Thalamic activation during an attention-to-prepulse startle modification paradigm: a functional MRI study.

BACKGROUND: Prepulse inhibition (PPI) of the startle reflex reflects early stages of information processing and is modulated by selective attention. Animal models indicate medial frontal-thalamic circuitry is important in PPI modulation. We report data from the first functional magnetic resonance imaging (fMRI) study examining whether attending to or ignoring a prepulse differentially activates brain areas within this circuitry. METHODS: Ten healthy subjects received structural and functional MRI. During fMRI acquisition, subjects heard intermixed attended and ignored tones serving as prepulses to the startle stimulus. Regions of interest were traced on structural MRI and coregistered to fMRI images. RESULTS: Greater amplitude fMRI blood-oxygen-level-dependent response to attended than ignored PPI conditions occurred in the right thalamus, and bilaterally in the anterior and mediodorsal thalamic nuclei, whereas the startle-alone condition showed deactivation. In transitional medial cortex (Brodmann Area 32), which is involved in affective processing of noxious stimuli, the startle-alone condition elicited the greatest response, the attended-PPI condition showed the smallest response, and the ignored-PPI condition was intermediate. CONCLUSIONS: These findings extend animal models to humans by indicating thalamic involvement in the modulation of PPI. Further fMRI investigations may elucidate other key structures in the circuitry underlying normal and disordered modulation of PPI.

Patterns of cortical activity and memory performance in Alzheimer's disease.

BACKGROUND: Declarative memory changes are the hallmark of Alzheimer's disease, although their functional neuroanatomy is not restricted to a single structure. Factor analysis provides statistical methods for evaluating patterns of cerebral changes in regional glucose uptake. METHODS: Thirty-three Alzheimer's patients and 33 age- and gender-matched control subjects were studied with magnetic resonance imaging and positron emission tomography with [(18)F] deoxyglucose. During the tracer-uptake period, subjects performed a serial verbal learning task. Cortical activity was measured in 32 regions of interest, four in each lobe on both hemispheres. RESULTS: Factor analysis with varimax rotation identified seven factors explaining 80% of the variance ("parietal cortex," "occipital cortex," "right temporo-prefrontal areas," "frontal cortex," "motor strip," "left temporal cortex," and "posterior temporal cortex"). Relative to control subjects, Alzheimer's patients showed significantly reduced values on the factors occipital cortex, right temporo-prefrontal areas, frontal cortex, and left temporal cortex. The factor temporo-prefrontal areas showed large differences between patients with good and poor performance, but little difference when control subjects were similarly divided. CONCLUSIONS: Findings suggest that Alzheimer's disease is characterized by altered patterns of cortical activity, rather than deficits in a single location, and emphasize the importance of right temporo-prefrontal circuitry for understanding memory deficits.

Age-related shift in brain region activity during successful memory performance.

Coregistered positron emission tomography (PET)/magnetic resonance imaging (MRI) was used to characterize brain function in 70 volunteers, aged 20-87 years, during a verbal memory task. Frontal activity showed an age-related decline that remained significant after statistical control for sulcal atrophy. Analyses of young and old subgroups matched for memory scores revealed that young good performers activated frontal regions, whereas old good performers relied on occipital regions. Although activating different cortical regions, good performers of all ages used the same cognitive strategy semantic clustering. Age-related functional change may reflect dynamic re-allocation in a network of brain areas, not merely anatomically fixed neuronal loss or diminished capacity to perform.

Limbic circuitry in patients with autism spectrum disorders studied with positron emission tomography and magnetic resonance imaging.

OBJECTIVE: Cytoarchitectonic changes in the anterior cingulate cortex, hippocampus, subiculum, entorhinal cortex, amygdala, mammillary bodies, and septum were reported in a postmortem study of autism. Previously, the authors found smaller cingulate volume and decreased metabolism of the cingulate in seven autistic patients. In this study, they measured the volume and glucose metabolism of the amygdala, hippocampus, and cingulate gyrus in an expanded group of 17 patients with autism spectrum disorders (autism [N=10] or Asperger's disorder [N=7]) and 17 age- and sex-matched healthy volunteers. METHOD: Subjects performed a serial verbal learning test during (18)F-deoxyglucose uptake. The amygdala, hippocampus, and cingulate gyrus were outlined on magnetic resonance imaging scans, volumes of the structures were applied to matching coregistered positron emission tomography scans, and three-dimensional significance probability mapping was performed. RESULTS: Significant metabolic reductions in both the anterior and posterior cingulate gyri were visualized in the patients with autism spectrum disorders. Both Asperger's and autism patients had relative glucose hypometabolism in the anterior and posterior cingulate as confirmed by analysis of variance; regional differences were also found with three-dimensional significance probability mapping. No group differences were found in either the metabolism or the volume of the amygdala or the hippocampus. However, patients with autism spectrum disorders showed reduced volume of the right anterior cingulate gyrus, specifically in Brodmann's area 24'. CONCLUSIONS: Compared with age- and sex-matched healthy volunteers, patients with autism spectrum disorders showed significantly decreased metabolism in both the anterior and posterior cingulate gyri.

