Local shape volume alterations in subcortical structures of suicide attempters with major depressive disorder.

Suicide is among the most important global health concerns; accordingly, an increasing number of studies have shown the risks for suicide attempt(s) in terms of brain morphometric features and their clinical correlates. However, brain studies addressing suicidal vulnerability have been more focused on demonstrating impairments in cortical structures than in the subcortical structures. Using local shape volumes (LSV) analysis, we investigated subcortical structures with their clinical correlates in depressed patients who attempted suicide. Then we compared them with depressed patients without a suicidal history and age- and sex-matched healthy controls (HCs; i.e., 47 suicide attempters with depression, 47 non-suicide attempters with depression, and 109 HCs). Significant volumetric differences were found between suicidal and nonsuicidal depressed patients in several vertices: 16 in the left amygdala; 201 in the left hippocampus; 1,057 in the left putamen; and 140 in the left pallidum; 1 in the right pallidum; and 6 in the bilateral thalamus. These findings indicated subcortical alterations in LSV in components of the limbic-cortical-striatal-pallidal-thalamic circuits. Moreover, our results demonstrated that the basal ganglia was correlated with perceived stress levels, and the thalamus was correlated with suicidal ideation. We suggest that suicidality in major depressive disorder may involve subcortical volume alterations.

Comparison of shape alterations of the thalamus and caudate nucleus between drug-naïve major depressive disorder patients and healthy controls.

BACKGROUND: Although structural alterations have been reported in patients with major depressive disorder (MDD), very few studies have compared the shape alterations of the subcortical regions between drug-naïve MDD patients and healthy controls (HCs). Therefore, we investigated and compared the subcortical shape alterations and volumetric changes between drug-naïve MDD patients and HCs in this study. METHODS: This study included 45 drug-naïve MDD patients and 83 HCs, who underwent three-dimensional (3-D) T1-weighted structural magnetic resonance imaging. Surface-based vertex analysis (SVA) was performed with automated segmentation of the bilateral caudate nuclei, putamina, nuclei accumbens, thalami, pallidum, hippocampi, amygdalae, and brainstem. SVA revealed regional contractions of the thalamus (bilateral medial and lateral nuclei) and right caudate nucleus (medial wall and anterosuperior areas) in the drug-naïve MDD patients when compared to HCs RESULTS: In volume analysis, the drug-naïve MDD patients showed a significant decrease in the volume of bilateral thalami compared with HCs (after Bonferroni correction p < 0.003). We identified morphometric contractions in bilateral thalami and right caudate nucleus in the drug-naïve MDD patients (p < 0.05). CONCLUSIONS: The present study implied that with cortical shape changes, the subcortical brain alterations could contribute to emotional dysregulation in the drug-naïve MDD patients.

Functional MRI evidence of the cortico-olivary efferent pathway during active auditory target processing in humans.

Auditory target detection has been explored by a number of studies, but none have demonstrated activity in the auditory subcortical centers evoked by the top-down attentional mechanism related to target detection in humans. We applied functional magnetic resonance imaging (fMRI) with sparse sampling to explore activity in the auditory centers, particularly in the subcortex, during an active auditory target detection task. Fourteen healthy subjects with normal hearing tapped the left index finger in response to target tonal stimuli presented among other (non-target) stimuli during continuous white noise stimulation. General linear model, region-of-interest, and connectivity analyses were performed. In the cortex, bilateral auditory cortices as well as the cingulate gyrus, thalamus, and supramarginal gyrus were activated to target stimuli and functionally connected to each other. In the subcortex, the superior olivary complex (SOC) and locus coeruleus were activated to the target but not to the non-target or background noise stimuli. The SOC was the only auditory subcortical center that displayed connectivity to the auditory cortical areas as well as the cingulate and supramarginal gyri during target presentation but not during other conditions. SOC activation appears to be the first fMRI evidence of direct cortico-olivary projections in the human brain as well as SOC participation in auditory target detection. Our results may be an initial step towards developing a noninvasive methodology to evaluate the functional integrity of the auditory efferent system in humans.

Changes in the regional shape and volume of subcortical nuclei in patients with tinnitus comorbid with mild hearing loss.

