Crucial role of thalami and basal ganglia in emotional memory and cognition: association with the recognition of Niigata Ken Chuetsu earthquake 2004

Authors


Dr K. Imai, 1713-8, Fujikawa, Nagaoka, Niigata 940-2302, Japan. Email: gkgmk482@ybb.ne.jp

Abstract

Objective:  It is suggested that thalami, basal ganglia, putamina and caudate heads play a crucial role in strong emotion such as the fear of serious earthquake. The aim of this study was to elucidate the radiographic findings (mainly the lacunae) in these regions, mental abilities and the extent of the activities of daily livings (ADL) of moderately demented patients who could recognize the Niigata Ken (prefecture) Chuetsu earthquake 2004 Japan.

Methods:  In patients with moderate dementia, mainly Alzheimer’s disease, who could recognize the Niigata Ken (prefecture) Chuetsu earthquake 2004 in Niigata prefecture in Japan, their radiographic findings regarding thalami, basal ganglia, putamina and caudate heads were investigated by counting the numbers of lacunae using magnetic resonance imaging. In addition, their mental abilities were examined by Mini-Mental Examination Score and Hasegawa Dementia Scale–Revised. Their activities of daily living were also assessed.

Results:  The patients who could recognize the earthquake have statistically fewer lacunae in the thalami, basal ganglia, putamina and caudate heads, than those who could not (P < 0.01 by Student’s t-test). This analysis revealed that the patients who could recognize the earthquake have statistically significant higher scores in both Mini-Mental Examination Score, Hasegawa Dementia Scale–Revised (P < 0.05 by Student’s t-test) and activities of daily living (P < 0.01 by Student’s t-test). However, statistical significance was not obtained regarding education between two groups.

Conclusion:  Thalami and the structures around them such as basal ganglia, putamina and caudate heads play an important role in emotion and cognition. Therefore, we concluded that numbers of lacunae might be a valuable marker in evaluating the cognitive abilities of the demented patients.

INTRODUCTION

The 2004 Niigata Ken (prefecture) Chuetsu earthquake was one of the most serious disasters in Japan to date. The magnitude was identified as 8.5 on the Richter scale and 48 persons died in Niigata prefecture as a result of the earthquake. Fortunately, nobody was injured or dead by this disaster in our hospital but many windows were broken and many cracks appeared in the walls. If patients with serious dementia could not recognize the earthquake and take refuge independently, it was possible that many could have been injured or killed. However, some patients among those with Alzheimer’s disease or other demented disorders could recognize this disaster but others could not. Even the relatively demented patients may have recognized the disastrous earthquake less than the normal subjects because they are seriously emotionally charged by enhancing effect of this terrible disaster.1,2

As reported previously, the ADL of the demented patients such as walking, eating and grooming are affected as mental abilities deteriorate.3,4 Furthermore, it is considered that emotion and cognition are also impaired as mental abilities deteriorated.

On the other hand, it is widely accepted that thalami and the structures around them, including the hypothalami, play not only an important homeostatic role but also have a role to play in the functioning of memory, emotions and cognition in human beings.5 Concerning the earthquake, the relationship in demented patients between amnesia, cognition and the volume of the medial temporal lobe, including the hippocampus, has previously been discussed.6 However, radiographic investigation of thalami and the structures around them in addition to the evaluation of mental abilities and the activities of daily livings (ADL) has scarcely been performed. Therefore, we tried to perform radiographic analysis of the numbers of lacunae (NL index; NLI) in thalami, basal ganglia, putamina and caudate heads and obtained statistically significant findings as a result.7 Associated with Yakovlev’s and Papez’s circuits, the insults to these structures would induce serious emotional, memory and cognitive impairment.

MATERIALS AND METHODS

Patient selection

Consecutive patients were admitted to our institute from July 1998 to November 2004. There were 120 patients (40 men, 80 women). Their ages ranged from 57 to 98 years (mean 80.32 ± 8.71). With regard to the classification of the types of dementia, 65 cases were classified as Alzheimer’s disease (AD) and 13 cases were classified as vascular dementia (VD). Others (42 cases) were unclassified (UC). We divided them into two groups. Group A consisted of the 46 patients (11 men, 35 women aged from 57 to 95 years, mean 79.36 ± 8.33) who could recognize the earthquake. They were classified as AD, 28; VD, 7; and UC, 11. On the other hand, the 74 patients (29 men, 45 women, aged from 60 to 98 years mean 80.82 ± 8.96) of group B could not recognize it. They were classified as AD, 37; VD, 6; and UC, 31. The patients of group A were identified as recognizing and being afraid of the earthquake because they complained of fear, cried loudly, felt tension, sought safety under a table, gripped the bedhead, shivered with fear or were ambulatory, activities that are not normally noted in such patients.8 On the other hand, the patients of group B were not observed to react to this disaster.