Three-dimensional analysis with MRI and PET of the size, shape, and function of the thalamus in the schizophrenia spectrum.

OBJECTIVE: In an exploration of the schizophrenia spectrum, the authors compared thalamic size, shape, and metabolic activity in unmedicated patients with schizophrenia and schizotypal personality disorder to findings in age- and sex-matched healthy control subjects. METHOD: Coregistered magnetic resonance imaging (MRI) and positron emission tomography scans were obtained in 27 schizophrenic patients, 13 patients with schizotypal personality disorder, and 32 control subjects who performed a serial verbal learning test during tracer uptake. After thalamus edges were outlined on 1.2-mm MRI scans, a radial warping program yielded significance probability mapping in three dimensions. RESULTS: Significance probability mapping (with resampling) identified an area in the region of the mediodorsal nucleus bilaterally with significantly lower relative metabolism in the schizophrenia group than in either the control or schizotypal personality disorder groups, which did not differ from each other. The three groups did not differ significantly in total thalamic volume in square millimeters or thalamic volume relative to brain volume. Shape analyses revealed that schizophrenic patients had significantly fewer pixels in the left anterior region, whereas patients with schizotypal personality disorder had significantly fewer pixels in the region of the right mediodorsal nucleus than did control subjects. CONCLUSIONS: Schizophrenic patients showed significant metabolism and shape differences from control subjects in selective subregions of the thalamus, whereas patients with schizotypal personality disorder showed only a difference in shape. Because the mediodorsal and anterior nuclei have different connections with limbic and prefrontal structures, the anterior thalamic shrinkage and mediodorsal metabolic and shape changes might relate to the different clinical pictures in schizotypal personality disorder and schizophrenia.

Differential amygdala activation during emotional decision and recognition memory tasks using unpleasant words: an fMRI study.

This study used fMRI to examine the response of the amygdala in the evaluation and short-term recognition memory of unpleasant vs. neutral words in nine right-handed healthy adult women. To establish specificity of the amygdala response, we examined the fMRI BOLD signal in one control region (visual cortex). Alternating blocks of unpleasant and neutral trials were presented. During the emotional decision task, subjects viewed sets of three unpleasant or three neutral words while selecting the most unpleasant or neutral word, respectively. During the memory task, subjects identified words that were presented during the emotional decision task (0.50 probability). Images were detrended, filtered, and coregistered to standard brain coordinates. The Talairach coordinates for the center of the amygdala were chosen before analysis. The BOLD signal at this location in the right hemisphere revealed a greater amplitude signal for the unpleasant relative to the neutral words during the emotional decision but not the memory task, confirmed by Time Course x Word Condition ANOVAs. These results are consistent with the memory modulatory view of amygdala function, which suggests that the amygdala facilitates long-term, but not short-term, memory consolidation of emotionally significant material. The control area showed only an effect for Time Course for both the emotional decision and memory tasks, indicating the specificity of the amygdala response to the evaluation of unpleasant words. Moreover, the right-sided amygdala activation during the unpleasant word condition was strongly correlated with the BOLD response in the occipital cortex. These findings corroborate those by other researchers that the amygdala can modulate early processing of visual information in the occipital cortex. Finally, an increase in subject's state anxiety (evaluated by questionnaire) while in the scanner correlated with amygdala activation under some conditions.

Regional and global changes in cerebral diffusion with normal aging.

