Visual rating versus volumetry to detect frontotemporal dementia.

BACKGROUND/AIMS: Automated, volumetrically defined atrophy in the left anterior cingulate (LAC) and anterior temporal regions (LAT) on MRI can be used to distinguish most patients with frontotemporal dementia (FTD) from controls. FTD and Alzheimer's disease (AD) can differ in the degree of anterior temporal atrophy. We explored whether clinicians can visually detect this atrophy pattern and whether they can use it to classify the 2 groups of dementia patients with the same accuracy. METHODS: Four neurologists rated atrophy in the LAC and LAT regions on MRI slices from 21 FTD, 21 controls, and 14 AD participants. Inter-rater reliability and diagnostic accuracy were assessed. RESULTS: All 4 raters agreed on the presence of clinically significant atrophy, and their atrophy scoring correlated with the volumes, but without translation into high inter-rater diagnostic agreement. CONCLUSIONS: Volumetric analyses are difficult to translate into routine clinical practice.

Normal-pressure hydrocephalus: is there a genetic predisposition?

BACKGROUND: Normal-pressure hydrocephalus (NPH) is characterized by gait disturbance, cognitive impairment, with or without urinary incontinence, enlarged ventricles with or without cerebral atrophy and normal cerebrospinal fluid pressure. METHODS: We report two sisters with NPH who lived together their entire lives and whose natural history might provide insights into genetic and environmental mechanisms underlying this disorder. Both patients were in their early seventies, single, had similar daily habits and hypertension. No other family members had NPH. RESULTS: They both underwent shunt placement and showed improvement documented by history and neuropsychological assessment. Both showed a delayed deterioration due to vasculopathy. Both patients were homozygous for the apolipoprotein E (ApoE) e3 allele on chromosome 19. No environmental factors that might have influenced the development of NPH were identified. CONCLUSION: Our report of two sisters with NPH may indicate the presence of genetic predisposition and further studies involving genetics and environmental factors are necessary to elucidate their role in the pathogenesis of NPH.

Impulsivity and risk-taking behavior in focal frontal lobe lesions.

Frontal lobe dysfunction may underlie excessively impulsive and risky behavior observed in a range of neurological disorders. We devised a gambling task to examine these behavior tendencies in a sample of patients who had sustained focal damage to the frontal lobes or nonfrontal cortical regions as well as in a matched sample of healthy control subjects. The main objectives of the study were: (1) to behaviorally dissociate impulsivity and risk-taking; (2) to examine potential associations between specific frontal lesion sites and impulsivity or risk-taking; (3) to investigate the influence of reinforcement and trial timing on both behaviors. Our results indicated that patients and controls were equally likely to perform impulsively. Risk-taking performance strategies, however, were related to left ventrolateral and orbital lesion sites. Moreover, risk-taking was also associated with blunted response alteration following a nonrewarded trial. Patients and control subjects showed identical responses to reward-timing manipulations consistent with formal decision-making theory. These findings suggest that ventrolateral and orbital lesions are related to the reward-based aspects of decision-making (risk-taking) rather than to simple response disinhibition (impulsivity). Reduced reaction to the negative consequences of one's actions may underlie this behavior pattern.

Assessing cognitive functioning in ALS: A focus on frontal lobe processes.

OBJECTIVE: It is generally acknowledged that at least 50% of individuals with amyotrophic lateral sclerosis (ALS) will exhibit cognitive deficits outside of the characteristic motor neuron involvement. However, a specific cognitive profile has been difficult to ascertain due to disease-related testing barriers and limitations in the sensitivity and specificity of available assessment methods. This study assessed the level of functioning of extramotor frontal cognitive processes in ALS, and the amount of change in the functioning in these processes over time as disease progresses. METHODS: Empirical tests validated for a model of frontal lobe functioning were modified into an assessment battery appropriate for individuals with ALS in a clinical setting (the ALS-CFB, Computerised Frontal Battery). Twenty ALS participants and 36 age- and education-matched neurologically healthy controls were tested, and a sub-sample of each group (11 ALS and 20 controls) re-tested after approximately nine months. RESULTS AND CONCLUSIONS: Compared to standard neuropsychological screening tests that did not show a difference between ALS participants and healthy controls, the ALS-CFB illustrated a profile of extramotor frontal dysfunction involving energisation (preparing the neural system to respond) and executive functions, a profile that may be indicative of the nature of neurodegeneration in ALS.

Neurobiology of conscious experience.

Recent research and theory suggest that conscious experience involves a modelling process. The human brain generates an internal model to fit incoming information about the external world, and experiences the model rather than the information. The modelling occurs at the level of the neocortex and may be associated with specific oscillatory field potentials. Imagining exercises the modelling system independently of sensory information. General disorders of consciousness are caused by damage to those areas of the brain that energize and direct the modelling process Specific deficits of consciousness are caused by focal lesions to sensory or motor cortex that prevent the modelling of particular input and output patterns.