The earthquake struck at 5:56 pm on the 23 October 2004, when almost all the patients admitted to our hospital were having supper at the hospital dinning hall. Therefore, it was not necessarily difficult for us to observe the patients intensively. Their reactions to this earthquake were observed by five or six staff including nurses. Whether or not the patients present recognized this earthquake was identified by those symptoms such as saying ‘I’m scared’, crying, shivering with fear, hiding under the desk or table, grasping a bedpost, being unusually strained or being unusually ambulatory, as described above. The information about the reactions was obtained from the five or six staff, respectively, in the one month after this disaster to avoid errors of memory.

Magnetic resonance imaging

For this study, patients who had contraindications for MR study were excluded. Fifty-two patients were excluded because of motion artifacts that affected their MRI findings. Of course, informed consent was obtained from all patients studied and their family members. In all cases, T2 weighted (T2W) and proton density images (PDI) were obtained with magnetic resonance imaging (MRI) (Philips Infera 1.0T/1.5T Nova Dual, Andover MA, USA). MRIs were performed between 14 and 30 days after the disaster.9 Transverse T2-weighted scans (repetition time, 2500 ms; echo time, 90 ms; FOV, 220; Matrix, 512; flip angle, 90β; photographing time, 104 s) and proton density images (repetition time, 2500 ms; echo time, 20 ms) were obtained at a slice thickness of 8 mm.9,10 Lacunae were defined as penetrating artery occlusions 3–15 mm in diameter in horizontal sections with high intensity on both T2-weighted images (T2WI) and proton density images (PD).9,10 On the slice that includes anterior commissure (AC) and posterior commissure (PC) line, we counted the numbers of lacunae of bilateral thalami, putamina, basal ganglia and caudate heads because the silent lacunae are intensively related to cognitive impairments (Table 1, Fig. 1).8,10,11 The numbers of these lacunae were counted by one neurosurgeon and four neuropsychiatrists with a neuroradiologist who were blinded to the histories and neurological conditions of the presented patients.9,11 When there were disagreements, the final decision was reached through a consensus meeting with a third investigator.10 Then, patients who showed cortical infarcts or subcortical infarcts in which diameters were ≥15 mm on MRI were excluded because Yamamoto et al. designated the diameters of these infarcts as <15 mm.8 There were 18 such cases. These measures were designated as Index of thalami, basal ganglia, putamina, caudate heads as NLI (TI, BI, PI and CI), respectively.12 The numbers of lacunae were equal to the scores of these indices. This method was already demonstrated to be available in other reports.8,11 We compared NLI values between these two groups.

Table 1.  Numbers of lacunae index around basal ganglia and thalamus
 Group AGroup BStudent’s t-test
Left thalamus0.65 ± 0.15 4.9 ± 3.68P < 0.01
Right thalamus0.45 ± 1.003.75 ± 3.04P < 0.01
Left basal ganglia0.15 ± 0.37 2.5 ± 2.82P < 0.01
Right basal ganglia 0.2 ± 0.70 2.6 ± 2.93P < 0.01
Left putamen2.55 ± 2.507.15 ± 5.33P < 0.01
Right putamen2.75 ± 3.218.05 ± 5.77P < 0.01
Left caudate head 0.4 ± 0.944.05 ± 3.30P < 0.01
Right caudate head 0.6 ± 1.10 3.2 ± 2.89P < 0.01
Figure 1.

Magnetic resonance imaging showing a lacunar infarct in the right thalamus and two in the left putamen.

Dementia scale

In evaluating the mental abilities of the presented patients, all underwent screening using Mini-Mental Examination Score (MMSE) and Hasegawa Dementia Scale–Revised (HDS-R). The diagnosis of these dementing disorders were performed using neurological, neuropsychological and functional examinations, electroencephalograms (EEG), computerized tomography (CT), magnetic resonance imaging (MRI).4,8,13–17 Finally, we obtained the classical diagnosis of these demented cases according to the diagnostic and statistical manual of mental disorders, fourth edition (DSM-IV).

