Frontal Lobe In Patients Research Articles

Meta-analysis of the Correlation Between Cognitive Function and Imaging Features in Hepatic Encephalopathy

Objectives: This study aimed to systematically evaluate the correlation between cognitive function and brain imaging findings in patients with hepatic encephalopathy (HE). Methods: We searched PubMed, China National Knowledge Infrastructure, and Wanfang databases to obtain literature on cognitive function and the diagnosis of HE via brain imaging from the establishment of the databases to March 20, 2023. Two researchers independently screened the literature, extracted data, and evaluated the risk of bias in the included studies. RevMan v. 5.3 software was used in the meta-analysis. Results: A total of 14 articles were included. The meta-analysis showed that digit symbol test (DST) scores and psychometric HE scores (PHES) were positively correlated with the imaging findings of the frontal lobe in patients with HE, with correlation coefficients of 0.49 (Z = 0.53; 95% confidence interval [CI]: 0.23 ~ 0.83) and 0.52 (Fisher’s Z: 0.58; 95% CI: 0.41 ~ 0.76), respectively. The number connection test-A reaction times were negatively correlated with the signal in the globus pallidus, with a correlation coefficient of -0.23 (Z = - 0.23; 95% CI: - 0.43~ - 0.03); DST scores were positively correlated with the signal in the globus pallidus, with a correlation coefficient of 0.45 (Z = 0.49; 95% CI: 0.29 ~ 0.69); and PHES were positively correlated with the mean peak of grey matter, with a correlation coefficient of 0.52 (Z = 0.57; 95% CI: 0.46 ~ 0.73). Conclusions: Imaging findings are related to the cognitive function of patients with HE. Therefore, they can be used to evaluate the cognitive function of these patients and promptly intervene in and prevent the progression of the disease.

Analysis of splicing abnormalities in the white matter of myotonic dystrophy type 1 brain using RNA sequencing

Myotonic dystrophy type 1 (DM1) is a neuromuscular disorder caused by the genomic expansion of CTG repeats, in which RNA-binding proteins, such as muscleblind-like protein, are sequestered in the nucleus, and abnormal splicing is observed in various genes. Although abnormal splicing occurs in the brains of patients with DM1, its relation to central nervous system symptoms is unknown. Several imaging studies have indicated substantial white matter defects in patients with DM1. Here, we performed RNA sequencing and analysis of CTG repeat lengths in the frontal lobe of patients with DM1, separating the gray matter and white matter, to investigate splicing abnormalities in the DM1 brain, especially in the white matter. Several genes showed similar levels of splicing abnormalities in both gray and white matter, with an observable trend toward an increased number of repeats in the gray matter. These findings suggest that white matter defects in DM1 stem from aberrant RNA splicing in both gray and white matter. Notably, several of the genes displaying abnormal splicing are recognized as being dominantly expressed in astrocytes and oligodendrocytes, leading us to hypothesize that splicing defects in the white matter may be attributed to abnormal RNA splicing in glial cells.

Study on brain function of the frontal lobe in patients with functional gastroduodenal disease by near-infrared functional imaging

functional gastroduodenal disease is the main type of functional gastrointestinal disease in the clinical department of Gastroenterology and psychosomatic medicine at present, which accounts for a large proportion of outpatients in gastroenterology. The main manifestations are epigastric pain, dyspepsia, belching, chronic nausea, and vomiting. The purpose of this study is to explore the changes in brain function in patients with functional gastroduodenal diseases through experiments to reveal the possible central etiology and development process. the functional changes of the prefrontal lobe in patients with functional gastroduodenal diseases and normal controls were detected and analyzed by near-infrared brain imaging. At the same time, SCL-90 was used to evaluate the mental health status of patients with functional gastroduodenal diseases and normal controls. The changes in the autonomic nerve system in patients and normal controls were detected and compared by heart rate variability trend chart. the activity of left prefrontal lobe areas s8-d8, s10-d4, s10-d10 and s10-d15 in patients with functional gastroduodenal disease was significantly lower than normal controls (p<0.05). The SCL-90 scale showed that there were significant differences between patients with functional gastroduodenal disease and normal controls, especially in depression, compulsion, anxiety, somatization, interpersonal sensitivity and hostility (p<0.05). There was no significant difference in lf/hf values detected by the HRV trend chart (p>0.05). the function of the left frontal lobe is decreased in patients with functional gastroduodenal disease. The autonomic nervous system may be related to the connection system between the brain center and internal organs.

