Ventrolateral prefrontal cortex activity associated with individual differences in arbitrary delayed paired-association learning performance: a functional magnetic resonance imaging study.

To describe the neural substrates of successful episodic long-term memory encoding, we collected functional magnetic-resonance imaging data as participants completed an arbitrary delayed auditory paired-association learning task. During the task, subjects learned predefined but hidden stimulus pairs by trial and error based on visual feedback. Delay period activity represents the retrieval of the relationship between the cue item and its candidate for associates, that is, working memory. Our hypothesis was that the neural substrates of working memory would be related to long-term memory encoding in a performance-dependent manner. Thus, inter-individual variance in performance following a fixed learning set would be associated with differing neural activations during the delay period. The number of learning trials was adjusted such that performance following completion of the learning set varied across subjects. Each trial consisted of the successive presentation of two stimuli (first stimulus and second stimulus [S2]) with a fixed delay interval, allowing extraction of sustained activity during the delay period. Sustained activities during the delay period were found in the bilateral dorsolateral prefrontal cortex, intraparietal sulcus, and left ventrolateral prefrontal cortex, as well as the premotor and pre-supplementary motor areas. The activities did not change in strength across learning, suggesting that these effects represent working memory components. The sustained activity in the ventrolateral prefrontal region was correlated with task performance. Task performance was also positively correlated with the decrement in S2/feedback-related activity during learning in the superior temporal sulcus, a region previously shown to be involved in association learning. These findings are consistent with lesion and neuroimaging studies showing that the ventrolateral prefrontal cortex plays an important role in long-term memory encoding, and raise the possibility that working memory processes interact with long-term memory formation as represented by the covariation of activity in the superior temporal sulcus and the ventrolateral prefrontal cortex.

Selective inhibition of vascular smooth muscle cell proliferation by coptisine isolated from Coptis rhizoma, one of the crude drugs composing Kampo medicines Unsei-in.

Acceleration of vascular smooth muscle cell (VSMC) proliferation is closely linked to the pathogenesis of vascular diseases. We, therefore, focused on traditional Japanese herbal medicines (Kampo medicines) used to ameliorate the impairment of microcirculation or blood stasis and screened them for their ability to inhibit rat VSMC proliferation. Among them, Unsei-in was found to effectively suppress VSMC proliferation, and Coptis rhizome was the responsible constituent crude drug. The extract of Coptis rhizome inhibited VSMC proliferation with the GI(50) value of 4.4 microg/ml, which was much lower than those against the proliferation of 3Y1, dRLh-84, B16, and HeLa cells. The Coptis rhizome extract inhibited the progression of VSMC arrested at G(0)/G(1) phase from G(0)/G(1) to S phase, but not that of 3Y1 cells. Biological assay-guided fractionation revealed that an alkaloid of Coptis rhizome, coptisine, was the active ingredient in selectively preventing VSMC proliferation with GI(50) of 3.3 microM (1.2 microg/ml). When the structurally-related isoquinoline alkaloids of protoberberine class were studied for their inhibitory activities, berberine decreased the VSMC proliferation with GI(50) of 95.1 microM (35.4 microg/ml), about 30 times higher concentration than coptisine, while palmatine failed to show any activity. This study provides evidence that coptisine, an ingredient of Unsei-in, prevents VSMC proliferation selectively at lower concentrations compared with various cells or other structurally related alkaloids.

Comparison of hemorrhagic effect of heparin and human activated protein C with use of Thrombostat 4000.

The importance of bleeding as a complication of anticoagulant therapy is clearly recognized. We previously reported that amelioration of hemorrhage associated with disseminated intravascular coagulation by the human activated protein C (APC) was greater than that by heparin. In this study, we compared the bleeding complication of intravenously administered APC and heparin in rabbits, and also estimated primary hemostasis. When both anticoagulants were intravenously infused, the bleeding time from a punctured ear vein was prolonged dose-dependently. However, at doses which prolonged the activated partial thromboplastin time nearly equally, the prolongation of bleeding was greater in heparin-administered rabbits. Blood withdrawn from heparin-administered animals showed increases in in vitro bleeding parameters which correlated with the in vivo bleeding time. However, only small changes were observed in the blood withdrawn from APC-administered animals. Both drugs induced either no change or only a slight decrease in the platelet count, hematocrit and fibrinogen content. These observations suggest that APC may be a more useful anticoagulant than heparin since it causes less bleeding tendency.

[A case of predominant right thalamic infarction with severe verbal memory disturbance].

