The circuitry of abulia: insights from functional connectivity MRI.

BACKGROUND: Functional imaging and lesion studies have associated willed behavior with the anterior cingulate cortex (ACC). Abulia is a syndrome characterized by apathy and deficiency of motivated behavior. Abulia is most frequently associated with ACC damage, but also occurs following damage to subcortical nuclei (striatum, globus pallidus, thalamic nuclei). We present resting state functional connectivity MRI (fcMRI) data from an individual who suffered a stroke leading to abulia. We hypothesized that, although structural imaging revealed no damage to the patient's ACC, fcMRI would uncover aberrant function in this region and in the relevant cortical networks. METHODS: Resting state correlations in the patient's gray matter were compared to those of age-matched controls. Using a novel method to identify abnormal patterns of functional connectivity in single subjects, we identified areas and networks with aberrant connectivity. RESULTS: Networks associated with memory (default mode network) and executive function (cingulo-opercular network) were abnormal. The patient's anterior cingulate was among the areas showing aberrant functional connectivity. In a rescan 3 years later, deficits remained stable and fcMRI findings were replicated. CONCLUSIONS: These findings suggest that the aberrant functional connectivity mapping approach described may be useful for linking stroke symptoms to disrupted network connectivity.

Neuropsychological issues in the assessment of refugees and victims of mass violence.

Brain injury, stressor severity, depression, premorbid vulnerabilities, and PTSD are frequently intertwined in trauma populations. This interaction is further complicated when the neuropsychologist evaluates refugees from other cultures. In addition, the observed psychiatric symptoms reported in refugees and victims of mass violence may in fact not be the primary features of PTSD and depression but psychiatric symptoms secondary to the effects of traumatic brain injury. This paper reviews the occurrence of starvation, torture, beatings, imprisonment, and other head injury experiences in refugee and POW populations to alert treators to the presence of chronic and persistent neuropsychiatric morbidity, with implications for psychosocial adjustment. The concept of fixed neural loss may also interact with environmental and emotional stresses, and a model of neuropsychological abnormalities triggered by traumatic events and influenced by subsequent stress will also be considered. Neuropsychologists working with refugees play an important role in assessing the possibility of traumatic brain injury with tools that are relatively culture-fair.

Age and neuropsychologic function in schizophrenia: a decline in executive abilities beyond that observed in healthy volunteers.

BACKGROUND: Kraepelin originally conceptualized schizophrenia as a degenerative brain disorder. It remains unclear whether the illness is characterized by a static encephalopathy or a deterioration of brain function, or periods of each condition. Assessments of cognitive function, as measured by neuropsychologic assessment, can provide additional insight into this question. Few studies of patients with schizophrenia have investigated the effect of aging on executive functions, in an extensive neuropsychologic battery across a wide age range, compared to healthy volunteers. METHODS: We examined the interaction of aging and neuropsychologic function in schizophrenia through a cross-sectional study in patients (n = 87) and healthy control subjects (n = 94). Subjects were divided into three age groups (20-35, 36-49, and 50-75), and performance on an extensive neuropsychologic battery was evaluated. RESULTS: Compared to control subjects, patients with schizophrenia demonstrated similar age-related declines across most neuropsychologic functions, with the exception of abstraction ability, in which significant evidence of a more accelerated decline was observed. CONCLUSIONS: These results are consistent with previous reports indicating similar age effects on most aspects of cognition in patients with schizophrenia and healthy adults, but they support the hypothesis that a degenerative process may result in a more accelerated decline of some executive functions in older age in schizophrenia.

Glucose-induced increase in memory performance in patients with schizophrenia.