PURPOSE: Tinnitus, the perception of sound without an external source, is a prevalent disease, but its underlying mechanism has not been fully elucidated. Recent studies have suggested the involvement of subcortical nuclei in tinnitus generation. We investigated changes in the local shape and volume of subcortical nuclei in relation to tinnitus. METHODS: The participants included 53 patients with tinnitus and 52 age- and gender-matched normal controls. Individual 3D T1-weighted structural images were obtained using 3-T magnetic resonance imaging. Surface-based vertex analysis (SVA) was performed with automated segmentation of the bilateral caudate nuclei, putamina, nucleus accumbens, thalami, pallidum, hippocampi, amygdalae, and brainstem. The scalar distances from the mean surface and volumes of 15 nuclei were compared between the tinnitus and control groups and correlated with tinnitus handicap score (THI) and tinnitus duration. RESULTS: SVA revealed regional contractions in the accessory basal and lateral nuclei of the right amygdala and expansions in the left medial and right ventral posterior nuclei and lateral dorsal nucleus of both thalami. The surface distances of the right nucleus accumbens were positively correlated with tinnitus duration, while those of the left nucleus accumbens and left hippocampus were negatively correlated with THI. CONCLUSION: Regional atrophy of the amygdala may indicate self-modulation of emotional response regulation to diminish tinnitus-related emotional distress. Thalamic regional expansion may signify dysfunctional auditory gating in the thalamus, where inhibition of the tinnitus signal at the thalamus level is disrupted due to abnormal changes in the limbic system, ultimately leading to the tinnitus percept.

Spatiotemporal Segregation of Neural Response to Auditory Stimulation: An fMRI Study Using Independent Component Analysis and Frequency-Domain Analysis.

Although auditory processing has been widely studied with conventional parametric methods, there have been a limited number of independent component analysis (ICA) applications in this area. The purpose of this study was to examine spatiotemporal behavior of brain networks in response to passive auditory stimulation using ICA. Continuous broadband noise was presented binaurally to 19 subjects with normal hearing. ICA was performed to segregate spatial networks, which were subsequently classified according to their temporal relation to the stimulus using power spectrum analysis. Classification of separated networks resulted in 3 stimulus-activated, 9 stimulus-deactivated, 2 stimulus-neutral (stimulus-dependent but not correlated with the stimulation timing), and 2 stimulus-unrelated (fluctuations that did not follow the stimulus cycles) components. As a result of such classification, spatiotemporal subdivisions were observed in a number of cortical structures, namely auditory, cingulate, and sensorimotor cortices, where parts of the same cortical network responded to the stimulus with different temporal patterns. The majority of the classified networks seemed to comprise subparts of the known resting-state networks (RSNs); however, they displayed different temporal behavior in response to the auditory stimulus, indicating stimulus-dependent temporal segregation of RSNs. Only one of nine deactivated networks coincided with the "classic" default-mode network, suggesting the existence of a stimulus-dependent default-mode network, different from that commonly accepted.

Demonstration of decreased gray matter concentration in the midbrain encompassing the dorsal raphe nucleus and the limbic subcortical regions in major depressive disorder: an optimized voxel-based morphometry study.

BACKGROUND: Previous neuroimaging studies in patients with major depressive disorder (MDD) have reported changes in several brain areas, such as the medial and dorsolateral orbital cortex, amygdala, hippocampus, and basal ganglia. However, the results of these studies are inconsistent, and relatively few studies have been conducted using voxel-based morphometry (VBM) to detect gray matter concentration (GMC) abnormalities in patients with MDD. METHODS: We examined 47 MDD patients and 51 healthy controls to investigate structural abnormalities using a 1.5 T magnetic resonance imaging system, which was normalized to a customized T1 template and segmented with optimized VBM. Analysis of covariance with age and gender as covariates was adopted for the VBM statistics; the level of statistical significance was set at P<0.05 for the corrected false discovery rate. RESULTS: Decreased GMC was found in MDD patients in the bilateral amygdalae, hippocampi, fusiform gyri, lingual gyri, insular gyri, middle-superior temporal gyri, thalami, cingulate gyri, the central lobule of the cerebellum, and the midbrain encompassing the dorsal raphe nuclei (DRN). LIMITATIONS: Half of our study subjects were taking antidepressants. This may have been a potential confounding factor if any of the medications affected cortical volume. CONCLUSIONS: The results suggest that the GMC of several regions associated with emotion regulation was lower in MDD patients. In particular, we found decreased GMC in the DRN. These findings may provide a better understanding of the anatomical properties of the neural mechanisms underlying the etiology of MDD.

Cerebral blood flow changes in man by wake-promoting drug, modafinil: a randomized double blind study.

