Absent-mindedness and injury of the ascending reticular activating system in a patient with mild traumatic brain injury: A case report.

RATIONALE: No study on the association of absent-mindedness and injury of the ascending reticular activating system (ARAS) has been reported. We report on a patient who showed absent-mindedness and injury of the ARAS following mild traumatic brain injury. PATIENT CONCERNS: The patient complained of absent-mindedness since the head trauma, which was mainly observed while dining for several (5-10) minutes approximately 3 to 4 times a day: according to the patient's family, he usually stopped eating while holding the spoon in the air for approximately 5∼10 minutes. DIAGNOSES: A 19-year-old man suffered from head trauma resulting from being hit on his head by a falling glass from a large window (1.5 × 2 m, approximately 100 kg) at a cafe. INTERVENTIONS: His absent-mindedness showed slow improvement with the passage of time and had almost disappeared at seven months after onset. OUTCOMES: The lower portion of both lower dorsal ARAS and the upper portion of the left lower ventral ARAS of the patient were thinner, and partial tearing was observed in the right lower ventral ARAS. Decreased neural connectivity of the intralaminar thalamic nucleus to the prefrontal cortex, basal forebrain, parietal cortex, and occipital cortex was detected in both hemispheres. LESSONS: Injury of the ARAS and injury of the cerebral cortex was demonstrated in a patient with absent-mindedness following mild traumatic brain injury. The absent-mindedness in this patient might be related to the injury of the ARAS.

Lesions of the anterior thalamic nuclei and intralaminar thalamic nuclei: place and visual discrimination learning in the water maze.

Medial thalamic damage produces memory deficits in humans (e.g., Korsakoff's syndrome) and experimental animals. Both the anterior thalamic nuclei (ATN) and rostral intralaminar plus adjacent lateral thalamic nuclei (ILN/LT) have been implicated. Based on the differences in their main connections with other neural structures, we tested the prediction that ATN lesions would selectively impair acquisition of spatial location discrimination, reflecting a hippocampal system deficit, whereas ILN/LT lesions would impair acquisition of visual pattern discrimination, reflecting a striatal system deficit. Half the rats were first trained in a spatial task in a water maze before switching to a visual task in the same maze, while the remainder were tested with the reverse order of tasks. Compared with sham-operated controls, (1) rats with ATN lesions showed impaired place learning, but normal visual discrimination learning, (2) rats with ILN/LT lesions showed no deficit on either task. Rats with ATN lesions were also hyperactive when their home cage was placed in a novel room and remained more active than ILN/LT or SHAM rats for the subsequent 21 h, especially during the nocturnal phase. These findings confirmed the influence of ATN lesions on spatial learning, but failed to support the view that ILN/LT lesions disrupt striatal-dependent memory.

Memory enhancement with event-related stimulation of the rostral intralaminar thalamic nuclei.

The rostral intralaminar thalamic nuclei (ILn) are organized to activate pathways originating in medial prefrontal cortex (mPF) that mediate memory-guided responding during alert, wakeful states. Previous studies have shown that rostral ILn or mPF lesions produce deficits in delayed matching to position (DMTP). Here, we manipulated rostral ILn activity in rats by microinjecting drugs or applying electrical current and examined effects on DMTP. Inhibiting activity with the GABA(A) agonist muscimol impaired DMTP. Decreasing GABA(A) tone with FG-7142 (N-methyl-beta-carboline-3-carboxamide) improved DMTP at low but not high doses. Orexin A, which depolarizes thalamocortical neurons locally within the ILn, improved DMTP, whereas the cholinergic agonist carbachol impaired performance at the highest dose tested. These drug effects were unaffected by partial mPF lesions in a subset of animals. Microinjection results are consistent with an inverted-U relationship between thalamic activity and DMTP. This relationship was confirmed by event-related electrical stimulation, which produced improvement at low stimulation currents and impairment at higher currents. Electrical stimulation affected DMTP when applied at the start of the memory delay or choice response, but not earlier when trials began or the sample lever was presented. Our results are consistent with evidence that the rostral ILn play a role in retrieval, carrying response-related information across brief memory delays and facilitating memory-guided responding. They also provide evidence that treatments stimulating rostral ILn activity may be an effective means to enhance working memory and related cognitive processes and thus to treat disorders that affect these functions.

Unconditioned stimulus pathways to the amygdala: effects of posterior thalamic and cortical lesions on fear conditioning.