Grading of the activities of daily living

We investigated the extent of ADL (mainly eating, walking, excretion) of the presented patients. Scoring was performed as below. Total ADL scores were determined by summing the scores for eating, excretion and gait and movement. The individual scores were determined as follows:

  • 1Eating: 10–9, normal; 8–7, eating meals independently; 6–5, partially dependent but able to finish meals by himself (herself); 4–3, almost completely dependent and unable to finish meals by himself (herself); 2–1, completely dependent; 0, tube nutrition or hyper alimentation
  • 2Excretion; 9, able to go to the toilet independently; 8–7, able to use the portable toilet; 6–4, partially dependent and urinary or fecal incontinence is sometimes noted; 2–3, partially dependent and urinary or fecal incontinence is often noted; 1–0, completely dependent and urinary or fecal incontinence
  • 3Gait and movement: 9, able to walk independently; 8–7, able to walk with a stick; 6–5, able to walk with assistance; 4–3, sit without assistance but able to drive a wheel chair skillfully; 2–1, almost bed-ridden but able to turn in bed; 0, completely bed-ridden and unable to turn in bed

Furthermore, the level of education presented patients had received was also investigated and statistical analysis was performed.

Statistical analysis

A comparison of clinical variables between the two groups was performed with Student’s t-test. Probability values <0.05 were considered significant.

RESULTS

According to the informants, patients of group A but not B had recognized the earthquake well. Based on the radiographic investigations using MRI, the NLI in thalami, basal ganglia, putamina and caudate heads were different between the two groups and statistical significances of any index were noted. Namely, the NLI in group A was significantly smaller than in group B (Table 1). The score for the MMSE in the former (14.7 ± 4.34) was significantly higher than in the latter (11.05 ± 5.78) (P < 0.05 only by Student’s t-test). Those of HDS-R in the former (13.65 ± 5.02) was significantly higher than in the latter (9.55 ± 6.44) (P < 0.05 only by Student’s t-test). Concerning the total ADL scores, the former (24 ± 6.66) was significantly higher than the latter (8.5 ± 7.59) (P < 0.01 by Student’s t-test). The cases who could recognize this earthquake (Group A) have statistically fewer lacunae in the thalami, basal ganglia, putamina, caudate heads, than those who could not (Group B) (P < 0.01 by Student’s t-test). However, in terms of education, no statistical significance was identified between group A and B (8.3 ± 3.33 vs 8.15 ± 2.74, respectively). No statistically significant difference in ages was found between group A and B (79.36 ± 8.33 vs 80.82 ± 8.96).

DISCUSSION

Experimental work in animals and humans has demonstrated that the thalamus and frontal lobe play a crucial role in both emotions and cognition.12,18 The thalamus is a structure that is the part of the well noted memory circuit of the hippocampo-fornic-mammillo-thalamo-cingulate system known as the Papez’s circuit.7 The inferior thalamic peduncle serves as the reciprocal pathway between the medial inferior nucleus and medial temporal lobe, especially the amygdala (component of Yakovlev’s circuit).18,19 In fact, selective injuries to the thalamus may induce consciousness disturbances in Wernicke encephalopathy with cognitive impairments resulting in third ventricular dilatation and atrophy of the mamillary body and mesencephalic tegmentum. That is to say, these two circuits are intensively related to emotional memory and cognition.18 Furthermore, anterior or inferior thalamic peduncles contain fibers that connect the nucleus with the frontal lobe.18 According to the references, we note that the dorsomedial nucleus, mamillothalamic tract, genu or the anterior limb of the internal capsule, outside the thalamus and frontal lobe (orbital cortex) are tightly related to cognition.18,19 Apart from these significant circuits or tracts, it has been reported that lentiform nuclei, putamina and basal ganglia play an important role both in emotional memory and in cognition.20–22 It was radiographically demonstrated that bilateral basal ganglia were selectively insulted in some kinds of metabolic disorders such as portal systemic encephalopathy resulting in cognitive impairments in some reports.23,24 Otherwise, methanol intoxication may induce bilateral hemorrhagic necrosis of the putamina, caudate heads and basal ganglia and cause cognitive impairment.1,24,25 Therefore, we paid the close attention to the four indices (thalami (TI), basal ganglia (BI), putamina (PI), caudate heads (CI)) described in under ‘Materials and methods’. Taking the functional systems of thalami and the structures around them into consideration, the results of this investigation demonstrate that insults to these structures may induce serious damage to emotions and cognition because the lacunae of some structures are considered to be significant insults to them as described as below (Table 1).