To investigate the effects of a wake-promoting drug, modafinil on regional cerebral blood flow (rCBF) in healthy volunteers, we performed (99m)Tc-ethylcysteinate dimer single photon emission computed tomography (SPECT) before and after modafinil or placebo administration. Twenty-one healthy subjects received single doses of 400 mg modafinil or placebo in a double blind randomized crossover study design. Administrations of modafinil or placebo in a subject were separated by a 2-week washout. Brain SPECT was performed twice before and 3 h after modafinil or placebo administration. For statistical parametric mapping analysis, all SPECT images were spatially normalized to the standard SPECT template and then smoothed using a 12-mm full width at half-maximum Gaussian kernel. The paired t-test was used to compare pre- versus post-modafinil and pre- versus post-placebo SPECT images. Differences in rCBF between post-modafinil and post-placebo conditions were also tested. Modafinil decreased Epworth and Stanford sleepiness scales whereas placebo did not. The post-modafinil condition was associated with increased rCBF in bilateral thalami and dorsal pons, whereas the post-placebo condition showed increased rCBF in a smaller area of the dorsal pons when compared with the drug naïve baseline condition. Compared with the post-placebo condition, the post-modafinil condition showed higher rCBF in bilateral frontopolar, orbitofrontal, superior frontal, middle frontal gyri, short insular gyri, left cingulate gyrus, left middle/inferior temporal gyri, left parahippocampal gyrus, and left pons. In healthy volunteers, modafinil increased wakefulness and rCBF in the arousal-related systems and in brain areas related to emotion and executive function.

Episodic diencephalic hypoperfusion in Kleine-Levin syndrome.

A 22 year-old woman suffered from recurrent episodes of hypersomnia, apathy, and hyperphagia. The symptoms occurred 3 to 4 times per year, and each attack lasted 2 to 3 weeks. 99mTc-ethylcysteinate dimer brain single photon emission computed tomography (SPECT) was performed during symptomatic and asymptomatic periods. To localize brain regions with perfusion changes during symptomatic period, asymptomatic SPECT was subtracted from symptomatic SPECT. The subtracted SPECT showed significant hypoperfusion in the left hypothalamus, bilateral thalami, basal ganglia, bilateral medial and dorsolateral frontal regions, and left temporal lobe during the symptomatic period. These cerebral hypoperfusion areas support the diencephalic hypothesis and clinical symptoms of Kleine-Levin syndrome.

Cerebral perfusion abnormality in narcolepsy with cataplexy.

To investigate abnormal cerebral perfusion in narcoleptics with cataplexy, 25 narcoleptics with cataplexy and 25 normal controls were enrolled in this study. Cerebral perfusion was measured by brain single photon emission computed tomography (SPECT) using 99mTc-ethylcysteinate dimer. Patients and normal controls had not received any medication prior to the SPECT scan. Differences in cerebral perfusion between narcoleptics and normal controls were subjected to statistical parametric mapping (SPM) analysis. Overnight polysomnography and multiple sleep latency test (MSLT) were performed in all patients. Brain SPECT was carried out on all patients and normal controls during the waking state. Clinical symptoms and MSLT results of all patients are in accord with the International Classification of Sleep Disorders criteria for narcolepsy. MSLT showed a short mean sleep latency (1.69 +/- 1.0 min) and 2-5 sleep onset REM periods in individual patient. SPM analysis of brain SPECT showed hypoperfusion of the bilateral anterior hypothalami, caudate nuclei, and pulvinar nuclei of thalami, parts of the dorsolateral/ventromedial prefrontal cortices, parahippocampal gyri, and cingulate gyri in narcoleptics [P < 0.05 by Student's t test with false discovery rate (FDR) correction]. Significant hypoperfusion in the white matter of frontal and parietal lobes was also noted in narcoleptics. This study shows reduced cerebral perfusion in subcortical structures and cortical areas in narcoleptics. The distribution of abnormal cerebral perfusion is concordant with the pathway of the cerebral hypocretin system and may explain the characteristic features of narcolepsy, i.e., cataplexy, emotional lability, and attention deficit.

Cerebral perfusion changes in mesial temporal lobe epilepsy: SPM analysis of ictal and interictal SPECT.

