Ethical issues in the clinical application of fMRI: factors affecting the validity and interpretation of activations

The ability of functional magnetic resonance imaging (fMRI) to localize activations in a single patient, along with the safety and widespread availability of this methodology, has lead to an increasing use of fMRI for clinical purposes such as pre-surgical planning. As methodology continues to improve and more experience with fMRI in the clinical setting is acquired, clinical functional neuroimaging will likely have an increasing influence over patient care. Therefore, ethical use of fMRI, as with other medical techniques, requires understanding the factors impacting the interpretation of the methodology. Issues affecting the validity and interpretation of clinical functional neuroimaging, including effects of altered hemodynamic response function, head motion, and structural changes in the brain, are reviewed. The distinction between correlated and necessary activation in a clinical context is discussed. Different types of statistical errors in fMRI analysis are described, along with their consequences to the patient. Finally, for the future of clinical fMRI development, the need for normative patient data, as well as standardized tasks, scan protocols, and data analyses, is discussed.     

Category and letter fluency in semantic dementia, primary progressive aphasia, and Alzheimer's disease

This study examined the impact of various degenerative dementias on access to semantic knowledge and the status of semantic representations. Patients with semantic dementia, primary progressive aphasia, and Alzheimer's disease were compared with elderly controls on tasks of category and letter fluency, with number of words generated, mean lexical frequency and errors recorded. The findings are consistent with the view that category and letter fluency rely on both common and unique cognitive processes. Fluency tasks, with the richness of data obtained, are valuable in distinguishing different dementia syndromes from one another.     

A brief review on the use of functional near-infrared spectroscopy (fNIRS) for language imaging studies in human newborns and adults

Upon stimulation, real time maps of cortical hemodynamic responses can be obtained by non-invasive functional near-infrared spectroscopy (fNIRS) which measures changes in oxygenated and deoxygenated hemoglobin after positioning multiple sources and detectors over the human scalp. The current commercially available transportable fNIRS systems have a time resolution of 1-10 Hz, a depth sensitivity of about 1.5 cm, and a spatial resolution of about 1 cm. The goal of this brief review is to report infants, children and adults fNIRS language studies. Since 1998, 60 studies have been published on cortical activation in the brain’s classic language areas in children/adults as well as newborns using fNIRS instrumentations of different complexity. In addition, the basic principles of fNIRS including features, strengths, advantages, and limitations are summarized in terms that can be understood even by non specialists. Future prospects of fNIRS in the field of language processing imaging are highlighted.     

Neural substrates of cognitive skill learning in Parkinson's disease

While cognitive skill learning is normally acquired implicitly through frontostriatal circuitry in healthy individuals, neuroimaging studies suggest that patients with Parkinson's disease (PD) do so by activating alternate, intact brain areas associated with explicit memory processing. To further test this hypothesis, 10 patients with PD and 12 healthy controls were tested on a modified, learning version of the Tower of London task while undergoing positron emission tomography at four different time points over the course of learning. Despite having less accurate problem solving abilities than controls, PD patients were able to acquire the skill learning task. However, as compared to controls, they maintained higher levels of cerebral blood flow activity in the dorsolateral prefrontal cortex and hippocampus and showed an increase in activity in the frontopolar cortex and posterior cingulate over the course of learning. These findings reflect a shift to the explicit memory system in PD patients, enabling them to learn this cognitive skill, which is normally acquired by control subjects using implicit learning strategies and frontostriatal circuitry.     

Recollection training and transfer effects in Alzheimer's disease: effectiveness of the repetition-lag procedure

Objective

This study was designed to extend the use of a memory training technique, known as the repetition-lag procedure, to Alzheimer patients. The specificity of this procedure is to target the process of recollection for improvement.

Method

A group of 12 patients were trained individually for 6 h. The training procedure consisted of a series of yes/no recognition tasks in which some words were repeated throughout the test list across gradually increasing delays. Their performance was evaluated on pre-and-post tests and compared with a recognition practice group and a no contact control group.

Results

Initially, recollection training patients only performed accurately when the delay between repetitions consisted of one intervening word, but by the end of training their performance increased up to four-word intervals. Interestingly, these benefits generalized to other measures of memory, such as working memory, visual memory and source recognition.

Conclusions

Effectiveness of the repetition-lag procedure in Alzheimer’s disease is discussed.     

An attenuation of the 'normal' category effect in patients with Alzheimer's disease: a review and bootstrap analysis

There is a consensus that Alzheimer's disease (AD) impairs semantic information, with one of the first markers being anomia i.e. an impaired ability to name items. Doubts remain, however, about whether this naming impairment differentially affects items from the living and nonliving knowledge domains. Most studies have reported an impairment for naming living things (e.g. animals or plants), a minority have found an impairment for nonliving things (e.g. tools or vehicles), and some have found no category-specific effect. A survey of the literature reveals that this lack of agreement may reflect a failure to control for intrinsic variables (such as familiarity) and the problems associated with ceiling effects in the control data. Investigating picture naming in 32 AD patients and 34 elderly controls, we used bootstrap techniques to deal with the abnormal distributions in both groups. Our analyses revealed the previously reported impairment for naming living things in AD patients and that this persisted even when intrinsic variables were covaried; however, covarying control performance eliminated the significant category effect. Indeed, the within-group comparison of living and nonliving naming revealed a larger effect size for controls than patients. We conclude that the category effect in Alzheimer's disease is no larger than is expected in the healthy brain and may even represent a small diminution of the normal profile.     

