Manes F, Ruiz Villamil A, Ameriso S, Roca M, Torralva T.  Real life Executive Deficits in Patients with Focal Vascular Lesions Affecting the Cerebellum. Journal of Neurological Sciences 2009 10.1186/1744-9081-9-47

Real life Executive Deficits in Patients with Focal Vascular Lesions Affecting the Cerebellum. Autores Manes F, Ruiz Villamil A, Ameriso S, Roca M, Torralva T.  Año 2009 Journal  Manes F, Ruiz Villamil A, Ameriso S, Roca M, Torralva T.  Volumen 283(1-2): 95-98 Abstract   Otra información    

Gleichgerrcht E, Ibanez A, Roca M, Torralva T, Manes F.  Decision-making cognition in neurodegenerative diseases. Nature Reviews Neurology 2010

A large proportion of human social neuroscience research has focused on the issue of decision-making. Impaired decision-making is a symptomatic feature of a number of neurodegenerative diseases, but the nature of these decision-making deficits depends on the particular disease. Thus, examining the qualitative differences in decision-making impairments associated with different neurodegenerative diseases could provide valuable information regarding the underlying neural basis of decision-making. Nevertheless, few comparative reports of decision-making across patient groups exist. In this Review, we examine the neuroanatomical substrates of decision-making in relation to the neuropathological changes that occur in Alzheimer disease, frontotemporal dementia, Parkinson disease and Huntington disease. We then examine the main findings from studies of decision-making in these neurodegenerative diseases. Finally, we suggest a number of recommendations that future studies could adopt to aid our understanding of decision-making cognition.

Manes F, Torralva T, Roca M, Gleichgerrcht E, Bekinschtein T, Hodges J R.  Frontotemporal dementia presenting as pathological gambling. Nature Reviews Neurology 2010

BACKGROUND: A 69 year-old woman presented to an interdisciplinary medical group with pathological gambling, and went on to develop disinhibition, loss of empathy, and perseverative, stereotyped and ritualistic behavior. An initial neuropsychological evaluation showed selective impairment on the Iowa Gambling Task similar to that of patients with behavioral variant frontotemporal dementia, despite normal performance on standard neuropsychological tasks. MRI scans showed frontal lobe atrophy, which was consistent with findings on hexamethylpropyleneamine oxime single photon emission CT (HMPAO-SPECT). INVESTIGATIONS: Physical examination, neuropsychiatric and neuropsychological assessments, MRI brain scan, HMPAO-SPECT. DIAGNOSIS: Behavioral variant frontotemporal dementia. MANAGEMENT: Pharmacological treatment with the selective serotonin reuptake inhibitor paroxetine for impulsive behavior and carbamazepine to stabilize mood. The patient and her family also received counseling to advise on behavioral and legal issues.

Popat RA, VanDenEeden S, Tanner CM, Kushida CA, Rama AN, Black JE, Bernstein A, Kasten M, Chade AR, Leimpeter A,Cassidy J, McGuire V, Nelson LM.  Reliability and validity of two self-administered questionnaires for screening restless legs syndrome in population-based studies. Sleep Medicine 2010 10.3389/fnagi.2013.00080

BACKGROUND: A reliable and valid questionnaire for screening restless legs syndrome (RLS) is essential for determining accurate estimates of disease frequency. In a 2002 NIH-sponsored workshop, experts suggested three mandatory questions for identifying RLS in epidemiologic studies. We evaluated the reliability and validity of this RLS-NIH questionnaire in a community-based sample and concurrently developed and evaluated the utility of an expanded screening questionnaire, the RLS-EXP. METHODS: The study was conducted at Kaiser Permanente of Northern California and the Stanford University Sleep Clinic. We evaluated test-retest reliability in a random sample of subjects with prior physician-assigned RLS (n=87), subjects with conditions frequently misclassified as RLS (n=31), and healthy subjects (n=9). Validity of both instruments was evaluated in a random sample of 32 subjects, and in-person examination by two RLS specialists was used as the gold standard. RESULTS: For the first three RLS-NIH questions, the kappa statistic for test-retest reliability ranged from 0.5 to 1.0, and sensitivity and specificity was 86% and 45%, respectively. For the subset of five questions on RLS-EXP that encompassed cardinal features for diagnosing RLS, kappas were 0.4-0.8, and sensitivity and specificity were 81% and 73%, respectively. CONCLUSIONS: Sensitivity of RLS-NIH is good; however, the specificity of the instrument is poor when examined in a sample that over-represents subjects with conditions that are commonly misclassified as RLS. Specificity can be improved by including separate questions on cardinal features, as used in the RLS-EXP, and by including a few questions that identify RLS mimics, thereby reducing false positives.