Most of the patients with Alzheimer’s disease who encountered the terrible earthquake remembered what happened around the time of the earthquake better than less emotional events. The main finding in this study is to demonstrate that emotional and cognitive performance concerning the earthquake was correlated with the radiographic normalization of the, thalami, caudate heads, putamina and basal ganglia in addition to the level of ADL and their mental abilities as quantified by MMSE or HDS-R (Table 1).5,6,26

At this time, we would like to discuss whether our radiographic methods using MRI are useful or not in investigating the organic lesions of thalami, caudate heads, putamina and basal gangli.9 In other reports, in order to evaluate the region of interest, amygdalar and hippocampal volumes were quantified by MRI.18 However, it was not necessarily easy for us to quantify the volume of the thalami, caudate heads, putamina and basal ganglia by MRI because these structures are too small to measure the volumes of them correctly and analyze the volumetric statistical significance. On the other hand, we considered that positron emission tomography could not evaluate the metabolism of oxygen or glucose in these structures selectively and correctly because of the smallness of their volumes.27 Therefore, we considered that counting the numbers of lacunae in these structures might be one of the most useful procedures in evaluating the insults to them. Some reports described that silent lacunae are intensively related to cognitive impairments.11 Furthermore, it is considered that the lacunae in these structures indicate a decrease in the total number of neurons in the degenerative demented diseases including Alzheimer’s disease or vascular dementia.8

In relation to volumetric loss due to neuronal loss, we considered that the more lacunae the patients have, the more serious they may manifest dementia resulting in atrophy of the brain associated with neuronal loss.28 Some reports described cases with multiple lacunae as being apt to not only suffer systemic diseases such as hypertension (HT; both diastolic and systolic) or diabetes mellitus (DM), but also manifest poor cerebrovascular reactivity to oxygen bicarbonate compared with those with single or no lacunae.4,9,28,29 In those cases, they indicated that these systemic disorders, including hypertension might induce arteriosclerosis medullary arteries.28,29 We speculated that these mechanisms might cause neurological symptoms such as cognitive impairments and emotional memory disturbance in the demented patients.9,28,29 In other words, the morphological deformation relates to intrinsic damage to these structures resulting from these systemic disorders such as HT or DM.8 However, the shapes and sizes of these lacunae are varied.30 So it may be difficult for us to count the numbers of lacunae without bias. To minimize bias, the numbers of lacunae of the thalami and the structures around them were scored by several independent investigators, including a neuroradiologist who was blind to the history and neurological status of the presented patients. At the same time, we are able to find significance in counting them because we can quantify the radiographic findings in thalami to a statistically significant degree. Then, we considered that those cases with more radiographic findings in the thalami are more seriously damaged and that those with fewer are less seriously injured.

At the same time, we were able to identify that the extent of ADL of these patients was closely related to their cognitive abilities. However, the relationship between the cognitive impairments and ADLs of the presented patients has not been discussed in detail to date except in some reports (mainly ours).3,4 We speculated that patients with multiple lacunae in thalami and in the structures around them might also manifest degenerative disorders in the frontal lobes that relate to volition via various neuronal connective fibers including Yakovlev’s and Papez’s circuits and disorders in the pyramidal and extrapyramidal tracts that influence walking and various activities that are assessed in ADL. In this way, it is considered that those patients with significant multiple lacunae in these interesting structures would be disabled in ADL. On the other hand, it was interesting that we could find no significant difference in terms of education that the patients received between the subjects and control groups.

In conclusion, it is considered that we can evaluate the emotional memory and cognition of the demented patients by quantifying the lacunae in thalami and the structures around them radiographically. Namely, these NLI may be valuable in evaluating emotional and cognitive abilities.7

ACKNOWLEDGMENTS

We sincerely appreciated Dr Yoshinori Fujiwara, PhD, Tokyo Metropolitan Institute of Gerontology for his valuable advice.

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