Self-Directed Neurofeedback Treatment for Subjective Tinnitus Patients Evaluated by Multimodal Functional Imaging.

Neurofeedback (NFB) is a relatively novel approach to the treatment of tinnitus, and prior studies have demonstrated that the increases in alpha activity rather than reduced delta power seem to drive these NFB-related improvements in tinnitus symptoms. The present study was therefore designed to explore whether the implementation of an alpha training protocol with a portable neurofeedback apparatus would achieve improvements in tinnitus patient symptoms. In this study, 38 tinnitus patients underwent NFB training while 18 were enrolled in a control group. The study was single-blinded such that only participants were not aware of their group assignments. Those in the NFB group underwent 15 NFB training sessions over 5 weeks, in addition to pre- and posttraining tests including the Tinnitus Handicap Inventory (THI), Tinnitus Handicap Questionnaire (THQ), visual analog scales (VAS), electroencephalography (EEG), and functional magnetic resonance imaging (fMRI). Our result find that when the THI, THQ, and VAS scores of patients in the two groups were assessed after a 5-week training period, these scores were unchanged in control patients whereas they had significantly improved in the NFB group patients. EEG analyses revealed that the alpha band was increased in the occipital lobe following NFB treatment, while fMRI indicated an increase in regional homogeneity (ReHo) in the right frontal lobe of patients in the NFB group after treatment that was negatively correlated with THI and VAS scores. The results of this analysis indicate that alpha NFB training can be effectively used to reduce tinnitus-related distress and sound perception in patients.

Cerebral Metabolic Network in Patients With Anti-N-Methyl-D-Aspartate Receptor Encephalitis on 18F-FDG PET Imaging.

BackgroundAnti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is the most common autoimmune encephalitis (AE), and the prognosis may significantly be improved if identified earlier and immune-related treated more effectively. This study evaluated the brain metabolic network using fluorodeoxyglucose positron emission tomography (FDG PET).Material and methodsFDG PET imaging of patients with NMDAR encephalitis was used to investigate the metabolic connectivity network, which was analyzed using the graph theory. The results in patients were compared to those in age- and sex-matched healthy controls.ResultsThe hub nodes were mainly in the right frontal lobe in patients with NMDAR encephalitis. The global and local efficiencies in most brain regions were significantly reduced, and the shortest characteristic path length was significantly longer, especially in the temporal and occipital lobes. Significant network functions of topology properties were enhanced in the right frontal, caudate nucleus, and cingulate gyrus. In addition, the internal connection integration in the left cerebral hemisphere was poor, and the transmission efficiency of Internet information was low.ConclusionThe present findings indicate that those characteristic and connections of metabolic network were changed in the brain by graph theory analysis quantitatively, which is helpful to better understand neuropathological and physiological mechanisms in patients with anti-NMDAR encephalitis.

