Structural 'connectomic' alterations in the limbic system of multiple sclerosis patients with major depression.

Background: Major depression (MD) is a common psychiatric disorder in multiple sclerosis (MS). Despite the negative impact of MD on the quality of life of MS patients, little is known about its underlying brain mechanisms.

Objective: We studied the whole-brain connectivity patterns that were associated with MD in MS.

Hippocampal BOLD response during category learning predicts subsequent performance on transfer generalization.

To test a prediction of our previous computational model of cortico-hippocampal interaction (Gluck and Myers [1993, 2001]) for characterizing individual differences in category learning, we studied young healthy subjects using an fMRI-adapted category-learning task that has two phases, an initial phase in which associations are learned through trial-and-error feedback followed by a generalization phase in which previously learned rules can be applied to novel associations (Myers et al. [2003]). As expected by our model, we found a negative correlation between learning-related hippocampal responses and accuracy during transfer, demonstrating that hippocampal adaptation during learning is associated with better behavioral scores during transfer generalization.

Dysfunctions within limbic-motor networks in amyotrophic lateral sclerosis.

Previous studies have shown that affective symptoms are part of the clinical picture in amyotrophic lateral sclerosis (ALS), the most common motor neuron disorder in elderly people. Diffuse neurodegeneration of limbic regions (e.g.

Dopamine-transporter levels drive striatal responses to apomorphine in Parkinson's disease.

Dopaminergic therapy in Parkinson's disease (PD) can improve some cognitive functions while worsening others. These opposite effects might reflect different levels of residual dopamine in distinct parts of the striatum, although the underlying mechanisms remain poorly understood. We used functional magnetic resonance imaging (fMRI) to address how apomorphine, a potent dopamine agonist, influences brain activity associated with working memory in PD patients with variable levels of nigrostriatal degeneration, as assessed via dopamine-transporter (DAT) scan.

The BDNF Val66Met polymorphism has opposite effects on memory circuits of multiple sclerosis patients and controls.

Episodic memory deficits are frequent symptoms in Multiple Sclerosis and have been associated with dysfunctions of the hippocampus, a key region for learning. However, it is unclear whether genetic factors that influence neural plasticity modulate episodic memory in MS. We thus studied how the Brain Derived Neurotrophic Factor Val(66)Met genotype, a common polymorphism influencing the hippocampal function in healthy controls, impacted on brain networks underlying episodic memory in patients with Multiple Sclerosis.

Altered cortical-cerebellar circuits during verbal working memory in essential tremor.

Essential tremor is a common neurological disorder characterized by motor and cognitive symptoms including working memory deficits. Epidemiological research has shown that patients with essential tremor are at a higher risk to develop dementia relative to age-matched individuals; this demonstrates that cognitive impairments reflect specific, although poorly understood, disease mechanisms. Neurodegeneration of the cerebellum has been implicated in the pathophysiology of essential tremor itself; however, whether cerebellar dysfunctions relate to cognitive abnormalities is unclear.

The effects of BDNF Val66Met polymorphism on brain function in controls and patients with multiple sclerosis: an imaging genetic study.

Relatively little is known about genetic determinants of cognitive dysfunction in multiple sclerosis (MS). A growing body of evidence demonstrates that a functional variant of the brain-derived neurotrophic factor (BDNF) gene, the Val(66)Met polymorphism, contributes to poor hippocampal and prefrontal functions, particularly memory processes, in healthy controls. In contrast, findings from previous association studies examining this polymorphism and memory performance in MS patients yielded conflicting results.

Neurofunctional correlates of personality traits in relapsing-remitting multiple sclerosis: an fMRI study.

Extraversion and Neuroticism are two fundamental dimensions of human personality that influence cognitive functioning in healthy subjects. Little is known about personality changes that may occur in patients with multiple sclerosis (MS) nor about, in particular, their neurofunctional basis. The aim of this study is to determine the impact of personality characteristics on brain activity in patients with MS.

Neurobiological mechanisms underlying emotional processing in relapsing-remitting multiple sclerosis.