We encountered a 45-year-old right-handed man who had suffered a predominant right thalamic infarction and complained of memory loss. Performance on the Miyake Test (recall of ten pairs of related and unrelated words), the Rey Osterrieth Complex Figures, the Benton Test of Visual Retention and the Wechsler Memory Scale-R disclosed a severe verbal memory disturbance associated with a little, if any, visual memory disturbance. An MRI study revealed bilateral lesions limited to the thalamus involving most of the right anterior nucleus (AN), mediodorsal nucleus (MD), ventrolateral nucleus (VL), and centromedial nucleus (CM), as well as a small part of the left MD, and CM. HM-PAO-SPECT scans showed areas of decreased cerebral blood flow not only in the right thalamus but in the medial and basilar region of the right temporal lobe. It is noteworthy that our patient had a predominant right thalamic lesion and exhibited a severe verbal memory disturbance rather than visual memory disturbance. This suggests that the right hemisphere is dominant for verbal memory function in this patient.

Traumatic intracranial foreign body embolization--case report.

A 27-year-old male presented with intracranial embolization due to accidental penetration of his neck by an iron fragment at work. Cerebral angiography revealed foreign body embolization of the left middle cerebral artery. The foreign body was successfully removed via craniotomy and arteriotomy. The extended period from onset to surgical treatment prevented acute hemodynamic reconstruction. However, he had good collateral circulation and was discharged with mild hemiparesis and moderate motor aphasia. The possibility of intracranial embolization should be considered in patients presenting with penetrating injury of the neck.

[MRI imaging of purulent cerebral ventriculitis].

This report concerns a 68-year-old male who was diagnosed as having purulent ventriculitis based on CT and MRI findings. He was first admitted to a nearby hospital with fever and impaired consciousness and thought to be suffering from herpes simplex encephalitis based on laboratory findings. In spite of treatment with acyclovir and antibiotics, his symptoms persisted for one and a half months. Because of gradual deterioration of his neurological status, he was transferred to our hospital. On admission he was stuporous with nuchal rigidity and a fever of 38.5 degrees C. The CSF leukocyte count was elevated (217/mm3) with predominantly polymorphonuclear cells (mononuclear 20, polymorphonuclear 197). Gd-DTPA MRI (T1-weighted) showed marked enhancement of the ependyma of the fourth ventricle and both lateral ventricles. A diagnosis of purulent ventriculitis was made and high-dose antibiotics (ABPC 12g, CTX 9g) were started intravenously. Gradual improvement in the clinical signs was observed with rapid normalization of the CSF cell-count. The patient had completely recovered one month after the start of treatment and this was associated with disappearance of abnormal enhancement on the MRI images. Although cerebral ventriculitis occasionally occurs as a complication of neonatal meningitis, it is rare in adult purulent meningitis. In our patient, persistent meningitis combined with impaired drainage of CSF from the ventricles are presumed to have caused ventriculitis. Serial enhanced MRI is particularly helpful in diagnosing ventriculitis, and can serve as a good index for monitoring the effects of treatment.

[Acute encephalopathy with symmetrical lesions of the thalamus, the putamen and the cerebellum on magnetic resonance imaging].

A 19-year-old boy was admitted to our hospital because of impaired consciousness after experiencing fever and headaches for 7 days. The patient was in a deep coma or generalized convulsions, with retrocollis and decorticate posture. He never regained consciousness, remaining in an apallic state. The initial CSF pressure was 290 mm H2O, CSF cell count 18/3 mm3, protein 75 mg/100 ml, and sugar 74 mg/100 ml. There was no significant elevation in the viral titer in the serum or CSF. Plain CT on admission showed marked brain edema. MRI three months thereafter demonstrated symmetrical high intensity in the thalamus, the putamen and the cerebellum on both T1- and T2-weighted images, probably representing petechial bleeding. The lesions in the medial portion of the occipital lobes showed iso intensity on T1-weighted images and high intensity on T2-weighted images. These lesions were consistent with infarction of both posterior cerebral arteries, which may have been due to severe brain edema. The clinical and MRI findings were similar to those of patients with acute encephalopathy with low-density areas in the thalamus or bilateral striatal necrosis in childhood. To the best of our knowledge, there have been no reports of cases like ours in adults.

[A case of epileptic laughter associated with temporal epidermoid cyst: surgical treatment combined with subdural grid electrode study].

