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Abstract: Neurocognitive impairment is a well-documented consequence of methamphetamine addiction. Not surprising, methamphetamine-associated neurocognitive impairment has been identified as an important target of treatment. Thus, this study sought to determine whether rivastigmine, an acetylcholinesterase inhibitor and cognition enhancing agent, could improve neurocognitive performance in a sample of long-term, high-dose methamphetamine addicts who were not seeking treatment at the time of enrollment in the study. This double-blind, placebo-controlled study evaluated whether a daily dose 0, 3, or 6mg of rivastigmine, administered over six consecutive days, would enhance performance on measures of attention/information processing speed, episodic memory, and executive/frontal lobe functioning relative to test performance at baseline. The results revealed that rivastigmine did not alter neurocognition in this cohort. There are a number of factors that may have mitigated the effects of rivastigmine in this particular study, including especially the short-term, low-dose treatment regimen utilized. The negative findings notwithstanding, the study serves as a springboard for future investigations that will examine whether other medications can alter neurocognition in methamphetamine dependent study participants. [Copyright &y& Elsevier]

In addition to motor symptomatology, idiopathic Parkinson's disease is characterized by emotional dysfunction. Depression affects some 30 to 40 percent of Parkinson patients and other psychiatric co-morbidities include anxiety and apathy. Neuropsychological and neuroimaging studies of emotional dysfunction in Parkinson patients suggest abnormalities involving mesolimbic and mesocortical dopaminergic pathways. There is also evidence suggesting that the interaction between serotonin and dopamine systems is important in the understanding and treatment of mood disorders in Parkinson's disease. In this review we discuss the neuropsychiatric abnormalities that accompany Parkinson's disease and describe their neuropsychological, neuropharmacologic, and neuroimaging concomitants. [ABSTRACT FROM AUTHOR]

Background: We previously published findings from our clinical trial comparing treatment outcomes for substance-dependent veterans with co-occurring depression who received Integrated Cognitive Behavioral Therapy (ICBT) or Twelve-Step Facilitation (TSF) Therapy. Objectives: This study is a secondary analysis that examined whether neuropsychological functioning at baseline moderated substance use and depression outcomes in ICBT relative to TSF. Methods: This study was a randomized clinical trial in which 164 veterans with major depressive disorder and comorbid alcohol, cannabinol, and//or stimulant dependence were randomly assigned to either ICBT or TSF group therapy. A comprehensive neuropsychological test battery was administered at baseline. Results: Contrary to our hypothesis, participants with poor neuropsychological functioning had better substance use outcome in ICBT than in TSF, whereas participants with good neuropsychological functioning had comparable substance use outcomes in TSF and ICBT by 18-month follow-up. Depression outcomes, in contrast, were not moderated by neuropsychological functioning by 18-month follow-up. Conclusions and Scientific Significance: The substance use outcomes may suggest that substance-dependent depressed adults with poorer neuropsychological functioning should be offered ICBT over TSF. These individuals may be less able to develop and use novel coping skills for managing substance use and depressive symptoms on their own without formal structured training in cognitive and behavioral skills provided in ICBT. [ABSTRACT FROM AUTHOR]

The aim of the study was to examine the relationship between neuropsychological impairment in severe alcohol dependence and relapse. This was assessed following inpatient detoxification over a period of three months. Participants were tested on measures of neuropsychological functioning at the end of a seven to ten day stay in an inpatient alcohol detoxification unit. Participants were followed up three months later by telephone to ascertain the number of days in which alcohol was consumed during this period using the Timeline Follow Back procedure (TLFB). A correlation and regression design was used to analyse results. An inpatient alcohol detoxification unit. Thirty-four residents in an inpatient alcohol detoxification unit. Executive dysfunction during detoxification was found to predict number of days drinking in the three months following discharge. Neuropsychological impairment, and specifically executive dysfunction, appears to be a significant barrier to ability to remain abstinent from alcohol following a period of detoxification. Given the high rates of relapse found within the current study it suggests that the cognitive domains that executive functioning describe are particularly relevant in facilitating abstinence in alcohol dependence. [ABSTRACT FROM AUTHOR]

Executive Clock Drawing Tasks (CLOX parts 1 and 2) can predict functional impairment. This study determined the correlation between CLOX and other psychometric screening instruments with the Structured Assessment of Independent Living Skills (SAILS)-defined performance-based functional status in people with combat-related mild traumatic brain injury (TBI) and comorbid posttraumatic stress disorder (PTSD). We hypothesized that CLOX would correlate significantly with functional performance. This prospective, cross-sectional study design determined the correlation between a structured neuropsychological battery and functional status assessment. We calculated Pearson correlation coefficients between neuropsychological instruments and functional status scores. We entered neuropsychological measures correlating p <0.1 with functional status into a linear regression model to determine independent contributions. Fifteen Operation Iraqi Freedom veterans participated. Only CLOX1 correlated significantly with functional competency and efficiency. Only mean CLOX1 scores were significantly lower in those scoring below the median for SAILS competency and in those scoring above the median for SAILS efficiency. CLOX1 contributed significant variance to functional status independent of mood or anxiety symptoms and was not affected by age or time since injury. Executive dysfunction per the brief, easily administered CLOX1 is sensitive to functional status following combat-related mild TBI, independent of PTSD anxiety with or without depression. [ABSTRACT FROM AUTHOR]

Objectives: The paper summarizes neuropsychological monitoring of employees exposed to TCDD during mass industrial intoxication in years 1965 - 1968 in an herbicides producing factory. Sample and methods: About 350 persons were exposed, the signs of poisoning expressed themselves in about 80 workers. 13 men in the years 1996 and 2001, 14 men in 2004, and 10 men in 2008 were examined. 1. Basic cognitive performance (WAIS-R), 2. Memory, attention, executive functions (WMS, HRNB, WCST, and others), 3. Self-assessment of examined persons, and 4.Symptom validity (TOMM, Retest Consistency Index - RCI and the performance pattern in Digit span and Vocabulary subtests) were evaluated. Statistical analysis: Methods of descriptive statistics and Spearman's rank correlation were used. Results: Even forty years after the intoxication, the level of TCDD in fat was still 100 times higher in the group of examined men than in the general population. During the whole period of monitoring, there was the evidence of neuropsychological impairment, first of all in the executive functions, in the examined group. Significant correlations of TCDD levels and neuropsychological achievements were found. Study limitation: The small scope of the sample limits the possibility of the generalization of results. Nevertheless, the results are in correspondence with a number of quoted publications. [ABSTRACT FROM AUTHOR]

