Tag: brain

Proton and 31-phosphorus neurospectroscopy in the study of membrane phospholipids and fatty acid intervention in schizophrenia, depression, chronic fatigue syndrome (myalgic encephalomyelitis) and dyslexia

Abstract:

Neurospectroscopy allows biochemical processes in the brain to be studied non-invasively. At magnetic field strengths of 1.5 T or higher, cerebral proton neurospectroscopy allows the ascertainment of values of myo-inositol, choline-containing compounds, creatine, glutamate, glutamine, and N-acetyl aspartate. At similar field strengths, cerebral 31-phosphorus neurospectroscopy allows the ascertainment of values of phosphomonoesters, inorganic phosphate, phosphodiesters, phosphocreatine, and the gamma, alpha and beta nucleotide triphosphate (mainly adenosine triphosphate) resonances.

Since choline is a common polar head group at the Sn3 position of membrane phospholipid molecules, a raised level of free choline, as indexed by proton neurospectroscopy, can indicate relatively low anabolism of membrane phospholipid molecules. Furthermore, the choline peak includes phosphorylcholine and glycerophosphorylcholine and even ethanolamine. The phosphomonoesters peak measured using 31-phosphorus spectroscopy includes major contributions from phosphocholine, phosphoethanolamine and L-phosphoserine, which are important precursors of membrane phospholipids, while the phosphodiesters peak includes contributions from glycerophosphocholine and glycerophosphoethanolamine, which are important products of membrane phospholipid catabolism. Hence proton neurospectroscopy and 31-phosphorus neurospectroscopy can yield important information relating to the metabolism of cerebral membrane phospholipids.

The application of these techniques to the investigation of membrane phospholipid metabolism in schizophrenia, depression, chronic fatigue syndrome (myalgic encephalomyelitis or M.E.) and dyslexia is described.

 

Source: Puri BK. Proton and 31-phosphorus neurospectroscopy in the study of membrane phospholipids and fatty acid intervention in schizophrenia, depression, chronic fatigue syndrome (myalgic encephalomyelitis) and dyslexia. Int Rev Psychiatry. 2006 Apr;18(2):145-7. https://www.ncbi.nlm.nih.gov/pubmed/16777668

 

Reduced responsiveness is an essential feature of chronic fatigue syndrome: a fMRI study

Abstract:

BACKGROUND: Although the neural mechanism of chronic fatigue syndrome has been investigated by a number of researchers, it remains poorly understood.

METHODS: Using functional magnetic resonance imaging, we studied brain responsiveness in 6 male chronic fatigue syndrome patients and in 7 age-matched male healthy volunteers. Responsiveness of auditory cortices to transient, short-lived, noise reduction was measured while subjects performed a fatigue-inducing continual visual search task.

RESULTS: Responsiveness of the task-dependent brain regions was decreased after the fatigue-inducing task in the normal and chronic fatigue syndrome subjects and the decrement of the responsiveness was equivalent between the 2 groups. In contrast, during the fatigue-inducing period, although responsiveness of auditory cortices remained constant in the normal subjects, it was attenuated in the chronic fatigue syndrome patients. In addition, the rate of this attenuation was positively correlated with the subjective sensation of fatigue as measured using a fatigue visual analogue scale, immediately before the magnetic resonance imaging session.

CONCLUSION: Chronic fatigue syndrome may be characterised by attenuation of the responsiveness to stimuli not directly related to the fatigue-inducing task.

 

Source: Tanaka M, Sadato N, Okada T, Mizuno K, Sasabe T, Tanabe HC, Saito DN, Onoe H, Kuratsune H, Watanabe Y. BMC Neurol. 2006 Feb 22;6:9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1397862/ (Full article)

 

Patients with chronic fatigue syndrome have reduced absolute cortical blood flow

Abstract:

Prior studies on brain blood flow in chronic fatigue syndrome (CFS) did not find consistent results. This may be because they used single-photon emission computed tomography to measure brain blood flow, which could not measure absolute blood flow. Therefore, the aim of this study was to test the hypothesis that patients with CFS have reduced absolute cerebral blood flow. Xenon-computed tomography blood flow studies were done on 25 CFS patients and seven healthy controls. Analyses were done after stratifying the CFS patients based on the presence or absence of a current psychiatric disorder.

Flow was diminished in both groups as follows: patients with no current psychiatric disorders had reduced cortical blood flow in the distribution of both right and left middle cerebral arteries (P<0.05 for both) while those with current psychiatric disorders had reduced blood flow only in the left middle cerebral artery territory (P<0.05). These data indicate that patients with CFS have reduced absolute cortical blood flow in rather broad areas when compared with data from healthy controls and that those devoid of psychopathology had the most reductions in cortical flow. These data support, in part, our earlier findings that patients devoid of psychopathology are the group most at risk of having some of the symptoms of CFS due to brain dysfunction.

