How attentional boost interacts with reward: the effect of dopaminergic medications in Parkinson's disease

There is widespread evidence that dopamine is implicated in the regulation of reward and salience. However, it is less known how these processes interact with attention and recognition memory. To explore this question, we used the attentional boost test in patients with Parkinson's disease (PD) before and after the administration of dopaminergic medications. Participants performed a visual letter detection task (remembering rewarded target letters and ignoring distractor letters) while also viewing a series of photos of natural and urban scenes in the background of the letters. The aim of the game was to retrieve the target letter after each trial and to win as much virtual money as possible. The recognition of background scenes was not rewarded. We enrolled 26 drug‐naïve, newly diagnosed patients with PD and 25 healthy controls who were evaluated at baseline and follow‐up. Patients with PD received dopamine agonists (pramipexole, ropinirole, rotigotine) during the 12‐week follow‐up period. At baseline, we found intact attentional boost in patients with PD: they were able to recognize target‐associated scenes similarly to controls. At follow‐up, patients with PD outperformed controls for both target‐ and distractor‐associated scenes, but not when scenes were presented without letters. The alerting, orienting and executive components of attention were intact in PD. Enhanced attentional boost was replicated in a smaller group of patients with PD (n = 15) receiving l ‐3,4‐dihydroxyphenylalanine (L‐DOPA). These results suggest that dopaminergic medications facilitate attentional boost for background information regardless of whether the central task (letter detection) is rewarded or not.     

Malignant involvement of the spine: assessment by 18F-FDG PET/CT.

The purpose of the study was to assess the role of (18)F-FDG PET/CT in the assessment of secondary malignant involvement of the spinal column. METHODS: In 51 patients, 242 lesions at the spinal region detected on (18)F-FDG PET/CT were interpreted separately on PET, CT, and fused PET/CT images, including differentiation between benign and malignant lesions and the level in the vertebral column. CT evaluation also included the type of bony lesion (osteolytic, osteoblastic, or mixed) and accompanying soft-tissue abnormalities; for example, epidural masses and tumor involvement of the neural foramina. RESULTS: Of the 242 lesions detected on PET/CT, PET alone identified 220 lesions and CT alone identified 159; 217 (90%) were malignant and 25 benign. (18)F-FDG PET alone detected significantly more malignant lesions than did CT alone (96% vs. 68%, respectively, P < 0.001). The specificity was 56% for both PET alone and CT alone. PET alone was incorrect in determining the level of abnormality within the vertebral column in 33 (15%) lesions and in determining the part of the vertebra involved in 40 (18%) lesions. In 17 (33%) patients, either epidural extension of tumor (n = 7 lesions), neural foramen involvement of tumor (n = 7 lesions), or a combination of both (n = 11 lesions) was detected. On a patient-based analysis, the sensitivity of PET and of PET/CT for the detection of spinal metastasis was 98% and 74%, respectively (P < 0.01). CONCLUSION: (18)F-FDG PET/CT has better specificity for detection of malignant involvement of the spine than does (18)F-FDG PET. It allows for precise localization of lesions and identifies accompanying soft-tissue involvement, which is of potential neurologic significance.     

Long waiting period to enter methadone maintenance treatment: relation to patient characteristics and outcome

Methadone maintenance treatment is a chronic treatment for opiate addicts. After having reached full capacity, new admissions to our clinic were delayed (through a waiting list) for all but opiate addicts with HIV and pregnant women. We compared characteristics and outcomes between patients admitted without delay (1993-2002) and those admitted through a waiting list (2003-2009). All 704 patients admitted between June 1993 and June 2009 were followed up until June 2010. There were 470 patients in the early period and 234 in the late period (56 patients were admitted immediately and 178 after 1.1 ± 0.8 years of waiting). Predictors for 1-year retention in treatment (logistic regression model) were if a patient self-referred during the late period, on a waiting list. The waiting list patient group was characterized by older age and self-referral - two known independent predictors of better retention that were attributed to their superior retention rate.     