Neuropsychological (NP) impairment is multiply determined among HIV-infected and HIV-uninfected individuals who are also dually diagnosed with depression and who use illicit substances. The purpose of the present study was to assess the impact of HIV status, depression, and problematic substance use on NP performance. A total of 160 opiate-dependent outpatients undergoing methadone maintenance (80 HIV-infected, 80 HIV-uninfected) completed diagnostic and NP evaluations. Raw scores from individual NP tests were converted to Z scores relative to standard norms and were averaged to form a composite score. HIV-infected participants had significantly lower overall NP performance—as well as lower performance on tests of attention, motor speed, and verbal memory—than HIV-uninfected participants. In multiple regression analyses considering the role of depression and substance use, only HIV status emerged as a significant predictor of NP impairment. These findings confirm NP impairment in HIV-infected substance abusing patients independent of comorbid depression and severity of substance use. [ABSTRACT FROM AUTHOR]

Patients exposed at home to molds and mycotoxins and those exposed to chemicals (CE) have many similar symptoms of eye, nose, and throat irritation and poor memory, concentration, and other neuro-behavioral dysfunctions. To compare the neuro-behavioral and pulmonary impairments associated with indoor exposures to mold and to chemicals. 105 consecutive adults exposed to molds (ME) indoors at home and 100 patients exposed to other chemicals were compared to 202 community referents without mold or chemical exposure. To assess brain functions, we measured 26 neuro-behavioral functions. Medical and exposure histories, mood states score, and symptoms frequencies were obtained. Vital capacity and flows were measured by spirometry. Groups were compared by analysis of variance (ANOVA) after adjusting for age, educational attainment, and sex, by calculating predicted values (observed/predicted x 100 = % predicted). And p < .05 indicated statistical significance for total abnormalities, and test scores that were outside the confidence limits of the mean of the percentage predicted. People exposed to mold had a total of 6.1 abnormalities and those exposed to chemicals had 7.1 compared to 1.2 abnormalities in referents. Compared to referents, the exposed groups had balance decreased, longer reaction times, and blink reflex latentcies lengthened. Also, color discrimination errors were increased and visual field performances and grip strengths were reduced. The cognitive and memory performance measures were abnormal in both exposed groups. Culture Fair scores, digit symbol substitution, immediate and delayed verbal recall, picture completion, and information were reduced. Times for peg-placement and trail making A and B were increased. One difference was that chemically exposed patients had excess fingertip number-writing errors, but the mold-exposed did not. Mood State scores and symptom frequencies were greater in both exposed groups than in referents. Vital capacities were reduced in both groups. Neuro-behavioral and pulmonary impairments associated with exposures to indoor molds and mycotoxins were not different from those with various chemical exposures. [ABSTRACT FROM AUTHOR]

Cocaine use is becoming an alarming health problem in developed countries. This issue has important economic, social and public health implications. Currently, efforts are focused on research in metabolic, neuropsychological and emotional changes resulting from chronic use. However, theoretical and critical reviews in this area are not available. The aim of our study is to review and integrate the latest findings and results regarding metabolic, neuropsychological and emotional abnormalities related to cocaine abuse. The results show a significant impairment of dopaminergic pathways in the frontal lobe, both in the number of receptors and depletion of the neurotransmitter, as well as an important executive function deficit in response inhibition, in attention and in working memory. In addition, alterations in the ability to identify emotions, impulsiveness, decision-making, anxiety and depression are shown in different studies. [ABSTRACT FROM AUTHOR]

The paper informs about the battery and its development, including recent projects of screening batteries (Horwitz et al., 2008; Vanderlice-Barr et al., 2008). It sums up the discussions about psychometric features of HRNB, about relation of fixed and flexible batteries, and quite flexible test selection, about rightfulness of court expert examinations in the USA. According to the author, the objections of some critics that the HRNB battery is outclassed by the development do not stand. HRNB is being developed due to numerous studies, the norms and interpretations are precised, new procedures originate in its framework. The sample consisting of more than 520 persons was examined by the Czech translation of the method, with useful application among others in schizophrenia (comparison of ill and their healthy twins, relation of neuropsychological tests to monitoring eye-movements and to density of white cortex), in epilepsy (pharmacotherapy and compensation), and in persons with chronic intoxication by toxic substances (toluene, mercury, dioxin). [ABSTRACT FROM AUTHOR]

Male players from football and rugby clubs and sportsmen from a variety of noncontact sports clubs at a UK university were compared on biographical and neuropsychological test measures. A data analysis paradigm was developed and employed to control the inflation of Type 1 error rate due to multiple hypotheses testing. Rugby players sustained most head injuries in their chosen sport, but neuropsychological tests of attention, memory, and executive function provided no evidence of performance impairment attributable to the number of head injuries sustained or the football, rugby, or noncontact sport groups. Footballers' heading frequency was related to the number of football head injuries sustained, but no relationship was detected between footballers' heading frequency and their neuropsychological test performance. Following discussion of pertinent methodological limitations it is concluded that there was no evidence in this dataset of neuropsychological impairment consistent with either mild head injury incidence or football heading frequency. However, a need for further research examining the long-term neuropsychological consequences of such head injuries was identified. [ABSTRACT FROM AUTHOR]

Aims: Evidence suggests a relationship between peripheral Aβ and AD. We hypothesized that higher levels of serum Aβ1-42 would be associated with memory impairment, thought to occur early in the disease, and rises in serum Aβ1-40, which occur later, would be associated with impairment in non-memory measures. Methods: Using a cross-sectional design, we examined the relationship of serum Aβ1-40, Aβ1-42, and the ratio of Aβ1-42/1-40 to neuropsychological measures in 40 cognitively normal controls, 13 MCI subjects, and 25 AD patients. Results: Serum Aβ1-42 and the ratio of Aβ1-42/1-40 were significantly higher in the MCI group compared to the controls. A significant relationship in the hypothesized direction (poorer scores associated with higher Aβ1-40 serum levels) was found between Aβ1-40 and measures of executive functions across the entire cohort of individuals tested and with measures of language and processing speed in the AD group. Regression analysis found that neuropsychological measures accounted for 26% of the variance in serum Aβ1-40, in the MCI/AD but not the controls. Furthermore that language and executive measures were significant predictors. Conclusions: Results provide preliminary data to partially support our hypotheses and suggest that changes in serum Aβ levels may be attributed to pathological changes within the brain. [ABSTRACT FROM AUTHOR]