Plasticity in the lateral nucleus of the amygdala is thought to be critical for the acquisition of Pavlovian fear conditioning. The pathways that transmit auditory conditioned stimulus information originate in auditory processing regions of the thalamus and cortex, but the pathways mediating transmission of unconditioned stimuli to the amygdala are poorly understood. Recent studies suggest that somatosensory (footshock) unconditioned stimulus information is also relayed in parallel to the lateral nucleus of the amygdala from the thalamus (the posterior intralaminar thalamic complex, PIT) and the cortex (parietal insular cortex). In the present study we reexamined this issue. Our results showed that bilateral electrolytic lesions of the PIT alone blocked fear conditioning, whereas bilateral excitotoxic PIT lesions had no effect. These electrolytic PIT lesions did not affect fear conditioning using a loud noise as unconditioned stimulus, defining the effects of PIT lesions as a disruption of somatosensory as opposed to auditory processing. Finally, we performed combined bilateral excitotoxic lesions of the PIT nuclei and electrolytic lesions of the parietal insular cortex. These, like excitotoxic lesions of PIT alone, had no effect on the acquisition of fear conditioning. Thus, somatosensory regions of the thalamus and cortex may well be important routes of unconditioned stimulus transmission to the amygdala in fear conditioning, but information about the unconditioned somatosensory stimulus is also transmitted from other sources that send fibers through, but do not form essential synapses in, the thalamus en route to the amygdala.

[Damaging nucleus centromedianus thalami for treatment of cancer pain in experimental and clinical aspects].

BACKGROUND & OBJECTIVE: There is no perfect method to control cancer pain. It is reported that nucleus centromedianus thalami plays a crucial role in the analgesia of central nerve system. The authors conducted this study, based on rat experiments, together with the clinical treatment of more than 90 cases involving various cancer pains, to explore the pain-relieving effects after damaging nucleus centromedianus thalami. METHODS: Ten SD rats, whose nucleus centromedianus thalami were damaged by electrolysis, were chosen, and then measured the pain degree by applying electricity to stimulate the tails of the rats. Meanwhile, another 10 rats, whose nucleus centromedianus thalami were not damaged, were chosen as the control group, among whom the same operation procedure as the above mentioned was carried out. The range of pain scale of the rats was measured by the alteration of the electric intensity. A total of 90 cases of intractable cancer pain were treated, including 36 cases of lung cancer, 21 cases of nasopharyngeal carcinoma, 10 cases of intestinal cancer, 8 cases of cancer of pancreas, 8 cases of osteocarcinoma, 4 cases of carcinoma of kidney, 3 cases of hepatocarcinoma. The brain stereotactic technique was used to damage the nucleus centromedianus thalami with radiofrequency coagulation lesions. The 10-grade method recommended by WHO was used to rank pain degree. RESULTS: Pain scale of rats in the first group rose from 0.152+/-0.034 mA prior to the damage to 0.326+/-0.05 afterwards, with a significant difference (P< 0.001), while the pain scale of the control group dropped from 0.142+/-0.027 mA prior to the operation to 0.138+/-0.035 mA afterwards, with no remarkable difference (P > 0.05). To patients with cancer pain, the average pain grade in this study went above 7 scores, but dropped to 0-3 scores after operation, according to the 10 grade method by WHO. A life-long tracing observation indicted that cancer pain in 24 cases relapsed to varying degrees but below 5 scores, the rest of the patients were analgesic persistently, 3 cases among whom lasted for as long as 2 years. The incidence cases of operational complications were 15 of somnolence, 10 of urinary incontinence, 8 of divagation, and 3 of unilateral oculomotor paralysis. These complications released after symptomatic treatments. CONCLUSION: Nucleus centromedianus thalami damage is an effective way to relieve cancer pain, as well as the complications should be paid attention.

Effects of intralaminar thalamic nuclei lesion on glutamic acid decarboxylase (GAD65 and GAD67) and cytochrome oxidase subunit I mRNA expression in the basal ganglia of the rat.

This study investigated the influence of thalamic inputs on neuronal metabolic activity in the rat basal ganglia. By means of in situ hybridization histochemistry, we examined the consequences of ibotenate-induced unilateral lesion of intralaminar thalamic nuclei on mRNA expression of cytochrome oxidase subunit-I (CoI) in the striatum and the subthalamic nucleus (STN) and of the two isoforms of glutamate decarboxylase (GAD65 and GAD67) in the striatum, globus pallidus (GP), entopeduncular nucleus (EP) and substantia nigra pars reticulata (SNr). In the striatum, GAD67 mRNA expression decreased selectively in the rostral part of the structure at 5 and 12 days postlesion (approximately -30%), whereas, GAD65 mRNA levels was downregulated only in the caudal striatum at 12 days (-29%). In both the striatum and STN, CoI mRNA expression decreased ipsilaterally at 5 and bilaterally at 12 days. In GP, GAD67 and GAD65 mRNA expression decreased ipsilaterally at 5 (-20% and -26%) and 12 days (-23% and -36%). In EP, selective bilateral decreases in GAD67 mRNA expression were found at 5 and 12 days (-50% and -40%). Conversely, in SNr, only GAD65 mRNA expression was reduced bilaterally at both time points. These data show that the thalamus exerts a widespread excitatory influence on the basal ganglia network that cannot be accounted for solely by its known direct connections. Given the recent data showing that intralaminar thalamic nuclei are a major nondopaminergic site of neurodegeneration in Parkinson's disease, these results may have a critical bearing on understanding the cellular basis of basal ganglia dysfunction in parkinsonism.