Functional Connectivity Assessment in Patients with Chronic-type

Tension Headaches after Applying Osteopathic Correction

A. V.

Fokin, M. L Pospelova, G. E. Trufanov, A. A. Medenikov, E. D. Vyshedkevich,

I. A. Mashchenko, T. A.

Bukkieva, D. S. Chegina, E. A. Gorbunova, T. M. Alekseeva and

A. S. Lepekhina

MRI Department, Almazov National Medical Research Centre, Akkuratova str., 2, Saint-Petersburg, Russia Federation

Keywords: Chronic Tension-type Headache, Osteopathic Correction, Functional MRI at Rest, Connectome.

Abstract: Clinical and neuroimaging comparison of the dynamics of changes in the pain connectome against the

background of osteopathic correction in patients with chronic tension-type headaches. We examined 24

patients with chronic tension type headaches, aged 24 to 43 years. Patients underwent resting-state functional

MRI before and after first osteopathic manipulation. Complaints were evaluated and patients were surveyed

to assess the intensity of headache and its impact on different areas of life, quality of life, situational and

personal anxiety before and after therapy. Changes in the functional connectivity of the in patients with tension

headaches after osteopathic manipulation were found to correlate with a positive clinical picture. Changes in

the functional connections of the medial prefrontal cortex with other areas of the brain were detected in

patients with chronic tension-type headaches when using a single osteopathic correction. There was an

improvement in the condition of patients both in the subjective assessment of complaints and in the objective

assessment of their condition on scales. The use of methods for statistical analysis of neuroimaging data, in

particular resting-state functiontional MRI, made it possible to see the differences objectively by mapping

different colors using color scales, which greatly simplifies the entire analytical process. Clinical and

neuroimaging comparison of the dynamics of changes in the pain connectome against the background of

osteopathic correction in patients with chronic tension-type headaches provides potentially new approaches

to the diagnosis and treatment of pain syndrome.

ABBREVIATIONS

DMN – default mode nerwork

CTTH – chronic tension-type headache

FC – functional connectivity

MPFC – medial prefrontal cortex

TTH – tension-type headache

1 INTRODUCTION

Among all types of headaches, the leading role

belongs to tension-type headache (TTH), the

prevalence of which among the population is up to

45-64%, while chronic tension-type headache

(CTTH) accounts for 1,7–4% (Mathew, 2006;

Jensen,

2008). CTTH is a serious medical and social problem

that leads to a decrease in the working capacity and

quality of life of patients. It is proved that the

etiopathogenesis of TTH involves extensive neural

networks that can extend beyond the somatosensory

system (central divisions) (Filatova, 2020). It should

be noted that in the treatment of tension-type

headaches, there is an excessive use of medications.

That is why the approach based on non-drug methods

of influence seems to be relevant.

One of the promising methods of non-drug

correction of tension headaches is osteopathic

correction. There are studies that show a decrease in

Fokin, A., Pospelova, M., Trufanov, G., Medenikov, A., Vyshedkevich, E., Mashchenko, I., Bukkieva, T., Chegina, D., Gorbunova, E., Alekseeva, T. and Lepekhina, A.

Functional Connectivity Assessment in Patients with Chronic-type Tension Headaches after Applying Osteopathic Correction.

DOI: 10.5220/0010390702490254

In Proceedings of the 14th International Joint Conference on Biomedical Engineering Systems and Technologies (BIOSTEC 2021) - Volume 1: BIODEVICES, pages 249-254

ISBN: 978-989-758-490-9

249

pain sensitivity and pain intensity after treatment

using osteopathic techniques (Bredikhin, 2015;

Miroshnichenko, 2017).

One of the serious problems of modern Algology

is the objectification of pain intensity and the

effectiveness of analgesic treatment. In addition to

subjective assessment using pain scales with low

validity, attempts are being made to develop methods

for objectively measuring the intensity of tension

headaches during treatment – by determining the

concentration of serotonin in the blood plasma of

patients or by studying the latency of P300, but these

approaches are difficult to reproduce and also have

low validity (Rachin, 2005). The most objective and

valid analysis of connections between different areas

of the brain and the assessment of neural networks is

possible using resting-state functional MRI, which is

used to evaluate the effectiveness of evidence-based

medicine methods.

Currently, the issue is devoted to the study of

neuroplasticity in patients with CTTH during the use

of osteopathic correction, and objectively proved the

effectiveness of this method remains poorly

understood. Determining changes in functional

relationships is promising in forming a new view of

the etiology and pathogenesis of CTTH and makes it

possible to develop effective tactics for treating

patients (Patil,2017; Jutzeler, 2015; Baliki 2014,

Lepekhina, 2020).