BACKGROUND AND PURPOSE: We used quantitative diffusion MR imaging to investigate the microstructural changes that occur in white matter during normal aging in order to identify regional changes in anisotropy and to quantify global microstructural changes by use of whole-brain diffusion histograms. METHODS: Full diffusion tensor MR imaging was performed in 20 healthy volunteers, 20 to 91 years old. Thirteen subjects also underwent high-resolution T1-weighted imaging, so that diffusion images could be coregistered and standardized to normal coordinates for statistical probability mapping. Relative anisotropy (RA) was calculated, as was linear regression of RA with age for each pixel; pixels with a significant correlation coefficient were displayed. For histographic analysis, the average apparent diffusion coefficient (ADC) histograms were calculated on a pixel-by-pixel basis. Subjects were divided into two equal groups by the median age (55 years) of the population and plotted for statistical comparison. RESULTS: Regional analysis showed statistically significant decreases in RA with increasing age in the periventricular white matter, frontal white matter, and genu and splenium of the corpus callosum, despite the absence of signal abnormalities on visual inspection of conventional images. Significant increases in RA were found in the internal capsules bilaterally. ADC histograms showed higher mean ADC and reduced peak height and skew in the older age group on group comparisons. CONCLUSION: Quantitative diffusion histograms correlate with normal aging and may provide a global assessment of normal age-related changes and serve as a standard for comparison with neurodegenerative diseases.

A method of basal forebrain anatomical standardization for functional image analysis.

Functional as well as structural assessment of the basal forebrain has mostly focused on the dorsal caudate and putamen in axial slices where they are easily outlined or their centers located with stereotaxic methods. The more ventral extent of the basal forebrain, where the irregular form and indistinct boundaries of the nucleus accumbens and substantia innominata are difficult to trace and where the brain's ventral surface may contribute partial volume artifacts to measurement, has been less studied. We present a method based on coronal sections, landmarks placed on clearly visible anchor points, and the computational technique of thin-plate spline warping which allows the alignment of groups of individuals to common coordinates for pixel-by-pixel statistical mapping. The reliability of the landmarks across independent raters yields a median absolute difference of 1.3-1.6 mm. The validity of the method is confirmed by variance maps which reveal significant decreases in variance over spindle and bounding box alignment.

Focused image recovery from two defocused images recorded with different camera settings.

Two new methods are presented for recovering the focused image of an object from only two blurred images recorded with different camera parameter settings. The camera parameters include lens position, focal length, and aperture diameter. First a blur parameter sigma is estimated using one of our proposed depth-from-defocus methods. Then one of the two blurred images is deconvolved to recover the focused image. The first method is based on a spatial domain convolution/deconvolution transform. This method requires only the knowledge of sigma of the camera's point spread function (PSF). It does not require information about the actual form of the camera's PSF. The second method, in contrast to the first, requires full knowledge of the form of the PSF. As part of the second method, we present a calibration procedure for estimating the camera's PSF for different values of the blur parameter sigma. In the second method, the focused image is obtained through deconvolution in the Fourier domain using a Wiener filter. For both methods, the results of experiments on actual defocused images recorded by a CCD camera are given. The first method requires much less computation than the second method. The first method gives satisfactory results for up to medium levels of blur and the second method gives good results for up to relatively high levels of blur.

Molecular dynamics of water in foods and related model systems: multinuclear spin relaxation studies and comparison with theoretical calculations.

A review of recent studies of molecular dynamics of water in foods and model systems is presented, and the theoretical results are compared with experimental data obtained by several techniques. Both theoretical and experimental approaches are discussed for electrolytes, carbohydrates, and food proteins in solution. Theoretical results from Monte Carlo simulations are compared with experimental NMR relaxation data for quadrupolar nuclei such as those of deuterium and oxygen-17. Hydration studies of wheat, soybean, corn, and myofibrillar proteins by multinuclear spin relaxation techniques are discussed, and several new approaches to the analysis of the experimental data are considered. Correlation times of water motions in hydrated food systems are determined from NMR and dielectric relaxation data. The values of the correlation times for dilute solutions of electrolytes and carbohydrates estimated by NMR are in good agreement with those calculated from dielectric relaxation data, but seem to differ significantly from those proposed from Monte Carlo simulations. Several new and important results concerning the hydration of potato and cereal starches are presented, showing the very different hydration behaviors of these two major groups of starches. The combination of molecular dynamics computations with NMR relaxation techniques will hopefully stimulate novel technological developments in food engineering based on such fundamental studies.

Experiences in surgical management of cavernous hemangioma of the liver.

BACKGROUND/AIMS: Observation is usually recommended for managing patients with cavernous hemangioma of the liver. To assess the indications for surgical management, we make a retrospective analysis. PATIENTS AND METHODS: There were 14 patients with cavernous hemangioma of the liver who were surgically treated in National Taiwan University Hospital from 1984 to 1993. RESULTS: The surgical indications included uncertain diagnosis in 10 patients, progressive tumor enlargement in two, symptomatic tumor in one and subcapsular bleeding in one. The tumors were 2-15 cm in diameter and the median was 6 cm. The operation procedures included atypical hepatectomy in 6 patients, lateral segmentectomy in 4, right lobectomy in one, extended right lobectomy in one and open biopsy in two. There was no mortality. Wound infection occurred in one patient. The average blood transfusion was 0.79 unit (range: 0-3 units)(1 unit=500 ml). The postoperative hospital stay was 13.2 days (range: 10-18 days). CONCLUSION: Surgical management of cavernous hemangioma of the liver is safe.

