Into the future with little past: exploring mental time travel in a patient with damage to the mammillary bodies/fornix.

OBJECTIVE: Remembering the past and imaging the future are both manifestations of 'mental time travel'. These processes have been found to be impaired in patients with bilateral hippocampal lesions. Here, we examined the question of whether future thinking is affected by other Papez circuit lesions, namely: damage to the mammillary bodies/fornix. METHOD: Case (SL) was a 43-year-old woman who developed dense anterograde and retrograde amnesia suddenly, as a result of Wernicke-Korsakoff's syndrome. A region of interest volumetric Magnetic resonance imaging (MRI) analysis was performed. We assessed past and future thinking in SL and 11 control subjects of similar age and education with the adapted Autobiographical Interview (AI). Participants also completed a battery of neuropsychological tests. RESULTS: Volumetric MRI analyses revealed severely reduced fornix and mammillary body volumes, but intact hippocampi. SL showed substantial, albeit temporally graded retrograde memory deficits on the adapted AI. Strikingly, whilst SL could not provide any specific details of events from the past two weeks or past two years and had impaired recall of events from her late 30s, her descriptions of potential future events were normal in number of event details and plausibility. CONCLUSIONS: This dissociation of past and future events' performance after mammillary body and fornix damage is at odds with the findings of the majority of patients with adult onset hippocampal amnesia. It suggests that these non-hippocampal regions of the Papez circuit are only critical for past event retrieval and not for the generation of possible future events.

Regional cerebral blood flow in patients with alcohol-related dementia: a SPECT study.

The purpose of this study was to investigate regional cerebral blood flow (rCBF) changes using 1110 MBq of Tc-99m ECD SPECT in alcohol-related dementia (ARD) patients. Twenty-five patients with ARD and 22 healthy control subjects were included in the study. Mini-Mental Status Examination was applied to the patients and controls. The ARD patients showed drastically reduced rCBF in the frontal cortices, basal ganglia, and thalami. The results indicate that ARD is associated with hypoperfusion in both cortical and subcortical regions. These findings support previous studies suggesting the association with both cortical and subcortical neuropathology in ARD patients.

Regional cerebral blood flow and oxygen metabolism in a patient with Korsakoff syndrome.

We report a functional neuroimaging study of a patient clinically diagnosed with Korsakoff syndrome. Positron emission tomography (PET) with the 15O inhalation method showed decreased regional cerebral blood flow (rCBF) and decreased regional cerebral metabolic ratio for oxygen (rCMRO2) in the bilateral fronto-temporal areas and in the left thalamus. These results suggest that dysfunction of the frontal-thalamic neural network plays a role in the disturbance of Korsakoff syndrome.

Temporal and spatial context memory in patients with focal frontal, temporal lobe, and diencephalic lesions.

Patients with focal frontal, temporal lobe, or diencephalic lesions were investigated on measures of temporal (recency) and spatial (position) context memory, after manipulating exposure times to match recognition memory for targets (pictorial stimuli) as closely as possible. Patients with diencephalic lesions from an alcoholic Korsakoff syndrome showed significant impairment on the temporal context (recency) task, as did patients with frontal lesions penetrating the dorsolateral frontal cortex, according to MRI (and PET) evidence. Patients with temporal lobe lesions showed only a moderate (non-significant) impairment on this task, and patients with medial frontal lesions, or large frontal lesions not penetrating the dorsolateral cortical margins, performed as well as healthy controls at this task. On the spatial context memory task, patients with lesions in the temporal lobes showed significant impairment, and patients with right temporal lesions performed significantly worse than patients with left temporal lesions. Patients with diencephalic lesions showed only a modest (non-significant) impairment on this task, and the frontal lobe group performed normally. When a group of patients with temporal lobe lesions resulting from herpes encephalitis were examined separately, an identical pattern of results was obtained, the herpes group being significantly impaired on spatial memory and showing a trend towards impairment for temporal context memory. There were strong correlations between anterograde memory quotients and context memory performance (despite the use of an exposure time titration procedure) and a weak association in the frontal group with one frontal/executive task [corrected] (card-sorting perservations). It is predicted that correlations between temporal context memory and frontal/executive tasks will be greater in samples of patients all of whom have frontal lesions invading the dorsolateral cortical margin.

Decreased cingulate and precuneate glucose utilization in alcoholic Korsakoff's syndrome.

Localized cerebral glucose utilization was determined for nine abstinent alcoholic men with Korsakoff's syndrome and 10 age-matched normal men who underwent positron emission tomography with [18F]2-fluoro-2-deoxyglucose (FDG). Patients with Korsakoff's syndrome showed relatively decreased glucose utilization in cingulate and precuneate areas. These decreases persisted even after correction for group differences in ventricular and sulcal cerebrospinal fluid measured on computed tomography. Electroencephalographic recordings at the time of FDG uptake showed no group differences, a finding that demonstrates that the metabolic differences could not be explained by differences in physiological arousal at the time of scanning. It is concluded that the decreased glucose utilization in the patients reflects a disruption of memory circuitry, the Papez circuit, caused by diencephalic lesions induced by thiamine deficiency.

