To examine the hypothesis that abnormalities in those cognitive functions for which cerebellar components have been implicated contribute to the pathophysiology of autism, tests of judgment of explicit time intervals and procedural learning were administered to 11 participants with autism and 17 age-and-IQ-matched controls. Results indicated that the group with autism demonstrated significant impairments in procedural learning compared with the group of controls. No significant difference in judgment of explicit time intervals was found. The data suggest that deficits in procedural learning may contribute to the cognitive and behavioral phenotype of autism; these deficits may be secondary to abnormalities in cerebellar–frontal circuitry. (JINS, 2000, 6, 752–759.)

Objectives: Recent advances in neuroimaging methodologies sensitive to axonal injury have made it possible to assess in vivo the extent of traumatic brain injury (TBI) -related disruption in neural structures and their connections. The objective of this paper is to review studies examining connectivity in TBI with an emphasis on structural and functional MRI methods that have proven to be valuable in uncovering neural abnormalities associated with this condition. Methods: We review studies that have examined white matter integrity in TBI of varying etiology and levels of severity, and consider how findings at different times post-injury may inform underlying mechanisms of post-injury progression and recovery. Moreover, in light of recent advances in neuroimaging methods to study the functional connectivity among brain regions that form integrated networks, we review TBI studies that use resting-state functional connectivity MRI methodology to examine neural networks disrupted by putative axonal injury. Results: The findings suggest that TBI is associated with altered structural and functional connectivity, characterized by decreased integrity of white matter pathways and imbalance and inefficiency of functional networks. These structural and functional alterations are often associated with neurocognitive dysfunction and poor functional outcomes. Conclusions: TBI has a negative impact on distributed brain networks that lead to behavioral disturbance. (JINS, 2016, 22, 120–137)

Hepatitis C virus (HCV) infection is a major public-health-care problem, with over 170 million infected worldwide. Patients with chronic HCV infection often complain of various cognitive problems as well as symptoms of depression, anxiety, and fatigue. Relatively little is known, however, about the specific cognitive deficits that are common among HCV patients, and the influence of psychiatric symptomatology on cognitive functioning. In the current study of 21 chronically infected HCV patients, we assessed subjective cognitive dysfunction, depression, anxiety, and fatigue and compared these symptom areas to cognitive tests assessing visuoconstruction, learning, memory, visual attention, psychomotor speed, and mental flexibility. Results revealed that cognitive impairment ranged from 9% of patients on a visuoconstruction task to 38% of patients on a measure of complex attention, visual scanning and tracking, and psychomotor speed, and greater HCV disease severity as indicated by liver fibrosis was associated with greater cognitive dysfunction. Objective cognitive impairment was not related to subjective cognitive complaints or psychiatric symptomatology. These findings suggest that a significant portion of patients with chronic HCV experience cognitive difficulties that may interfere with activities of daily living and quality of life. Future research using cognitive measures with HCV-infected patients may assist researchers in identifying if there is a direct effect of HCV infection on the brain and which patients may be more likely to progress to cirrhosis and hepatic encephalopathy. (JINS, 2003, 9, 847–854.)

Fifty-eight studies of the neuropathological and neuropsychological outcomes of cerebral anoxia were reviewed. Neuropathological reports were examined for the variety, extent, and specificity of lesions resulting from an anoxic event. While most attention has focused on damage to the hippocampus following anoxic brain injury, the review indicated that watershed cerebral cortex and the basal ganglia were both more frequently damaged than the hippocampus. The hippocampus was the sole affected structure in only 18% of reported cases. Neurological, neuropsychological and psychiatric studies were analyzed. Of 67 individual case reports, a memory disturbance was documented in 36 (54%), but a memory disturbance without report of additional cognitive deficits occurred in only 13 (19.4%). Changes in personality and behavior were noted in 31 (46.2%). Visuospatial or, less frequently, visual recognition problems were noted in 21 individual cases (31.3%) reviewed. Memory deficits were found in all 14 group studies reviewed, while in 9 papers changes in behavior or personality were also documented. Six studies also reported visuospatial deficits. Careful reading of the literature reveals a range of cognitive and behavioral changes that reflect very well the neuropathological outcomes of anoxic episodes. (JINS, 2000, 6, 86–99.)