Children with very low birth weight (VLBW, <1500 g) or very preterm birth (VPTB, <32 weeks gestational age or GA) have more mathematics disabilities or deficiencies (MD) and higher rates of mathematics learning disabilities (MLD) than normal birth weight term-born children (NBW, >2500 g and >36 weeks GA). MD are found even in children without global disorders in cognition or neurosensory status and when IQ is controlled, and they are associated with other learning problems and weaknesses in perceptual motor abilities and executive function. Factors related to poorer mathematics outcomes include lower birth weight and GA, neonatal complications, and possible abnormalities in brain structure. While little is known about the nature of MD in these children, studies of MLD in other neurodevelopmental disorders and in children with learning disabilities provide useful models for further investigation. Further investigation of the neuropsychological and neuropathological correlates of distinct types of mathematics difficulties is also needed. Studies along these lines will yield information about the unique features of MD in children with VLBW/VPTB and about the nature and origins of poor mathematics achievement more generally. © 2009 Wiley-Liss, Inc. Dev Disabil Res Rev 2009;15:52–59. [ABSTRACT FROM AUTHOR]

The present investigation examined neurocognitive functioning, focusing on executive functioning (EF), in 39 children and adolescents with Major Depressive Disorder (MDD) and 24 healthy control subjects all ages 8 to 17 years. The Wechsler Intelligence Scale for Children-Third Edition along with several measures of executive functioning including the Wisconsin Card Sorting Task, Trail Making Test, Controlled Oral Word Association Test, and the Stroop Color Word Test were administered. The neurocognitive profiles for the group of depressed children and adolescents were grossly intact as most scores on intellectual and EF measures fell within the average range and did not differ from the comparison group. Mental processing speed was decreased in the MDD versus normal control group and 27% of the depressed group performed below average on the Trail Making Test. This investigation provided a good base from which to compare future literature on EF in outpatients with early-onset MDD. [ABSTRACT FROM AUTHOR]

A significant proportion of children diagnosed with Autistic Spectrum Disorder experience a developmental regression characterized by a loss of previously-acquired skills. This may involve a loss of speech or social responsitivity, but often entails both. This paper critically reviews the phenomena of regression in autistic spectrum disorders, highlighting the characteristics of regression, age of onset, temporal course, and long-term outcome. Important considerations for diagnosis are discussed and multiple etiological factors currently hypothesized to underlie the phenomenon are reviewed. It is argued that regressive autistic spectrum disorders can be conceptualized on a spectrum with other regressive disorders that may share common pathophysiological features. The implications of this viewpoint are discussed. [ABSTRACT FROM AUTHOR]

Objective: To investigate the cognitive impairment of a sample of euthymic bipolar patients treated with lithium monotherapy at baseline in a 2-year longitudinal study. Method: Fifteen DSM-IV-TR bipolar out-patients and 15 healthy-matched controls were cognitively assessed twice over a 2-year follow-up. All patients underwent lithium monotherapy on the first evaluation, and they were euthymic in both evaluations. Cognitive assessment was performed by means of a neuropsychological test battery tapping into the main cognitive domains (executive function, attention, processing speed, verbal memory and visual memory). Results: Repeated measures multivariate analysis of variance showed that the bipolar disorder group was cognitively impaired in the executive domain, attention and processing speed, and such deficits were maintained over time. Conclusion: Our results showed that executive dysfunction is the main long-term neuropsychological deficit of bipolar disorder. Also, the persistence of these deficits did not seem to be influenced by any clinical or pharmacological variables. [ABSTRACT FROM AUTHOR]

This study investigates changes in neuropsychological functioning during early abstinence from alcohol. 30 alcohol-dependent inpatients were tested at intake (day 4 of admission) and post detoxification (day 26), using a test-retest design. The neuropsychological battery included measures of pre-morbid IQ, full-scale IQ, verbal and non-verbal measures of memory and executive function. IQ was within the normal range at intake and comparable with age-adjusted normative values and there were some impairments in memory and executive function. There were significant increases in performance scores post detoxification in working memory, verbal fluency and verbal inhibition but not in non-verbal executive function tasks (mental flexibility and planning ability). Despite increased scores on tests of verbal and memory skills after 3 weeks of abstinence, complex executive abilities showed little change. These may have a negative impact on engagement and response to treatment and compromise clinical outcomes, heightening the risk of relapse. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Aims: Research into neuropsychological consequences of HIV has focused mainly on male subjects, and therefore very little is known about the disease in female subjects and, of course, about gender differences. The aim of the present research was therefore to investigate neuropsychological impairment rates and pattern in HIV male and female patients, with regard to the study of gender differences in tasks assessing attention, memory for texts, digits and words, psychomotor speed, verbal intelligence and abstract reasoning. Methods: A clinical sample was recruited consisting of 122 subjects, divided into four groups: (i) 57 HIV+ men; (ii) 31 HIV+ women; (iii) 18 HIV− men and (iv) 16 HIV− women. All the subjects had more than 18 years, being the average of age of 34.08 for men and 33.35 for women. The evaluation of each subject consisted of a semistructured interview investigating sociodemographic, clinical and toxicological aspects and a neuropsychological assessment, with a battery of tests specifically selected for this study and chosen for their validity and because they have been shown to be sensitive to neuropsychological impairment in HIV-infected patients in other studies. Results: None of HIV− male and female groups fulfilled impairment criteria. Regarding the HIV+ group, a rate of neuropsychological impairment of 51.9% was obtained for the men and 54.8% for the women, but there were no significant differences between groups. Nevertheless, were detected significant differences in neuropsychological impairment rates between HIV+ and HIV− women, and also between HIV+ and HIV− men. Although HIV+ women presented multiple factors that could increase their neuropsychological vulnerability to the effects of HIV, HIV+ men had the same probability of having neuropsychological impairment as HIV+ women. Conclusions: A different neuropsychological impairment pattern was detected between genders: while HIV+ men had greater impairment in visual memory, attention, psychomotor speed and abstract reasoning, HIV+ women had greater impairment on attention, psychomotor speed and verbal memory for texts. [ABSTRACT FROM AUTHOR]