Clinical Study on a Modified Hematoma Puncture Drainage Treatment in Patients with Hypertensive Basal Ganglia Hemorrhage

We aim to investigate the clinical efficacy and safety of a modified hematoma puncture drainage treatment through the burr hole lateral to Kocher's point from the frontal lobe in patients with hypertensive basal ganglia hemorrhage. Twenty-six patients were enrolled in the retrospective study. The volume of hematoma in those patients was between 25 and 35mL, and the Glasgow Coma Scale scores were between 9 and 11; they were divided into a hematoma puncture drainage treatment group and a traditional conservative treatment group. The volume of remaining hematoma, neurological function defect scores, and life quality after treatment, duration of hospitalization, and cost of hospitalization were analyzed in these 2 groups. The volume of remaining hematoma was significantly less in the drainage group than that in the traditional group on the first day and the third day after treatment (P < 0.05). Posttreatment neurological function defect scores in the drainage group were statistically lower than those in the traditional group (P < 0.05). The duration of hospitalization was significantly shorter and the cost of hospitalization was also significantly less in the drainage group than that in the traditional group (P < 0.05). The Extended Glasgow Outcome Scale and Barthel Index scores were significantly higher in the drainage group than those in the traditional group (P < 0.05). There were no significant differences between the 2 groups in the complication rates (P > 0.05). The modified hematoma puncture drainage treatment represents an effective and safe way to treat hypertensive basal ganglia hemorrhage.

The alterations of degree centrality in the frontal lobe of patients with panic disorder.

Objective: The brain network in panic disorder (PD) is still an intriguing issue for research. In this study, we hoped to investigate the role of DC (degree centrality) for the pathophysiology of PD, especially for the fear network.Methods: We enrolled 60 patients with PD and 60 controls in the current study. The gender and age were matched for two groups. All participants received the resting-state functional magnetic resonance imaging to survey the baseline brain activity. Then the DC values of all participants were using REST toolbox. We also compared the DC values between PD and controls. The statistical threshold was set as FDR (false discovery rate) < 0.05.Results: The DC values were significantly lower in the right superior frontal gyrus of PD patients compared to controls (FDR < 0.05). In addition, a negative correlation between the DC values and panic severity was observed in the right superior frontal gyrus and left inferior frontal gyrus. However, there was no significant association between the DC values and illness duration.Conclusion: The DC seemed significantly altered in the frontal lobe of PD patients. The role of the frontal lobe might be more emphasized in the pathophysiology research for PD.

Relaxation-weighted 23Na magnetic resonance imaging maps regional patterns of abnormal sodium concentrations in amyotrophic lateral sclerosis.

Objectives:Multiparametric magnetic resonance imaging (MRI) is established as a technical instrument for the characterisation of patients with amyotrophic lateral sclerosis (ALS). The contribution of relaxation-weighted sodium (23NaR) MRI remains to be defined. The aim of this study is to apply 23NaR MRI to investigate brain sodium homeostasis and map potential alterations in patients with ALS as compared with healthy controls.Materials and Methods:Seventeen patients with ALS (mean age 61.1 ± 11.4 years, m/f = 9/8) and 10 healthy control subjects (mean age 60.3 ± 15.3 years, m/f = 6/4) were examined by 23NaR MRI at 3 T. Regional sodium maps were obtained by the calculation of the weighted difference from two image data sets with different echo times (TE1 = 0.3 ms, TE2 = 25 ms). Voxel-based analysis of the relaxation-weighted maps, together with 23Na concentration maps for comparison, was performed.Results:ROI-based analyses of relaxation-weighted brain sodium concentration maps demonstrated increased sodium concentrations in the upper corticospinal tracts and in the frontal lobes in patients with ALS; no differences between ALS patients and controls were found in reference ROIs, where no involvement in ALS-associated neurodegeneration could be anticipated.Conclusion:23NaR MRI mapped regional alterations within disease-relevant areas in ALS which correspond to the stages of the central nervous system (CNS) pathology, providing evidence that the technique is a potential biological marker of the cerebral neurodegenerative process in ALS.