 

Source: Yoshiuchi K, Farkas J, Natelson BH. Patients with chronic fatigue syndrome have reduced absolute cortical blood flow. Clin Physiol Funct Imaging. 2006 Mar;26(2):83-6. https://www.ncbi.nlm.nih.gov/pubmed/16494597

 

Heterogeneity of serum tryptophan concentration and availability to the brain in patients with the chronic fatigue syndrome

Abstract:

We assessed the serotonin status of patients with the chronic fatigue syndrome (CFS). Tryptophan (Trp) availability to the brain, expressed as the ratio of concentration of serum Trp to the sum of those of its five competitors (CAA), and other parameters of Trp disposition were compared in 23 patients with the CFS and 42 healthy controls.

The serum [free Trp]/[CAA] ratio was 43% higher in CFS patients, due to a 48% higher [free Trp]. [Total Trp] was also significantly higher (by 19%) in CFS patients, and, although the [total Trp]/[CAA] ratio did not differ significantly between the control and patient groups, the difference became significant when the results were co-varied with age and gender. [CAA] was not significantly different between groups, but was significantly lower in females, compared to males, of the CFS patient group.

We have established normal ranges for Trp disposition parameters and propose criteria for defining the serotonin-biosynthetic status in humans. We have provisionally identified two subgroups of CFS patients, one with normal serotonin and the other with a high serotonin status. The relevance of our findings to, and their implications for, the pharmacological and other therapies of the chronic fatigue syndrome are discussed.

 

Source: Badawy AA, Morgan CJ, Llewelyn MB, Albuquerque SR, Farmer A. Heterogeneity of serum tryptophan concentration and availability to the brain in patients with the chronic fatigue syndrome. J Psychopharmacol. 2005 Jul;19(4):385-91. http://www.ncbi.nlm.nih.gov/pubmed/15982993

 

Gray matter volume reduction in the chronic fatigue syndrome

Abstract:

The chronic fatigue syndrome (CFS) is a disabling disorder of unknown etiology. The symptomatology of CFS (central fatigue, impaired concentration, attention and memory) suggests that this disorder could be related to alterations at the level of the central nervous system. In this study, we have used an automated and unbiased morphometric technique to test whether CFS patients display structural cerebral abnormalities.

We mapped structural cerebral morphology and volume in two cohorts of CFS patients (in total 28 patients) and healthy controls (in total 28 controls) from high-resolution structural magnetic resonance images, using voxel-based morphometry. Additionally, we recorded physical activity levels to explore the relation between severity of CFS symptoms and cerebral abnormalities.

We observed significant reductions in global gray matter volume in both cohorts of CFS patients, as compared to matched control participants. Moreover, the decline in gray matter volume was linked to the reduction in physical activity, a core aspect of CFS. These findings suggest that the central nervous system plays a key role in the pathophysiology of CFS and point to a new objective and quantitative tool for clinical diagnosis of this disabling disorder.

 

Source: de Lange FP, Kalkman JS, Bleijenberg G, Hagoort P, van der Meer JW, Toni I. Gray matter volume reduction in the chronic fatigue syndrome. Neuroimage. 2005 Jul 1;26(3):777-81. Epub 2005 Apr 7. http://www.ncbi.nlm.nih.gov/pubmed/15955487

 

Objective evidence of cognitive complaints in Chronic Fatigue Syndrome: a BOLD fMRI study of verbal working memory

Abstract:

Individuals with Chronic Fatigue Syndrome (CFS) often have difficulties with complex auditory information processing. In a series of two Blood Oxygen Level Dependent (BOLD) functional Magnetic Resonance Imaging (fMRI) studies, we compared BOLD signal changes between Controls and individuals with CFS who had documented difficulties in complex auditory information processing (Study 1) and those who did not (Study 2) in response to performance on a simple auditory monitoring and a complex auditory information processing task (mPASAT).

We hypothesized that under conditions of cognitive challenge: (1) individuals with CFS who have auditory information processing difficulties will utilize frontal and parietal brain regions to a greater extent than Controls and (2) these differences will be maintained even when objective difficulties in this domain are controlled for.

Using blocked design fMRI paradigms in both studies, we first presented the auditory monitoring task followed by the mPASAT. Within and between regions of interest (ROI), group analyses were performed for both studies with statistical parametric mapping (SPM99).

Findings showed that individuals with CFS are able to process challenging auditory information as accurately as Controls but utilize more extensive regions of the network associated with the verbal WM system. Individuals with CFS appear to have to exert greater effort to process auditory information as effectively as demographically similar healthy adults. Our findings provide objective evidence for the subjective experience of cognitive difficulties in individuals with CFS.

 

Source: Lange G, Steffener J, Cook DB, Bly BM, Christodoulou C, Liu WC, Deluca J, Natelson BH. Objective evidence of cognitive complaints in Chronic Fatigue Syndrome: a BOLD fMRI study of verbal working memory. Neuroimage. 2005 Jun;26(2):513-24. Epub 2005 Apr 7. http://www.ncbi.nlm.nih.gov/pubmed/15907308

 

Brain 5-HT1A receptor binding in chronic fatigue syndrome measured using positron emission tomography and [11C]WAY-100635

Abstract:

BACKGROUND: Research from neuroendocrine challenge and other indirect studies has suggested increased central 5-HT function in chronic fatigue syndrome (CFS) and increased 5-HT1A receptor sensitivity. We assessed brain 5-HT1A receptor binding potential directly using the specific radioligand [11C]WAY-100635 and positron emission tomography (PET).