Background Families with a parent suffering from multiple sclerosis (MS) must cope with the unpredictable course of the disease. Most studies analyzing factors that influence coping abilities in families with a member affected with MS used questionnaires to assess this ability. Methods On the contrary, the present study used a semi-structured psychiatric interview and used the resulting information to calculate a general measure of coping ability (coping index [CI]). We administered this interview to 44 MS patients, their partners and offspring and conducted a neuropsychological and physical evaluation of the patients to determine the impact of physical disability, cognitive dysfunction, and depression on the process of coping by the patient, the healthy partner, and children. Results The CI of patients was best predicted by measures of their depressive symptoms, divided attention, and estimated verbal intelligence. None of the patient variables predicted the CI of healthy partners or their offspring. We found an association between the CI of the healthy partner and the children. Conclusions These findings suggest that MS patients' emotional and neuropsychological functions are associated with their ability to cope with the disease. These should be carefully assessed at the beginning of treatment so that those factors known to negatively influence patient coping are targeted in the treatment plan if necessary. Comprehensive care of a patient with MS should include support of coping abilities of the family members. [ABSTRACT FROM AUTHOR]

Abstract: This study examined the utility of a screening battery developed by Reitan & Wolfson, 2006 for predicting neuropsychological impairment on the Halstead–Reitan neuropsychological test battery for adults. Using archival neuropsychological data from 69 litigants seen in a private practice setting, the Pearson correlation between the General Neuropsychological Deficit Scale (GNDS) score and the total Neuropsychological Deficit Scale (NDS) score from the screening battery (SBNDS) was .82. ROC curve analysis determined that the AUC was .88. Using a cutoff score of 9, as recommended by Reitan and Wolfson, the screening battery had excellent specificity but only fair sensitivity for identifying individuals with neuropsychological impairment on the Halstead–Reitan battery. Using a cutoff score of 8, the sensitivity and specificity of the screening battery was comparable to the findings of Reitan and Wolfson. The findings from this study indicate the optimal cutoff score for the screening battery may vary with different populations. The positive predictive power (PPP) and negative predictive power (NPP) were calculated for various base rates for cut scores with both sensitivity and specificity of greater than .600, and this information is provided. [Copyright &y& Elsevier]

Abstract: Cognitive Behavioral Social Skills Training (CBSST) is a 24-session weekly group therapy intervention to improve functioning in people with schizophrenia. In our prior randomized clinical trial comparing treatment as usual (TAU) with TAU plus group CBSST (Granholm, E., McQuaid, J.R., McClure, F.S., Auslander, L., Perivoliotis, D., Pedrelli, P., Patterson, T., Jeste, D.V., 2005. A randomized controlled trial of cognitive behavioral social skills training for middle-aged and older outpatients with chronic schizophrenia. Am. J. Psychiatry 162, 520–529.), participants with schizophrenia in CBSST showed significantly better functional outcome than participants in TAU. The present study was a secondary analysis of neuropsychological predictors of functional outcome in our prior CBSST trial. We examined (1) whether neuropsychological impairment at baseline moderated functional outcome in CBSST relative to TAU, and (2) whether improvement in neuropsychological abilities mediated improvement in functional outcome in CBSST. Attention, verbal learning/memory, speed of processing, and executive functions were assessed at baseline, end of treatment, and 12-month follow-up. Greater severity of neuropsychological impairment at baseline predicted poorer functional outcome for both treatment groups (nonspecific predictor), but the interaction between severity of neuropsychological impairment and treatment group was not significant (no moderation). Effect sizes for the difference between treatment groups on functional outcome measures at 12-month follow-up were similar for participants with relatively mild (d =.44–.64) and severe (d =.29–.60) neuropsychological impairment. Results also did not support the hypothesis that improvement in neuropsychological abilities mediated improvement in functioning in CBSST. Adding CBSST to standard pharmacologic care, therefore, improved functioning relative to standard care alone, even for participants with severe neuropsychological impairment, and this improvement in functioning was not related to improvement in neuropsychological abilities in CBSST. [Copyright &y& Elsevier]

Although cognitive impairment is common in multiple sclerosis (MS), its pathophysiology is still poorly understood. Abnormalities of cerebral blood flow (CBF) have long been acknowledged in MS and advances in perfusion magnetic resonance imaging (MRI) allow for their assessment in vivo. We investigated the relationship between regional perfusion changes and neuropsychological (NP) dysfunctions in patients with relapsing-remitting and primary-progressive MS. Absolute CBF, cerebral blood volume (CBV) and mean transit time were measured in 32 MS patients and 11 healthy controls using dynamic susceptibility contrast-enhanced T2*-weighted MRI. A comprehensive NP test battery was administered to all patients. A mixed model analysis of covariance was performed for group comparisons in terms of perfusion measures in normal-appearing white matter (NAWM) and deep gray matter (GM). Pearson's correlations were used to describe the association of perfusion metrics with NP Z-scores. CBF and CBV values were significantly decreased in both NAWM and deep GM in MS patients compared with controls (P=0.01). In all patients, deep GM CBF was significantly associated with Rey Complex Figure Test (RCFT)-Copy (r=0.5; P=0.001) and deep GM CBV and NAWM CBV were significantly associated with Color-Word Interference Inhibition Switching test (D-KEFSIS) (r=0.4; P=0.008 and r=0.4; P=0.02). However, the only associations that remained significant after Bonferroni correction were between deep GM CBF and RCFT-Copy (P=0.006), and deep GM CBV and D-KEFSIS (P=0.04). Our results suggest a role for tissue perfusion impairment in NP dysfunction in MS. Large-scale studies are needed to characterize better this association.Journal of Cerebral Blood Flow & Metabolism (2008) 28, 164–171; doi:10.1038/sj.jcbfm.9600504; published online 2 May 2007 [ABSTRACT FROM AUTHOR]