Beam orientation optimization for coherent X-ray scattering from distributed deep targets

BackgroundAmyloid deposits in the temporal and frontal lobes in patients with Alzheimer’s disease make them potential targets to aid in early diagnosis. Recently, spectral small-angle X-ray scattering techniques have been proposed for interrogating deep targets such as amyloid plaques.ResultsWe describe an optimization approach for the orientation of beams for deep target characterization. The model predicts the main features of scattering profiles from targets with varying shape, size and location. We found that increasing target size introduced additional smearing due to location uncertainty, and incidence angle affected the scattering profile by altering the path length or effective target size. For temporal and frontal lobe targets, beam effectiveness varied up to 2 orders of magnitude.ConclusionsBeam orientation optimization might allow for patient-specific optimal paths for improved signal characterization.

Effects of donepezil on the amplitude of low-frequency fluctuations in the brain of patients with Alzheimer's disease: evidence from resting-state functional magnetic resonance imaging.

ObjectivesTo monitor the effects of donepezil on spontaneous neuronal activity (SNA), and the mechanisms underlying these effects in patients with mild-to-moderate Alzheimer’s disease, using the amplitude of low-frequency fluctuations (ALFFs), a metric of resting-state functional MRI (rs-fMRI).MethodsEleven patients with Alzheimer’s disease were treated with donepezil for 6 months. Before and after treatment, the Mini-Mental State Examination (MMSE), Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-cog), Clinical Dementia Rating (CDR), Neuropsychiatric Inventory and Activities of Daily Living scores, along with rs-fMRI of patients were assessed. Eleven age-, sex-, and education-matched controls underwent MMSE and CDR assessments and rs-fMRI at enrollment. The ALFFs of the whole brain were obtained and compared between the groups.ResultsFollowing donepezil treatment, MMSE scores increased (P = 0.043) and ADAS-cog scores decreased (P = 0.010). Regarding SNA post-treatment, ALFF increased significantly in the right triangular part of the inferior frontal gyrus (IFGtriang; P = 0.030; d = −0.595) and the right orbital part of the inferior frontal gyrus (P = 0.044; d = −0.628) and decreased significantly in the left medial orbital part of the superior frontal gyrus (P = 0.039; d = 0.606) and the right gyrus rectus (P = 0.010; d = 0.609). Furthermore, the changes in ADAS-cog scores from before to after treatment were positively correlated with the changes in ALFF in the right IFGtriang (r = 0.645; P = 0.032).ConclusionsDonepezil improved SNA in the frontal lobe of patients with Alzheimer’s disease. Therefore, ALFF was demonstrated to be a potential tool for assessing the effectiveness of Alzheimer’s disease treatment.

Cognitive Performance and Neuro-Metabolites in HIV Using 3T Magnetic Resonance Spectroscopy: A Cross-Sectional Study from India.

Cognitive impairment in patients with human immunodeficiency virus (HIV) is associated with higher morbidity. The prevalence of the metabolite changes in the brain associated with cognitive impairment in anti-retroviral therapy naïve patients with HIV is unknown. To estimate the prevalence of the neurometabolites associated with cognitive impairment in antiretroviral therapy (ART) naïve patients with HIV. We conducted a cross-sectional study among ART naïve patients with HIV aged 18-50 years in a tertiary care center in India. Cognition was tested using the Post Graduate Institute battery of brain dysfunction across five domains; memory, attention-information processing, abstraction executive, complex perceptual, and simple motor skills. We assessed the total N-acetyl aspartyl (tNAA), creatine (tCr) and glutamate + glutamine (Glx) using 3T magnetic resonance spectroscopy. Cognitive impairment was defined as an impairment in ≥2 domains. Among 43 patients eligible for this study, the median age was 32 years (IQR 29, 40) and 30% were women. Median CD4 count and viral load were 317 cells/μL (IQR 157, 456) and 9.3 copies/ μL (IQR 1.4, 38), respectively. Impairment in at least one cognitive domain was present in 32 patients (74.4%). Impairment in simple motor skills and memory was present in 46.5% and 44% of patients, respectively. Cognitive impairment, defined by impairment in ≥2 domains, was found in 22 (51.2%) patients. There was a trend towards higher concentration of tNAA (7.3 vs. 7.0 mmol/kg), tGlx (9.1 vs. 8.2 mmol/kg), and tCr (5.5 vs. 5.2 mmol/kg) in the frontal lobe of patients with cognitive impairment vs. without cognitive impairment but it did not reach statistical significance (p>0.05 for all). There was no difference in the concentration of these metabolites in the two groups in the basal ganglia. There is a high prevalence of cognitive impairment in ART naïve patients with HIV. There is no difference in metabolites in patients with or without cognitive impairment. Further studies, with longitudinal follow-up are required to understand the underlying pathophysiological mechanisms.

