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Take a look at a selection of our recent media coverage:

Transcranial magnetic stimulation brain changes in depressed patients visible during MRI scan

27th May 2022

Transcranial magnetic stimulation (TMS) induced brain connectivity changes that improve depression symptoms can be viewed during an MRI scan

Changes in brain connectivity during treatment for depression with transcranial magnetic stimulation (TMS) and which improve symptom scores can be seen during an MRI scan. This was the key finding of a study by a team of researchers from Canada and the US.

Depression affects an estimated 3.8% of the world’s population and a 2022 meta-analysis found the point prevalence of major depression to be 8%. Repetitive transcranial magnetic stimulation (TMS) is a non-invasive technique which uses magnetic pulses to influence the excitability and connection strength of the cortical neurons and has been used as a treatment modality for major depression. It involves placing an electromagnetic coil on the scalp and delivery of a brief pulsatile magnetic field that depolarises cortical neurons. Treatment with TMS has been shown to be effective for reducing suicidal ideation and in alleviating depression. The treatment is normally applied to the left or right dorsolateral prefrontal cortex (DLPFC) although use on either side appears to be equally effective. The mode of action for TMS remains uncertain although the effects of TMS on brain activity that can now be studied by combining it with neuroimaging methods such as functional magnetic resonance imaging. In a 2020 study combining TMS with MRI imaging, researchers observed how the magnetic stimulation induced lasting connectivity and excitability changes such that after treatment, the DLPFC appeared better able to engage in top-down control of the amygdala

However, the particular changes in brain connectivity affected by TMS among those with major depression are unknown. For the present study, the team wanted to visualise these changes with MRI but also determine whether such changes led to a clinical response in patients with major depression. They recruited adults with major, treatment-resistant depression and performed an open-label trial of TMS. The team initially acquired MRI scans without TMS and compared these to scans when TMS was delivered. The treatment was applied to the right DLPFC once daily for a period of 4 weeks. The TMS-induced changes were assessed by pairwise comparison between the MRI scan with and without TMS. Depression symptoms were assessed using the Montgomery-Asberg Depression rating scale (MADRS) which was measured at baseline and at the end of the study.

Transcranial magnetic stimulation and depression

A total of 38 patients with a mean age of 41.8 years (68% female) were included in the study.

When comparing the two scans, the researchers observed 43 edges that were changed after use of TMS with a preponderance of inter-hemispheric functional connectivity. As the changes were absent from the baseline MRI scan, these were indicative of the response to TMS and hence an index of short-term macro-scale neuroplasticity. The observed TMS-induced changes were short-lived and the authors suggested that repeated stimulation might be necessary to induce long-lasting connectivity effects.

More importantly however, the observed were associated with an improvement in depression symptom scores, with a drop in MADRS of 10.87.

The authors concluded that the observed TMS-induced effect on connectivity may index macro-level neuroplasticity changes and which might be indicative of an individual’s response to TMS treatment. They called for further studies to assess the generalisability of these findings and their relevance to connectivity changes after repeated TMS therapy.

Citation
Ge R et al. Predictive Value of Acute Neuroplastic Response to rTMS in Treatment Outcome in Depression: A Concurrent TMS-fMRI Trial Am J Psychiatry 2022

Generalised and visceral body fat levels on MRI linked with reduced cognitive scores

11th February 2022

Higher generalised and visceral body fat levels on MRI scans correlate with lower cognitive scores after adjustment for cardiovascular risk

Elevated generalised and visceral body fat levels seen on a magnetic resonance imaging scan have been found to be associated with reduced cognitive scores even after adjustment for cardiovascular risk factors. This was according to a study by researchers from the Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Canada.

Increased levels of body fat and in particular central adiposity, measured by the waist-to-hip ratio, has been found to have a highly significant association with myocardial infarction risk. The use of magnetic resonance imaging (MRI) enables the detection of visceral fat volume and accumulated evidence shows that visceral adipose tissue is an independent risk marker of cardiovascular and metabolic morbidity and mortality. However, whether elevated levels of both generalised and visceral fat are linked with an impairment of cognitive functioning remain unclear. One prospective study of older adults concluded that abdominal fat in late life appears to confer an increased risk for dementia and cognitive impairment and where body fat levels have been assessed through electrical impedance, visceral fat accumulation was also associated with mild cognitive impairment. In contrast, however, a study in 1047 individuals aged 60 years and older concluded that abdominal obesity might be a protective factor for cognitive function.

With some uncertainty over the relationship between generalised and visceral fat and cognitive function, the Canadian team set out to examine this relationship based on MRI scan results. They turned to data from the Canadian Alliance of Healthy Hearts and Healthy Minds and the Prospective Urban Rural Epidemiological–Mind (PURE-MIND) studies. These studies recruited adults between the ages of 30 and 75 years of age and who had their body fat levels measured by bioelectrical impedance and MRI of the abdomen to measure visceral adipose tissue levels. In addition, all participants underwent MRI of the brain to measure vascular brain injury and cardiovascular risk factors were assessed using lifestyle questionnaires and physical measures. Cognitive assessment was measured using the Digital Symbol Substitution Test (DSST) and the Montreal Cognitive Assessment (MoCA). The DSST scores range from 0 to 133 with lower scores indicative of worse performance. In contrast, the MoCA score ranges from 0 to 30, with higher scores denoting normal cognitive function.