No evidence of risk-taking or impulsive behaviour in a person with episodic amnesia: Implications for the role of the hippocampus in future-regarding decision-making.

Does advantageous decision-making require one to explicitly remember the outcome of a series of past decisions or to imagine future personal consequences of one's choices? Findings that amnesic people with hippocampal damage cannot form a clear preference for advantageous decks over many learning trials on the Iowa Gambling Task (IGT) have been taken to suggest that complex decision-making on the IGT depends on declarative (episodic) memory and hippocampal integrity. Alternatively, impaired IGT performance in amnesic individuals could be secondary to risk-taking and/or impulsive behaviour resulting from impaired episodic future thinking (i.e. prospection) known to accompany amnesia. We tested this possibility in the amnesic individual K.C. using the IGT and the Toronto Gambling Task (TGT), a novel task that dissociates impulsivity from risk-taking without placing demands on declarative memory. K.C. did not develop a preference for advantageous over disadvantageous decks on the IGT and, instead, showed a slight preference for short-term gains and an inability to acquire a more adaptive appreciation of longer-term losses. He also did not display impulsive or risk-taking behaviour on the TGT, despite a profound inability to imagine personal future experiences. These findings suggest that impaired decision-making on the IGT in amnesia is unlikely to reflect a predilection to act in the moment or failure to take future consequences into account. Instead, some forms of future-regarding decision-making may be dissociable, with performance on tasks relying on declarative learning or on episodic-constructive processes more likely to be impaired.

Leucotomized and nonleucotomized schizophrenics: comparison on tests of attention.

Deficits in attention have been strongly linked with both schizophrenia and pathology in the prefrontal cortex. This observation was tested by administering a battery of commonly used tests of attention, sustained mental activity, and tracking to 16 patients who had undergone prefrontal leucotomy approximately 25 years earlier. Presurgical diagnosis in each patient was schizophrenia. The 16 were divided into three groups based on their recovery after surgery. A control group of nonleucotomized schizophrenics was established to control for psychiatric symptomatology. A second control group consisted of subjects without history of psychiatric or CNS disorder. In general, there was no statistically significant impairment of performance in attention tests between the patients with prefrontal psychosurgery and the normal control subjects. The nonoperated schizophrenic control group performed most poorly. Lesion chronicity, interaction of leucotomy and presurgical psychiatric state, and conditions of test administration are suggested as possible explanations for the unexpected results.

Do long tests yield a more accurate diagnosis of dementia than short tests? A comparison of 5 neuropsychological tests.

OBJECTIVE: To provide comparative evidence for a valid and practical measure of mental-status functioning that could be used in dementia clinics. DESIGN: Five mental-status neuropsychological tools for dementia screening were administered to patients in a memory disorder clinic. These included the Mini-Mental State Examination, the Dementia Rating Scale, the 6-item derivative of the Orientation-Memory-Concentration Test, a short Mental Status Questionnaire, and a composite tool we labeled the Ottawa Mental Status Examination, which assessed orientation, memory, attention, language, and visual-constructive functioning. The tools were compared using various criteria, including the statistical factors of sensitivity and reliability; effects of gender, native language, and language of testing; the utility of these tests for the differential diagnosis of Alzheimer-type and vascular dementia; and sensitivity to cognitive decline in the entire sample and among patients with severe dementia. RESULTS: All of the tests were highly intercorrelated, suggesting that they are interchangeable. CONCLUSION: The comparisons along the various criteria indicate that if the objective is to have a general index of dementia of the Alzheimer type, short tests are at least as good and sometimes better than the longer tests.

Diagnosis of dementia. Methods for interpretation of scores of 5 neuropsychological tests.

OBJECTIVE: To provide methods to interpret and compare different neurobehavioral screening tests for the diagnosis of dementia. DESIGN: Five mental-status neuropsychological tools for dementia screening were administered to patients in a memory disorder clinic. These included the Mini-Mental State Examination, the Dementia Rating Scale, the 6-item derivative of the Orientation-memory-Concentration Test, a short Mental Status Questionnaire, and a composite tool we labeled the Ottawa Mental Status Examination, which assessed orientation, memory, attention, language, and visual-constructive functioning. RESULTS: To obtain z and percentile scores, norms are for the different tests, computed separately for patients with dementia of the Alzheimer type, vascular dementia, or no dementia. Another set of norms is reported in which a test score is translated directly into the posttest probability of dementia. Translation formulas are given to allow the estimation of the score on one test from the result on another test. CONCLUSION: The interpretation of tests used to diagnose dementia must be based on an understanding of the meaning of an individual score, which is based on the question asked and the population to which the patient is referenced.