NCREASED CEREBRAL BLOOD FLOW IN MIDDLE-AGED TREATMENT NAIVE HYPERTENSIVE PATIENTS RECEIVING FIXED COMBINATION TREATMENT WITH PERINDOPRIL ARGININE/INDAPAMIDE

Objective: To investigate the effect of perindopril arginine/indapamide fixed-dose combination (FC Pa/I) on cerebral blood flow (CBF) in treatment-naive middle-aged patients with uncomplicated grade 1–2 essential arterial hypertension (EAH). Design and method: 22 treatment-naive patients with EAH (mean age 47,6 ± 6,9 years, 10 men, mean blood pressure (BP) 146.2 ± 4.6/93.1 ± 4.3 mm Hg) and 41 healthy normotensive controls (mean age 46,2 ± 4,6 years, 26 men) were recruited. At the baseline all subjects underwent brain MRI (MAGNETOM Skyra 3.0T, Siemens AG, Germany). Arterial spin labeling (ASL) CBF maps were used to calculate the perfusion defects in the cortical plate of both frontal lobes. Patients with EAH received perindopril arginine 5 mg /indapamide 1.25 FC once daily in the morning; if necessary, after 2 weeks (if office blood pressure was 140/90 mm Hg or higher) the dosage was increased up to perindopril 10 mg/ indapamide 2.5. The follow-up period was 14–16 weeks. 22 patients with EAH underwent an additional MRI at the end of follow-up. Results: At the baseline patients with EAH had significantly (p < 0,001) lower CBF in cortical plate of both left (36,2 ± 8,3 vs. 45,3 ± 3,5 ml/100 g/ min) and right (37,9 ± 7,9 vs. 45,8 ± 3,2 ml/100 g/ min) frontal lobes, compared to normotensive controls. At the end of follow-up we found a significant (p < 0,001) increase in CBF in cortical plate of both left (36,2 ± 8,3 vs. 47,5 ± 9,8 ml/100 g/ min) and right (37,9 ± 7,9 vs. 47,4 ± 10,05 ml/100 g/ min) frontal lobes, compared to baseline. Furthermore, no significant difference was found between CBF level at the end of follow-up period in both frontal lobes of patients with EAH, compared to CBF level of healthy controls at baseline. Conclusions: Treatment with FC Pa/I may additionally increase CBF, measured by ASL, in cortical plate of frontal lobes to the normotensive controls’ level in treatment-naïve middle-aged patients with the earliest stages of EAH, which is essential in prevention of hypertension-mediated brain damage.

Effects of Subthalamic Stimulation on Olfactory Function in Parkinson Disease

Olfactory dysfunction is a nonmotor symptom of Parkinson disease (PD) associated with reduction in quality of life. There is no evidence on whether improvements in olfaction after subthalamic deep brain stimulation (STN-DBS) may be directly attributable to motor improvement or whether this reflects a direct effect of DBS on olfactory brain areas. The aim of the present study was to evaluate the effect of DBS on olfactory function in PD, as well as to explore the correlation between these changes and changes in motor symptoms and brain metabolism. Thirty-two patients with PD were screened for STN-DBS. Patients were evaluated before and 1 year after surgery. Primary outcome was the change in olfactory function (Sniffin' Sticks odor-identification test [SST]) after surgery among the patients with hyposmia at baseline. Secondary outcomes included the relationship between motor outcomes and olfactory changes and [18F]fluorodeoxyglucose-positron emission tomography analysis between subgroups with improvement versus no improvement of smell. STN-DBS improved SST after surgery (preoperative SST, median 7.3 ± 2.4 vs. postoperative SST, median 8.2 ± 2.1; P= 0.045) in a subset of patients among 29 of 32 patients who presented with hyposmia at baseline. The improvement in SST was correlated with DBS response (r= 0.424; P= 0.035). There was also an increase in glucose metabolism in the midbrain, cerebellum, and right frontal lobe in patients with SST improvement (P < 0.001). STN-DBS improves odor identification in a subset of patients with PD. Motor improvement together with changes in the brain metabolism may be linked to this improvement.

