Bringing memory fMRI to the clinic: comparison of seven memory fMRI protocols in temporal lobe epilepsy.

fMRI is increasingly implemented in the clinic to assess memory function. There are multiple approaches to memory fMRI, but limited data on advantages and reliability of different methods. Here, we compared effect size, activation lateralisation, and between-sessions reliability of seven memory fMRI protocols: Hometown Walking (block design), Scene encoding (block design and event-related design), Picture encoding (block and event-related), and Word encoding (block and event-related). All protocols were performed on three occasions in 16 patients with temporal lobe epilepsy (TLE). Group T-maps showed activity bilaterally in medial temporal lobe for all protocols. Using ANOVA, there was an interaction between hemisphere and seizure-onset lateralisation (P = 0.009) and between hemisphere, protocol and seizure-onset lateralisation (P = 0.002), showing that the distribution of memory-related activity between left and right temporal lobes differed between protocols and between patients with left-onset and right-onset seizures. Using voxelwise intraclass Correlation Coefficient, between-sessions reliability was best for Hometown and Scenes (block and event). The between-sessions spatial overlap of activated voxels was also greatest for Hometown and Scenes. Lateralisation of activity between hemispheres was most reliable for Scenes (block and event) and Words (event). Using receiver operating characteristic analysis to explore the ability of each fMRI protocol to classify patients as left-onset or right-onset TLE, only the Words (event) protocol achieved a significantly above-chance classification of patients at all three sessions. We conclude that Words (event) protocol shows the best combination of between-sessions reliability of the distribution of activity between hemispheres and reliable ability to distinguish between left-onset and right-onset patients.

Thalamotemporal impairment in temporal lobe epilepsy: a combined MRI analysis of structure, integrity, and connectivity.

OBJECTIVE: Thalamic abnormality in temporal lobe epilepsy (TLE) is well known from imaging studies, but evidence is lacking regarding connectivity profiles of the thalamus and their involvement in the disease process. We used a novel multisequence magnetic resonance imaging (MRI) protocol to elucidate the relationship between mesial temporal and thalamic pathology in TLE. METHODS: For 23 patients with TLE and 23 healthy controls, we performed T1 -weighted (for analysis of tissue structure), diffusion tensor imaging (tissue connectivity), and T1 and T2 relaxation (tissue integrity) MRI across the whole brain. We used connectivity-based segmentation to determine connectivity patterns of thalamus to ipsilateral cortical regions (occipital, parietal, prefrontal, postcentral, precentral, and temporal). We subsequently determined volumes, mean tractography streamlines, and mean T1 and T2 relaxometry values for each thalamic segment preferentially connecting to a given cortical region, and of the hippocampus and entorhinal cortex. RESULTS: As expected, patients had significant volume reduction and increased T2 relaxation time in ipsilateral hippocampus and entorhinal cortex. There was bilateral volume loss, mean streamline reduction, and T2 increase of the thalamic segment preferentially connected to temporal lobe, corresponding to anterior, dorsomedial, and pulvinar thalamic regions, with no evidence of significant change in any other thalamic segments. Left and right thalamotemporal segment volume and T2 were significantly correlated with volume and T2 of ipsilateral (epileptogenic), but not contralateral (nonepileptogenic), mesial temporal structures. SIGNIFICANCE: These convergent and robust data indicate that thalamic abnormality in TLE is restricted to the area of the thalamus that is preferentially connected to the epileptogenic temporal lobe. The degree of thalamic pathology is related to the extent of mesial temporal lobe damage in TLE.

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.

Mapping the brain in younger and older asymptomatic HIV-1 men: frontal volume changes in the absence of other cortical or diffusion tensor abnormalities.

INTRODUCTION: Over the past decade the developments made in treating people with human immune deficiency virus (HIV) have greatly improved quality of life and life expectancy. However, the nature of asymptomatic HIV-associated minor neurocognitive disorder (HAND) remains unclear. In this study we explored the occurrence of neuropsychological and neuroimaging changes in medically and psychiatrically stable HIV-1 infected patients on highly active antiretroviral treatment (HAART) from two separate age groups. METHODS: Participants included 20 HIV-1 infected younger (aged 20-40) and 20 HIV-1 older patients (aged 50-75). Comparisons were made with 20 age- and education-matched younger and 22 matched older healthy seronegative males. Participants were stable on treatment and asymptomatic at study onset with undetectable HIV-1 viral loads, and free of medical or psychiatric co-morbidity, alcohol or substance misuse. A detailed neuropsychological assessment was used and volumetric-magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) performed to assess grey and white-matter integrity. RESULTS: We found significant effects of ageing on memory, grey and white matter measures. Comparison of the HIV-positive and HIV-negative groups did not show significant differences on the neuropsychological tests after Bonferroni correction, and there were no significant age by HIV status interactions. However, we did find reduced grey matter volume on MRI in our HIV-positive participants within the medial and superior frontal gyri. We also found significant ageing effects in fronto-temporal grey and white matter, independent of the effect of HIV. CONCLUSIONS: The results from this study suggest that HIV-1 disease by itself does not significantly impair cognitive function when patients are otherwise asymptomatic. Nevertheless, the imaging techniques were sensitive enough to detect subtle grey matter changes not normally evident until much later in the disease. If confirmed in a longitudinal study this frontal grey matter change could represent an important biomarker for trials in HIV disease.

Advantages of the multiple case series approach to the study of cognitive deficits in autism spectrum disorder.

