Objectives: The negative effect of changes in social behavior following traumatic brain injury (TBI) are known, but much less is known about the neuropsychological impairments that may underlie and predict these changes. The current study investigated possible associations between post-injury behavior and neuropsychological competencies of emotion recognition, understanding intentions, and response selection, that have been proposed as important for social functioning. Methods: Forty participants with TBI and 32 matched healthy participants completed a battery of tests assessing the three functions of interest. In addition, self- and proxy reports of pre- and post-injury behavior, mood, and community integration were collected. Results: The TBI group performed significantly poorer than the comparison group on all tasks of emotion recognition, understanding intention, and on one task of response selection. Ratings of current behavior suggested significant changes in the TBI group relative to before the injury and showed significantly poorer community integration and interpersonal behavior than the comparison group. Of the three functions considered, emotion recognition was associated with both post-injury behavior and community integration and this association could not be fully explained by injury severity, time since injury, or education. Conclusions: The current study confirmed earlier findings of associations between emotion recognition and post-TBI behavior, providing partial evidence for models proposing emotion recognition as one of the pre-requisites for adequate social functioning. (JINS, 2017, 23, 400–411)

Atypical amygdala development may play a key role in the emergence of social disability and other symptoms of autism (Baron-Cohen et al., 2000; Schultz, 2005). The mechanisms by which this may occur have received little attention, however, and most support from behavioral and imaging studies has been concerned with socially relevant stimuli such as faces. Given the complexity of amygdala function and its known role in many other emotional tasks, we examined whether individuals with autism would demonstrate impaired performance on several tasks that have been shown to require activation of the amygdala but that do not have any explicit social meaning. Relative to a typical comparison group matched for age and IQ, our sample of 37 adolescents and adults with autism (mean age = 19.7 years) demonstrated equivalent facilitation for perception and learning of emotionally relevant stimuli. On each of four tasks, there were significant main effects of emotion condition on performance for both groups. Future research regarding atypical amygdala function and emotion processing in autism should consider whether the response to nonsocial emotion factors (including negative valence or high arousal) may be intact, despite difficulties in responding to socially relevant stimuli. (JINS, 2008, 14, 42–54.)

Participants with mild cognitive impairment (MCI) have a higher likelihood of developing Alzheimer's disease (AD) compared to those without MCI, and functional magnetic resonance neuroimaging (fMRI) used with MCI participants may prove to be an important tool in identifying early biomarkers for AD. We tested the hypothesis that functional connectivity differences exist between older adults with and without MCI using resting-state fMRI. Data were collected on over 200 participants of the Rush Memory and Aging Project, a community-based, clinical-pathological cohort study of aging. From the cohort, 40 participants were identified as having MCI, and were compared to 40 demographically matched participants without cognitive impairment. MCI participants showed lesser functional connectivity between the posterior cingulate cortex and right and left orbital frontal, right middle frontal, left putamen, right caudate, left superior temporal, and right posterior cingulate regions; and greater connectivity with right inferior frontal, left fusiform, left rectal, and left precentral regions. Furthermore, in an alternate sample of 113, connectivity values in regions of difference correlated with episodic memory and processing speed. Results suggest functional connectivity values in regions of difference are associated with cognitive function and may reflect the presence of AD pathology and increased risk of developing clinical AD. (JINS, 2012, 18, 39–48)

White matter (WM) change plays an important role in age-related cognitive decline. In this review, we consider methodological advances with particular relevance to the role of WM in age-related changes in processing speed. In this context, intra-individual variability in processing speed performance has emerged as a sensitive proxy of cognitive and neurological decline while neuroimaging techniques used to assess WM change have become increasingly more sensitive. Together with a carefully designed task protocol, we emphasize that the combined implementation of intra-individual variability and neuroimaging techniques hold promise for specifying the WM-processing speed relationship with implications for normative and clinical samples. (JINS, 2014, 20, 1–6)

Performance of different episodic memory processes in patients with amnestic mild cognitive impairment (aMCI) and mild Alzheimer’s disease (AD) and their anatomical correlates are not completely understood. We evaluated the performance of 48 subjects (17 with aMCI, 15 with mild AD, and 16 controls) on the Rey Auditory Verbal Learning Test (RAVLT). A brain MRI voxel-based morphometry (VBM) analysis was run with the aim of evaluating the correlations between RAVLT and gray matter density. All memory processes were compromised in aMCI and mild AD. Also, the same cerebral structures were involved in all RAVLT stages. Learning and delayed recall were more related to the medial prefrontal cortex and hippocampi, whereas recognition was more related to the thalamic nuclei and caudate nucleus, particularly in the left side. Our findings suggest that these structures may act as a complex functional system and are involved in the acquisition of new information. (JINS, 2010, 16, 205–209.)