Kasar M, Gleichgerrcht E, Keskinkilic C, Tabo A, Manes F.  Decision-making in people who relapsed to driving under the influence of alcohol. Alcoholism: Clinical and Experimental Research 2010

BACKGROUND: Alcohol use has been previously associated with neurocognitive impairments, especially in decision-making cognition. However, some studies have shown little to no decision-making deficits in relation to different characteristics of people with drinking problems. Relapsing to driving under the influence (DUI) of alcohol is an important issue with legal and psychosocial aspects. We evaluated decision-making performance in second-time DUI offenders by using the Iowa Gambling Task (IGT). METHOD: Thirty-four male second-time DUI offenders who had been selected for an official psychoeducational rehabilitation program and 31 healthy controls that were matched for age, education, and alcohol use were included. Along with psychiatric assessment, we applied conventional neuropsychological testing comprising cognitive set-shifting, response inhibition, attention, and visuospatial abilities. Also, we used the Temperament and Character Inventory (TCI) to assess personality patterns. A computerized version of IGT was used. RESULTS: No significant differences were found between the groups in regard to sociodemographics and conventional neuropsychological testing. DUI participants had significantly higher scores only in «self-transcendence » subdomain of TCI. On the fifth block of the IGT, DUI participants had significantly lower net scores than controls (U = 380.0, p < 0.05). Also, DUI participants chose significantly more risky decks compared to controls. CONCLUSIONS: Our results suggest that there may be subtle decision-making deficits in DUI participants, which goes undetected on conventional neuropsychological testing and which is not correlated with TCI subdomains related with impulsivity patterns.

Martino D, Strejilevich S, Torralva T, Manes F.  Decision making in euthymic bipolar I and bipolar II disorders. Psychological Medicine 2010

BACKGROUND: The main aim of this study was to compare a large population of patients with bipolar disorder (BD) types I and II strictly defined as euthymic with healthy controls on measures of decision making. An additional aim was to compare performance on a decision-making task between patients with and without a history of suicide attempt.MethodEighty-five euthymic patients with BD-I or BD-II and 34 healthy controls were included. All subjects completed tests to assess verbal memory, attention and executive functions, and a decision-making paradigm (the Iowa Gambling Task, IGT). RESULTS: Both groups of patients had worse performance than healthy controls on measures of verbal memory, attention and executive function. No significant differences were found between BD-I, BD-II and healthy controls on measures of decision making. By contrast, patients with a history of suicide attempt had lower performance in the IGT than patients without a history of suicide attempt. CONCLUSIONS: Patients with euthymic BD-I and BD-II had intact decision-making abilities, suggesting that this does not represent a reliable trait marker of the disorder. In addition, our results provide further evidence of an association between impairments in decision making and vulnerability to suicidal behavior.

Roca M, Torralva T, Gleichgerrcht E, Chade AR, Gómez Arévalo G, Gershanik O, Manes F.  Impairments in social cognition in early medicated and unmedicated Parkinson disease. Cognitive and Behavioral Neurology 2010

BACKGROUND: Theory of mind (ToM) refers to the ability to infer others’ mental states, including intentions and feelings, and is considered to be a critical part of social cognition. Earlier studies in individuals with Parkinson disease (PD) have shown ToM deficits in the more advanced stages of the disease. There is currently no evidence of social cognition deficits in patients in the early stages of PD. METHODS: In this study, we compared patients with early PD (n=36) and a control group of healthy subjects (n=36). Patients were assessed with 2 ToM tasks designed to differentially detect subtle deficits in the affective and cognitive aspects of ToM. Patients were also assessed with a complete neuropsychologic battery which included classic executive tests aimed at investigating the relationship between ToM and executive functions. Performance of medicated (n=16) and unmedicated (n=20) patients was also compared. RESULTS: Our results are the first to indicate that ToM is affected in the early stages of PD. As has already been reported in more advanced stages of PD, such deficits seem to be related to the cognitive aspects of this domain. In our study, these deficits were not related with performance on executive functioning, depression, or medication usage. CONCLUSIONS: These results provide evidence for ToM impairments early in the course of PD. Recognition of ToM impairments in early PD is important, as these deficits may impact patients’ social interactions and quality of life.