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Abstract: The aim of this study was to explore local brain atrophy of patients with alcohol dependence using a voxel-based analysis of magnetic resonance images and to investigate the relationship of those atrophic regions with drinking history and neuropsychological performances. Statistical parametric mapping was applied for the global and regional comparison of segmented gray matter and white matter images from 20 patients with alcohol dependence and with those from 20 controls. The Rey auditory-verbal learning test, Rey-Osterrieth complex figure test, Stroop test, trail-making test, and Wisconsin card sorting test were conducted as neuropsychological evaluations. There was a significant decrease in both gray matter and white matter globally in alcohol dependence. Bilateral parahippocampal white matter areas were reduced in particular. Perseverative responses and perseverative errors in the Wisconsin card sorting test had significant correlation with the decrease of gray matter decrease including the left superior temporal gyri and right postcentral region. The psychological performance measures correlated with gray matter rather than white matter, whereas right temporal white matter correlated with drinking amount for last 4 weeks. This may imply that alcohol consumption in heavy amounts damages both gray matter and white matter, and gray matter atrophy mainly leads to cognitive impairment, whereas white matter is related to drinking history. [Copyright &y& Elsevier]

Primary objective: To the authors' knowledge no study comparing very long-term neuropsychological outcome after mild paediatric and adult traumatic brain injury (TBI) has been published. The primary objective of this study was to compare neuropsychological outcome 23 years after mainly mild paediatric and adult TBI. Research design: The study was a neuropsychological follow-up 23 years after a prospective head injury study conducted at a Norwegian public hospital. Methods and procedures: One hundred and nineteen patients were assessed with a comprehensive neuropsychological test battery. Of these, 45 were paediatric TBI and 74 were adult TBI. Main outcomes and results: Both the paediatric and adult groups obtained scores in the normal range. In the paediatric group significant relationships were found between head injury severity and current neuropsychological function. The most important predictors of poor outcome were length of post-traumatic amnesia (PTA) and a combination of PTA and EEG pathology within 24 hours of injury. No influence of pre- and post-injury risk factors on current neuropsychological function was evident. Conclusions: The findings indicate that children sustaining complicated mild TBI may be more vulnerable to development of chronic mild neuropsychological dysfunction than adults sustaining similar head injuries. [ABSTRACT FROM AUTHOR]

Abstract: Functional magnetic resonance imaging (fMRI) has revealed much about altered CNS function in HIV/AIDS. In this study, we compared the blood oxygen level dependent hemodynamic response function (BOLD HRF) signal in HIV/AIDS and control subjects as a necessary pre-condition for fMRI studies of higher level cognitive function. Using event-related fMRI, subjects performed a simple sensory-motor activity allowing the measurement of the BOLD HRF in the precentral gyrus. There were no significant differences in the HRF when viewed as a function of age, hemisphere, or HIV serostatus. However, significant results were found after dividing the subjects by NIMH impairment classifications. There were 16 control subjects, 19 Normal/Asymptomatic Neuropsychological Impairment (ANI), and 11 Minor Neurocognitive Disorder (MNCD)/HIV-Associated Dementia (HAD) subjects. The HRF of MNCD/HAD subjects did not return to baseline after 16s, suggesting subtle alterations in neuronal function, which may affect event-related fMRI studies. [Copyright &y& Elsevier]

The objectives of this study is to clarify whether there are phases critical for the infection of the central nervous system (CNS) as defined by active viral replication in the cerebrospinal fluid (CSF) in human immunodeficiency virus (HIV) infection. One hundred and nine HIV-1-positive homo- and bisexual patients in early and late disease stages with or without highly active antiretroviral therapy (HAART) were included in the cross-sectional, diagnostic (phase I) multicenter study. No patients had any overt neurological deficits; all underwent venous and lumbar puncture as well as neuropsychological testing. In untreated early-stage patients, cerebrospinal fluid (CSF) viral load correlated with inflammatory parameters, but not significantly with neuropsychological abnormalities. CSF viral load and inflammatory reactions were suppressed in HAART-treated early-stage patients. In HAART-treated late-stage patients, there was a weak correlation between CSF viral load and CSF cell count as well as a moderate correlation with immune activation markers and with distinct cerebral deficits independent of CSF viral load. Seventeen of the 109 patients had higher CSF than plasma viral loads and marked inflammatory reactions and immune activation. In patients with greater plasma than CSF viral loads, the factors contributing to cerebral deficits still need to be identified. The results suggest not only that there is an early "set point" for CSF/central nervous system (CNS) infection, but also that there is a subgroup of patients in whom intrathecal viral replication correlates with cerebral deficits. Lumbar puncture should be performed in all positive patients to identify members of this subgroup and to ascertain what characteristic factors they have in common in order to improve therapy. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the cognitive deficits that accompany different levels of severity of obstructive sleep apnea–hypopnea syndrome (OSAHS). The sample originally consisted of 71 adult male volunteers with at least 11 years of education. Participants were assigned to groups based on their apnea–hypopnea index (AHI). There were 20 participants in the mild-to-moderate OSAHS group (AHI 6–28; mean age 41.8 ± 8.96 years), 16 in the severe OSAHS group (AHI 38–86; mean age 44.5 ± 7.96 years), and 35 in the non-OSAHS group (AHI 0–3; mean age 41.8 ± 8.96 years). Neuropsychological functions were measured using Stroop Test TBAG version, Cancellation Test, Auditory Verbal Learning Test, Serial Digit Learning Test, and Raven Standard Progressive Matrices. Analyses were conducted on z-transformed scores. Multivariate analysis of variance (education as covariate) showed decrease in various functions such as processing speed, disturbance in selective and sustained attention, deficit in visual perception, search and scan, deficit in recognition memory, increase in susceptibility to interference, and decrease in visuospatial reasoning and general ability. Correctness of estimation increased as severity of OSAHS increased. However, principal component analysis showed that OSAHS severity represents impairment in the basic processes of processing speed and vigilance/sustained attention. Untreated OSAHS patients are potential risks to themselves and to others. Controlled studies are necessary for unraveling the functional correlates of OSAHS. [ABSTRACT FROM AUTHOR]

Neuropsychological methods and techniques have much to offer in the evaluation of the individual suspected as having Attention-Deficit/Hyperactivity Disorder (ADHD). After a review of the historical evolution of the ADHD concept, incidence and prevalence, and DSM-IV criteria for diagnosis, especially as regards omission related to gender differences, and other associated cultural, familial, socioenvironmental, and subject influences, this paper describes a number of dilemmas and obstacles encountered in clinical practice. Included are the confounds associated with the wide range of possible comorbidities, the insufficiency of current DSM-IV criteria, the emergence of subtype differentiation and its impact on diagnosis and treatment. The complex relationship between neuropsychological constructs and ADHD, and obstacles to valid assessment are also addressed. The complexities associated with a thorough ADHD evaluation are viewed within an impressive and expansive existing scientific framework and recommendations are made for future directions. [ABSTRACT FROM AUTHOR]