We examined cerebral perfusion changes in mesial temporal lobe epilepsy (mTLE) by the statistical parametric mapping of brain single photon emission computed tomography (SPECT) images of 38 mTLE patients and 19 normal controls. Ictal and interictal SPECTs were compared with control SPECTs by independent t test, and ictal and interictal SPECTs by paired t test. We evaluated the number of heterotopic neurons in temporal lobe white matter, white matter changes of the anterior temporal lobe (WCAT) and ictal hyperperfusion of the temporal stem (IHTS). Left mTLE showed interictal hypoperfusion in the ipsilateral hippocampus, bilateral thalami, and paracentral lobules. Right mTLE showed hypoperfusion in bilateral hippocampi, contralateral insula, bilateral thalami, and paracentral lobules. Both mTLEs showed ictal hyperperfusion in bilateral temporal lobes with ipsilateral predominance, and in the anterior frontal white matter bilaterally. By paired t test, ictal hyperperfusion was found in the ipsilateral temporal lobe, temporal stem, hippocampus, thalamus, putamen, insula, and bilateral precentral gyri, whereas ictal hypoperfusion was found in bilateral frontal poles and middle frontal gyri. Fifteen patients showed WCAT and 19 showed IHTS, a weak correlation was observed between WCAT and IHTS (r = 0.377, P = 0.02). WCAT was found to correlate with an early seizure onset age. In 35 patients, heterotopic neurons were found in the white matter of the resected temporal lobe, but the number of heterotopic neurons did not correlate with WCAT or IHTS. In summary, the cerebral perfusion patterns of mTLE suggest interictal hypofunction and ictal activation of the cortico-thalamo-hippocampal-insular network and ictal hypoperfusion of the anterior frontal cortex.

Glucose hypometabolism of hypothalamus and thalamus in narcolepsy.

It has been hypothesized that hypothalamus is involved in narcolepsy. The relative difference between cerebral glucose metabolism of 24 narcoleptic patients and 24 normal controls was studied using 18F-fluorodeoxy glucose positron emission tomography. Patients with narcolepsy showed significantly reduced cerebral glucose metabolism in bilateral rectal and subcallosal gyri, the medial convexity of right superior frontal gyrus, bilateral precuneus, right inferior parietal lobule, and in left supramarginal gyrus (uncorrected p < 0.001). Bilateral posterior hypothalami and mediodorsal thalamic nuclei showed hypometabolism with significance at the level of corrected p < 0.05, with small volume correction. This study showed cerebral glucose hypometabolism of the hypothalamus-thalamus-orbitofrontal pathways in the narcoleptic brain.

Regional cerebral hyperperfusion with ictal dystonic posturing: ictal-interictal SPECT subtraction.

PURPOSE: Ictal-interictal single-photon emission computed tomography (SPECT) subtraction was performed to find brain structures related to ictal dystonic posturing (DP) in patients with temporal lobe epilepsy (TLE). METHODS: Thirty-two patients with mesial TLE who had ictal and interictal SPECTs were included. They were divided into two groups; DP group with ictal dystonia during ictal SPECT (n = 15) and Non-DP group without ictal DP (n = 17). Ictal-interictal SPECT subtraction was performed, and then subtracted SPECT was coregistered with brain spoiled gradient recalled (SPGR) magnetic resonance imaging (MRI). The ictal hyperperfusion on subtracted SPECT was analyzed in basal ganglia, frontal cortex, thalamus, temporal lobe, and insular cortex. RESULTS: The incidences of ictal hyperperfusion on brain regions in DP versus Non-DP groups were 80.0% (12 of 15 patients) versus none (0 of 17), p = 0.001, chi2, in caudate nucleus; 93.3% (14 of 15) versus 47.0% (eight of 17), p = 0.005, in putamen; and 80.0% (12 of 15) versus 41.2% (seven of 17), p = 0.026, in thalamus. No significant difference of ictal hyperperfusion was found in globus pallidus, temporal lobes, insular and frontal cortices between DP and Non-DP groups. DP patients showed an earlier age at seizure onset [8.6 years (DP) vs. 15.7 years (Non-DP) (p = 0.015)] and a longer duration of seizure history [19.0 years (DP) vs. 11.9 years (Non-DP) (p = 0.015)]. CONCLUSIONS: Caudate nucleus, putamen, and thalamus were significantly related to the ictal DP during TLE seizures. Our study showed first an active involvement of the caudate nucleus in the generation of ictal DP.

Serial positron emission tomography findings in a patient with hydrocephalic dementia and Alzheimer's disease.

Comorbidity of normal pressure hydrocephalus (NPH) and Alzheimer's disease (AD) is not uncommon. However, few studies have reported the clinical courses of these patients in depth. A 73-year-old woman was confirmed to have AD by a biopsy performed during a shunt operation for NPH after a head trauma. She was followed for 4 years using serial neuropsychological tests and positron emission tomography (PET). Her clinical symptoms remained improved for 2.5 years and then declined. The 1-year minus the presurgical PET scan highlighted the bilateral frontal area, basal ganglia, and thalamus, which may reflect brain regions associated with the improvement of hydrocephalic dementia. On the other hand, the 1-year minus the 4-year scan highlighted the bilateral temporoparietal area and the posterior cingulate gyrus, which may reflect brain regions associated with the aggravation of AD. This subtraction method may be useful for monitoring the clinical course in patients with NPH and AD.