The current investigation compared neuropsychological test performance among nondemented literate and illiterate elders. The sample included participants in an epidemiological study of normal aging and dementia in the Northern Manhattan community. All participants were diagnosed as nondemented by a neurologist, and did not have history of Parkinson's disease, stroke, or head injury. Literacy level was determined by self-report. MANOVAs revealed a significant overall effect for literacy status (literate vs. illiterate) on neuropsychological test performance when groups were matched on years of education. The overall effect of literacy status remained significant after restricting the analyses to elders with no formal education, and after controlling for the effects of language of test administration. Specifically, illiterates obtained lower scores on measures of naming, comprehension, verbal abstraction, orientation, and figure matching and recognition. However, tests of verbal list delayed recall, nonverbal abstraction, and category fluency were unaffected by literacy status, suggesting that these measures can be used to accurately detect cognitive decline among illiterate elders in this sample. Differences in organization of visuospatial information, lack of previous exposure to stimuli, and difficulties with interpretation of the logical functions of language are possible factors that contribute to our findings. (JINS, 1999, 5, 191–202.)

Attention-deficit/hyperactivity disorder (ADHD) is characterized by inattention and/or hyperactivity/impulsivity. Impulsivity persists in adults with ADHD and might be the basis of much of the impairment observed in the daily lives of such individuals. The objective of this study was to address the presence, and more importantly, the three dimensions of impulsivity: attentional, non-planning and motor, in how they may relate to neuropsychological mechanisms of impulse control. We studied a sample of 50 adults with ADHD and 51 healthy comparison controls using the Barratt Impulsivity Scale Version 11 (BIS), and neuropsychological tasks, namely the Continuous Performance Task (CPT-II) and the Iowa Gambling Task (IGT). The ADHD group showed more signs of impulsivity on the three dimensions of BIS, committed more errors of omission and commission on the CPT-II, and made more disadvantageous choices on the IGT. These results support the existence of deficits related to three components of impulsivity: motor, cognitive, and attentional among adults with ADHD. Most importantly, this study also highlights the complementary nature of self-report questionnaires and neuropsychological tasks in the assessment of impulsivity in ADHD adults. (JINS, 2007, 13, 693–698.)

The frequency and determinants of abnormal test performance by normal individuals are critically important to clinical inference. Here we compare two approaches to predicting rates of abnormal test performance among healthy individuals with the rates actually shown by 327 neurologically normal adults aged 18–92 years. We counted how many participants produced abnormal scores, defined by three different cutoffs with test batteries of varied length, and the number of abnormal scores they produced. Observed rates generally were closer to predictions based on a series of Monte Carlo simulations than on the binomial model. They increased with the number of tests administered, decreased as more stringent cutoffs were used to identify abnormality, varied with the degree of correlation among test scores, and depended on individual differences in age, education, race, sex, and estimated premorbid IQ. Adjusting scores for demographic variables and premorbid IQ did not reduce rates of abnormal performance. However, it eliminated the contribution of these variables to rates of abnormal test performance. These findings raise fundamental questions about the nature and interpretation of abnormal test performance by normal, healthy adults. (JINS, 2008, 14, 436–445.)

Parkin's criticisms of the central executive are based on a series of misconceptions. The central executive is not an organ that might or might not exist, but a scientific concept. Part of its function is to separate the analysis of executive processes from the question of their anatomical location. Like other components of working memory, it is fractionable into subsystems. How the subsystems interrelate and how they map onto the anatomical substrate are empirical questions under active current investigation. (JINS, 1998, 4, 523–526.)