Fully automated segmentation of cerebrospinal fluid in computed tomography.

A method is presented for automated delineation and measurement of cerebrospinal fluid (CSF) regions in computed tomographic (CT) sections. Regions of skull and scalp are removed by using a linear discriminant analysis approach. Beam-hardening artifact is reduced by subtracting from each section the average radial intensity profile, characterized by a polynomial function. Remaining intensity gradients are suppressed by implementing CSF segmentation with a local thresholding technique based on maximum-entropy principles. CSF fractions from 12 regions of interest (ROIs) were measured in 10 patients with alcoholic Korsakoff syndrome and 9 normal volunteers. The same ROIs were also assessed by an interactive segmentation method, which enabled the operator to compensate for beam-hardening distortions by selecting suitable threshold values for each ROI. Both methods identified the same ROIs as displaying statistically significant differences between the two subject groups. However, interactive segmentation underestimated sulcal CSF by 20-70%, which was confirmed by applying both methods to CT scans of an anthropomorphic phantom. Hence, in contrast to interactive thresholding, unsupervised segmentation relies on firmly fixed criteria that reduce the influence of beam-hardening distortions and provide more objective results.

Componential analysis of problem-solving ability: performance of patients with frontal lobe damage and amnesic patients on a new sorting test.

A new sorting task designed to isolate and measure specific components of problem-solving ability was administered to four subject groups: patients with focal frontal lobe lesions, patients with both frontal dysfunction and amnesia (Korsakoff's syndrome), patients with circumscribed (non-Korsakoff) amnesia, and normal control subjects. The patients with circumscribed (non-Korsakoff) amnesia, and normal control subjects. The patients with frontal lobe lesions and patients with Korsakoff's syndrome were impaired on eight of the nine components of the task. The findings run counter to theories of a single or primary impairment in patients with frontal lobe dysfunction. Rather, the results suggest that a wide spectrum of deficits in abstract thinking, cognitive flexibility, and use of knowledge to regulate behavior contributes to the problem-solving impairment of these patients. Although the (non-Korsakoff) amnesic patients performed similarly to normal subjects on most measures, a finer analysis suggested that successful performance on this complex sorting task, in addition to being strongly dependent upon frontal lobe function, is mildly dependent upon memory function.

Regional cerebral glucose utilization in chronic organic mental disorders associated with alcoholism.

Localized cerebral utilization rates for glucose (CMRglu) were determined in 10 detoxified patients with alcoholic organic mental disorders and in 7 age-equivalent normal volunteers using [18F]2-fluoro-2-deoxyglucose positron emission tomography. Although gray and white matter CMRglu were not significantly different, normalized CMRglu was increased in the left cerebellar and parietal cortical regions and decreased in the right posterior white matter and anterior temporal regions of alcoholic patients, and the pattern of regional CMRglu differed between the two groups. The results suggest functional disruption of right-sided and frontal brain regions and hyperactivity of cerebellar-cortical connections in alcoholic chronic organic mental disorders.

Cortical and diencephalic lesions in Korsakoff's syndrome: a clinical and CT scan study.

Twenty-five male alcoholic Korsakoff patients were compared with age and sex-matched non-Korsakoff chronic alcoholics and healthy volunteers on clinical and CT brain scan parameters. The scans were assessed by planimetry, visual grading procedures and computerized analysis. Reliable measures of third ventricular size were developed. The Korsakoff patients had wider third ventricles, larger lateral ventricles and wider interhemispheric fissures than the comparison groups; but sulcal and Sylvian fissure widths were equivalent in Korsakoff and non-Korsakoff alcoholics. The results suggest that, in addition to their well-established diencephalic lesions, many Korsakoff patients have sustained widespread cerebral damage. Shrinkage in the frontal brain regions appears to be especially pronounced. The implications for a dual aetiology of alcoholic Korsakoff's syndrome involving thiamine deficiency and features associated with alcoholism, probably direct alcohol neurotoxicity, are discussed.

Positron emission tomography as a technique for studying the chronic effects of alcohol on the human brain.

Positron emission tomography is a neuroradiographic imaging technique that is beginning to be used to study cerebral pathophysiology in detoxified alcoholics. Localized cerebral glucose utilization in alcoholics at rest is not dramatically affected in comparison to the relatively large alterations in anatomic structure, cognition, and brain electrical activity. It is anticipated that future research studies will include cognitive challenges and utilization of PET ligands being developed to bind to specific receptors in the brain.

[Single-photon emission-computed tomography in the differential diagnosis of dementia]. / Single-Photon-Emissions-Computertomographie bei der Differentialdiagnose der Demenz.