Intratumor injection of absolute ethanol under ultrasound guidance for the treatment of small hepatocellular carcinoma.

For the treatment of small hepatocellular carcinoma, intratumor injection of absolute ethanol under ultrasound guidance was performed in 27 tumors in 23 patients, with a tumor diameter of between 1.0 and 3.3 cm. The initially elevated serum alpha-fetoprotein levels in 15 patients decreased during treatment, with 13 returning to normal after this regimen. In the 6 patients who finally received surgical resection, 4 had complete necrosis of the tumor, while the other 2 had a small peripheral residual cancer nest. In the remaining non-resected 17 cases, follow-up CT, multiple biopsies and angiography revealed evidence of viable tumor in only 3 cases. After additional ethanol injections, these 3 cases were successfully treated. Inhomogeneous distribution of the injected ethanol and difficulty in identifying the tumor after previous injections accounted for the incomplete necrosis of the tumor. To cope with these problems, a steel coil was implanted in the tumor before treatment, and a needle with multiple side holes was used in the last 3 cases, with satisfactory results. Ethanol injection is promising and may even be curative in the treatment of small hepatocellular carcinoma.

Intraoperative irrigation of the colon and primary anastomosis: report of three cases.

Three male patients with obstructive left-sided colonic lesions received intraoperative irrigation of the colon and primary anastomosis after resection of the lesions. Their postoperative courses were smooth except for one patient with mild wound infection. Intraoperative irrigation of the colon is an effective method of facilitating primary anastomosis in the management of obstructive left-sided colonic lesions.

Can cecal diverticulitis be differentiated from acute appendicitis?

Cecal diverticulitis is a rare disease entity, the diagnosis of which remains a difficult problem. The clinical picture of cecal diverticulitis is almost indistinguishable from acute appendicitis. We reviewed 11 cases of pathologically documented cecal diverticulitis who underwent treatment from May 1981 to April 1992. They were diagnosed incorrectly as acute appendicitis, ruptured appendicitis or appendiceal abscess prior to operative intervention. Thirty patients diagnosed correctly with acute appendicitis from March 1992 to April 1992 were included for a comparative study. We found that cecal diverticulitis presented with a longer duration of symptoms, initial pain over the right lower quadrant of the abdomen, older age, less migration of pain, nausea, vomiting, fever and leukocytosis, and an incidence of Alvarado's score > or = 7 than acute appendicitis.

An uncommon cause of biliary obstruction (Mirizzi syndrome): report of five cases.

Mirizzi syndrome is a rare form of common hepatic duct obstruction resulting from an inflammatory response secondary to a gallstone impacted in the cystic duct or neck of the gallbladder. Herein, we report five patients with this syndrome. Clinically, all patients had prominent jaundice. Ultrasound examination showed a large stone in the neck of the gallbladder. Endoscopic retrograde cholangiopancreaticography demonstrated a filling defect in the biliary tract the cystic duct level. Four patients possessed cholecystobiliary fistulas. Two patients also had common bile duct stones. Operations included simple cholecystectomy in one patient, and partial cholecystectomy with choledochoplasty with the use of gallbladder flap and T-tube insertion in the other four patients. All patients were uneventfully discharged. If a patient has clinical obstructive jaundice, a huge stone encased in the neck of the gallbladder and a filling defect of the biliary tract at the cystic duct level shown on a cholangiogram, Mirizzi syndrome must be considered. A cholecystobiliary fistula will probably be present if the cholangiogram further reveals an excavated filling defect or a block of the common duct; in this case, partial cholecystectomy and choledochoplasty with a gallbladder flap is the treatment of choice. Mirizzi syndrome is a contraindication for laparoscopic cholecystectomy which can easily result in common duct injury.

Carcinoma of the ampulla of Vater: long-term survival after surgical treatment.