A group of 317 healthy participants between 54 and 99 years of age performed a verbal fluency task. The participants included Chinese, Hispanic, and Vietnamese immigrants, as well as White and African American English speakers. They were given 1 min to name as many animals as possible in their native language. The results showed that more animal names were produced by younger people and those with more education. Language background was also an important factor: The Vietnamese produced the most animal names and the Spanish speakers produced the fewest. The exaggerated difference between these two groups is attributed to the fact that Vietnamese animal names are short (predominantly 1 syllable) while the Spanish animal names are longer than any other language in this study (2 and 3 syllables per word). Finally, although the ethnic groups named different animals, and appeared to vary in the variety of animal names they used, these factors did not affect overall verbal fluency performance. (JINS, 1998, 4, 531–538.)

The present study explored the explanatory power of Mittenberg's “expectation as etiology” theory for the persistence of postconcussion syndrome (PCS) complaints. One hundred forty-one participants completed a PCS symptom checklist under 2 conditions. Normal controls, healthy athletes and depressed individuals reported current symptoms and symptoms expected following a hypothetical mild head injury. Head-injured athletes, chronic headache sufferers, and a 2nd sample of normal controls reported current symptoms and retrospective symptoms (prior to their injury/illness or from some point in the past). Depressed individuals reported more current symptoms than normal controls and healthy athletes, demonstrating that “PCS” symptoms are not specific to PCS. All groups expected more symptoms following mild head injury than currently experienced, supporting the idea that individuals expect negative consequences following head injury. However, healthy athletes expected fewer symptoms than normals or depressed individuals, possibly due to preexisting expectations for speedy recovery. Both head-injured athletes and headache sufferers reported more current symptoms than the past, but not at a rate lower than baseline of normal controls. Results suggest that the “expectation as etiology” hypothesis may be too specific, and that, following any negative event, people may attribute all symptoms to that negative event (the “good old days” hypothesis). (JINS, 2001, 7, 323–333.)

Patients with a history of mild (n = 134) or moderate-to-severe (n = 91) TBI were asked to complete the Neurobehavioral Symptom Inventory (NSI) and the Posttraumatic Stress Disorder Checklist. Consistent with prior research, significantly more postconcussion symptoms were endorsed by the mild group. After controlling for age, time since injury, and mechanism of injury, TBI severity continued to be significantly related to postconcussion complaints on the NSI. However, after controlling for these same variables, along with posttraumatic stress disorder symptom severity, there no longer were differences between the TBI severity groups. That is, patients with mild TBI did not endorse significantly more complaints (adjusted mean = 22.4) than the moderate-to-severe group (adjusted mean = 21.8). These findings suggest that much of the symptom complaints in mildly injured patients may be due to emotional distress. (JINS, 2010, 16, 194–199.)

Although body dysmorphic disorder (BDD) is receiving increasing empirical attention, very little is known about neuropsychological deficits in this disorder. The current study investigated the nature of memory dysfunction in BDD, including the relationship between encoding strategies and verbal and nonverbal memory performance. We evaluated 17 patients with BDD and 17 healthy controls using the Rey–Osterrieth Complex Figure Test (RCFT) and the California Verbal Learning Test (CVLT). BDD patients differed significantly from healthy controls on verbal and nonverbal learning and memory indices. Multiple regression analyses revealed that group differences in free recall were statistically mediated by deficits in organizational strategies in the BDD cohort. These findings are similar to patterns previously observed in obsessive–compulsive disorder (OCD), suggesting a potential relationship between OCD and BDD. Studies in both groups have shown that verbal and nonverbal memory deficits are affected by impaired strategic processing. (JINS, 2000, 6, 673–681.)