It is well known that interferon (IFN) has various side effects including neuropsychiatric complications such as depression. We examined the relationship between neuropsychological impairment and regional cerebral blood flow (CBF) in chronic hepatitis patients treated with and without IFN-α. Eight patients with chronic hepatitis participated in this study. Four patients were treated with IFN-α (IFN group) and 4 patients were not treated (control group). The entire IFN group and half of the control group were diagnosed with hepatitis C and the rests of the control group had hepatitis B. Neuropsychological tests were conducted. The Self-Rating Depression Scale and the State-Trait Anxiety Inventory were also completed by the subjects. In addition, cerebral single photon emission computed tomography (SPECT; 3DSRT) was performed in all patients. Neuropsychological tests and SPECT were performed in the IFN group 2 months after starting IFN treatment and in the control group 2 months after starting follow-up. A significant reduction of regional CBF in the IFN group was observed in two cerebral regions (lt-angular and lt-temporal region) ( P<0.05), which have reported associations with memory and language function. In addition, the Auditory-Verbal Learning Test (AVLT), a measure of memory function, showed a decreased tendency in the IFN group. A decrease of regional CBF by IFN treatment was shown, suggesting that a decrease of regional CBF may contribute to the neuropsychological impairment by IFN treatment. [ABSTRACT FROM AUTHOR]

Previous studies suggest that neuropsychological impairment following mild to moderate pediatric head injury may become persistent and interrupt the normal course of intellectual development. In this study 45 subjects were assessed with a standardized neuropsychological test battery 25 years after sustaining mild to moderate head injury as children. Although the group scores in the normal range, significant relations between head injury severity and current neuropsychological function were found. The most important predictor of poor outcome was length of PTA at injury, EEG pathology, and loss of consciousness at injury. No significant influence of pre- and post-injury risk factors on current neuropsychological function was evident. The findings support the view that complicated mild and moderate paediatric head injury may heighten the risk of developing subtle neuropsychological problems later in life. [ABSTRACT FROM AUTHOR]

Cognitive impairments are common in patients with end-stage liver disease (ESLD). The aim of the present study was to identify and characterize the neuropsychological deficits between groups of patients with a variety of causes of ESLD and to assess the impact of heavy alcohol use on cognitive functioning. Cognitive functioning in 300 consecutive outpatients presenting for liver transplantation evaluation was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). All patients underwent a psychiatric interview and a physical and laboratory assessment. The prevalence of neuropsychological impairment was highest among patients with liver disease secondary to alcohol. Poor performance on neuropsychological testing was correlated strongly with the severity of liver disease as measured by the model for end-stage liver disease (MELD). After controlling for the linear effects of MELD in subsequent analysis, a group difference emerged in patients with cholestatic liver disease showing less cognitive impairment when compared to all other groups. After controlling for the severity of liver disease, those patients with a history of alcohol abuse or dependence were found to perform more poorly on neuropsychological testing than those patients without such a history. Furthermore, the presence of these cognitive impairments predicted disability independent of the severity of the underlying liver disease. [ABSTRACT FROM AUTHOR]

Objectives The aims of this study were to follow a cohort of HIV-infected individuals for 2 years to assess changes in depression and neuropsychological performance over time, to explore the relationship between depression, HIV illness and neuropsychological performance, and to examine the natural history of the effect of highly active antiretroviral therapy (HAART) on depression and neurocognitive performance. Methods HIV-seropositive out-patients were assessed at baseline and at 2-year follow-up. At each assessment, patients were assessed for depression [using the Beck Depression Inventory (BDI) and Structured Clinical Interview (SCID-CV)] and completed a battery of neuropsychological tests including the Cambridge Neuropsychological Test Automated Battery (CANTAB) and the Hopkins HIV Dementia Scale (HDS). Results At baseline, 34.8% scored ≥14 on the BDI [≥14 suggests depressive symptoms (DS)]. The SCID-CV revealed that 27% of participants met the criteria for current mood disorder. Seven per cent of the participants' scores on the HDS indicated HIV-associated cognitive changes. Eighty participants were re-tested at 2-year follow-up and were split into two groups based on BDI scores at baseline. CANTAB results revealed that the cohort were significantly impaired on nine of 10 measures compared with age-matched normative data. Neurocognitive performance significantly improved for participants with no DS at baseline, whereas participants with DS at baseline did not show as much improvement. Multivariate analysis revealed that 40% of the change in cognitive performance was attributable to the variables age, AIDS and HAART regimen. Conclusion These results suggest a significant decline in depression scores and an improvement in several neurocognitive domains over time, with a relationship between HIV illness, HAART, symptoms of depression and neurocognitive performance. [ABSTRACT FROM AUTHOR]

Our study examined the relation between neuropsychological impairment of executive functions and explanatory styles, according to the Abramson model of learned helplessness in humans, in a sample of substance abusers. Thirty-eight polysubstance abusers were assessed during an abstinence period using a selective neuropsychological battery for the evaluation of the executive functions, as well as the Attributional Style Questionnaire (ASQ) for the assessment of the three dimensions of explanatory style: Internality–Externality, Stability–Instability and Globality–Specificity. Multiple regression analyses showed significant relationships among performance on different neuropsychological tasks sensitive to executive functions and characteristic cognitive styles. The results showed the performance on cognitive flexibility and response inhibition tasks is directly related to making more internal attributions for positive situations, and inversely related to the appearance of more stable attributions for negative events. Likewise, adequate performance on working memory tasks was related to development of more global attributions for failures. These results are partially congruent with the learned helplessness model and particularly relevant for the clinical management of substance abusers and the success on the treatment and rehabilitation of these subjects. [Copyright &y& Elsevier]

Abstract: CCR2 is a minor coreceptor for human immune deficiency virus-1 (HIV-1) and its impact on HIV-1-related neuropsychological impairment (NPI) remains unknown. We studied the impact of CCR2-V64I polymorphisms on the development of NPI in 121 HIV-1 patients. The CCR2-64-I allele was associated with rate of progression to NPI when measured from the first study visit (Log Rank p=0.01) or from the estimated time of seroconversion (p=0.02). CCR2-V64I was not associated with plasma or CSF HIV-1 RNA load, suggesting that the impact of CCR2 on neuropathogenesis may involve alterations in inflammatory responses within the CNS rather than a direct impact on viral entry or replication. [Copyright &y& Elsevier]