Ninety-one patients were identified as having carcinoma arising from the ampulla of Vater. Radical pancreaticoduodenectomy, using either a standard or pylorus-preserving method, was performed in 69 consecutive patients over a 30-year period. Frequent clinical findings included jaundice (84%), a weight loss of more than 10% of the body weight (75%), abdominal pain (59%), chills and fever (52%), pruritus (48%) and a palpable gallbladder (38%). Acute pancreatitis was present in 10%. Postoperative mortality was 11.6%. Surgical mortality was 23.1% from 1962 to 1971 and 12.5% from 1972 to 1981, but was reduced to 6.3% from 1982 to 1991. Surgical mortality was primarily due to pancreaticojejunostomy leaks. The five-year survival rate was 52% and the 10-year rate was 50%. Radical pancreaticoduodenectomy for ampullary carcinoma has a low mortality and should remain the procedure of choice for ampullary carcinoma.

Distributional pattern of diverticular disease of the colon in Taiwan.

From May 1981 to October 1991, 66 patients with diverticular disease of the colon were analyzed retrospectively. Data were obtained from medical records. There were 29 men and 37 women, ranging in age from 32 to 85 years, with a mean age of 58.7 years. Forty-nine patients had a singular site of distribution in the diverticulum, and 17 patients had more than two sites of distribution in the diverticula. The locations of the diverticular disease were sigmoid colon (45.4%), ascending colon (36.4%), cecum (33.3%), descending colon (18.2%), transverse colon (12.1%) and rectum (1.5%). The left-sided lesions (46.9%) were approximately equal to the right-sided lesions (43.9%).

Gonadoblastoma and chroiocarcinoma in dysgenic gonads: report of a case.

Dysgenetic gonads are well known to be associated with gonadoblastoma and various germ cell tumors, but very rarely with choriocarcinoma. We describe a 16-year-old, phenotypic female patient with a 46XY karyotype who developed gonadoblastoma on the right gonad and choriocarcinoma on the left. There was no co-existence of the two tumor cell types in the same gonad. This case emphasizes the importance of bilateral gonadectomy for "46XY female" patients, as soon as the cytogenetic evidence is known.

Liver resection for hepatic metastasis from colorectal carcinoma.

One hundred and eighteen patients who suffered from metastatic liver tumors from colorectal carcinoma during the period from January 1980 to June 1991 at the National Taiwan University Hospital were retrospectively reviewed. The modes of treatment included hepatic resection (n = 18), transarterial embolization (TAE, n = 17), chemotherapy only (C/T, n = 36), and no treatment (n = 47). In the 18 patients who underwent hepatic resection during the last 10 years, the types of surgery included: wedge resection (n = 8), segmentectomy (n = 2), right hepatic lobectomy (n = 5), left hepatic lobectomy (n = 2) and extended right hepatic lobectomy (n = 1). There were no operative mortalities in this series. The overall three-year actuarial survival rate of the resection group was 57.5%. It was better than that of the TAG group (17%, p < 0.05). For a solitary tumor, the three-year actuarial survival rate rose to 64% in the resection group. There were no three-year survivors in the nonsurgical solitary tumor group. This experience defends aggressive surgical treatment of resectable hepatic metastatic liver cancer from colorectal carcinoma as a safe procedure which is able to prolong a patient's life.

Therapeutic effect of liver resection in patients with metastatic liver tumors.

Thirty-five hepatectomies for metastatic liver malignancy were performed from January 1986 to July 1992 at the National Taiwan University Hospital. Twenty-six of them were of colorectal origin and nine were of other origins. We analyzed the risk factors for recurrence and survival rate after hepatectomy of colorectal origin under curative intention with both univariate and multivariate analysis. The calculated median disease free interval after hepatectomy was 11 months (recurrence rate 65% in one year and 85% in two years). The median survival rate was 24 months (calculated one-year survival 86%, two-year survival 41%). In univariate analysis, the number of metastatic lesions and operation procedures significantly affect the recurrence rate (p = 0.033 and p = 0.042, respectively). In survival univariate analysis, only a safety margin > 1 cm and age > 50 years had significant benefit (p = 0.0014 and p = 0.045, respectively). By multivariate analysis, only solitary metastasis was beneficial to the recurrence rate (p = 0.013), an age > 50 years had a borderline beneficial effect to the recurrence rate (p = 0.052), while earlier liver stage, older age, larger safety margin and minor operative procedures positively affected the survival rate (p = 0.039, 0.018, 0.034 and 0.017, respectively). As the sample number was small, it was hard to draw any conclusions for metastatic liver tumors of other origins. The complication rate (5/35) and mortality rate (1/35) of hepatectomy were low. We concluded that for selected cases of metastatic hepatic malignancy, especially from colorectal cancer, hepatectomy is a promising treatment of choice.