2 PURPOSE

Сonnectome study in patients with chronic-type

tension headaches with the use of osteopathic

correction.

3 MATERIALS AND METHODS

3.1 Study Population

An open, single-center, uncontrolled study of the

connectome condition was conducted in patients with

tension headaches during a course of treatment with

osteopathic methods.

We observed 24 patients (aged from 24 to 43

years, age - 33±0.5 years) with CTTH, duration of the

disease from 1 year to 18 years (duration - 4.4±0.7 g).

Other causes of headache were excluded.

The diagnosis of CTTH was based on anamnesis

and complaints. All patients complained of

paroxysmal and / or persistent headaches of one - or

two-sided localization of aching (41%), pulsating

character of weak (23%) and moderate intensity

(36%). Headaches were more often of two-sided

localization, were of a pressing/compressing/ non-

pulsating nature, lasting from 60 minutes to several

days, of mild or moderate intensity, which did not

increase with normal physical activity, and were not

accompanied by nausea and vomiting. Patients

reported headache more than 15 days a month, for the

last 6 months. The study was approved by the ethics

committee of the Federal State Budgetary Institution

«National Medical Research Center n.a. V.A.

Almazova» of the Ministry of Health of Russia

(extract from the protocol No. 41 of 02/12/2018).

Criteria for exclusion of patients from the study

were: 1. The presence of a history of psycho-organic

pathology, epilepsy, brain tumors, injuries of the

brain and spinal cord. 2. The presence of severe

concomitant pathology (exacerbation of rheumatism,

acute infections, cirrhosis, alcoholism, drug

addiction, cardiomyopathy with thromboembolism in

the arteries of the brain, acute myocardial infarction,

heart failure 3-4 severity, blood diseases). 3. The

simultaneous administration of drugs that can distort

the results of treatment (anxiolytics, antidepressants,

barbiturates, lithium preparations, narcotic

analgesics, reserpine).

3.2 MR Imaging Protocol

All patients underwent structural MRI with obtaining

T1 and T2 weighted images and FLAIR (Fluid

attenuated inversion) to exclude brain tumors, strokes

and other pronounced pathological changes. All

patients underwent functional resting state MRI at 3

time points – before and after 10 minutes after

applying the first osteopathic technique. Pulse

sequence data of a T1-weighted gradient echo (MP-

RAGE – Magnetization Prepared Rapid Acquired

Gradient Echoes) was collected to combine fMRI

data with anatomical structures of the brain, slice

thickness – 4.5 mm, number of slices – 29, the

number of repetitions – 120, scan time – 6 minutes.

The main feature of this sequence is its high

resolution and 0.8 mm isotropic voxel. BOLD (Blood

Oxygenation Level Dependent) were using with

repetition time (TR) = 3000 ms, echo time (TE) = 50

ms, field of view (FOV) = 230 mm and matrix size

128*128, slice thickness – 4.0 mm, the number of

repetitions – 120, scan time – 6 minutes.

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3.3 Image Analyses

Analyzing the data of functional MRI, when

performing an intergroup statistical analysis (two-

sample t-test, comparing the resting state before

treatment and after osteopathic correction) with the

choice of the medial prefrontal cortex (MPFC) as the

region of interest.

3.4 Statistical Analyses

For statistical analysis, the non-parametric McNemar

test for dependent binary indicators was used.

Statistical processing and evaluation of the results of

neuroimaging studies of each patient individually, as

well as their group totality (resting state fMRI data)

were carried out using the CONN v.18 software

package (Functional connectivity toolbox), designed

to determine the relationships between different parts

of the brain, statistical mapping of activation zones,

determining the structure of various resting state

networks and functional networks of the brain.

3.5 Results

According to the results of the study, after the use of

osteopathic manipulations according to resting-state

fMRI data, changes in the functional connectivity

(FC) were observed. When performing osteopathic

correction, there is a functional reorganization of

neural networks involving, first of all, of default

mode network (DMN). The choice of the medial

prefrontal cortex (MPFC) as a region of interest in the

study is due to its importance as one of the central

links in the DMN.

When selecting the MPFC as the region of interest

in the right hemisphere, the positive functional

connection with the right parahippocampal gyrus was

determined to be enhanced. In the left hemisphere,

there was an increase in the positive FC with the

putamen and a decrease in the negative FC with the

upper left parietal region.

Functional MRI data were obtained when

comparing the state at rest before and immediately

after 10 minutes following osteopathic manipulation:

when performing an intergroup statistical analysis

(p<0.005) (two-sample t-test, seed-to-voxel), the

result of an intergroup comparison is presented,

which demonstrates changes in activity (table 1).

Table 1: The degree of activations severity before and after

10 minutes following osteopathic manipulation. Region of

interest - the medial prefrontal cortex.