The contribution of functional near-infrared spectroscopy (fNIRS) to the presurgical assessment of language function in children

Before performing neurosurgery, an exhaustive presurgical assessment is required, usually including an investigation of language cerebral lateralization. Among the available procedures, the intracarotid amobarbital test (IAT) was formerly the most widely used. However, this procedure has many limitations: it is invasive and potentially traumatic, especially for children. To overcome these limitations, neuroimaging techniques such as functional magnetic resonance imaging (fMRI) have been used. Again, these methods are difficult to use with children, who must remain motionless during data acquisition. Functional near-infrared spectroscopy (fNIRS) is a noninvasive functional imaging technique that is easily applied to pediatric and cognitively limited patients. It has been used recently in epileptic children for presurgical assessment of expressive and receptive language brain lateralization. The aim of this review is to present the contribution of fNIRS to the presurgical assessment of language function in children with neurological diseases.     

Measuring the impact on relatives of caring for people with Alzheimer's disease: Quality of life,burden and well-being

Abstract

This study compared key correlates of caregiver stress in 50 Alzheimer's disease patients and their primary caregivers. in relation to three outcome measures - perceived burden, psychological well-being, and quality of life (QoL). These were evaluated using the Zarit Burden Interview. General Health Questionnaire (GHQ-30), and Schedule for the Evaluation of Individual QoL (SEIQoL-DW) respectively. Informal social support was evaluated on Vaux's Social Support Appraisal Scale. Patients' cognitive. functional, and behavioural status were rated on Mini-Mental State Examination, Blessed-Roth Dementia Scale. and Baumgarten Dementia Behaviour Disturbance Scale respectively. Standardised multiple regression analysis was used to compare the outcome measures. In this model burden was highly related to behaviour disturbance. and also to social support (adjusted R² = 0.45). Well-being was significantly related to behaviour disturbance, and also to functional status (adjusted R² = 0.40). With regard to QoL the model performed poorly as most of the variance in QoL was not accounted for by the model (adjusted R² = 0.14). These findings highlight differences in factors determining caregiver QoL. burden and well-being.     

Rigidity in social and emotional memory in the R6/2 mouse model of Huntington's disease

Four experiments were conducted to examine social and emotional memory in the R6/2 transgenic mouse model of Huntington’s disease. First, R6/2 mice were tested in a social transmission of food preference task where they had to acquire a preference for a flavoured food (acquisition) and subsequently to learn a preference for a different flavour (shifted reinforcement). R6/2 mice performed well in the acquisition trial. However, they were impaired in the shifted reinforcement trial and perseverated on the first preference learned. Second, mice were trained in an inhibitory avoidance paradigm, with either one or two footshocks delivered during the training. WT mice given one footshock showed retention levels lower than those of mice trained with two footshocks. By contrast, there was no difference in retention levels of R6/2 mice given either one or two footshocks. Third, mice were tested in an active avoidance task that paired a mild footshock with a warning light. R6/2 mice had a strong age-dependent deficit in this task. Finally, mice were tested in a conditioned taste aversion task that paired a saccharine solution with a nausea-inducing agent (LiCl). R6/2 mice displayed normal aversion, however this was not extinguished following repeated exposure to saccharine solution alone. Our data show that while R6/2 mice have functional hippocampus-based memory, they have deficits in striatum-based memory skills. Further, social and emotional memories appear to be encoded in a rigid way that is not influenced by subsequent learning or by arousal levels.     

Analyzing feature distinctiveness in the processing of living and non-living concepts in Alzheimer’s disease

The conceptual structure account (CSA) is a model specifying the role of the living and non-living domain dichotomy in the structure of semantic memory. According to this model, feature distinctiveness and the perceptual–functional inter-correlation of concepts are assumed to play a major role in impairing the ability to discriminate between living and non-living concepts in Alzheimer’s disease (AD). The hypothesis was tested in this study by using naming and sorting tasks traditionally considered as assessing distinctiveness, and a property verification task where distinctiveness and perceptual–functional inter-correlation were objectively controlled against norms especially created for this purpose. Alzheimer’s patients (n = 59) with minimal, mild or moderate dementia and normal elderly adults (n = 31) participated in the study. Overall, the findings did not support the CSA predictions. They revealed a distinctiveness effect on response accuracy with shared features dominating distinctive features regardless of domain. They also revealed more difficulties in the tasks involving effortful processes. The results stress the need to consider both cognitive demands of tasks and structural aspects of knowledge in the evaluation of semantic memory in AD.