Phenotypic regional functional imaging patterns during memory encoding in mild cognitive impairment and Alzheimer's disease.

BACKGROUND: Reliable blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) phenotypic biomarkers of Alzheimer's disease (AD) or mild cognitive impairment (MCI) are likely to emerge only from a systematic, quantitative, and aggregate examination of the functional neuroimaging research literature. METHODS: A series of random-effects activation likelihood estimation (ALE) meta-analyses were conducted on studies of episodic memory encoding operations in AD and MCI samples relative to normal controls. ALE analyses were based on a thorough literature search for all task-based functional neuroimaging studies in AD and MCI published up to January 2010. Analyses covered 16 fMRI studies, which yielded 144 distinct foci for ALE meta-analysis. RESULTS: ALE results indicated several regional task-based BOLD consistencies in MCI and AD patients relative to normal control subjects across the aggregate BOLD functional neuroimaging research literature. Patients with AD and those at significant risk (MCI) showed statistically significant consistent activation differences during episodic memory encoding in the medial temporal lobe, specifically parahippocampal gyrus, as well superior frontal gyrus, precuneus, and cuneus, relative to normal control subjects. CONCLUSIONS: ALE consistencies broadly support the presence of frontal compensatory activity, medial temporal lobe activity alteration, and posterior midline "default mode" hyperactivation during episodic memory encoding attempts in the diseased or prospective predisease condition. Taken together, these robust commonalities may form the foundation for a task-based fMRI phenotype of memory encoding in AD.

Neuroanatomical correlates of malingered memory impairment: event-related fMRI of deception on a recognition memory task.

PRIMARY OBJECTIVE: Event-related, functional magnetic resonance imaging (fMRI) data were acquired in healthy participants during purposefully malingered and normal recognition memory performances to evaluate the neural substrates of feigned memory impairment. METHODS AND PROCEDURES: Pairwise, between-condition contrasts of neural activity associated with discrete recognition memory responses were conducted to isolate dissociable neural activity between normal and malingered responding while simultaneously controlling for shared stimulus familiarity and novelty effects. Response timing characteristics were also examined for any association with observed between-condition activity differences. OUTCOMES AND RESULTS: Malingered recognition memory errors, regardless of type, were associated with inferior parietal and superior temporal activity relative to normal performance, while feigned recognition target misses produced additional dorsomedial frontal activation and feigned foil false alarms activated bilateral ventrolateral frontal regions. Malingered response times were associated with activity in the dorsomedial frontal, temporal and inferior parietal regions. Normal memory responses were associated with greater inferior occipitotemporal and dorsomedial parietal activity, suggesting greater reliance upon visual/attentional networks for proper task performance. CONCLUSIONS: The neural substrates subserving feigned recognition memory deficits are influenced by response demand and error type, producing differential activation of cortical regions important to complex visual processing, executive control, response planning and working memory processes.

Neurocognitive functioning and HAART in HIV and hepatitis C virus co-infection.

OBJECTIVES: This study examined the effects of HAART on neurocognitive functioning in persons with hepatitis C virus (HCV) and HIV co-infection. DESIGN: A prospective study examining neurocognitive performance before and after HAART initiation. METHOD: Participant groups included a mono-infected group (45 HIV+/HCV- participants) and a co-infected group (20 HIV+/HCV+ participants). A neuropsychological battery (attention/concentration, psychomotor speed, executive functioning, verbal memory, visual memory, fine motor, and gross motor functioning) was used to evaluate all participants. After 6 months of HAART, 31 HIV+ mono-infected and 13 HCV+/HIV+ co-infected participants were reevaluated. RESULTS: Neurocognitive functioning by domain revealed significantly worse performance in the co-infected group when compared to the monoinfected group on domains of visual memory and fine motor functioning. Assessment of neurocognitive functioning after antiretroviral therapy revealed that the co-infected group was no longer performing worse than the monoinfected group. CONCLUSIONS: The findings of the current study suggest that persons with HCV+/HIV+ co-infection may have greater neurocognitive declines than persons with HIV infection alone. HCV+/HIV+ co-infection may accelerate the progression of HIV related neurocognitive decline.

Cue-induced brain activity changes and relapse in cocaine-dependent patients.

This study used functional magnetic resonance imaging (fMRI) to examine the association between brain activation during exposure to cocaine-related cues and relapse to drug use in cocaine-dependent (CD) patients. We imaged 17 CD subjects during a 2-week in-patient stay. The subjects then entered a 10-week outpatient placebo-controlled, double-blind randomized clinical trial where urine toxicologies were assessed three times weekly to calculate the treatment effectiveness score (TES). Worse TES correlated with BOLD activation in the left precentral, superior temporal, and posterior cingulate cortices (PCC), and right middle temporal and lingual cortices (R>0.65; P<0.005). The left PCC activation also distinguished eight nonrelapsers (TES above mean and completed treatment) from nine relapsers. Cocaine-free urines were significantly greater in the nonrelapsers (92%) than in the relapsers (66%), who also remained in treatment for an average of only 3.2 weeks. Self-reports of craving during fMRI did not differ between nonrelapsers and relapsers and did not correlate with TES. Relapse to cocaine abuse was associated with increased activation in the sensory association cortex, the motor cortex, and PCC while viewing images of cocaine-related cues. These results suggest that relapse to cocaine abuse is associated with increased brain activation to cocaine cues in sensory, motor, and cognitive-emotional processing areas. This physiological activation was a better predictor of relapse than subjective reports of craving, and may be a useful target for treatment development.