Identification of Host-Response in Cerebral Malaria Patients Using Quantitative Proteomic Analysis.

The objective of this study was to study the altered proteome in the frontal lobe of patients with CM. Unbiased analysis of differentially abundant proteins could lead to identification of host responses against Plasmodium falciparum infection, which will aid in better understanding of the molecular mechanism of pathophysiology in CM. TMT-based quantitative proteomic analysis using high-resolution mass spectrometry is employed. In brief, proteins are isolated from frontal lobe samples, which are collected at autopsy from three cases of CM and three control subjects. Equal amounts of protein from each case are digested using trypsin and labeled with different TMT reagents. The pooled sample is fractionated using strong cation exchange chromatography and analyzed on Orbitrap Fusion in triplicates. For accurate quantitation of peptides, the samples are analyzed in MS3 mode. The data is searched against a combined database of human and P. falciparum proteins using Sequest and Mascot search engines. A total of 4174 proteins are identified, of which, 107 are found to be differentially abundant in the test samples with significant p-value (<0.05). Proteins associated with biological processes such as innate immune response, complement system, coagulation, and platelet activation are found to be elevated in CM cases. In contrast, proteins associated with myelination, oxidative phosphorylation, regulation of reactive oxygen species, and sodium and calcium ions transport are found to be depleted in response to CM. In addition, three P. falciparum proteins exclusively in CM brain samples are also identified. The study signifies neuronal assault due to axonal injury, altered sodium and calcium ion channels, deregulated inflammation and demyelination as a part of host response to CM. Enhanced oxidative stress, repressed oxidative phosphorylation, and demyelination of axons may contribute to the severity of the disease. Further validation of these results on a large cohort can provide leads in the development of neuroprotective therapies for CM.

Impairments of gray matter in MRI-negative epileptic patients with different seizure types

Objective: To investigate the damage of gray matter structure in MRI-negative epilepsy patients with different symptoms by voxel-based morphometry (VBM). Methods: From June, 2009 to October, 2016, ninety MRI-negative epilepsy patients and thirty-five healthy volunteers underwent the 3T magnetic resonance imaging scan in Nanjing General Hospital. The patients were divided into three groups, including idiopathic generalized tonic-clonic seizure (I-GTCS), secondarily generalized tonic-clonic seizure (S-GTCS), and partial seizure (PS) according to different symptoms. The three-dimensional high-resolution T1 structural MRI data was obtained for the voxel-based morphometry. Data of gray matter structure from four groups were compared using one-way analysis of variance (ANOVA). An independent-sample t test was performed in order to compare gray matter volume of the three patient groups with controls respectively. According the results of ANOVA, impaired brain regions were selected as regions of interest in order to carry out correlation analysis between gray matter volume and disease duration. Results: ANOVA showed significant differences in gray matter structure of bilateral thalamus and frontal lobe between four groups (alphasim correction, P<0.01). Independent-sample t test showed that the volume of bilateral thalamus and frontal lobe decreased in all three patients groups (alphasim correction, P<0.01) .The volume of bilateral thalamus showed significantly negatively correlation with disease duration in I-GTCS patients (r=-0.466, P<0.01). Conclusions: Generalized seizures and partial seizures all can cause damage to the gray matter structure, especially in thalamus and frontal lobe. The impairments of thalamus and frontal lobe in patients with different seizure types are different with the progression of disease, which suggests that influences of different epilepsy seizures on the thalamo-cortical network are different.