Frontal leukotomy size and hemispheric asymmetries on computerized tomographic scans of schizophrenics with variable recovery. Northampton Veterans Administration study.

The computerized tomographic (CT) scans of 17 schizophrenic men who had had bilateral prefrontal leukotomy performed 25 years earlier were examined to determine the relationship among leukotomy site, size, hemispheric asymmetries, and recovery. Six cases of good recovery (GR), five of moderate recovery (MR), and six of no recovery (NR) were studied; 16 of 17 patients were right-handed. Results showed that the GR cases had significantly larger lesions in the low orbitofrontal region (especially on the left) than did the other MR and NR cases. Also, five of six of the GR cases had significantly greater lesion size asymmetry in the low orbitofrontal region and overall than did the other MR and NR cases. There was no consistent asymmetry of lesion size (larger right or left) that was associated with recovery. Significant differences were observed in the hemispheric asymmetries of the right-handed schizophrenics vs normal subjects. Only half the cases had the expected increased left occipital width, and half had unexpected equal or increased right occipital widths. All of the GR cases had either an increased left or right occipital width; none had equal widths. Additional observation of long-standing leukotomy sites on CT scans in schizophrenia cases is recommended.

The long-term effects of prefrontal leukotomy.

To explore the long-term effects of bilateral prefrontal destruction, 16 schizophrenics who had undergone prefrontal leukotomy approximately 25 years earlier were studied by neurologic examination, psychiatric outcome, EEG, computerized tomography (CT), and a battery of neuropsychological tests. Five nonleukotomized chronic schizophrenics and five age-matched normal subjects served as controls. We report details on the subjects, outline the test procedures, and offer an overview of the long-term residua. In general, the larger the frontal lesion demonstrated by CT, particularly if asymmetric, the better the psychiatric outcome and the better the performance on psychological testing, but there was no correlation between frontal lesion size and either neurological or EEG abnormality.

Motor abilities after frontal leukotomy.

The effect of bilateral frontal leukotomy on motor function was evaluated by neurologic examination, tests of praxis, and appropriate neuropsychologic tests administered to five groups of subjects. Postleukotomy schizophrenic patients were subdivided into three degrees of recovery. Two nonleukotomized groups served as controls for effects of schizophrenia, age, and education. The results indicate that the size of the bifrontal damage was not significant in the response to the motor tests, whereas the severity of schizophrenia clearly affected results. As tested, bilateral orbitofrontal white matter lesions did not disturb motor competency.

An extraordinary form of confabulation.

We describe five patients with spontaneous, persistent confabulation. While the basis of confabulation in general is not known, the evidence in this specific group of patients with spectacular, impulsive, and spontaneous confabulation suggests a marked deficit in frontal function, superimposed upon a basic defect in memory, as a possible mechanism.

Capgras syndrome: a reduplicative phenomenon.

A patient recovering from a severe head injury developed a prolonged Capgras syndrome in which he believed his wife and five children had been replaced by nearly identical substitutes. Although this phenomenon is considered a functional disorder in the psychiatric literature, recent reports postulate an organic basis. Recent studies of the comparable neurologic disorder, reduplicative paramnesia, have stressed the importance of bilateral frontal and right hemisphere pathology. Neuropsychologic and neuroradiologic data in our patient revealed this combination, suggesting that the Capgras syndrome may be a form of reduplicative paramnesia with the same pathologic substrate.

Prediction of recovery of continuous memory after traumatic brain injury.

OBJECTIVE: To evaluate the ability of measures of initial severity, tests of attention, and demographic characteristics to predict recovery of continuous memory for words over a 24-hour period in patients with acute traumatic brain injury. METHODS: Recovery of continuous memory was assessed prospectively in 94 patients with nonpenetrating traumatic brain injury. A classification and regression tree analysis identified a hierarchical subset of variables that may be used as a simple guideline for predicting recovery of continuous memory. Weibull regression models evaluated and compared the predictive ability of multiple variables. RESULTS: Four groups of patients were identified based on measures of severity of injury and demographic characteristics. These four groups had recovery profiles that were more precise than could be obtained by using the Glasgow Coma Scale alone: mild, about 1 week to recovery of continuous memory; moderate, 1 to 4 weeks; severe, 2 to 6 weeks; and extremely severe, 4 to 8 weeks. Regression analysis confirmed that measures of capacity (inherent resources such as indicated by age) and compromise (general functional brain state measured neuropsychologically) improved prediction over models based only on injury severity measures, such as the Glasgow Coma Scale. CONCLUSIONS: Approaches to predicting recovery of continuous memory in the acute period after traumatic brain injury that take into account multiple measures provide a more sensitive predictive index.