Syntactic and semantic modulation of neural activity during auditory sentence comprehension

In previous functional neuroimaging studies, left anterior temporal and temporal-parietal areas responded more strongly to sentences than to randomly ordered lists of words. The smaller response for word lists could be explained by either (1) less activation of syntactic processes due to the absence of syntactic structure in the random word lists or (2) less activation of semantic processes resulting from failure to combine the content words into a global meaning. To test these two explanations, we conducted a functional magnetic resonance imaging study in which word order and combinatorial word meaning were independently manipulated during auditory comprehension. Subjects heard six different stimuli: normal sentences, semantically incongruent sentences in which content words were randomly replaced with other content words, pseudoword sentences, and versions of these three sentence types in which word order was randomized to remove syntactic structure. Effects of syntactic structure (greater activation to sentences than to word lists) were observed in the left anterior superior temporal sulcus and left angular gyrus. Semantic effects (greater activation to semantically congruent stimuli than either incongruent or pseudoword stimuli) were seen in widespread, bilateral temporal lobe areas and the angular gyrus. Of the two regions that responded to syntactic structure, the angular gyrus showed a greater response to semantic structure, suggesting that reduced activation for word lists in this area is related to a disruption in semantic processing. The anterior temporal lobe, on the other hand, was relatively insensitive to manipulations of semantic structure, suggesting that syntactic information plays a greater role in driving activation in this area.     

Task alternation cost without task alternation: measuring intentionality

A behavioral dissociation between intention and action was demonstrated by patient AF who sustained damage to the left-hemisphere including the basal ganglia. The patient was tested in a task switching paradigm involving two choice reaction-time tasks: SIZE (small/large) and SHAPE (circle/square). The last block in each of the two sessions involved only one task. AF switched tasks reasonably well in the first 40 trials, but unlike her matched control group, in all the remaining trials when two tasks were involved, she performed only the SIZE task. Interestingly, although no task switching took place, AF continued to demonstrate behaviorally her intention to switch tasks. First, she exhibited "task alternation cost", poorer performance relative to instructed single-task trials. Second, shifting to an instructed single-task condition was accompanied by an initial response slowing, indicating a change in goal-state. Finally, when instructed to switch tasks, AF demonstrated the "task-congruency effect", indicating interference from the instructed but competing stimulus-response mapping. Two groups of university students were instructed to perform only the SIZE task, after initial switching, either while ignoring the SHAPE cues ("Ignore") or while being prepared for the SHAPE task only when the cue appeared in red, which never happened ("Attend color"). AF's performance resembled the one of the "Attend color" group and not the "Ignore" group. The results indicate that AF had a partially activated intention to switch tasks. The implications to intentionality and task switching theory are discussed.     

Isolation and Chimerization of a Highly Neutralizing Antibody Conferring Passive Protection against Lethal Bacillus anthracis Infection

Several studies have demonstrated that the passive transfer of protective antigen (PA)-neutralizing antibodies can protect animals against Bacillus anthracis infection. The standard protocol for the isolation of PA-neutralizing monoclonal antibodies is based upon a primary selection of the highest PA-binders by ELISA, and usually yields only few candidates antibodies. We demonstrated that by applying a PA-neutralization functionality-based screen as the primary criterion for positive clones, it was possible to isolate more than 100 PA-neutralizing antibodies, some of which exhibited no measurable anti-PA titers in ELISA. Among the large panel of neutralizing antibodies identified, mAb 29 demonstrated the most potent activity, and was therefore chimerized. The variable region genes of the mAb 29 were fused to human constant region genes, to form the chimeric 29 antibody (cAb 29). Guinea pigs were fully protected against infection by 40LD₅₀ B. anthracis spores following two separate administrations with 10 mg/kg of cAb 29: the first administration was given before the challenge, and a second dose was administered on day 4 following exposure. Moreover, animals that survived the challenge and developed endogenous PA-neutralizing antibodies with neutralizing titers above 100 were fully protected against repeat challenges with 40LD₅₀ of B. anthracis spores. The data presented here emphasize the importance of toxin neutralization-based screens for the efficient isolation of protective antibodies that were probably overlooked in the standard screening protocol. The protective activity of the chimeric cAb 29 demonstrated in this study suggest that it may serve as an effective immunotherapeutic agent against anthrax.