A case of epileptic laughter associated with deep right temporal epidermoid cyst is reported. Interictal EEG with subdural grid electrodes demonstrated multifocal spike discharges in the right temporal lobe. Ictal EEG localized the epileptogenic foci at the base of the anterior medial temporal lobe. After standard temporal lobectomy, the tumor was completely removed. The patient is free from seizures postoperatively.

Paramedian thalamic infarction following blunt head injury--case report.

A 19-year-old male was admitted following a blow to the face. Computed tomographic (CT) scans 1 hour after injury revealed low-density areas in the bilateral thalami and midbrain, which were enhanced postcontrast except for the core 3 hours later. CT scans 2 days after injury revealed that the size of the low-density areas had increased. CT scans and magnetic resonance images 3 weeks after injury disclosed only small infarcted lesions in the bilateral thalami, the right side of the midbrain, and the left internal capsule. These findings suggest that the injury initially caused thrombus on the basilar arterial wall, leading to occlusion of the perforators, but almost all affected perforators were recanalized. Bilateral thalamic infarction resulting from head injury is unusual, as is the transient nature of the infarction in this case.

Chronic progressive spinobulbar spasticity with disturbance of voluntary eyelid closure. Report of a case with special reference to MRI and electrophysiological findings.

We describe a 56-year-old man who had a progressive pseudobulbar palsy, spastic tetraparesis, forced laughing and disturbance of voluntary eyelid closure, and was clinically compatible with chronic progressive spinobulbar spasticity. Magnetic resonance images (MRI) revealed atrophy of the bilateral motor cortices and single photon emission tomography after intravenous injection of N-isopropyl-p-iodoamphetamine iodine-123 (IMP-SPECT) showed hyporadioactivity in the same regions. Electrophysiological studies on supranuclear paralysis of eyelid closure demonstrated that so-called apraxia and motor impersistence coexisted and that in attempts to keep the eyelid closed the inhibition of basal activity of the levator palpebrae superioris muscle and activation of the orbicularis oculi muscle were insufficient, indicating the impaired reciprocity of these ocular muscles. The corresponding lesion of these eyelid symptoms was considered to be the bilateral motor cortices.

Manic delirium and frontal-like syndrome with paramedian infarction of the right thalamus.

A disinhibition syndrome affecting speech (with logorrhoea, delirium, jokes, laughs, inappropriate comments, extraordinary confabulations), was the main manifestation of a right-sided thalamic infarct involving the dorsomedian nucleus, intralaminar nuclei and medial part of the ventral lateral nucleus. Resolution of conflicting tasks was severely impaired, suggesting frontal lobe dysfunction. These abnormalities correlated with the finding on SPECT of a marked hypoperfusion in the overlying hemisphere predominating in the frontal region. We suggest that this behavioural syndrome was produced by disconnecting the dorsomedian nucleus from the frontal lobe and limbic system.

Auditory extinction to nonverbal and verbal stimuli.

The so-called auditory extinction phenomenon in a verbal dichotic listening test was investigated in seven brain damaged patients from the qualitative standpoint. As the result, it became evident that the phenomenon could result from competition between verbal materials presented to both ears in at least two different levels of auditory processing i.e., sound perception and linguistic recognition. From the present study, we emphasize the following: If Bender's definition is followed, it is advisable to use the term extinction only for the phenomenon at the acoustic level. If the use of the term extinction for the phenomenon is to be continued at the linguistic level, the presence of auditory extinction and/or obscuration to nonverbal stimuli should be noted.

A sporadic juvenile case of the amyotrophic lateral sclerosis with neuronal intracytoplasmic inclusions.

In an autopsy case of the sporadic juvenile ALS (a 17-year-old girl) intracytoplasmic inclusions are found in the upper and lower motor neurons and in nerve cells of the dentate nucleus, pontine nucleus, brain stem reticular formation, substantia nigra, thalamus, globus pallidus and others. Histochemically they contain RNA-Protein compounds. Electron microscopically, they consist of randomly interwoven tubules with granular endoplasmic reticulums and free ribosomes in the margin. Each tubule measures 90--150 A in diameter and shows no distinct periodic constiction. Amorphous substances as well as ribosome granules are scattered and associated with those tubules. The inclusion-bearing cells are usually swollen and chromatolytic and have a large hydropic nucleus, suggesting a close relation between the development of the inclusion and chromatolysis. Clinically, a rapid progress of the symptoms (total duration: about 12 months) and conspicuous disturbances of the autonomic nerve, such as sinus tachycardia and bladder sphincter dysfunction, should be noticed.