Interaction between DRD2 and lead exposure on the cortical thickness of the frontal lobe in youth with attention-deficit/hyperactivity disorder

The dopamine receptor D2 receptor (DRD2) gene and lead exposure are both thought to contribute to the pathophysiology of attention-deficit/hyperactivity disorder (ADHD). ADHD is characterized by delay in brain maturation, most prominent in the prefrontal cortex (PFC). The D2 receptor is also mainly located in the PFC, and animal studies show that lead exposure affects the dopaminergic system of the frontal lobe, indicating an overlap in neural correlates of ADHD, DRD2, and lead exposure. We examined the interaction effects of DRD2 rs1800497 and lead exposure on the cortical thickness of the frontal lobe in patients with ADHD. A 1:1 age- and gender-matched sample of 75 participants with ADHD and 75 healthy participants was included in the analysis. The interaction effects of DRD2 and lead exposure on the cortical thickness of 12 regions of interest in the frontal lobe were examined by multivariable linear regression analyses. When we investigated the DRD2×lead effects in the ADHD and HC groups separately, significant DRD2×lead effects were found in the ADHD group, but not in the healthy control group in multiple ROIs of the frontal lobe. There was a significant negative correlation between the cortical thickness of the right superior frontal gyrus and inattention scores. The present findings demonstrated significant interaction effects of DRD2 and lead exposure on the cortical thickness of the frontal lobe in ADHD. Replication studies with larger sample sizes, using a prospective design, are warranted to confirm these findings.

The hypothalamus at the crossroads of psychopathology and neurosurgery.

The neurosurgical endeavor to treat psychiatric patients may have been part of human history since its beginning. The modern era of psychosurgery can be traced to the heroic attempts of Gottlieb Burckhardt and Egas Moniz to alleviate mental symptoms through the ablation of restricted areas of the frontal lobes in patients with disabling psychiatric illnesses. Thanks to the adaptation of the stereotactic frame to human patients, the ablation of large volumes of brain tissue has been practically abandoned in favor of controlled interventions with discrete targets. Consonant with the role of the hypothalamus in the mediation of the most fundamental approach-avoidance behaviors, some hypothalamic nuclei and regions, in particular, have been selected as targets for the treatment of aggressiveness (posterior hypothalamus), pathological obesity (lateral or ventromedial nuclei), sexual deviations (ventromedial nucleus), and drug dependence (ventromedial nucleus). Some recent improvements in outcomes may have been due to the use of stereotactically guided deep brain stimulation and the change of therapeutic focus from categorical diagnoses (such as schizophrenia) to dimensional symptoms (such as aggressiveness), which are nonspecific in terms of formal diagnosis. However, agreement has never been reached on 2 related issues: 1) the choice of target, based on individual diagnoses; and 2) reliable prediction of outcomes related to individual targets. Despite the lingering controversies on such critical aspects, the experience of the past decades should pave the way for advances in the field. The current failure of pharmacological treatments in a considerable proportion of patients with chronic disabling mental disorders is reminiscent of the state of affairs that prevailed in the years before the early psychosurgical attempts. This article reviews the functional organization of the hypothalamus, the effects of ablation and stimulation of discrete hypothalamic regions, and the stereotactic targets that have most often been used in the treatment of psychopathological and behavioral symptoms; finally, the implications of current and past experience are presented from the perspective of how this fund of knowledge may usefully contribute to the future of hypothalamic psychosurgery.