Shape and letter cancellation test performance was investigated among large samples of African American, Hispanic, and White non-demented elders. Ethnic minority elders took significantly longer to complete both tasks compared to Whites. An index of task efficiency, which simultaneously measures time and accuracy, suggested that slower time by minority elders was not related to a measurable effort to achieve greater accuracy. The frequency of commission errors was greater in our sample than in previous reports, especially among ethnic minority elders. Although significant differences were observed between the ethnic groups when matched for years of education, equating for literacy level eliminated all performance differences between African Americans and Whites on both cancellation tasks. (JINS, 2004, 10, 401–411.)

The purpose of this study was to examine the relationships between lobar volumes and set shifting. We studied 101 subjects, including 36 normal controls, 16 patients with probable Alzheimer's disease, 30 patients with frontotemporal dementia (FTD), and 19 patients with semantic dementia (SD), using a shifting paradigm that carefully controlled for component abilities. Subjects were administered two conditions of the Delis–Kaplan Executive Function System (D-KEFS) Design Fluency Test. In the control condition (DF:Control), examinees generated as many unique designs as possible in 60 s by drawing lines connecting only unfilled dots. In the switching condition (DF:Switch), examinees generated designs by drawing lines alternating between filled and unfilled dots. We used BRAINS2 software to generate volumes of the right and left frontal, temporal, and parietal lobes. Partial correlations and multiple regressions showed that, after controlling for Mini-Mental State Examination and DF:Control, only the right and left frontal lobe volumes significantly correlated with the DF:Switch, most clearly in the FTD and SD groups. Follow-up analyses indicated that frontal contributions to shifting were not related to working memory. Results highlight the importance of carefully controlling for component cognitive processes when studying executive functioning. (JINS, 2007, 13, 386–392.)

Objectives: It is well known that the carotenoids lutein (L) and zeaxanthin (Z) improve eye health and an accumulating evidence base suggests cognitive benefits as well. The present study investigated underlying neural mechanisms using functional magnetic resonance imaging (fMRI). It was hypothesized that lower L and Z concentrations would be associated with neurobiological inefficiency (i.e., increased activation) during cognitive performance. Methods: Forty-three community-dwelling older adults (mean age=72 years; 58% female; 100% Caucasian) were asked to learn and recall pairs of unrelated words in an fMRI-adapted paradigm. L and Z levels were measured in retina (macular pigment optical density) and serum using validated procedures. Results: Following first-level contrasts of encoding and retrieval trials minus control trials (p<.05, family-wise error corrected, minimum voxel cluster=8), L and Z were found to significantly and negatively relate to blood-oxygen-level-dependent signal in central and parietal operculum cortex, inferior frontal gyrus, supramarginal gyrus, planum polare, frontal and middle temporal gyrus, superior parietal lobule, postcentral gyrus, precentral gyrus, occipital cortex bilaterally, and cerebellar regions. Conclusions: To the authors’ knowledge, the present study represents the first attempt to investigate neural mechanisms underlying the relation of L and Z to cognition using fMRI. The observed results suggest that L and Z promote cognitive functioning in old age by enhancing neural efficiency. (JINS, 2017, 23, 11–22)