METHODS: We selected 10 patients from a tertiary referral clinic who fulfilled the CDC consensus criteria for CFS. To assemble a homogenous group and avoid confounding effects, we enrolled only subjects who were completely medication-free and did not have current comorbid psychiatric illness. We also scanned 10 healthy control subjects.

RESULTS: There was a widespread reduction in 5-HT1A receptor binding potential in CFS relative to control subjects. This was particularly marked in the hippocampus bilaterally, where a 23% reduction was observed.

CONCLUSIONS: There is evidence of decreased 5-HT1A receptor number or affinity in CFS. This may be a primary feature of CFS, related to the underlying pathophysiology, or a finding secondary to other processes, such as previous depression, other biological changes or the behavioral consequences of CFS.

 

Source: Cleare AJ, Messa C, Rabiner EA, Grasby PM. Brain 5-HT1A receptor binding in chronic fatigue syndrome measured using positron emission tomography and [11C]WAY-100635. Biol Psychiatry. 2005 Feb 1;57(3):239-46. http://www.ncbi.nlm.nih.gov/pubmed/15691524

 

Reduction of serotonin transporters of patients with chronic fatigue syndrome

Abstract:

To assess the involvement of serotonin in the symptoms of chronic fatigue syndrome, we investigated the serotonergic neurotransmitter system of chronic fatigue syndrome patients by the positron emission tomography (PET).

Here we show that the density of serotonin transporters (5-HTTs) in the brain, as determined by using a radiotracer, [C](+)McN5652, was significantly reduced in the rostral subdivision of the anterior cingulate as compared with that in normal volunteers. This subdivision is different from that in the dorsal anterior cingulate in which binding potential values of individual patient showed a weak negative correlation with self-reported pain score of the patients.

Therefore, an alteration of serotonergic system in the rostral anterior cingulate plays a key role in pathophysiology of chronic fatigue syndrome.

 

Source: Yamamoto S, Ouchi Y, Onoe H, Yoshikawa E, Tsukada H, Takahashi H, Iwase M, Yamaguti K, Kuratsune H, Watanabe Y. Reduction of serotonin transporters of patients with chronic fatigue syndrome. Neuroreport. 2004 Dec 3;15(17):2571-4. http://www.ncbi.nlm.nih.gov/pubmed/15570154

 

Mechanisms underlying fatigue: a voxel-based morphometric study of chronic fatigue syndrome

Abstract:

BACKGROUND: Fatigue is a crucial sensation that triggers rest, yet its underlying neuronal mechanisms remain unclear. Intense long-term fatigue is a symptom of chronic fatigue syndrome, which is used as a model to study the mechanisms underlying fatigue.

METHODS: Using magnetic resonance imaging, we conducted voxel-based morphometry of 16 patients and 49 age-matched healthy control subjects.

RESULTS: We found that patients with chronic fatigue syndrome had reduced gray-matter volume in the bilateral prefrontal cortex. Within these areas, the volume reduction in the right prefrontal cortex paralleled the severity of the fatigue of the subjects.

CONCLUSION: These results are consistent with previous reports of an abnormal distribution of acetyl-L-carnitine uptake, which is one of the biochemical markers of chronic fatigue syndrome, in the prefrontal cortex. Thus, the prefrontal cortex might be an important element of the neural system that regulates sensations of fatigue.

 

Source: Okada T, Tanaka M, Kuratsune H, Watanabe Y, Sadato N. Mechanisms underlying fatigue: a voxel-based morphometric study of chronic fatigue syndrome. BMC Neurol. 2004 Oct 4;4(1):14. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC524491/

 

Learning and memorization impairment in childhood chronic fatigue syndrome manifesting as school phobia in Japan

Abstract:

For the last 15 years, we have tried to understand the pathophysiology of childhood chronic fatigue syndrome (CCFS) in Japan. In this condition, two major symptoms are important: easy fatigability and disturbed learning and memorization. In CCFS patients we clinically evaluated autonomic nervous system function, circadian rhythm of hormonal secretion (melatonin, cortisol and 3-endorphin), core body temperature, and sleep-wake pattern.

Most patients showed autonomic nervous system dysfunction and circadian rhythm disturbances, similar to those observed in jet lag. Radiological imaging studies (SPECT, Xe-CT, and MRS) revealed decreased blood flow in the frontal and thalamic areas, and accumulation of choline in the frontal lobe. We analyzed the relationship between the laboratory data and clinical symptoms in CCFS.

 

Source: Miike T, Tomoda A, Jhodoi T, Iwatani N, Mabe H. Learning and memorization impairment in childhood chronic fatigue syndrome manifesting as school phobia in Japan. Brain Dev. 2004 Oct;26(7):442-7. http://www.ncbi.nlm.nih.gov/pubmed/15351079