Spectral editing in proton magnetic resonance spectroscopy. Determination of GABA level in the brains of humans with ultra-high risk for schizophrenia

The intravital level of γ-aminobutyric acid (GABA) was measured for the first time and the imbalance of the key excitatory and inhibitory neurotransmitters in the brain frontal lobes of patients with ultra-high risk for schizophrenia was studied. The proton magnetic resonance spectroscopy (1H MRS) with the MEGA-PRESS pulse sequence for separating the superimposed signals was used. The area of interest was the anterior cingulate cortex with account for lateralization in the right and left brain hemispheres. A statistically significant decrease in the GABA concentration (by 25%) and in the [GABA]/[GLX] ratio (GLX is glutamate + glutamine) (by 20%) were found for the patients in the left brain hemisphere, this ratio in the right brain hemisphere remaining at the normal level.

Predicting the neural effect of switching from donepezil to galantamine based on single-photon emission computed tomography findings in patients with Alzheimer's disease.

A number of neuroimaging studies have addressed the specific effect of treatment with cholinesterase inhibitors on the frontal lobe in patients with Alzheimer's disease (AD). However, the neural effects of cholinesterase inhibitors on both apathy and executive dysfunction remain unclear. We examined whether baseline regional cerebral blood flow, as determined by using single-photon emission computed tomography, is capable of predicting changes in apathy and executive dysfunction in response to AD patients switching from donepezil to galantamine therapy. We conducted a 24-week, prospective, open-label study of AD patients treated with galantamine who did not respond to previous treatment with donepezil. Single-photon emission computed tomography was performed at baseline, and behaviour and cognitive assessments including the Mini-Mental State Examination, the Japanese version of the Alzheimer's Disease Assessment Scale-cognitive subscale, the Frontal Assessment Battery, the Neuropsychiatry Inventory Brief Questionnaire Form, and the Dysexecutive Questionnaire were conducted at three time points (baseline and after 12 and 24 weeks of galantamine therapy). After galantamine therapy, the Neuropsychiatry Inventory Brief Questionnaire Form scores (apathy, irritability, and aberrant motor symptoms) and the Dysexecutive Questionnaire score improved significantly. The single-photon emission computed tomography findings showed that lower baseline regional cerebral blood flow values in several frontal areas, including the dorsolateral and ventrolateral prefrontal cortex, the anterior cingulate, and the orbitofrontal cortex, predicted greater reductions in the score for apathy (distress) on the Neuropsychiatry Inventory Brief Questionnaire Form and the Dysexecutive Questionnaire score after patients switched from donepezil to galantamine therapy. Our study suggests that galantamine therapy, unlike donepezil, is characterized by a dual mechanism of action that may increase acetylcholine and the nicotinic receptor-modulation effect within the frontal lobe, both of which are associated with apathy and executive dysfunction in AD patients.

1H-proton magnetic resonance spectroscopy in patients with multiple system atrophy and cognitive dysfunction

To detect metabolic changes of bilateral frontal lobe in patients with multiple system atrophy (MSA) and cognitive dysfunction by 1H-proton magnetic resonance spectroscopy (1H-MRS). N-acetylaspartate (NAA)/creatine(Cr), choline (Cho)/Cr, myoinositol (mI)/Cr in three sides of frontal lobe were detected by 1H-MRS in 48 healthy controls, 23 patients with MSA and cognitive dysfunction and 19 patients with MSA but without cognitive dysfunction. NAA/Cr of bilateral frontal lobes in patients with MSA and cognitive dysfunction was significantly decreased compared with MSA patients without cognitive dysfunction and healthy controls (P<0.05). mI/Cr of right frontal lobes was significantly increased in patients with MSA and cognitive dysfunction compared with healthy controls (P<0.05). There was a negative correlation between NAA/Cr of bilateral frontal lobes and duration while a positive correlation between NAA/Cr of bilateral frontal lobes and MoCA score in patients with MSA and cognitive dysfunction. There is a decrease in NAA/Cr and an increase in mI/Cr in frontal lobes in patients with MSA and cognitive dysfunction, which may be associated with cognitive dysfunction in MSA patients.