Generalised and visceral body fat levels and cognitive impairment

A total of 9189 adults with a mean age of 57.8 years (56.4% women) were included in the analysis. The women had a higher percentage of body fat compared to men (35.6% vs 25.1%) although men had a higher mean visceral adipose tissue volume (83.6 vs 64.1 ml). The mean DSST score was 72.6 and the MoCA score was 27 and both were slightly higher in women compared to men.

Overall, both a higher total percentage of body fat and visceral adipose score were associated with the lowest DSST score although this was not the case for visceral adipose scores and the MoCA. In regression models fully adjusted for age, sex, educational level and cardiovascular risk factors, the total percentage of body fat remained independently associated with reduced cognitive scores. The authors calculated that for each standard deviation increase in adiposity (9.2% for generalised fat and 36ml of visceral fat), there was a reduction of 0.8 in the DSST score, which was equivalent to 1 year of cognitive ageing. For example, comparing individuals in the highest versus the lowest percentage of body fat, was equivalent to 2.8 years of cognitive ageing. A similar amount of cognitive ageing was also seen between the highest and lowest levels of visceral adipose tissue. However, there were no significant associations between either total body or visceral fat with MoCA scores.

The authors concluded that based on these finding, excess adiposity was a risk factor for reduced cognitive scores and called for strategies to reduce or prevent adiposity as a means of preserving cognitive function in adults.

Citation
Anand SS et al. Evaluation of Adiposity and Cognitive Function in Adults JAMA Netw Open 2022

Atrophic changes seen with MRI at autopsy could be marker for chronic traumatic encephalopathy

10th December 2021

Atrophic changes observed with MRI on autopsies of those with chronic traumatic encephalopathy could be a disease marker in living patients

A number of atrophic changes detected with magnetic resonance imaging (MRI) in patients with chronic traumatic encephalopathy (CTE) could be an important marker of the disease if observed in living patients. This was the tentative conclusion of a study by a team from the Framingham Heart Study, Boston University School of Medicine, Boston, US.

CTE is defined as a progressive neurodegenerative disorder linked to repetitive traumatic brain injury from head impacts and is a common finding in deceased, retired American football players. The pathognomonic lesion of CTE is an abnormal accumulation of hyper-phosphorylated tau protein (p-tau) within neurons and a definitive diagnosis can only be made by post-mortem examination of brain tissue. Furthermore, CTE has been categorised into four pathological stages of CTE, stages I (mild) to IV(severe), based on the density and regional deposition of p-tau.

Although imaging studies in living patients at a higher risk of CTE such as former American football players have revealed some changes, these studies could not definitively characterise the specific in vivo structural MRI patterns of CTE.

For the present study, the US researchers turned to MRI scans of patients with autopsy confirmed CTE together with a brain samples obtained from patients with normal cognition to compare atrophic changes. The researchers were interested in testing the associations between p-tau severity in those with CTE with atrophy changes seen on MRI. The neuropathological evaluations were undertaken by three neurologists, blinded to clinical data from the participants and who rated regional atrophy changes on a scale of 0 (none) to 4 (severe) in 14 different regions. In addition, the presence of cavum septum pellucidum (CPS), which is a common neuropathological feature of chronic traumatic encephalopathy, was recorded on a binary (absent/present) scale. For their analysis, the researchers used linear regression models to compare the brains of those with CTE and normal cognition donors. For those with CTE, the regression models examined the association between p-tau severity and atrophy changes seen on MRI.

Findings

A total of 55 donors with CTE and 31 men (11 who were deceased) with normal cognition were included in the analysis. The mean age at the time of the scan was 71 years for donors with CYE and 76 for those with normal cognition. In the majority of cases (65%), the MRI scan had been requested in CTE donors because of dementia or neurodegenerative disease. Among those with normal cognition, requests for the scans were for a wider range of conditions including cardiovascular causes (22.6%) and memory complaints (16.1%).

Compared to those with normal cognition, CTE donors had greater mean differences in atrophic changes in a number of areas. For example, orbital-frontal atrophy (mean difference, MD = 1.29, p = 0.009), dorsolateral frontal (MD = 1.31, p = 0.013), superior frontal (MD = 1.05, p = 0.046) and anterior temporal (MD = 1.57, p = 0.009). There were no differences for posterior atrophy or microvascular disease. In addition, among donors with CTE, there was a 6-fold increased odds of CSP (Odds ratio, OR = 6.7, p < 0.05) and a greater degree of tau severity across the different regions of the brain which was associated with a greater total brain atrophy on the MRI scan.

The authors concluded that in men with autopsy-confirmed CTE, there was more severe atrophy changes and more severe p-tau pathology. They suggested that if validated with prospective studies, their findings could support the use of structural MRI as a valuable tool to support a diagnosis of CTE during life.

Citation

Alosco ML et al. Structural MRI profiles and tau correlates of atrophy in autopsy-confirmed CTE. Alzheimers Res 2021 Ther