Background: A comprehensive approach to assessing neuropsychological deficits in CFS patients is developed by assessing cognitive function across a number of domains using a battery of tests, rather than relying on any single instrument. Objective: A factor analytic approach was employed to examine the underlying dimensionality of 15 standard cognitive function related test variables in CFS patients. A cognitive function index (CFI) was then developed using appropriately weighted and interpreted factors. Methods: Factor analysis was applied to an initial sample of 65 CFS patients, identifying eight factors accounting for over 70% of total variation. This factor structure was then independently verified on a separate sample of 124 CFS patients. An overall combined CFS sample of 212 was then used to derive the CFI using an appropriately interpreted and weighted average of the derived factors. Results: After including age and education as separate factors, the CFI consists of nine factors accounting for 70% of total variation in the overall CFS group. The CFI was not affected by the presence of current psychiatric comorbidity. A cut-off score for cognitive dysfunction was established using the lower quartile value of a group of sedentary controls on the same index. Conclusions: The CFI will provide a useful summary measure for researchers investigating cognitive function performance in CFS patients. It does not replace existing individual specialized tests. [ABSTRACT FROM PUBLISHER]

Chronic consumption of several drugs of abuse (cannabis, stimulants, opioids) has been associated with the presence of neuropsychological impairments in a broad range of functions. Nevertheless, in recent years neuropsychological research on substance abuse has focused on the study of impairments in the executive functions linked to the prefrontal cortex and their influence on the personality, cognitions, and behaviors of the substance abusers. The aim of our review is, first, to summarize the main neuropsychological impairments shown by classic studies, as well as these new discoveries in executive functioning; second, to consider the mediating role of neuropsychological status on treatment outcomes and analyze the impact of these impairments in clinical practice with drug addicts; and third, to review the principal methodological challenges associated with research in the field of the neuropsychology of substance abuse. We also highlight the convenience of intervening in those functions most relevant to the abusers' persistence in consumption and risk of relapse. [ABSTRACT FROM AUTHOR]

Objective: The present study assessed the relationship of depression, pain, and fatigue to subjective cognitive complaints and objective impairment in patients with fibromyalgia (FM), patients with other chronic pain disorders, and healthy controls.Method: Neuropsychological assessment was conducted on 28 FM patients, 27 chronic pain patients, and 21 healthy controls. Five FM patients and five chronic pain patients were excluded due to poor effort on cognitive tasks. Assessment included measures of depression, pain, fatigue, subjective cognitive complaints, memory, executive functioning, intellect, attention, and psychomotor speed. Analysis of covariance was used to assess group differences in cognitive complaints and cognitive test performance, after controlling for depression, pain, and fatigue. Hierarchical regression was used to assess whether objective test performance was related to subjective cognitive complaints, after controlling for depression, pain, and fatigue.Results: FM patients had more memory complaints and reported more fatigue, pain, and depression than other groups. Groups were not different in cognitive performance, after controlling for fatigue, pain, and depression; depression was related to memory performance and fatigue was related to psychomotor speed. Neuropsychological test results did not add significantly to the variance accounted for in subjective cognitive complaints, after accounting for depression, pain, and fatigue.Conclusion: Psychological factors, particularly effort, depression, and fatigue, are important in understanding both subjective cognitive complaints and objective cognitive impairment in FM and other chronic pain disorders. [Copyright &y& Elsevier]

Research on the HIV-related neuropsychological impairment has been marked by the variety and discrepancy of results, mainly in regards to asymptomatic phases. These discrepancies have been associated with the different types of methodology used in these studies. In this article, we review the main methodological problems present in studies about HIV-related neuropsychological impairment. Our aim is to gather the suggestions contained in the literature, to help overcome these problems in future studies in the field. These suggestions consider the samples used, the way in which they are selected, their size, the sampling methods used, the risk group studied, the criteria for inclusion/exclusion applied, or the selection of the control group. References are also included for the measuring instruments or neuropsychological tests used, statistical methods and criteria for defining the presence of neuropsychological impairment, and for dealing with confounding factors. There can be no doubt that a precise and thorough examination of these issues will make it possible to achieve more conclusive results on the incidence and nature of HIV-related neuropsychological impairment, and the factors that are associated with it. [ABSTRACT FROM AUTHOR]

This paper examines the commonalities and the differences between schizophrenia and bipolar disorder. Recent studies suggest a possible overlap in genetic susceptibility to the two conditions. However, while the influence of early environmental effects, particularly obstetric complications, has been established for schizophrenia, no such replicable association with bipolar disorder has been found. Structural abnormalities of the brain have been identified in both schizophrenia and bipolar disorder, but while the volume of the amygdala and hippocampus appears decreased in schizophrenia, this is not the case in bipolar disorder; indeed, there are some suggestions of increased volume of the amygdala. Furthermore, schizophrenia is characterised by lower IQ, executive function and verbal memory, but there is little evidence of trait neuropsychological deficits in bipolar disorder. Similarly, premanic children do not show the cognitive and neuromotor impairments characteristic of those destined to develop schizophrenia. The most plausible explanation is that the two conditions share some genetic predisposition but differ in that schizophrenia but not bipolar disorder is subject to additional genes or early environmental hazards causing neurodevelopmental impairment. [ABSTRACT FROM AUTHOR]

Success for children and adults alike in educational, vocational, and social pursuits depends heavily on effective self-regulation of cognitive and social behaviour. Our goal in this article has been to summarize recent literature on executive self-regulatory functions, their importance, their development during childhood, the types of disability associated with EF impairment, and intervention approaches that have been shown to be useful for related disability groups. We also examined the literature on learned helplessness and learned optimism for clues to a comprehensive approach to helping children with EF impairment, in particular those with acquired brain injury. The central rehabilitation-relevant themes that we have derived from these reviews are: (a) although brain injury can directly impair executive self-regulation, aspects of the environment and the presence or absence of support behaviours of others can reduce or amplify the neurologic impairment; (b) interventions need to be context sensitive; (c) everyday routines of instruction and parent-child interaction are the ideal context within which to provide EF facilitation; and (d) a primary role for rehabilitation specialists is to help everyday people effectively organize and modulate their support for and everyday interactions with children with disability. In an ideal world, competent and optimistic rehabilitation professionals work collaboratively with children and their parents, teachers and others to ensure an optimistic vision of the future that includes an increasingly autonomous child with the executive self-regulatory skill needed to succeed in adult life. [ABSTRACT FROM AUTHOR]