Affective disorders are frequent and disabling conditions in multiple sclerosis; however, the underlying neurobiological mechanisms are still poorly understood and investigated. Previous structural imaging studies have suggested that damage of frontal and temporal cortices plays an important role in the genesis of emotional disorders in multiple sclerosis, although psychosocial factors have been also implicated. However, this initial research may not have fully characterized the brain's functional dynamics of emotional processes in multiple sclerosis.

A longitudinal observation of brain-derived neurotrophic factor mRNA levels in patients with relapsing-remitting multiple sclerosis.

This report is part of a 2-year study assessing the functional effect of Brain-Derived Neurotrophic Factor (BDNF) and its Val66Met polymorphism on a selected population of Relapsing-Remitting Multiple Sclerosis (RRMS) patients from Southern Italy. For this purpose, we measured the peripheral BDNF expression in RRMS patients compared to healthy controls. The influence of concomitant IFNbeta therapy was also evaluated.

Ventro-lateral prefrontal activity during working memory is modulated by MAO A genetic variation.

Several lines of evidence have highlighted the role of the serotonergic system in working memory (WM) processes. The X-linked Mono-Amine Oxidase A (MAO A) gene, coding for an enzyme especially involved in the serotonin (5-HT) catabolism, presents a well-characterized functional polymorphism consisting in a variable number of tandem repeats (VNTR) in the promoter region with high activity and low activity variants. The high activity allele carriers have been associated with higher enzyme expression, lower amine concentration and altered prefrontal cortex (PFC) function during motor inhibition, but a direct effect of MAO A genotype on WM-related brain activity has not been demonstrated.

Genetically dependent modulation of serotonergic inactivation in the human prefrontal cortex.

Previous research suggests that genetic variations regulating serotonergic neurotransmission mediate individual differences in the neural network underlying impulsive and aggressive behaviour. Although with conflicting findings, the monoamine oxidase-A (MAOA) and the serotonin transporter (5HTT) gene polymorphisms have been associated with an increased risk to develop impulsive and aggressive behaviour. Double knock-out mice studies have also demonstrated that MAOA and 5HTT genes strongly interact in the metabolic pathway leading to the serotonergic inactivation; however, their potential interactive effect in human brain remains uninvestigated.

MR imaging index for differentiation of progressive supranuclear palsy from Parkinson disease and the Parkinson variant of multiple system atrophy.

Purpose: To prospectively assess sensitivity and specificity of magnetic resonance (MR) imaging measurements of midbrain, pons, middle cerebellar peduncles (MCPs), and superior cerebellar peduncles (SCPs) for differentiating progressive supranuclear palsy (PSP) from Parkinson disease (PD) and Parkinson variant of multiple system atrophy (MSA-P), with established consensus criteria as reference standard.

Materials And Methods: All study participants provided informed consent; study was approved by the institutional review board. Pons area, midbrain area, MCP width, and SCP width were measured in 33 consecutive patients with PSP (16 possible, 17 probable), 108 consecutive patients with PD, 19 consecutive patients with MSA-P, and 50 healthy control participants on T1-weighted MR images.

Impact of individual cognitive profile on visuo-motor reorganization in relapsing-remitting multiple sclerosis.

Background: In multiple sclerosis (MS), relationships between disease-related MRI changes, cognitive function and brain responses are complex and still unclear. This study addresses the relative effects of cognitive impairment and brain atrophy on the cortical reorganization associated with a visuo-motor task.

Methods: Multivariate analysis was applied to compare functional MRI brain responses of 28 relapsing-remitting (RR) MS patients (16 cognitively preserved and 12 cognitively impaired) to that of 35 matched healthy controls during the execution of visuo-motor integration task.

Dopaminergic modulation of cognitive interference after pharmacological washout in Parkinson's disease.

The dopaminergic modulation of prefrontal function in Parkinson's disease (PD) has been consistently demonstrated. There is evidence that the effects of pharmacological manipulations on cognitive performances are described by an "Inverted-U" shaped curve. Neuroimaging studies performed before and after an overnight withdrawal from therapy showed significant differences between drug states, but did not control for the relative impact of the long duration response to levodopa.

