In spite of several evidences for a mitochondrial impairment in Parkinson's disease (PD), so far it has not been possible to show in vivo mitochondrial dysfunction in the human brain of PD patients. The authors used the high temporal and spatial resolution 31 phosphorus magnetic resonance spectroscopy ( 31 P MRS) technique, which they have previously developed in normal subjects and in patients with mitochondrial diseases to study mitochondrial function by observing high-energy phosphates (HEPs) and intracellular pH (pH) in the visual cortex of 20 patients with PD and 20 normal subjects at rest, during, and after visual activation. In normal subjects, HEPs remained unchanged during activation, but rose significantly (by 16%) during recovery, and pH increased during visual activation with a slow return to rest values. In PD patients, HEPs were within the normal range at rest and did not change during activation, but fell significantly (by 36%) in the recovery period; pH did not reveal a homogeneous pattern with a wide spread of values. Energy unbalance under increased oxidative metabolism requirements, that is, the postactivation phase, discloses a mitochondrial dysfunction that is present in the brain of patients with PD even in the absence of overt clinical manifestations, as in the visual cortex. This is in agreement with our previous findings in patients with mitochondrial disease without clinical central nervous system (CNS) involvement. The heterogeneity of the physicochemical environment (i.e., pH) suggests various degrees of subclinical brain involvement in PD. The combined use of MRS and brain activation is fundamental for the study of brain energetics in patients with PD and may prove an important tool for diagnostic purposes and, possibly, to monitor therapeutic interventions.

We sought to study brain temperature in patients with mitochondrial diseases in different functional states compared with healthy participants. Brain temperature and mitochondrial function were monitored in the visual cortex and the centrum semiovale at rest and during and after visual stimulation in seven individuals with mitochondrial diseases (n ¼ 5 with mitochondrial DNA mutations and n ¼ 2 with nuclear DNA mutations) and in 14 age-and sex-matched healthy control participants using a combined approach of visual stimulation, proton magnetic resonance spectroscopy (MRS), and phosphorus MRS. Brain temperature in control participants exhibited small changes during visual stimulation and a consistent increase, together with an increase in high-energy phosphate content, after visual stimulation. Brain temperature was persistently lower in individuals with mitochondrial diseases than in healthy participants at rest, during activation, and during recovery, without significant changes from one state to another and with a decrease in the high-energy phosphate content. The lowest brain temperature was observed in the patient with the most deranged mitochondrial function. In patients with mitochondrial diseases, the brain is hypothermic because of malfunctioning oxidative phosphorylation. Neuronal activity is reduced at rest, during physiologic brain stimulation, and after stimulation. Animal studies have shown a close relationship between brain temperature and cerebral oxygen metabolic rate (CMRO 2 ) 2 at rest and during brain activation. 3 There are only fragmentary data regarding T br and its regulation under different physiologic conditions and no temperature data are available regarding patients with mitochondrial disorders. Time-dependent variations in T br are caused by fluctuations of cerebral blood flow (CBF) and CMRO 2 , both of which appear to be coupled to changes in neuronal activity. 1 Increases in CBF reduce T br and increases in brain metabolism increase T br . 1 Intense heat production is an essential feature of normal brain energetics; most of the energy used for brain functioning is eventually released as heat. 4 In the brain, heat is produced mostly by mitochondrial oxidative chemical reactions. Most of the energy required for brain activity is generated from the net chemical reaction of oxygen and glucose; some of this energy (33%) is immediately dissipated into heat, and the rest (67%) is used to synthesize ATP. The final ATP hydrolysis releases part of the energy back to the system as heat. 4 Owing to rapid ATP turnover and the high cerebral metabolic rate of oxygen, basal heat production within the brain is high. Aerobic metabolism of glucose produces heat at a rate of 0.7 J/min per gram brain tissue. 4 In a closed system, this metabolism would lead to an increase in temperature of 0.281C/min. However, because the brain is an 'open' thermodynamic system, heat is dissipated through circulation and by conduction through the skull. Most of the heat is dissipated through CBF, with venous blood leavin...

Background PINK1 mutations are likely to affect mitochondrial function. The objective of this study was to study brain mitochondrial function in patients with early‐onset Parkinson's disease, with or without PINK1 mutations. Methods We investigated brain intracellular pH, mitochondrial activity, and energetics with functional magnetic resonance spectroscopy in patients with early‐onset Parkinson's disease with PINK1 mutations (n = 10), early‐onset Parkinson's disease without PINK1 mutations (n = 10), and healthy sex‐ and age‐matched subjects (n = 20). We measured peak areas of phosphocreatine and beta adenosine triphosphate. Results The EOPD‐ group had normal PCr + βATP contents at rest (P = NS) and under activation (P = NS), but reduced contents during recovery (P < 0.001). The EOPD+ group had abnormal PCr + βATP contents at rest (P < 0.001) and during activation (P < 0.001); during recovery, the contents only partially recovered (P < 0.001). Brain intracellular pH alterations were more severe with EOPD+ than with EOPD−. Conclusions Brain mitochondrial impairments were similar in early‐onset Parkinson's disease without PINK1 mutations and late‐onset Parkinson's disease. However, mitochondrial impairments were more severe in early‐onset Parkinson's disease with PINK1 mutations. © 2020 International Parkinson and Movement Disorder Society