Background Elderly people who develop depression have demonstrable changes in cerebral structure but little is known of the relationship between regional cerebral volumes, treatment response and cognitive impairment. Method Forty-four patients with major depression diagnosed according to DSM-IIIR criteria underwent magnetic resonance imaging and regional cerebral volumes were quantified using multispectral analysis. Response to antidepressant treatment was assessed prospectively and a neuropsychological test battery was administered. Results There was a trend for smaller fronto-temporal volumes in the treatment-resistant patients. Impaired immediate working memory was linked with reduced frontal and parietal lobe volume and impaired short-term memory functioning was associated with reduced temporal lobe volume. Ventricular enlargement was associated with prior administration of electro-convulsive therapy, poor physical health and later age at onset of first episode of depression. Conclusion In late-life depression, brain changes should not preclude vigorous antidepressant treatment. Regional cerebral volume changes may be a complication of poor physical health and are associated with memory dysfunction even upon recovery from depression. Copyright © 2001 John Wiley & Sons, Ltd [ABSTRACT FROM AUTHOR]

Introduction: Multiple sclerosis (MS) is a demyelinating and neurodegenerative disease of the central nervous system, characterized by inflammatory-driven demyelination. Symptoms in MS manifest as both physical and neuropsychological deficits. With time, inflammation is accompanied by neurodegeneration, indicated by brain volume loss on an MRI. Here, we combined clinical, imaging, and serum biomarkers in patients with iron rim lesions (IRLs), which lead to severe tissue destruction and thus contribute to the accumulation of clinical disability. Objectives: Subcortical atrophy and ventricular enlargement using an automatic segmentation pipeline for 7 Tesla (T) MRI, serum neurofilament light chain (sNfL) levels, and neuropsychological performance in patients with MS with IRLs and non-IRLs were assessed. Methods: In total 29 patients with MS [15 women, 24 relapsing-remitting multiple sclerosis (RRMS), and five secondary-progressive multiple sclerosis (SPMS)] aged 38 (22-69) years with an Expanded Disability Status Score of 2 (0-8) and a disease duration of 11 (5-40) years underwent neurological and neuropsychological examinations. Volumes of lesions, subcortical structures, and lateral ventricles on 7-T MRI (SWI, FLAIR, and MP2RAGE, 3D Segmentation Software) and sNfL concentrations using the Simoa SR-X Analyzer in IRL and non-IRL patients were assessed. Results: (1) Iron rim lesions patients had a higher FLAIR lesion count ( p = 0.047). Patients with higher MP2Rage lesion volume exhibited more IRLs ( p <0.014) and showed poorer performance in the information processing speed tested within 1 year using the Symbol Digit Modalities Test (SDMT) ( p <0.047). (2) Within 3 years, patients showed atrophy of the thalamus ( p = 0.021) and putamen ( p = 0.043) and enlargement of the lateral ventricles ( p = 0.012). At baseline and after 3 years, thalamic volumes were lower in IRLs than in non-IRL patients ( p = 0.045). (3) At baseline, IRL patients had higher sNfL concentrations ( p = 0.028). Higher sNfL concentrations were associated with poorer SDMT ( p = 0.004), regardless of IRL presence. (4) IRL and non-IRL patients showed no significant difference in the neuropsychological performance within 1 year. Conclusions: Compared with non-IRL patients, IRL patients had higher FLAIR lesion counts, smaller thalamic volumes, and higher sNfL concentrations. Our pilot study combines IRL and sNfL, two biomarkers considered indicative for neurodegenerative processes. Our preliminary data underscore the reported destructive nature of IRLs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Dal-Bianco, Schranzer, Grabner, Lanzinger, Kolbrink, Pusswald, Altmann, Ponleitner, Weber, Kornek, Zebenholzer, Schmied, Berger, Lassmann, Trattnig, Hametner, Leutmezer and Rommer.)

An updated review of the literature strongly supports the view that in schizophrenia there is an atypical left-ward shift in the handedness distribution that, while comprising different subtypes, is characterized by a more variable and less completely lateralized pattern of manual preference, referred to as mixed handedness (MH) or ambiguous handedness (AH). Only two studies revealed an increased prevalence of left-handedness suggestive of pathological left-handedness (PLH). This article also examines the current status of neurodevelopmental factors and mechanisms in schizophrenia that purport to explain these pathological shifts in handedness (PLH, MH, AH). Different theoretical positions were evaluated, each involving some aspect of left hemisphere insult (unilateral or bilateral). Finally, it was shown that these shifts predict certain key symptoms and neural substrates in schizophrenia including thought disorder, negative symptoms, neuropsychological impairment, family history, and brain anatomy. These subtypes may represent neurodevelopmental markers of insult during intrauterine life that are nongenetic in origin. [ABSTRACT FROM PUBLISHER]

Abstract Background Polydipsia frequently occurs in schizophrenia patients. The excessive water loading in polydipsia occasionally induces a hyponatremic state and leads to water intoxication. Whether polydipsia in schizophrenic patients correlates with neuropsychological impairments or structural brain changes is not clear and remains controversial. Methods Eight polydipsic schizophrenia patients, eight nonpolydipsic schizophrenia patients, and eight healthy controls were recruited. All subjects underwent magnetic resonance imaging (MRI) and neuropsychological testing. Structural abnormalities were analyzed using a voxel-based morphometry (VBM) approach, and patients’ neuropsychological function was assessed using the Brief Assessment of Cognition in Schizophrenia, Japanese version (BACS-J). Results No significant differences were found between the two patient groups with respect to the clinical characteristics. Compared with healthy controls, polydipsic patients showed widespread brain volume reduction and neuropsychological impairment. Furthermore, the left insula was significantly reduced in polydipsic patients compared with nonpolydipsic patients. These nonpolydipsic patients performed intermediate to the other two groups in the neuropsychological function test. Conclusions It is possible that polydipsia or the secondary hyponatremia might induce left insula volume reduction. Furthermore, this structural brain change may indirectly induce more severe neuropsychological impairments in polydipsic patients. Thus, we suggest that insula abnormalities might contribute to the pathophysiology of polydipsic patients.