In the neuropsychological case series approach, tasks are administered that tap different cognitive domains, and differences within rather than across individuals are the basis for theorising; each individual is effectively their own control. This approach is a mainstay of cognitive neuropsychology, and is particularly suited to the study of populations with heterogeneous deficits. However it has very rarely been applied to the study of cognitive differences in autism spectrum disorder (ASD). Here, we investigate whether this approach can yield information beyond that given by the typical group study method, when applied to an ASD population. Twenty-one high-functioning adult ASD participants and 22 IQ, age, and gender-matched control participants were administered a large battery of neuropsychological tests that would represent a typical neuropsychological assessment for neurological patients in the United Kingdom. The data were analysed using both group and single-case study methods. The group analysis revealed a limited number of deficits, principally on tests with a large executive function component, with no impairment in more routine abilities such as basic attending, language and perception. Single-case study analysis proved more fruitful revealing evidence of considerable variation in abilities both between and within ASD participants. Both sub-normal and supra-normal performance were observed, with the most defining feature of the ASD group being this variability. We conclude that the use of group-level analysis alone in the study of cognitive deficits in ASD risks missing cognitive characteristics that may be vitally important both theoretically and clinically, and even may be misleading because of averaging artifact.

Abnormal functional specialization within medial prefrontal cortex in high-functioning autism: a multi-voxel similarity analysis.

Multi-voxel pattern analyses have proved successful in 'decoding' mental states from fMRI data, but have not been used to examine brain differences associated with atypical populations. We investigated a group of 16 (14 males) high-functioning participants with autism spectrum disorder (ASD) and 16 non-autistic control participants (12 males) performing two tasks (spatial/verbal) previously shown to activate medial rostral prefrontal cortex (mrPFC). Each task manipulated: (i) attention towards perceptual versus self-generated information and (ii) reflection on another person's mental state ('mentalizing'versus 'non-mentalizing') in a 2 x 2 design. Behavioral performance and group-level fMRI results were similar between groups. However, multi-voxel similarity analyses revealed strong differences. In control participants, the spatial distribution of activity generalized significantly between task contexts (spatial/verbal) when examining the same function (attention/mentalizing) but not when comparing different functions. This pattern was disrupted in the ASD group, indicating abnormal functional specialization within mrPFC, and demonstrating the applicability of multi-voxel pattern analysis to investigations of atypical populations.

Psychosocial effects of harboring an untreated unruptured intracranial aneurysm.

OBJECTIVE: The primary purpose of the study was to investigate the psychosocial effects of harboring a known but untreated unruptured intracranial aneurysm (UIA), information considered important to the decision of whether to treat or not treat an unruptured aneurysm. METHODS: Over a 24-month period, 70 Auckland Hospital patients with UIAs were identified. Of these, 30 completed treatment, 2 patients died before treatment, and 38 were either not treated or treatment was unable to be completed during the time frame of the study. Of this group of 38 untreated UIA patients, 23 were enrolled in the study and were assessed on a brief cognitive screen and a battery of psychosocial measures. Their performance was compared with a group of 26 treated UIA patients. RESULTS: Poorer functioning was reported by the untreated UIA group on most psychosocial measures when compared with the treated UIA group 6 months posttreatment, and 36% of untreated UIA patients presented with a pattern of significant psychosocial impairment when compared with the treated UIA group. Qualitative data from the current study suggested that a factor contributing to the poorer reported psychosocial functioning in the untreated group was past or current fear about their untreated UIA. CONCLUSION: A decrease in overall quality of life was found to be associated with harboring an identified but untreated UIA. Findings from the current study suggest that further investigation of psychosocial outcome in other groups of untreated UIA patients is warranted. Results also suggest that some untreated UIA patients might benefit from psychological intervention.

Neurological, neuropsychological, and functional outcome following treatment for unruptured intracranial aneurysms.

The objective of this study was to carry out a detailed investigation of the neurological, neuropsychological, and return-to-work status of treatment for unruptured intracranial aneurysms (UIAs). A prospective design was used to evaluate the outcome of UIA treatment in a group of 26 UIA patients. Over a 24-month period UIA patients were assessed prior to treatment, during hospitalization, at three months and at six months following treatment. Their performance was compared to a group of 20 matched controls. Neurological morbidity as a result of the UIA treatment was 5%, as assessed by the Glasgow Outcome Scale (GOS) or Rankin at 3 months. The Telephone Interview for Cognitive Status (TICS) proved to be unreliable as a measure of cognitive change. Reliability of change analysis was more sensitive than group analysis, and revealed a pattern of cognitive deficits in 10% of patients as a result of the UIA treatment. In addition, 25% of patients reported a change in work role as a result of the UIA treatment. While 10% of patients sustained mild to moderate neurological and cognitive impairments 3 to 6 months following UIA treatment, their deficits were not as wide-ranging nor as severe as those sustained by patients who survive a subarachnoid hemorrhage (SAH).

Neurological, neuropsychological, and psychosocial outcome following treatment of unruptured intracranial aneurysms: a review and commentary.

Thirty studies published between 1977 and 2001 that focus on outcome following unruptured intracranial aneurysm (UIA) treatment are reviewed. Although findings from these studies suggest outcome from UIA treatment is reasonably good (between 5% and 25% morbidity and between 0-7% mortality), many of the complex issues associated with the treatment of UIAs remain controversial. Most of the studies reviewed address outcome in terms of mortality and neurological morbidity. Very few studies exist which include measures of outcome such as cognitive status, psychosocial functioning and quality of life. Given that patients facing treatment tend to be healthy middle-aged adults with many years of active working and social life ahead of them, it is important to take into account the long-term consequences of either harboring an UIA, or having it treated. The small number of studies that include cognitive, psychosocial and quality of life outcomes are reviewed in some detail and suggestions made for improving future UIA outcome research.