Perfusion abnormalities and decision making in cocaine dependence.

BACKGROUND: Previous studies have shown that cocaine abusers have cerebral perfusion deficits that may diminish cognitive functioning. This study examined whether cocaine-dependent patients have perfusion abnormalities associated with poor decision-making ability as measured by the Iowa Gambling Task (IGT). METHODS: Seventeen abstinent cocaine-dependent patients were administered the IGT after completion of resting 99mTc-HMPAO single-photon emission computed tomography (SPECT). RESULTS: Better IGT performance was negatively correlated with perfusion within the anterior cingulate gyrus, middle frontal gyrus, medial frontal gyrus, and superior frontal gyrus. The time to complete card selections was positively correlated with the severity of impairment. CONCLUSIONS: Resting hyperperfusion in brain regions previously implicated in decision making and response inhibition was associated with worse IGT scores. Impaired performance was related to a greater amount of time taken for card selections, suggesting that reduced ability was due to cognitive factors other than an impulsive response pattern.

Neuroimaging in human immunodeficiency virus infection.

Human immunodeficiency virus (HIV) is associated with central nervous system (CNS) changes that may affect cerebral blood flow (CBF), metabolism, structure, and diffusion. Each of the available neuroimaging techniques offers unique insight into the neural mechanisms underlying HIV, as well as a potential means of monitoring disease progression and treatment response. The purpose of the article is to provide a review of experimental studies evaluating changes related to HIV with imaging techniques, including single-photon emission computed tomography (SPECT), positron emission tomography (PET), volumetric magnetic resonance imaging (MRI), functional MRI (fMRI), magnetic resonance spectroscopy (MRS), diffusion tensor imaging (DTI), and perfusion MRI (pMRI).

Gender-specific vulnerability for rCBF abnormalities among cocaine abusers.

Fifty abstinent cocaine-dependent patients and 20 healthy controls were evaluated with 99mTc-HMPAO SPECT to examine gender differences in perfusion. Group contrasts with statistical parametric mapping revealed male and female patients exhibited not only different regions, but different types of perfusion abnormality, including decreased perfusion in the anterior cingulate/frontal regions among cocaine-dependent men, and increased perfusion in the posterior cingulate of cocaine-dependent women. The findings suggested that cocaine-dependent men have perfusion deficits previously associated with cocaine withdrawal and impaired response inhibition, whereas, cocaine-dependent women demonstrated perfusion abnormalities consistent with heightened stress responsivity and worse treatment outcome. The possibility of different neural mechanisms underlying relapse in men and women, and the implications for utilizing specialized treatments are discussed.

Examining the effect of cerebral perfusion abnormality magnitude on cognitive performance in recently abstinent chronic cocaine abusers.

BACKGROUND AND PURPOSE: Cerebral perfusion abnormalities and neuropsychological impairment are common sequelae of chronic cocaine abuse. While perfusion abnormalities have been shown to relate to cognitive deficits in this substance abuse population, the relationship between cognitive performance and the magnitude of perfusion abnormality has yet to be fully determined. METHODS: Thirty-seven abstinent cocaine abusers and 13 normal controls were administered resting 99m-Tc-HMPAO single photon emission computed tomography (SPECT) scans followed by a neuropsychological assessment battery tapping executive skills, attention, memory, and motor performance. Statistical parametric mapping (SPM99) techniques were used to analyze the SPECT data to detect significant regional perfusion abnormalities in the cocaine group relative to normal controls, and resulting abnormal SPECT counts were employed for comparison with the assessment measures to examine the relationship between cocaine-induced perfusion abnormalities and cognitive performance. RESULTS: SPECT data analysis revealed significant regional perfusion abnormalities in the cocaine abuse sample relative to controls and significant differences in neuropsychological functioning on measures of executive functioning, complex attention, memory, and manual dexterity. For chronic cocaine abusers, however, within-group comparisons of the magnitude of abnormal perfusion and neuropsychological performance were largely nonsignificant, with the exception of complex attention and motor speed. CONCLUSIONS: Perfusion abnormalities and neuropsychological impairments readily distinguished cocaine abusers from normal controls. However, when the magnitude of cocaine-induced perfusion abnormalities is examined in relation to cognitive performance, motor speed and complex attention appear to be the best behaviorial indicants of the severity of perfusion dysfunction within this substance abuse population.

Computer-related anxiety: examining the impact of technology-specific affect on the performance of a computerized neuropsychological assessment measure.

This study was conducted to examine the effect of impairment status and computer-specific anxiety on the performance of a computerized neuropsychological assessment measure. Computer related anxiety was measured using a standardized self-report measure tapping anxiety specific to computers and technology. Outcome on this measure was compared with error scores and response timing variables on a computerized version of the Category Test (CT) in both normal individuals and individuals with neurological, psychiatric, or substance abuse histories. Multivariate analysis results, controlling for psychomotor performance, revealed significant main effects for group status and computer-related anxiety. CT performance was significantly related to the level of computer-related anxiety, in that high anxiety resulted in higher CT error scores and longer response times, and the negative impact of computer-related anxiety on computerized neuropsychological assessment performance was stronger in individuals with impairment histories. Our results suggest that as computer-related anxiety increases, performance on computer administered neuropsychological assessment measures tends to decrease. Key words: computers, anxiety, computer-based task performance, clinical neuropsychology, Category Test