Multiple studies have explored the relationship between MRI-based volumetric measurements of the hippocampus and amygdala, the degree of volumetric asymmetry of these structures, and symptom manifestation. However, considerable variability exists with regard to the reported volumetric values of these structures. The present study employed meta-analytic procedures to provide a systematic analysis of the normal population parameters of hippocampal and amygdala volumetric asymmetry as well as the absolute intrahemispheric volumes of these structures in normal adults. A literature review of studies published between 1990 and 2002 resulted in a representative sample of 82 studies (N = 3,564 participants) providing volumetric information of the hippocampus and 51 studies (N = 2,000 participants) providing volumetric information of the amygdala. Results revealed that both the hippocampus and the amygdala are reliably asymmetrical structures in normal adults, with larger right hippocampal (D = 0.21, p < .001) and right amygdala (D = 0.09, p < .01) volumes. Additional analyses indicated that differences in MRI magnet field strength and slice thickness values might differentially contribute to volumetric asymmetry estimates. These results expand on previous volumetric normative studies and may be relevant to investigators studying the clinical correlates of hippocampal and amygdala volumes. (JINS, 2004, 10, 664–678.)

The Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS) is a consensus neuropsychological battery with established reliability and validity. One of the difficulties in implementing the MACFIMS in clinical settings is the reliance on manualized norms from disparate sources. In this study, we derived regression-based norms for the MACFIMS, using a unique data set to control for standard demographic variables (i.e., age, age2, sex, education). Multiple sclerosis (MS) patients (n = 395) and healthy volunteers (n = 100) did not differ in age, level of education, sex, or race. Multiple regression analyses were conducted on the performance of the healthy adults, and the resulting models were used to predict MS performance on the MACFIMS battery. This regression-based approach identified higher rates of impairment than manualized norms for many of the MACFIMS measures. These findings suggest that there are advantages to developing new norms from a single sample using the regression-based approach. We conclude that the regression-based norms presented here provide a valid alternative to identifying cognitive impairment as measured by the MACFIMS. (JINS, 2010, 16, 6–16.)

One hundred and ninety-five participants in the Cincinnati Lead Study were neuropsychologically evaluated in mid-adolescence. The neuropsychological measures yielded five factors labeled Memory, Learning/IQ, Attention, Visuoconstruction, and Fine-Motor. Prenatal, Average Childhood, and 78 month blood lead (PbB) levels were used in a series of multiple regression analyses. Following rigorous covariate pretesting and adjustment, a significant main effect of 78 month PbB on the Fine-Motor factor was found (p < .004). Significant interactions were also found between gender and lead exposure parameters for both Attention and Visuoconstruction indicating heightened risk in males. Finally, a trend toward significance was found for the PbB × SES interaction for Learning/IQ, consistent with previous evidence of increased educational and cognitive vulnerability for youth from more disadvantaged backgrounds. These results provide new evidence from the longest continuing prospective study of the remote effects of early lead exposure. They indicate the presence of selective neuropsychological effects in this population, and also that males and females are not uniformly affected. These results also underscore the complexity of models of neurobehavioral development, and the modest predictive power of any single determinant. (JINS, 2004, 10, 261–270.)

Obstructive sleep apnea (OSA) is a fairly common nocturnal breathing disorder, affecting 2–4% of individuals. Although OSA is associated with medical morbidity, its most functionally disruptive effects in adults appear to be neuropsychological in nature. Research on the neuropsychological effects of pediatric OSA has been limited. This study compared the neuropsychological functioning of school-aged children with OSA to that of healthy children. The primary goal was to clarify the presence and pattern of neuropsychological morbidity associated with pediatric OSA. Sleep was assessed with parent-report questionnaires and laboratory sleep studies. Neuropsychological functioning was assessed by formal tests and parent- and teacher-report questionnaires. Data indicated OSA-related cognitive and behavioral impairment that was particularly marked on measures of behavior regulation and some aspects of attention and executive functioning. Minimal effects were observed on measures of intelligence, verbal memory, or processing speed. Exploratory analyses failed to indicate any clear relationship between neuropsychological functioning and objective indexes of hypoxia or sleep disruption, though the sample was small. These data add to a growing literature which suggests that significant neuropsychological deficits are associated with pediatric OSA. Findings suggest a pattern of neuropsychological morbidity that is similar but not identical to that seen in adult OSA. (JINS, 2004, 10, 962–975.)