Older African Americans tend to perform poorly in comparison with older Whites on episodic memory tests. Observed group differences may reflect some combination of biological differences, measurement bias, and other confounding factors that differ across groups. Cognitive reserve refers to the hypothesis that factors, such as years of education, cognitive activity, and socioeconomic status, promote brain resilience in the face of pathological threats to brain integrity in late life. Educational quality, measured by reading test performance, has been postulated as an important aspect of cognitive reserve. Previous studies have not concurrently evaluated test bias and other explanations for observed differences between older African Americans and Whites. We combined data from two studies to address this question. We analyzed data from 273 African American and 720 White older adults. We assessed DIF using an item response theory/ordinal logistic regression approach. DIF and factors associated with cognitive reserve did not explain the relationship between race, and age- and sex-adjusted episodic memory test performance. However, reading level did explain this relationship. The results reinforce the importance of considering education quality, as measured by reading level, when assessing cognition among diverse older adults. (JINS, 2011, 17, 625–638)

Traumatic brain injury (TBI) is likely to disrupt structural network properties due to diffuse white matter pathology. The present study aimed to detect alterations in structural network topology in TBI and relate them to cognitive and real-world behavioral impairment. Twenty-two people with moderate to severe TBI with mostly diffuse pathology and 18 demographically matched healthy controls were included in the final analysis. Graph theoretical network analysis was applied to diffusion tensor imaging (DTI) data to characterize structural connectivity in both groups. Neuropsychological functions were assessed by a battery of psychometric tests and the Frontal Systems Behavior Scale (FrSBe). Local connection-wise analysis demonstrated reduced structural connectivity in TBI arising from subcortical areas including thalamus, caudate, and hippocampus. Global network metrics revealed that shortest path length in participants with TBI was longer compared to controls, and that this reduced network efficiency was associated with worse performance in executive function and verbal learning. The shortest path length measure was also correlated with family-reported FrSBe scores. These findings support the notion that the diffuse form of neuropathology caused by TBI results in alterations in structural connectivity that contribute to cognitive and real-world behavioral impairment. (JINS, 2014, 20, 1–10)

The corpus callosum (CC) is one of several brain structures affected in children prenatally exposed to alcohol. This structure plays a major role in coordinating motor activity from opposite sides of the body, and deficits in bimanual coordination have been documented in individuals with agenesis of or damage to the CC, particularly when the task is performed without visual feedback. The Bimanual Coordination Test was used to assess speed and accuracy on a task where both hands must coordinate to guide a cursor through angled pathways providing measures of interhemispheric interaction or the ability of the two hemispheres to coordinate activity via the corpus callosum. Twenty-one children with fetal alcohol spectrum disorders (FASD) and 17 non-exposed control children (CON), matched closely in age, sex, and ethnicity were tested. For trials with visual feedback (WV), children with FASD were slower than CON children but were equally accurate. Although statistically significant group differences were not observed on most trials completed without visual feedback (WOV), accuracy of the FASD group on WOV trials was highly variable. Group differences in accuracy on WOV angles approached significance after accounting for performance on the WV angles, and children with FASD were significantly less accurate on an individual angle believed to be particularly sensitive to interhemispheric interaction. These results indicate that children with FASD are slower than CON children but equally accurate on basic visuomotor tasks. However, as task complexity and reliance on interhemispheric interaction increases, children with FASD demonstrate variable and inaccurate performance. Preliminary analyses suggest that inaccurate performance on the bimanual coordination task, and presumably impaired callosal functioning, may be related to the attention and problem solving impairments commonly reported in children with FASD. (JINS, 2004, 10, 536–548.)

Difficulties in social communication in individuals with Klinefelter syndrome (XXY chromosomal pattern) have largely been attributed to deficits in left hemisphere-mediated, language functions. This study examined the ability of XXY men to decode emotions from tone of voice, a pragmatic aspect of social communication that may be associated with right hemisphere functioning. A total of 26 XXY men and 20 men from the general population completed tasks involving emotion discrimination in speech, based on verbal content or tone of voice. The XXY group displayed relative difficulties in discriminating emotions in tone of voice, and, to a lesser extend, in verbal content. This finding suggests that the XXY chromosomal pattern may not only be associated with difficulties in semantic aspects of language, but with prosodic aspects, as well. Our findings may contribute to the development of more comprehensive models addressing the role of the X chromosome in normal and abnormal development of social communication. (JINS, 2007, 13, 1065–1070.)