ROI Statistical indicator, T

The upper parietal

region, left

-3.13

Parahippocampal

rus, ri

2.43

Putamen -2.16

Schematic representation of data from the

intergroup analysis: shows how MPFC is related to

other areas of the study, where more pronounced

activity is observed in the parahippocampal gyrus,

and a decrease in activity in the upper parietal region

and the putamen (Fig. 1).

Figure 1: The results of the intergroup analysis of resting-

state functional MRI, before and after 10 minutes following

osteopathic manipulation. Schematic data.

For the most convenient visualization, we

combined fMRI data with anatomical structures of the

brain T1-weighted gradient echo MP-RAGE

(Magnetization Prepared Rapid Acquired Gradient

Echoes-gradient echo with magnetization preparation

and rapid data collection) (Fig. 2, 3). When selecting

the MPFC as the zone of interest in the right

hemisphere, the positive FC with the right

parahippocampal gyrus was determined to be

enhanced. In the left hemisphere, there was an

increase in the positive FC with the putamen and a

decrease in the negative FC with the upper left

parietal region.

Functional Connectivity Assessment in Patients with Chronic-type Tension Headaches after Applying Osteopathic Correction

251

Figure 2: (a - axial, b - sagittal, c - coronal). The results of

the inter-group analysis of the resting-state functional MRI

(roi-to-roi). 3-D reconstruction. Region of interest: MPFC.

The red color indicates a positive FC, and the blue color

indicates a negative FC.

Figure 3: (a - axial, b - sagittal, c - coronal). The results of

the inter-group analysis of the resting-state functional MRI

(seed-to-voxel). 3-D reconstruction. Region of interest:

MPFC. The red color indicates a positive FC, and the blue

color indicates a negative FC.

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The study was the first to identify changes in the

FC of the brain after a single procedure of osteopathic

correction in patients with CTTH. The use of methods

for statistical analysis of neuroimaging data, in

particular resting-state fMRI, made it possible to see

the differences objectively by mapping different

colors, which greatly simplified the entire analytical

process.

There were no adverse reactions due to

osteopathic correction, as well as deterioration of the

condition of patients with CTTH during the

treatment.

The possibilities of modern visualization methods

expand the understanding of the mechanisms of

neurological diseases by studying connectome of the

brain. Using resting-state fMRI allows you to

objectively assess neuronal activity and study

changes in CTTH.

When performing osteopathic manipulations, the

functional reorganization of neural networks occurs

with the involvement of the network of the DMN. The

study examined changes in the FC of the medial

prefrontal cortex with other parts of the brain. The

choice of the medial prefrontal cortex as a region of

interest in the study is due to its importance as one of

the central links in the DMN. The MPFC connects

large areas that include the orbitofrontal cortex and

structures such as the central gray matter of the

midbrain, amygdala, and hypothalamus, while

playing an important connecting role in transmitting

somatosensory information to structures that are

responsible for motor and visceral responses,

participating in the internal reward system and

responsible for decision-making. According to recent

data, the parahippocampal gyrus is an intermediate

link in the DMN, which connects the MPFC with the

limbic system, and participates in the processes of the

internal reward and memory system (Ward, 2014).

The increase in the positive FC of MPFC with the

parahippocampal gyrus in the right hemisphere in

patients with CTTH after performing osteopathic

manipulation revealed in our study may indicate

activation of the functional pathway associated with

a positive emotional response in the reward system.

In the left hemisphere, there was a weakening of

the negative FC with the upper left parietal region and

an increase in the positive FC with the putamen. The

upper parietal cortex is part of the vast preclinical

zone, which, along with the MPFC, is one of the

important links in the DMN, which are involved in

the processing of sensory-motor signals and attention.

Changes in the FC between the upper parietal region

and the MPFC may indicate a decrease in activity in

this area DMN. The putamen is a subcortical structure

that belongs to the significance determination

network, and the strengthening of links between this

area and the MPFC may indicate activation of DMN.

So, changes in the FC of the MPFC with other

areas of the brain were detected when applying a

single osteopathic correction in patients with CTTH.

4 CONCLUSIONS

To date, the number of full-fledged studies on

changes in the FC of the brain in patients with CTTH

is limited, which makes this area even more relevant.

The current study showed the importance of

evaluating the FC that ensure the interaction of brain

structures. Changes in the FC of the DMN were

identified in patients with CTTH after the use of

osteopathic correction, which require further study.

The results of the study of FC of the brain in patients

with CTTH expand the understanding of the

pathogenesis of this type of headache and improve the

treatment regimens used in patients.

CONFLICT OF INTERESTS

The authors declare no conflict of interest

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