Nobukatsu Sawamoto

Cognitive deficits and striato-frontal dopamine release in Parkinson's disease

Idiopathic Parkinsons disease (PD) is often accompanied by a pattern of executive deficits similar to those found in patients with frontal lobe lesions. We investigated whether such cognitive deficits are attributable to frontal lobe dysfunction as a direct consequence of impaired mesocortical dopaminergic transmission or an indirect consequence of impaired nigrostriatal dopaminergic function. For this purpose, changes in synaptic dopamine levels during task performance were monitored using a marker of dopamine D2-receptor availability (11)C-raclopride (RAC) PET. During RAC PET, seven patients with early symptomatic PD and seven age-matched healthy controls performed two types of behavioural task, a spatial working memory task (SWT) and a visuomotor control task (VMT). The SWT involves an executive process which is known to be impaired by both frontal lobe lesions and PD while the VMT is a control test for the visuomotor component of the SWT. Parametric images of RAC binding potential during performance of each task were generated, and compared between the tasks using voxel-based statistical parametric mapping as well as region of interest analysis. In controls, RAC binding was reduced in the dorsal caudate during performance of the SWT compared with the VMT, compatible with increased levels of endogenous dopamine release due to the executive process. In PD patients, this RAC binding reduction was not observed. In contrast, RAC binding in the anterior cingulate cortex within the medial prefrontal cortex was reduced by a comparable level during the SWT both in controls and PD patients. Statistical comparisons between controls and PD patients confirmed significantly attenuated dopamine release in the dorsal caudate in PD, but preserved levels of medial prefrontal dopamine release. Our data suggest that executive deficits in early patients with PD are associated with impaired nigrostriatal dopaminergic function resulting in abnormal processing in the cortico-basal ganglia circuit. In contrast, mesocortical dopaminergic transmission appears well preserved in early PD patients.

Primary somatosensory cortex is actively involved in pain processing in human

We recorded somatosensory evoked magnetic fields (SEFs) by a whole head magnetometer to elucidate cortical receptive areas involved in pain processing, focusing on the primary somatosensory cortex (SI), following painful CO(2) laser stimulation of the dorsum of the left hand in 12 healthy human subjects. In seven subjects, three spatially segregated cortical areas (contralateral SI and bilateral second (SII) somatosensory cortices) were simultaneously activated at around 210 ms after the stimulus, suggesting parallel processing of pain information in SI and SII. Equivalent current dipole (ECD) in SI pointed anteriorly in three subjects whereas posteriorly in the remaining four. We also recorded SEFs following electric stimulation of the left median nerve at wrist in three subjects. ECD of CO(2) laser stimulation was located medial-superior to that of electric stimulation in all three subjects. In addition, by direct recording of somatosensory evoked potentials (SEPs) from peri-Rolandic cortex by subdural electrodes in an epilepsy patient, we identified a response to the laser stimulation over the contralateral SI with the peak latency of 220 ms. Its distribution was similar to, but slightly wider than, that of P25 of electric SEPs. Taken together, it is postulated that the pain impulse is received in the crown of the postcentral gyrus in human.

Regional cerebral blood flow in Parkinson disease with nonpsychotic visual hallucinations

Background: Patients with Parkinson disease (PD) often experience visual hallucinations (VH) with retained insight (nonpsychotic) but the precise mechanism remains unclear. Objective: To clarify which neural substrates participate in nonpsychotic VH in PD, the authors evaluated regional cerebral blood flow (rCBF) changes in patients with PD and VH. Methods: The authors compared 24 patients with PD who had nonpsychotic VH (hallucinators) and 41 patients with PD who had never experienced VH (non-hallucinators) using SPECT images with N-isopropyl-p-[123I]iodoamphetamine. There were no significant differences in age, sex, duration of disease, doses of PD medications, Hoehn and Yahr scale, or Mini-Mental State Examination (MMSE) scores between the two groups. The rCBF data were analyzed using statistical parametric mapping (SPM). Results: The rCBF in the right fusiform gyrus was lower in the hallucinators than in the non-hallucinators (corrected p < 0.05 at cluster levels). The hallucinators revealed higher rCBF in the right superior and middle temporal gyri than the non-hallucinators (uncorrected p < 0.001). These significant differences were demonstrated after MMSE scores and duration of disease, which are the relevant factors associated with VH, were covariated out. Conclusions: Nonpsychotic visual hallucinations in Parkinson disease (PD) may be associated with hypoperfusion in the right fusiform gyrus and hyperperfusion in the right superior and middle temporal gyri. These temporal regions are important for visual object recognition and these regional cerebral blood flow changes are associated with inappropriate visual processing and are responsible for nonpsychotic visual hallucinations in PD.