Capture errors and sequencing after frontal brain lesions.

This study addresses the effect of strong routine associations (capture errors) in hindering the control of on-line serial or sequencing tasks. Patients with focal frontal lobe lesions were significantly inferior to normal control subjects and patients with posterior brain lesions, when conditions that may lead to capture errors were present. The results suggest that the primary dysfunction exhibited by patients with frontal lobe lesions on capture error tasks may lie not in the disengagement from the invalid associations but in focusing attention to alternative strategies of response.

Dissociation of attentional processes in patients with focal frontal and posterior lesions.

A location-based ('select-what, respond-where') priming task was used to examine three measures of selective attention (interference (INT), negative priming (NP), and inhibition of return (IOR)) as a function of focal brain pathology and the complexity of target selection. Control subjects showed different patterns of performance for the three attentional measures as a function of complexity, suggesting some independence among INT, NP, and IOR. Brain-damaged subjects showed significant response slowing, as well as a number of lesion-specific attentional abnormalities. Right frontal (including bifrontal) damage resulted in proportionally increased interference related to task complexity. Left posterior damage increased IOR in the most complex task, while left frontal damage reversed the control pattern of IOR as a function of complexity. Right hemisphere (right posterior and right frontal damage) pathology resulted in a virtual loss of negative priming at all levels of task complexity; left and bifrontal damage resulted in diminished NP only related to increases in the complexity of selection. INT, NP, and IOR are mediated by different brain regions and their expression can be modulated by the complexity of the selection task.

Stroop performance in focal lesion patients: dissociation of processes and frontal lobe lesion location.

There were three primary objectives: to examine the usefulness of the Stroop interference effect as a measure of frontal lobe function; to investigate the possibility of distinct lesion effects for word reading or color naming; and to specifically determine the brain regions necessary for the performance of the incongruent condition. Fifty-one patients with single focal brain lesions in frontal and non-frontal regions and 26 normal control subjects (CTL) were administered the word reading, color naming and incongruent conditions of the Stroop task. Only frontal lesions produced significant impairment. Patients with posterior lesions were not significantly deficient in any condition. Damage to the left dorsolateral frontal lobe resulted in increased errors and slowness in response speed for color naming. Contrary to Perret (Neuropsychology, 1974; 12: 323-330), lesions of the left frontal lobe did not result in a selective interference deficit on the Stroop incongruent condition. Rather, bilateral superior medial frontal damage was associated with increased errors and slowness in response time for the incongruent condition. This result is interpreted as failure of maintenance of consistent activation of the intended response in the incongruent Stroop condition. The results and conclusion are compatible with the prevalent theories of both the Stroop effect and the role of the superior medial frontal regions. The role of the anterior cingulate cortex on performance of the Stroop task is likely related to task and patient context.

The involvement of orbitofrontal cerebrum in cognitive tasks.

Although the frontal lobes are frequently associated with high-level cognitive functions, patients with significant frontal damage often maintain normal "intelligence". While recent research has clarified some aspects of this enigma, specific questions remain concerning the nature of the deficit in these patients and its relation to lesion localization within the frontal lobes. A group of psychiatric patients who had undergone prefrontal leucotomy 25 years earlier and whose frontal lesions were bilateral and maximal orbitofrontally were evaluated. Sixteen leucotomized schizophrenics, divided into three groups based upon recovery after psychosurgery, were compared to two control groups: (1) non-leucotomized chronic schizophrenics; (2) normal subjects. Four tests were administered: Wechsler Adult Intelligence Scale, Wisconsin Card Sorting test, Visual Metaphor test, and the Visual Verbal test of abstraction. The results suggest that orbitofrontal pathology does cause impaired performance on certain cognitive tests, which appeared independent of IQ measures.

Wisconsin Card Sorting Test performance in patients with focal frontal and posterior brain damage: effects of lesion location and test structure on separable cognitive processes.

Forty-six patients with single focal lesions (35 frontal, 11 nonfrontal) were administered the Wisconsin Card Sorting Test (WCST) under three conditions of test administration. The three conditions varied in the amount of external support provided via specificity of instructions. The WCST, while a multifactorial test, is specifically sensitive to the effects of frontal lobe damage if deficits in language comprehension and visual-spatial search are controlled. There is also specificity of functioning within the frontal lobes: patients with inferior medial frontal lesions, unilateral or bilateral, were not impaired on the standard measures although they had increased loss of set when informed of the sorting categories. Verbal instructions may provide a probe to improve diagnosis and prognosis, assessment of the potential efficacy of treatment, and the time frame of plasticity of specific cognitive operations.