Objective
Nicotine is a highly addictive substance, and cigarette smoking is a major cause of premature death among humans. Little is known about the NeuroPharmacology and sites of action of Nicotine in the human Brain.

Such knowledge might help in the development of new behavioral and pharmacological therapies to aid in treating Nicotine dependence and to improve smoking cessation success rates.

Design
Functional Magnetic Resonance Imaging, a real-time imaging technique, was used to determine the acute CNS effects of IntraVenous Nicotine in 16 active cigarette smokers.

An injection of saline followed by injections of three doses of Nicotine (0.75, 1.50, and 2.25 mg/70 kg of weight) were each administered IntraVenously over 1-minute periods.

In an ascending, cumulative-dosing paradigm while whole Brain gradient-echo, echo-planar images were acquired every 6 seconds during consecutive 20-minute trials.

Results
Nicotine induced a dose-dependent increase in several behavioral parameters, including feelings of "rush" and "high" and drug liking.

Nicotine also induced a dose-dependent increase in Neuronal activity in a distributed system of Brain regions, including the Nucleus Accumbens, Amygdala, Cingulate, and Frontal Lobes.

Activation in these structures is consistent with Nicotine's behavior-arousing and behavior-reinforcing properties in humans.

Conclusions
The identified Brain regions have been previously shown to participate in the reinforcing, mood-elevating, and Cognitive properties of other abused drugs such as Cocaine, Amphetamine, and Opiates.

Suggesting that Nicotine acts similarly in the human Brain to produce its reinforcing and dependence properties.

Objective
This article examines the Cognitive and Psychiatric features of Multiple Sclerosis. MS can manifest as a NeuroPsychiatric disturbance even in the absence of physical disabilities.

Design
Two MS patients with predominant behavioral symptoms are described, and the literature is reviewed.

Results
The first patient had an InterHemispheric Disconnection Syndrome, and the second patient had Cognitive fatigue and Depression.

Other patients have Slowed Information Processing Speed, Memory Retrieval Difficulty, Frontal-Executive Dysfunction, and VisuoSpatial Difficulty.

Conclusions
MS results in specific Cognitive deficits and Mood Disorders.

These two patients had organic mental disorders from Cerebral DeMyelination particularly affecting the Corpus Callosum.

Our patients have NeuroPsychiatric symptoms from extensive DeMyelination of PreFrontal-SubCortical circuits. Evaluation and management strategies are discussed.

The authors examined whether specific NeuroPsychological abnormalities in Multiple Sclerosis (MS) are associated with focal lesion areas detected by MRI.

Lesion area, regardless of distribution, correlated with performance on the vast majority of NeuroPsychological procedures.

No significant difference appeared between groups with normal/mild and moderate overall Cognitive Impairment on any of the MRI measures.

However, patients with severe Cognitive Impairment had greater lesion area, regardless of location, and had significant atrophy of the Corpus Callosum compared with the other two groups.

These results suggest that severe atrophy of the Corpus Callosum reflects global disease and provides a relatively focal morphological marker of severe Cognitive Impairment in MS.

Forty one moderately impaired patients with clinically confirmed Multiple Sclerosis (MS) and a Relapsing/Remitting course were submitted to a NeuroPsychological battery and Magnetic Resonance Imaging (MRI) to correlate the NeuroPsychological performances with the degree of Cerebral DeMyelination.

The NeuroPsychological results were indicative of a very mild overall impairment. The patients were subdivided into two groups (extensive PeriVentricular DeMyelination or discrete lesions on MRI) and the results of NeuroPsychological tests compared.

Patients with extensive PeriVentricular DeMyelination had an inferior performance on Concept Formation, Non-Verbal Reasoning and Verbal Memory tests.

We evaluated the correlations between Cognitive Impairment, clinical and Brain Magnetic Resonance Imaging (MRI) findings in 100 patients with Multiple Sclerosis (MS).

The performance on one or more NeuroPsychological tests was abnormal in 47% of the 64 patients who completed the entire NeuroPsychological battery; the Cognitive Impairment was mild in 14 (22%) and severe in 16 (25%).

Performance on any single NeuroPsychological test was unrelated to clinical parameters (age, duration of the disease, disability).

The NeuroPsychological performance of Relapsing/Remitting patients was better than in patients with a Chronic/Progressive disease.

The mean scores for almost all the NeuroPsychological tests were significantly lower in patients with severe Ventricular dilatation and Corpus Callosum atrophy than in patients in whom these structures were little affected.

Mean scores for WMS, performance Intelligence Quotient (IQ), total IQ and Token Test (TT) were also significantly correlated with the widening of Cortical Sulci and total lesional scores.

