reaching movements.

When the two hands act together to achieve a goal, the redundancy of the system makes it necessary to distribute the responsibility for error corrections across the two hands. In an experiment in which participants control a single cursor with the movements of both hands, we show that right-handed individuals correct for movement errors more with their nondominant left hand than with their right hand, even though the dominant right hand corrects the same errors more quickly and efficiently when each hand acts in isolation. By measuring the responses to rapid cursor and target displacements using force channels, we demonstrate that this shift is due to a modulation of the feedback gains of each hand rather than to a shift in the onset of the corrective response. We also show that the shift toward left-hand corrections is more pronounced for errors that lead to adaptation (cursor displacements) than for perturbations that do not (target displacements). This finding provides some support for the idea that the motor system assigns the correction to the most likely source of the error to induce learning and to optimize future performance. Finally, we find that the relative strength of the feedback corrections in the redundant task correlates positively with those found for the nonredundant tasks. Thus the process of responsibility assignment modulates the processes that normally determine the gains of feedback correction rather than completely overwriting them.

Dissociation between verbal response initiation and suppression after prefrontal lesions.

Some of the most striking symptoms after prefrontal damage are reduction of behavioral initiation and inability to suppress automatic behaviors. However, the relation between these 2 symptoms and the location of the lesions that cause them are not well understood. This study investigates the cerebral correlates of initiation and suppression abilities assessed by the Hayling Sentence Completion Test, using the human lesion approach. Forty-five patients with focal brain lesions and 110 healthy matched controls were examined. We combined a classical group approach with 2 voxel-based lesion methods. The results show several critical prefrontal regions to Hayling Test performance, associated with either common or differential impairment in "initiation" and "suppression" conditions. A crucial role for medial rostral prefrontal cortex (BA 10) in the initiation condition was shown by both group and lesion-mapping methods. A posterior inferolateral lesion provoked both initiation and suppression slowness, although to different degrees. An orbitoventral region was associated with errors in the suppression condition. These findings are important for clinical practice since they indicate that the brain regions required to perform a widely used and sensitive neuropsychological test but also shed light on the regions crucial for distinct components of adaptative behaviors, in particular, rostral prefrontal cortex.

The role of rostral prefrontal cortex in prospective memory: a voxel-based lesion study.

Patients with lesions in rostral prefrontal cortex (PFC) often experience problems in everyday-life situations requiring multitasking. A key cognitive component that is critical in multitasking situations is prospective memory, defined as the ability to carry out an intended action after a delay period filled with unrelated activity. The few functional imaging studies investigating prospective memory have shown consistent activation in both medial and lateral rostral PFC but also in more posterior prefrontal regions and non-frontal regions. The aim of this study was to determine regions that are necessary for prospective memory performance, using the human lesion approach. We designed an experimental paradigm allowing us to assess time-based (remembering to do something at a particular time) and event-based (remembering to do something in a particular situation) prospective memory, using two types of material, words and pictures. Time estimation tasks and tasks controlling for basic attention, inhibition and multiple instructions processing were also administered. We examined brain-behaviour relationships with a voxelwise lesion method in 45 patients with focal brain lesions and 107 control subjects using this paradigm. The results showed that lesions in the right polar prefrontal region (in Brodmann area 10) were specifically associated with a deficit in time-based prospective memory tasks for both words and pictures. This deficit could not be explained by impairments in basic attention, detection, inhibition or multiple instruction processing, and there was also no deficit in event-based prospective memory conditions. In addition to their prospective memory difficulties, these polar prefrontal patients were significantly impaired in time estimation ability compared to other patients. The same region was found to be involved using both words and pictures, suggesting that right rostral PFC plays a material nonspecific role in prospective memory. This is the first lesion study showing that rostral PFC is crucial for time-based prospective memory. The findings suggest that time-based and event-based prospective memory might be supported at least in part by distinct brain regions. Two particularly plausible explanations for the deficit rest upon a possible role for polar prefrontal structures in supporting in time estimation, and/or in retrieving an intention to act. More broadly, the results are consistent with the view that the deficit of rostral patients in multitasking situations might at least in part be explained by a deficit in prospective memory.