To assess the value of single photon emission computed tomography (SPECT) in the differential diagnosis of dementia SPECT and conventional computed tomography were performed in 77 patients (50 men, 27 women, mean age 59 [28-90] years) with dementia diagnosed by a battery of psychometric tests. In 13 out of 15 patients with dementia of Alzheimer type SPECT showed a typical Alzheimer pattern (bilateral parietotemporal perfusion defects). Both patients with dementia of Pick type had definite decreases in frontal perfusion. All 21 patients with dementia due to Huntington's chorea showed a typical pattern with absent perfusion of the head of the caudate nucleus, although in three of them conventional computed tomography didn't demonstrate complete atrophy of this structure. Out of 23 patients with multi-infarct dementia there were 17 with focal uptake deficits at various sites, while six displayed an Alzheimer pattern. In Korsakoff's syndrome (n = 11), Down's syndrome (n = 1), Fahr's syndrome (n = 2), senile chorea (n = 1) and HIV encephalopathy (n = 1) no typical distribution patterns were noted. Single photon emission computed tomography can make a contribution to the diagnosis and classification of primary degenerative dementias and can be used to differentiate them from other forms of dementia.

Korsakoff's syndrome: radiological (CT) findings and neuropsychological correlates.

Quantitative analyses were performed on computer tomography (CT) scans from 7 patients with Korsakoff's syndrome, 7 age-matched alcoholic subjects, and 7 age-matched healthy control subjects. CT values were used to estimate tissue density and fluid volume in specified brain areas. Tissue density was assessed by averaging CT values in small (5 x 5 mm) areas sampled bilaterally in 6 specified areas--thalamus, head of the caudate nucleus, putamen, anterior white matter, posterior white matter, and centrum semiovale. We assessed fluid volume using a semiautomated computer algorithm that estimated the proportion of fluid in 7 brain regions--total ventricular space, third ventricle, interventricular region, frontal sulci, peri-Sylvian region, medial cerebellum, and vertex. For the patients with Korsakoff's syndrome, we also assessed the correlation between CT measures and performance on 6 cognitive and 12 memory tests. Compared with alcoholic subjects and healthy control subjects, patients with Korsakoff's syndrome had lower CT density values bilaterally in the region of the thalamus and had greater estimated fluid bilaterally in the region of the third ventricle. Alcoholic and healthy control subjects did not differ on these measures. Significant cortical atrophy in frontal sulcal and peri-Sylvian areas was detected both in patients with Korsakoff's syndrome and in alcoholic subjects. For patients with Korsakoff's syndrome, impairment on behavioral tests, and on memory tests in particular, was correlated with low-density values in the thalamus and with high fluid values in the region of the frontal sulci. Damage to diencephalic and frontal areas may especially contribute to the memory and cognitive impairment exhibited by patients with Korsakoff's syndrome.

Examination of alcoholics by computed tomographic (CT) scans: a critical review.

Neuroradiological studies have consistently demonstrated that alcoholics have morphological abnormalities of cortical, ventricular, and cerebellar structures suggesting brain atrophy. This atrophy is weakly correlated with impaired psychological test performance. Because brain atrophy and intellectual impairment can also be found in normal aging it is necessary to compare alcoholics with age-matched control subjects. It is currently unknown if alcohol-associated brain atrophy and intellectual impairment are the result of conditions preceding alcohol consumption or conditions only indirectly related such as head trauma or other associated diseases. Direct alcohol toxicity would be supported by quantitative alcohol-atrophy dose-response relationships and by a partial reversal of atrophy and functional impairment following abstinence from alcohol. Because of methodological difficulties inherent in neuroradiological research, data on the exact pathogenesis of abnormalities in alcoholics have not been produced. The design of such studies can be improved to increase the probability that the causes of brain atrophy will be elucidated.

[Brain atrophy in chronic alcoholism. Clinical and computer tomographic study]. / Hirnatrophische Veränderungen bei chronischem Alkoholismus. Eine klinische und computertomographische Studie.

Fifty chronic alcoholics (37 men and 13 women, ages 26--55, mean age 39.9 years) with different clinical syndromes (alcoholic psychosis, alcoholic encephalopathies) were studied by computerized cranial tomography. Cerebral atrophy was detected in 96% of all cases. Combined cortical and subcortical signs were encountered in almost all cases. Cortical atrophy seemed to be detectable more easily by CT than by pneumencephalography. The computerized tomographic findings were studied in their relations to age, sex, duration of abuse, clinical syndromes, frequency of relapse (and seizures, too), etc. Cerebral atrophy was correlated primarily with the subjects' age and the duration, and less with the intensity of alcoholism. The most distinct changes were found in delirium syndromes and, in cases with relapse of psychosis, especially in combination with seizures. Wernicke-Korsakow encephalopathies showed the widest third ventricles when combined with repeated syndromes of withdrawal in their case histories. Computerized tomographic examinations of ten patients during acute psychosis as well as 4 weeks later showed identical findings; transitory changes, e.g., cerebral edema, were not detected. Computerized cranial tomography appears to be extremely useful to study the numerous open questions concerning the pathogenetic role of age, duration, and severity of abuse with cerebral atrophy.

Resting tremor in alcoholic brain disease.

Two patients with signs of alcoholic brain disease of the Wernicke-Korsakoff type were found to have an unusual movement disorder manifested basically as a resting tremor. Electrographic recording showed that the tremor wave comprised multiple elements, though the rate of the basic tremor was stable. Though the tremor was qualitatively similar to documented rubral tremor, a mesencephalic lesion could be defined in only 1 patient.