Our data support the contention that the involvement of pathways that are critical for a given Cognitive process.

As well as the progression of the Axonal degeneration and Sclerosis seem to play important roles in the PathoPhysiology of Cognitive Dysfunction in MS.

The frequency of Cognitive deficits in Multiple Sclerosis (MS) patients is rather high and the estimates vary between 43% and 72% depending on the patient samples studied as well as on the methods of Cognitive assessment.

Despite the great impact of Cognitive dysfunction on several aspects of the quality of life, the importance of accurate assessment and rehabilitation of NeuroPsychological deficits in MS patients has long been ignored.

In this article, we first describe tests for the assessment of impairments, disabilities and handicaps.

We emphasize that after screening with brief assessment instruments, detailed testing of the basic target deficits is mandatory for the planning of special Cognitive training programs.

Second, the correlation of certain Cognitive deficit patterns with important Magnetic Resonance Imaging (MRI) variables such as total lesion area, size of the Corpus Callosum and specific lesion location is outlined in detail.

Third, some recommendations are made with regard to general rehabilitation principles such as restitution, compensation and adaptation as well as for special rehabilitation techniques including Cognitive retraining of basic deficits and/or training of activities of daily living.

Finally, we emphasize that there is a need for the development of tailor-made NeuroPsychological rehabilitation techniques for MS patients.

Which take into account the course and stage of the disease as well as the specific psychosocial problems of the individual patient.

Nineteen moderately impaired patients with clinically definite Multiple Sclerosis and an initially Relapsing/Remitting course were included in a NeuroPsychological and Magnetic Resonance Imaging (MRI) follow-up study.

The average test/re-test interval was about 2 years. The NeuroPsychological findings were indicative of a very mild overall impairment; the patients, as a group, showed no evidence of Cognitive deterioration in the follow-up period.

A numerical estimation of the severity of Cerebral DeMyelination shown by MRI did not indicate a significant change. No correlation between Cognitive performance variations and MRI changes was found.

Objective
To assess the correlation between Cognitive Dysfunction and disease burden in Multiple Sclerosis (MS) during a 1-year period.

Design
The Brief, Repeatable Battery of NeuroPsychological Tests in Multiple Sclerosis was performed at entrance and 1 year.

Patients underwent at least 20 Proton Density (range, 20-24) and T₂-weighted axial Magnetic Resonance Imaging (MRI) Brain scans except for stable patients who were scanned monthly.

Magnetic Resonance Imaging was evaluated using computer-automated, 3-dimensional volumetric analysis.

Setting & Participants
A research clinic of a university hospital. Forty-four patients with MS of the following disease categories:

1. Relapsing/Remitting (14)
2. Relapsing/Remitting/Progressive (12)
3. Chronic/Progressive (13)
4. Stable (5)

Main Outcome Measures
The relationships between scores on the Brief, Repeatable Battery of NeuroPsychological Tests in Multiple Sclerosis and 2 MRI measures (total lesion volume and Brain to IntraCranial cavity volume ratio) were assessed using linear regression.

These MRI measures were also compared with Cognitive status at 1 year using analysis of variance.

Results
Overall, there was no decline in mean Cognitive test performance during 1 year.

Significant correlations were found between baseline NeuroPsychological test scores of NonVerbal Memory, Information-Processing Speed, and Attention and both MRI measures.

Patients with Chronic/Progressive MS demonstrated the strongest correlations. At 1 year, change in information-processing speed and attention correlated with change in total lesion volume.

The mean increase in total lesion volume was 5.7 mL for 4 patients whose Cognitive status worsened compared with 0.4 mL for 19 patients who improved and 0.5 mL for 21 patients who remained stable.

Conclusions
During a 1-year period mean Cognitive performance did not worsen.

Automated volumetric MRI measures of total lesion volume and Brain to IntraCranial cavity volume ratio correlated with NeuroPsychological performance.

Especially in patients with Chronic/Progressive MS. Worsening MRI lesion burden correlated with Cognitive decline.

The relationship between Cognitive Impairment in Multiple Sclerosis and Brain lesions seen on Magnetic Resonance Imaging (MRI) was studied.

Three groups of 11 patients with Multiple Sclerosis, matched for the variables of disability, duration of illness, age and sex, were included.

On the basis of NeuroPsychological testing, the groups were seen to differ in their level of Cognitive Impairment.

The first group showed no Cognitive Impairment, the second group a moderate, and the third group a serious Cognitive Impairment.

These differences between the groups were reflected by MRI, which revealed more abnormalities in the groups with Cognitive Impairment compared with the group with normal Cognitive function.

However, by MRI it was not possible to distinguish between the groups with moderate and that with serious Cognitive Impairment.