Aravena P, Hurtado E, Riveros R, Cardona JF, Manes F, Ibanez A. Applauding with closed hands: Neural signature of action sentence compatibility effects. PloS One 2010

Behavioral studies have provided evidence for an action-sentence compatibility effect (ACE) that suggests a coupling of motor mechanisms and action-sentence comprehension. When both processes are concurrent, the action sentence primes the actual movement, and simultaneously, the action affects comprehension. The aim of the present study was to investigate brain markers of bidirectional impact of language comprehension and motor processes. METHODOLOGY/PRINCIPAL FINDINGS: Participants listened to sentences describing an action that involved an open hand, a closed hand, or no manual action. Each participant was asked to press a button to indicate his/her understanding of the sentence. Each participant was assigned a hand-shape, either closed or open, which had to be used to activate the button. There were two groups (depending on the assigned hand-shape) and three categories (compatible, incompatible and neutral) defined according to the compatibility between the response and the sentence. ACEs were found in both groups. Brain markers of semantic processing exhibited an N400-like component around the Cz electrode position. This component distinguishes between compatible and incompatible, with a greater negative deflection for incompatible. Motor response elicited a motor potential (MP) and a re-afferent potential (RAP), which are both enhanced in the compatible condition. CONCLUSIONS/SIGNIFICANCE: The present findings provide the first ACE cortical measurements of semantic processing and the motor response. N400-like effects suggest that incompatibility with motor processes interferes in sentence comprehension in a semantic fashion. Modulation of motor potentials (MP and RAP) revealed a multimodal semantic facilitation of the motor response. Both results provide neural evidence of an action-sentence bidirectional relationship. Our results suggest that ACE is not an epiphenomenal post-sentence comprehension process. In contrast, motor-language integration occurring during the verb onset supports a genuine and ongoing brain motor-language interaction.

Torralva T, Gleichgerrcht E, Torrente F, Roca M, Strejilevich S, Cetkovich M, Lischinsky A, Manes F. Neuropsychological functioning in adult bipolar disorder and ADHD patients: a comparative study. Psychiatry Research 2010

Bipolar disorder (BD) and adult attention deficit hyperactivity disorder (ADHD) usually manifest with shared clinical symptoms, proving quite challenging to thoroughly differentiate one from another. Previous research has characterized these two disorders independently, but no study compared both pathologies from a neuropsychological perspective. The aim of this study was to compare the neuropsychological profile of adult ADHD and BD with each other and against a control group, in order to understand the way in which comprehensive cognitive assessment can contribute to their discrimination as distinct clinical entities as well as their differential diagnosis. All groups were successfully matched for age, sex, years of education, and premorbid IQ. Participants were assessed with an extensive neuropsychological battery evaluating multiple domains. Compared to controls, BD patients had a poorer performance on immediate verbal memory tasks. Both clinical groups exhibited significantly lower scores than controls on the recognition phase of verbal and non-verbal memory tasks, as well as on a task of executive functioning with high working memory demand. Noticeably, however, ADHD had significantly better performance than BD on the recognition phase of both the Rey list memory task and the Rey Figure. The better performance of ADHD patients over BD may reflect the crucial role of the executive component on their memory deficits and gives empirical support to further differentiate the neuropsychological profile of BD and adult ADHD patients in clinical practice.

San Martin R, Manes F, Hurtado E, Isla P, Ibanez A.  Size and probability of rewards modulate the feedback error-related negativity associated with wins but not losses in a monetarily rewarded gambling task. NeuroImage 2010

Feedback error-related negativity (fERN) has been referred to as a negative deflection in the event related potential (ERP), which distinguishes between wins and losses in terms of expected and unexpected outcomes. Some studies refer to the «expected outcome » as the probability to win vs. to lose, and others as expected size of rewards. We still do not know much about whether these alternative interpretations of «expected outcome » affect the fERN in a different manner, nor do we know the effect of their interaction in an expected value fashion. We set a gambling task with four game categories; two had the same expected value, while the other two categories were equivalent to the first ones, but alternatively in the size or probability of the offered rewards. Results show that fERN preceded by a P200, and followed by a Pe-like wave differentiates between losing in the category with a higher expected value and the rest of the experimental conditions. fERN differentiates between wins and losses, but changes in the size and probability of rewards impact the fERN amplitude only in win conditions. Results also show greater positivity following win feedback when the size and/or probability of the outcome rewards were higher, so that the higher the expected value the greater the positivity following win feedback. Our findings support the notion that both the probability and size of the offered rewards modulate the motivational value for the win feedback, this being also true for their interaction in an expected value fashion.