This study examined the relationship between processing speed (PS) and working memory (WM), as measured by performance on an n-back task, in relapsing-remitting multiple sclerosis (RRMS) patients. Simple PS was defined as reaction time (RT) on the 0-back task and complex PS was defined as RT on both the 1-back and 2-back tasks. Participants were administered all three n-back tasks (0-, 1-, and 2-back). Total correct responses, total dyads, and RTs were recorded. As expected, RT for all participants slowed as WM load increased. MS patients had slower RTs than controls across all tasks, and the difference between groups for RT was greatest during the 2-back task. When RT for simple PS (0-back) was parsed from the 1- and 2-back tasks, MS patients still showed impaired complex PS compared to controls. MS patients also made significantly fewer total correct responses and had fewer dyads than controls only on the 2-back task. These findings suggest that both WM and PS deficits are present in RRMS, and that as WM demand increases (from 1- to 2-back) both PS and WM deficits become more prominent. (JINS, 2007, 13, 417–423.)

Individuals suffering from Huntington's disease (HD) have been shown to present with poor self-awareness of a variety of symptoms. The aim of this study was to better assess the self-awareness of motor symptoms and activities of daily living (ADL) impairment in HD, in comparison to Parkinson's disease (PD) and cervical dystonia (CD). In particular, the anosognosia/anosodiaphoria of involuntary movements has been investigated. Self-awareness was tested in 23 patients with HD by comparing patient and caregiver ratings in reference to clinical control groups (25 PD with dyskinesias, PDdys; 21 PD without dyskinesias, PDndys; and 20 with CD). Patients were assessed neurologically by relevant rating scales. Self-awareness was tested using a scale based on 15 films demonstrating 3 types of motor symptoms (chorea/dyskinesias, parkinsonism, torticollis) as well as the Self-Assessment Parkinson's Disease Disability Scale. General cognitive status, verbal learning, cognitive control, and mood were also analyzed. Our results indicate that self-awareness of choreic movements was affected more severely in HD than in PDdys, despite comparable cognitive status. Patient–proxy agreement on ADL impairment was roughly similar in all clinical groups. The results are discussed in the context of orbitofrontal–limbic pathology as a potential trigger of anosognosia/anosodiaphoria in individuals with HD. (JINS, 2011, 17, 788–795)

Logopenic progressive aphasia (LPA) is a form of primary progressive aphasia (PPA) characterized by hesitant speech with marked impairment in naming and repetition. LPA is associated with brain atrophy in the left temporal and inferior parietal cortices and is predominantly associated with Alzheimer's disease (AD) pathology. In contrast to LPA, “typical” AD is commonly associated with episodic memory disturbance and bilateral medial temporal lobe atrophy. Recent evidence suggests verbal short-term memory is more impaired than visuospatial short-term memory in LPA. This study investigated verbal and visuospatial short-term memory in 12 LPA and 12 AD patients matched for disease severity, and in 12 age- and education-matched healthy controls. Overall, both patient groups showed significantly reduced verbal and visuospatial spans compared with controls. In addition, LPA patients performed significantly worse than AD patients on both forward and backward conditions of the Digit Span task. In contrast, no difference was present between patient groups on either version of the Spatial Span task. Importantly, LPA patients showed better visuospatial than verbal span whereas AD patients and controls did not differ across modality. This study demonstrates the specificity of the short-term memory disturbance in LPA, which arises from a breakdown of the phonological system. (JINS, 2012, 19, 1–7)

Objectives: Cognitive dysfunction is a core symptom dimension that cuts across the psychoses. Recent findings support classification of patients along the cognitive dimension using cluster analysis; however, data-derived groupings may be highly determined by sampling characteristics and the measures used to derive the clusters, and so their interpretability must be established. We examined cognitive clusters in a cross-diagnostic sample of patients with psychosis and associations with clinical and functional outcomes. We then compared our findings to a previous report of cognitive clusters in a separate sample using a different cognitive battery. Methods: Participants with affective or non-affective psychosis (n=120) and healthy controls (n=31) were administered the MATRICS Consensus Cognitive Battery, and clinical and community functioning assessments. Cluster analyses were performed on cognitive variables, and clusters were compared on demographic, cognitive, and clinical measures. Results were compared to findings from our previous report. Results: A four-cluster solution provided a good fit to the data; profiles included a neuropsychologically normal cluster, a globally impaired cluster, and two clusters of mixed profiles. Cognitive burden was associated with symptom severity and poorer community functioning. The patterns of cognitive performance by cluster were highly consistent with our previous findings. Conclusions: We found evidence of four cognitive subgroups of patients with psychosis, with cognitive profiles that map closely to those produced in our previous work. Clusters were associated with clinical and community variables and a measure of premorbid functioning, suggesting that they reflect meaningful groupings: replicable, and related to clinical presentation and functional outcomes. (JINS, 2018, 24, 382–390)