810 nm Wavelength light: an effective therapy for transected or contused rat spinal cord.

BACKGROUND AND OBJECTIVES: Light therapy has biomodulatory effects on central and peripheral nervous tissue. Spinal cord injury (SCI) is a severe central nervous system trauma with no effective restorative therapies. The effectiveness of light therapy on SCI caused by different types of trauma was determined. STUDY DESIGN/MATERIALS AND METHODS: Two SCI models were used: a contusion model and a dorsal hemisection model. Light (810 nm) was applied transcutaneously at the lesion site immediately after injury and daily for 14 consecutive days. A laser diode with an output power of 150 mW was used for the treatment. The daily dosage at the surface of the skin overlying the lesion site was 1,589 J/cm(2) (0.3 cm(2) spot area, 2,997 seconds). Mini-ruby was used to label corticospinal tract axons, which were counted and measured from the lesion site distally. Functional recovery was assessed by footprint test for the hemisection model and open-field test for the contusion model. Rats were euthanized 3 weeks after injury. RESULTS: The average length of axonal re-growth in the rats in the light treatment (LT) groups with the hemisection (6.89+/-0.96 mm) and contusion (7.04+/-0.76 mm) injuries was significantly longer than the comparable untreated control groups (3.66+/-0.26 mm, hemisection; 2.89+/-0.84 mm, contusion). The total axon number in the LT groups was significantly higher compared to the untreated groups for both injury models (P<0.05). For the hemisection model, the LT group had a statistically significant lower angle of rotation (P<0.05) compared to the controls. For contusion model, there was a statistically significant functional recovery (P<0.05) in the LT group compared to untreated control. CONCLUSIONS: Light therapy applied non-invasively promotes axonal regeneration and functional recovery in acute SCI caused by different types of trauma. These results suggest that light is a promising therapy for human SCI.

The case for the development and use of "ecologically valid" measures of executive function in experimental and clinical neuropsychology.

This article considers the scientific process whereby new and better clinical tests of executive function might be developed, and what form they might take. We argue that many of the traditional tests of executive function most commonly in use (e.g., the Wisconsin Card Sorting Test; Stroop) are adaptations of procedures that emerged almost coincidentally from conceptual and experimental frameworks far removed from those currently in favour, and that the prolongation of their use has been encouraged by a sustained period of concentration on "construct-driven" experimentation in neuropsychology. This resulted from the special theoretical demands made by the field of executive function, but was not a necessary consequence, and may not even have been a useful one. Whilst useful, these tests may not therefore be optimal for their purpose. We consider as an alternative approach a function-led development programme which in principle could yield tasks better suited to the concerns of the clinician because of the transparency afforded by increased "representativeness" and "generalisability." We further argue that the requirement of such a programme to represent the interaction between the individual and situational context might also provide useful constraints for purely experimental investigations. We provide an example of such a programme with reference to the Multiple Errands and Six Element tests.

The early effects of radiotherapy on intellectual and cognitive functioning in patients with frontal brain tumours: the use of a new neuropsychological methodology.

Investigations of the effects of radiation on neuropsychological functions have revealed variable outcomes, ranging from no effect to severe cognitive impairment. However, many of the previous studies have relied on retrospective data or have been limited by methodological problems. In this study, prospective neuropsychological assessments were compared at baseline (after surgery and before radiotherapy) and within 4 months of completion of radiotherapy (except one case), to examine early-delayed effects of radiation on intellectual and cognitive functioning. Sixteen adult patients with either low- or high-grade brain tumours, 15 of whom were treated with radiotherapy, were compared with 8 control participants with nonmalignant brain tumours whom did not undergo radiotherapy. All participants had lesions situated mainly in the frontal lobes. All groups of patients had evidence of intellectual and cognitive impairment at baseline. The low- and high-grade brain tumour groups showed a differential pattern of performance following radiotherapy, with the low-grade tumour group's performance being more competent on all of the five main neuropsychological measures. Their pattern of improvement was very similar to that of the nonmalignant brain tumour group who had not undergone radiotherapy. The present study provides some preliminary information about the neuropsychological deficits associated with primary brain tumours, their severity, and the relationship between neuropsychological functioning and brain tumours and radiotherapy.