Apparent diffusion coefficient measurements of the middle cerebellar peduncle differentiate the Parkinson variant of MSA from Parkinson's disease and progressive supranuclear palsy.

Clinical differentiation of parkinsonian syndromes such as the Parkinson variant of multiple system atrophy (MSA-P) and progressive supranuclear palsy (PSP) from Parkinson's disease is difficult in the early stage of the disease. In order to identify objective markers for differential diagnosis, we studied these three groups of patients with diffusion-weighted MRI (DWI). Sixteen MSA-P patients, 16 with PSP, 16 with Parkinson's disease and 15 healthy volunteers were studied.

Adaptive cortical changes and the functional correlates of visuo-motor integration in relapsing-remitting multiple sclerosis.

Cortical reorganization has been demonstrated during performance of a motor task in patients with multiple sclerosis. Converging evidence suggests that changes in gray matter volume represent an early hallmark of the disease. We used functional MRI to investigate the role of cortical adaptive mechanisms in maintaining visuo-motor function in the face of structural damage.

MR imaging of middle cerebellar peduncle width: differentiation of multiple system atrophy from Parkinson disease.

Purpose: To prospectively assess if middle cerebellar peduncle (MCP) atrophy, evaluated at magnetic resonance (MR) imaging, can help differentiate multiple system atrophy (MSA) from Parkinson disease (PD).

Materials And Methods: All participants provided informed consent for participation in the study, which was approved by the institutional review board. Sixteen consecutive patients with MSA, 26 consecutive patients with PD, and 14 healthy control subjects were examined with MR imaging.

Neural mechanisms underlying probabilistic category learning in normal aging.

Probabilistic category learning engages neural circuitry that includes the prefrontal cortex and caudate nucleus, two regions that show prominent changes with normal aging. However, the specific contributions of these brain regions are uncertain, and the effects of normal aging have not been examined previously in probabilistic category learning. In the present study, using a blood oxygenation level-dependent functional magnetic resonance imaging block design, 18 healthy young adults (mean age, 25.

Neurophysiological correlates of age-related changes in working memory capacity.

Cognitive abilities such as working memory (WM) capacity decrease with age. To determine the neurophysiological correlates of age-related reduction in working memory capacity, we studied 10 young subjects (<35 years of age; mean age=29) and twelve older subjects (>55 years of age; mean age=59) with whole brain blood oxygenation-level dependent (BOLD) fMRI on a 1.5 T GE MR scanner using a SPIRAL FLASH pulse sequence (TE=24 ms, TR=56 ms, FA=60 degrees , voxel dimensions=3.

Monoamine oxidase-a genetic variations influence brain activity associated with inhibitory control: new insight into the neural correlates of impulsivity.

Background: Previous evidence has shown that genetic variations in the serotonergic system contribute to individual differences in personality traits germane to impulse control. The monoamine oxidase-A (MAO-A) gene, coding for an enzyme primarily involved in serotonin and noradrenaline catabolism, presents a well-characterized functional polymorphism consisting of a variable number of tandem repeats in the promoter region, with high-activity and low-activity variants. High-activity allele carriers have higher enzyme expression, lower amine concentration, and present higher scores on behavioral measures of impulsivity than low-activity allele carriers.

Functional changes in the activity of brain regions underlying emotion processing in the elderly.

Aging is associated with a decline in both cognitive and motor abilities that reflects deterioration of underlying brain circuitry. While age-related alterations have also been described in brain regions underlying emotional behavior (e.g.

Comparison of different MR venography techniques for detecting transverse sinus stenosis in idiopathic intracranial hypertension.

Cerebral venous outflow abnormalities, as transverse sinuses (TSs) stenosis,may underlie a picture of idiopathic intracranial hypertension (IIH). To identify the best non-invasive MR venography (MRV) technique for exploring the disturbance of flow of TSs in IIH patients, we compared three dimensional phase contrast (3-DPC) MRV images, acquired with different velocity encodings (15 and 40 cm/s) with two-dimensional time-of-flight (2D-TOF) MR images in 6 subjects with IIH and 12 age-matched normal controls. In both groups, we also measured flow velocity in TSs by using single slice 2D-CINE PC acquisitions.