Social communication involves influencing what other people think and feel about themselves. We use the term conative theory of mind (ToM) to refer to communicative interactions involving one person trying to influence the mental and emotional state of another, paradigmatic examples of which are irony and empathy. This study reports how children with traumatic brain injury (TBI) understand ironic criticism and empathic praise, on a task requiring them to identify speaker belief and intention for direct conative speech acts involving literal truth, and indirect speech acts involving either ironic criticism or empathic praise. Participants were 71 children in the chronic state of a single TBI and 57 age- and gender-matched children with orthopedic injuries (OI). Group differences emerged on indirect speech acts involving conation (i.e., irony and empathy), but not on structurally and linguistically identical direct speech acts, suggesting specific deficits in this aspect of social cognition in school-age children with TBI. Deficits in children with mild-moderate TBI were less widespread and more selective than those of children with more severe injuries. Deficits in understanding the social, conative function of indirect speech acts like irony and empathy have widespread and deep implications for social function in children with TBI. (JINS, 2013, 19, 1–11)

Children with hydrocephalus have poor math skills. We investigated the nature of their arithmetic computation errors by comparing written subtraction errors in good readers with hydrocephalus, typically developing good readers of the same age, and younger children matched for math level to the children with hydrocephalus. Children with hydrocephalus made more procedural errors (although not more fact retrieval or visual–spatial errors) than age-matched controls; they made the same number of procedural errors as younger, math-level matched children. We also investigated a broad range of math abilities, and found that children with hydrocephalus performed more poorly than age-matched controls on tests of geometry and applied math skills such as estimation and problem solving. Computation deficits in children with hydrocephalus reflect delayed development of procedural knowledge. Problems in specific math domains such as geometry and applied math, were associated with deficits in constituent cognitive skills such as visual spatial competence, memory, and general knowledge. (JINS, 2002, 8, 72–82.)

Recent evidence suggests that HIV-seropositive drug users are impaired on tasks of visuospatial working memory compared with drug users seronegative for HIV. In the current study we evaluated the performance of 30 HIV-seropositive male drug users and 30 risk-matched seronegative controls on two measures of verbal working memory, the Listening Span and the verbal Self Ordered Pointing Task. Impaired working memory performance was significantly more common among HIV-seropositive persons compared to controls, with the highest incidence of deficit among symptomatic participants. These findings indicate that working memory deficits in persons with HIV are not domain-specific and can be demonstrated reliably in drug users. (JINS, 2000, 6, 548–555.)

Executive functions (EF) encompass a variety of higher-order capacities such as judgment, planning, decision-making, response monitoring, insight, and self-regulation. Measuring such abilities quantitatively and establishing their neural correlates has proven to be challenging. Here, using a lesion-deficit approach, we report the neural correlates of a variety of EF tests that were developed under the auspices of the NINDS-supported EXAMINER project (Kramer, 2011; www.examiner.ucsf.edu). We administered a diverse set of EF tasks that tap three general domains—cognitive, social/emotional, and insight—to 37 patients with focal lesions to the frontal lobes, and 25 patients with lesions outside the frontal lobes. Using voxel-based lesion-symptom mapping (VLSM), we found that damage to the ventromedial prefrontal cortex (vmPFC) was predominately associated with deficits in social/emotional aspects of EF, while damage to dorsolateral prefrontal cortex (dlPFC) and anterior cingulate was predominately associated with deficits in cognitive aspects of EF. Evidence for an important role of some non-frontal regions (e.g., the temporal poles) in some aspects of EF was also found. The results provide further evidence for the neural basis of EF, and extend previous findings of the dissociation between the roles of the ventromedial and dorsolateral prefrontal sectors in organizing, implementing, and monitoring goal-directed behavior. (JINS, 2013, 19, 1–12)