Previous investigations have found that increasing circulating glucose availability can increase memory performance in rodents, healthy humans, and individuals with dementia of the Alzheimer's type. In this study, patients with schizophrenia, healthy control subjects, and controls with bipolar affective disorder were tested using double-blind treatment with either 50 g anhydrous dextrose plus 4 mg sodium saccharin (for "taste") or 23.7 mg saccharin alone, followed by cognitive testing on a complex battery. At this glucose dose, verbal memory performance on a paragraph recall task was increased during the glucose condition relative to the saccharin condition in the patients with schizophrenia; this effect was not detected in either the psychiatric or normal controls. The results provide preliminary support for the hypothesis that memory performance can be improved in patients with schizophrenia by increasing circulating glucose availability and suggest the importance of further evaluation of therapeutic manipulations of glucose availability.

Age- and dose-dependent glucose-induced increases in memory and attention in schizophrenia.

Glucose is the principal energy substrate for the brain, and alterations in glucose availability can alter neuronal function, including cognitive performance. Investigators have previously demonstrated glucose-induced memory and attentional improvements in humans, including a previous report from this group in subjects with schizophrenia. However, the age- and dose-dependence of this effect in schizophrenia has not been addressed. This within-subjects, double-blind experiment evaluated the cognitive effects of placebo-controlled, multiple fixed-dose oral glucose administration (0 g, 25 g, 50 g, 75 g) in younger and older patients with schizophrenia (n = 20) and healthy age-matched controls (n = 20). Each dose condition was administered on a different morning after a 9-h fast, with cognitive testing and plasma sampling following dose administration on each day. Older patients demonstrated dose-dependent improvements in recall performance on a spatial delayed response task and reaction time on a delayed match to sample task, while younger patients had decreases in attentional performance at the 75-g dose compared to placebo. As in previous reports, patients demonstrated higher plasma glucose and insulin concentrations than controls in response to fixed glucose dosing. The results provide further evidence that glucose and/or insulin can regulate brain functions relevant to memory and attention, and suggest that systemic changes in glucose regulation in schizophrenia deserve further study.

Are there cognitive subtypes in adult attention deficit/hyperactivity disorder?

There has been increasing knowledge of the treatment, diagnosis, and demographics of adults with residual attention deficit/hyperactivity disorder (ADHD). However, less is known about the neuropsychological functioning in adults with residual ADHD. In comparing the clinical neuropsychological test performance of a group of adult clinic patients with residual ADHD (N = 30) with that of normal controls (N = 10), we found the patients performed worse on the Trail Making Test, a visual continuous performance test, and the "Brown-Peterson" Auditory Consonant Trigrams Test, but not on any other neuropsychological measures. This pattern indicated a deficit in the area of executive control type functioning, a functional deficit that could be linked to dysregulation of frontal lobe brain systems. Of equal interest was that patients diagnosed with ADHD/hyperactive impulsive type (ADHD+) and patients diagnosed with ADHD/inattentive type (ADHD-) had different types of executive system deficits. ADHD+ was associated with relative deficiency on the Wisconsin Card Sorting Test. ADHD- was associated with relative deficiency on the "Brown-Peterson" Auditory Consonant Trigrams Test, a measure of working memory, as well as less olfactory identification on a smell identification test. The data are discussed in terms of recent localization theories of frontal lobe function. The preliminary data suggest that the different cognitive weaknesses of ADD subtypes may be linked to dysregulation of separate frontal brain regions and/or neurotransmitter systems.

Distorted visual feedback effects on drawing in Parkinson's disease.

We investigated the effects of distorted visual feedback on the drawing performance of a group with Parkinson's disease (PD) and a control group. Twenty older healthy adults and 20 PD patients copied figures onto a digitizer tablet with a pen under normal and distorted visual feedback conditions. PD patients were less able than controls to adjust the size of their drawing to compensate for distortions in visual feedback. The effect was particularly pronounced when patients were required to draw smaller than normal. Nevertheless, with practice. PD patients showed a similar degree of improvement in size as controls, although they did not match the control group's level of performance. Overall, these findings support the notion that PD may have specific difficulty adjusting to a change in gain (or discrepancy) between visual and kinesthetic feedback when they must alter the size of their drawing. These findings point to the putative role of the basal ganglia in adjusting for the intermodal discrepancy between sensory feedback, and re-scaling the size of movements.