Psychosocial outcome at one year post-injury was examined prospectively in 466 hospitalized head-injured subjects, 124 trauma controls, and 88 friend controls. The results indicate that head injury is associated with persistent psychosocial limitations. However, the presence and extent of limitations are related to the demographics of the population injured, to other system injuries sustained in the same accident, and particularly to the severity of the head injury. More severe head injuries are associated with limitations implying greater dependence on others including poorer Glasgow Outcome Scale (GOS) ratings, dependent living, unemployment, low income, and reliance on family and social subsidy systems. Head injury severity is more closely related to more objective indices of psychosocial outcome (e.g., employment) than to self-perceived psychosocial limitations, such as measured by the Sickness Impact Profile (SIP). (JINS, 1995, I, 67–77.)

Amnestic mild cognitive impairment (aMCI) represents a high-risk factor for Alzheimer's disease (AD) and is characterized by a selective decline in episodic memory. Although by definition aMCI is not associated with impaired verbal fluency performance, we examined relative differences between fluency tasks because AD is characterized by poorer semantic than phonemic fluency. Phonemic and semantic fluency trials were administered to 46 healthy controls, 33 patients with aMCI, and 33 patients with AD. Results revealed a progressive advantage (controls > aMCI > AD) in semantic, relative to phonemic fluency. Difference scores between tasks distinguished each group from the others with medium to large effect sizes (d) ranging from 0.49 to 1.07. Semantic fluency relies more on semantic associations between category exemplars than does phonemic fluency. This aMCI fluency pattern reflects degradation of semantic networks demonstrating that initial neuropathology may extend beyond known early changes in hippocampal regions. (JINS, 2006, 12, 570–574.)The data were collected in accordance with the guidelines of the Helsinki Declaration and approved by the Research Ethics and Scientific Review Committee of Baycrest Centre. This is an original submission. Portions of these data were presented at the annual meeting of the International Neuropsychological Society, February 2005, St. Louis, Missouri. There is no conflict of interest.

fMRI was used to determine the frontal, basal ganglia, and thalamic structures engaged by three facets of language generation: lexical status of generated items, the use of semantic vs. phonological information during language generation, and rate of generation. During fMRI, 21 neurologically normal subjects performed four tasks: generation of nonsense syllables given beginning and ending consonant blends, generation of words given a rhyming word, generation of words given a semantic category at a fast rate (matched to the rate of nonsense syllable generation), and generation of words given a semantic category at a slow rate (matched to the rate of generating of rhyming words). Components of a left pre-SMA–dorsal caudate nucleus–ventral anterior thalamic loop were active during word generation from rhyming or category cues but not during nonsense syllable generation. Findings indicate that this loop is involved in retrieving words from pre-existing lexical stores. Relatively diffuse activity in the right basal ganglia (caudate nucleus and putamen) also was found during word-generation tasks but not during nonsense syllable generation. Given the relative absence of right frontal activity during the word generation tasks, we suggest that the right basal ganglia activity serves to suppress right frontal activity, preventing right frontal structures from interfering with language production. Current findings establish roles for the left and the right basal ganglia in word generation. Hypotheses are discussed for future research to help refine our understanding of basal ganglia functions in language generation. (JINS, 2003, 9, 1061–1077.)

The objective of this study is to determine if distinct cognitive phenotypes could be identified in temporal lobe epilepsy. Epilepsy patients (n = 96) and healthy controls (n = 82) underwent comprehensive neuropsychological assessment. Adjusted (age, gender, and education) test scores for epilepsy subjects were grouped into cognitive domains (intelligence, language, visuoperception, immediate and delayed memory, executive function, and cognitive/psychomotor speed). Cluster analysis revealed three distinct cognitive profiles types: (1) minimally impaired (47% of subjects); (2) memory impaired (24%); and (3) memory, executive, and speed impaired (29%). The three cluster groups exhibited different patterns of results on demographic, clinical epilepsy, brain volumetrics, and cognitive course over a 4-year interval. The specific profile characteristics of the identified cognitive phenotypes are presented and their implications for the investigation of the neurobehavioral complications of epilepsy are discussed. (JINS, 2007, 13, 12–20.)