Anterior and posterior cingulum abnormalities and their association with psychopathology in schizophrenia: A diffusion tensor imaging study

Evidence suggests that a disruption in limbic system network integrity and, in particular, the cingulate gyrus may play a role in the pathophysiology of schizophrenia. The cingulum bundles (CBs; posterior and anterior) are the most prominent white matter tracts in the limbic system, furnishing both input and output to the cingulate gyrus . In previous diffusion tensor imaging (DTI) studies, abnormal integrity has been demonstrated in the anterior CB portion, but not the posterior, in schizophrenia. As well, the relationships between the abnormalities of CB integrity and the psychopathology of schizophrenia remain to be elucidated. Using DTI acquired on a 3 T MRI machine, we examined fractional anisotropy (FA) in the anterior and posterior CBs of 42 patients with schizophrenia and 24 group-matched controls. Moreover, we investigated the relationships between CB abnormalities and the psychopathology of schizophrenia. Bilaterally reduced FA was demonstrated in both anterior and posterior CBs in schizophrenia patients. However, the pattern of FA reduction was different between anterior and posterior CBs: the reduction in FA was left-accentuated in anterior CBs, while no such lateralized abnormality was found in posterior ones. Finally, FA in posterior CBs correlated with positive symptom scores in patients with schizophrenia. These findings suggest that CB abnormalities in schizophrenia are not restricted to the anterior CB, but include the posterior as well. Pathology in the posterior CB would be one of the possible neural underpinnings of positive symptoms in schizophrenia.

The Role of the Uncinate Fasciculus in Memory and Emotional Recognition in Amnestic Mild Cognitive Impairment

Background: The putative neural bases of affected episodic memory and emotional recognition in early Alzheimer’s disease are suspected to be limbic and paralimbic pathological processes. The uncinate fasciculus (UF) is especially considered to be a critical structure. In the present study, we investigated microstructural UF pathology by diffusion tensor imaging in the subjects with amnestic mild cognitive impairment (aMCI), and its association with memory and emotional processing impairment. Methods: Subjects included 16 patients with aMCI and 16 healthy individuals. Diffusion tensor images were acquired and the fractional anisotropy (FA) of the UF was calculated. In addition, its association with verbal memory and emotional facial recognition was investigated. Results: The FA values of the left UF were significantly lower in aMCI, and strongly correlated with episodic memory performance in aMCI. For the emotional recognition task, the aMCI subjects performed worse in negative emotion recognitions. The FA values of the left UF were correlated with the performance of fearful facial expression recognition in aMCI. Conclusion: These results indicated that microstructural alterations of the UF had already occurred in aMCI. In addition, these alterations could be one of the causes of memory and emotional processing impairment in aMCI.

Prefrontal hypofunction in patients with intractable mesial temporal lobe epilepsy

We compared the cognitive functions and interictal cerebral glucose metabolism of 11 patients with mesial temporal lobe epilepsy (MTLE) with frequent seizures to those of 10 patients with MTLE with rare seizures; the groups were matched for age, sex, education, IQ, and focus side. The frequent-seizure group had more set-shifting impairment that correlated with glucose hypometabolism in the prefrontal cortices. Our results suggest that frequent seizures in MTLE are associated with hypofunction of the prefrontal cortex.

Hemispheric asymmetry of the arcuate fasciculus : A preliminary diffusion tensor tractography study in patients with unilateral language dominance defined by Wada test

ObjectiveLateralization of language function is a prominent feature of human brain function, and its underlying structural asymmetry has been recently reported in normal right-handed subjects. By means of diffusion tensor tractography (DTT), we investigated the asymmetry of the language network, namely, the arcuate fasciculus in patients in whom the unilateral language dominance was defined by Wada test.MethodsDTT was performed in 24 patients with a focal lesion or an epileptic focus outside the C-shaped segment of the arcuate fasciculus. The arcuate fasciculus was reconstructed by placing two regions-of-interest in the deep white matter lateral to the corona radiata. The pathway was then divided into one terminating in the temporal lobe (FT tract) and the other in the parietal lobe (FP tract). The relative number and volume of the FT and FP tracts in each hemisphere were submitted to repeated measure ANOVA separately, with the hemisphere as a within-subject factor and with the side of pathology as a betweensubject factor.ResultsThe FT tract showed a significantly larger number and volume in the language dominant hemisphere than in the non-dominant hemisphere, while, for the FP tract, no significant hemispheric difference was observed in the relative number or volume. There was a tendency that the FT tract was less lateralized when the pathology was located in the dominant hemisphere than in the non-dominant hemisphere.ConclusionDominance of the FT tract in the language dominant hemisphere was demonstrated for the first time in a patient population and implicated a clinical utility of DTT for non-invasive evaluation of language lateralization. Our preliminary study might indicate reorganization of the language network in conjunction with pathology.

Functional mapping of human medial frontal motor areas

Abstract. Two functional brain-mapping techniques, functional magnetic resonance imaging (fMRI) and cortical stimulation by chronically implanted subdural electrodes, were used in combination for presurgical evaluation of three patients with intractable, partial motor seizures. Brain mapping was focused on characterizing motor-related areas in the medial frontal cortex, where all patients had organic lesions. Behavioral tasks for fMRI involved simple finger and foot movements in all patients and mental calculations in one of them. These tasks allowed us to discriminate several medial frontal motor areas: the presupplementary motor areas (pre-SMA), the somatotopically organized SMA proper, and the foot representation of the primary motor cortex. All patients subsequently underwent cortical stimulation through subdural electrodes placed onto the medial hemispheric wall. In each patient, the cortical stimulation map was mostly consistent with that patients brain map by fMRI. By integrating different lines of information, the combined fMRI and cortical stimulation map will contribute not only to safe and effective surgery but also to further understanding of human functional neuroanatomy.

Intraoperative dorsal language network mapping by using single‐pulse electrical stimulation

The preservation of language function during brain surgery still poses a challenge. No intraoperative methods have been established to monitor the language network reliably. We aimed to establish intraoperative language network monitoring by means of cortico‐cortical evoked potentials (CCEPs). Subjects were six patients with tumors located close to the arcuate fasciculus (AF) in the language‐dominant left hemisphere. Under general anesthesia, the anterior perisylvian language area (AL) was first defined by the CCEP connectivity patterns between the ventrolateral frontal and temporoparietal area, and also by presurgical neuroimaging findings. We then monitored the integrity of the language network by stimulating AL and by recording CCEPs from the posterior perisylvian language area (PL) consecutively during both general anesthesia and awake condition. High‐frequency electrical stimulation (ES) performed during awake craniotomy confirmed language function at AL in all six patients. Despite an amplitude decline (≤32%) in two patients, CCEP monitoring successfully prevented persistent language impairment. After tumor removal, single‐pulse ES was applied to the white matter tract beneath the floor of the removal cavity in five patients, in order to trace its connections into the language cortices. In three patients in whom high‐frequency ES of the white matter produced naming impairment, this “eloquent” subcortical site directly connected AL and PL, judging from the latencies and distributions of cortico‐ and subcortico‐cortical evoked potentials. In conclusion, this study provided the direct evidence that AL, PL, and AF constitute the dorsal language network. Intraoperative CCEP monitoring is clinically useful for evaluating the integrity of the language network. Hum Brain Mapp 35:4345–4361, 2014.

Decrease in Cortical Benzodiazepine Receptors in Symptomatic Patients With Leukoaraiosis A Positron Emission Tomography Study

Background and Purpose— [11C]flumazenil (FMZ), a ligand that selectively binds to the central benzodiazepine receptor in the neuronal membrane, is useful for evaluating neuronal viability in a positron emission tomography (PET) scan. Using this ligand, we investigated whether there was a correlation between neuronal integrity in various brain structures and dementia in patients with leukoaraiosis. Methods— Twelve patients with extensive leukoaraiosis on magnetic resonance imaging were divided into groups of patients with or without dementia. Based on a 2-compartment, 2-parameter model that included metabolite-corrected arterial input and PET-measured cerebral radioactivity, the distribution volume of FMZ (FMZ-Vd) was calculated in various regions of interest by nonlinear curve fitting. Additionally, tracer kinetic analysis was applied for voxel-by-voxel quantification of FMZ-Vd, and data analysis was performed by statistical parametric mapping. Results— The presence of dementia was associated with a reduced FMZ-Vd in widespread areas of the cerebral cortex, including the bilateral frontopolar and frontal/insular areas, the left temporo-occipital border areas, and the left marginal cortical areas. Conclusions— Differences in neuronal integrity in the cerebral cortex might determine whether patients with leukoaraiosis become symptomatic or not.