Also, do not forget that artificially increasing the beta rhythm can lead to undesirable effects, such as feelings of fear, anxiety or panic.
Theta activity allows our body to heal itself, thereby improving our physical and spiritual well-being. Often, Specialists use its artificial increase in the treatment of mental trauma.
The ways to stimulate it are as follows:
- Listening to music that is associated with additional production of emotions and sensations, thereby increasing the theta rhythm
The influence of hypnosis, which allows you to enhance theta activity and regulate a person’s consciousness in the right direction
If overstimulated or when the theta rhythm is initially in a normal state, its increase can cause drowsiness. Drugs and alcohol are also considered undesirable ways to increase levels. However, these negative methods will lead to disorders of memory, speech and thinking.
It is one of the most inaccessible processes, since the delta rhythm forms the subconscious. Its activity is observed during deep sleep or in the absence of consciousness.
One way to increase it is rhythmic breathing, with a frequency of about 60 breaths per minute. This method also poses a huge danger, since oversaturation of the blood with carbon dioxide during such breathing can lead to respiratory arrest or death.
Alpha rhythm depression on EEG
2.1. Criteria for normal and pathological resting electroencephalogram
Electroencephalograms are recorded in the range from 0.3 to 50 Hz. It consists of the basic rhythms of the brain - delta rhythm from 0.3 to 4 Hz), theta rhythm (from 4 to 8 Hz), alpha rhythm (from 8 to 13 Hz), low-frequency beta rhythm or beta-1 -rhythm (from 13 to 25 Hz), high-frequency beta rhythm or beta 2 rhythm (from 25 to 35 Hz) and gamma rhythm or beta 3 rhythm (from 35 to 50 Hz). These rhythms correspond to activities - delta activity, theta activity, alpha activity, beta activity and gamma activity (Appendix 2). In addition, special types of bioelectrical activity can be seen on the EEG - flat EEG, high-frequency asynchronous low-amplitude (“march”) activity, low-amplitude slow polymorphic activity (LPMA) and polyrhythmic activity (Appendix 2). The main rhythms of the brain, the corresponding activities and the main types of bioelectrical activity are often expressed by a regular component and can have a high index. Periodically occurring graph elements of the EEG are called pathological images of the electroencephalogram. These include spike, peak, slow spike, sharp wave, complexes (spike-wave, wave-spike, peak-wave, wave-peak, slow spike-wave, wave-slow spike, helmet wave, multiple spike complex, multiple spike complex -slow waves), as well as flare, paroxysm and flare of hypersynchronization (Appendix 2).
Each frequency component of the EEG is assessed by its amplitude and severity on the electroencephalogram over time. Wave amplitude measurements are made “peak to peak” without taking into account the presence of an isoelectric line. The severity of the frequency component on the EEG is determined by the rhythm index (see Algorithm for describing the EEG, Appendix 2).
Normally, the alpha rhythm dominates in the occipital regions of the brain; decreases in amplitude from the back of the head to the forehead; in the frontal regions it is not registered with bipolar leads from electrodes placed along sagittal lines with small interelectrode distances; symmetrical in frequency and amplitude in the right and left hemispheres; there is a presence of functional asymmetry with a predominance in filling the convexital surface and a slight excess of amplitude in the right hemisphere, which is a consequence of functional asymmetry of the brain associated with greater activity of the left hemisphere; the image of the alpha rhythm is spindle-shaped, the waveform is sinusoidal; frequency fluctuations are small and do not exceed 0.5 vibrations/s, the amplitude of the alpha rhythm is 30-80 μV (usually 40-60 μV) when recording in the central-occipital leads during bipolar recording with large interelectrode distances from electrodes placed on the sagittal lines , or with a monopolar lead according to Goldman (with a monopolar lead with an indifferent electrode on the cheek - the amplitude of the alpha rhythm is 2 times higher; with a bipolar lead with small interelectrode distances along the sagittal lines - the amplitude of the alpha rhythm is 2 times lower), index 7595% .
Beta activity, which is observed in the frontal regions of the brain and at the junctions of the alpha spindles, is symmetrical in amplitude in the right and left hemispheres; the image is asynchronous, aperiodic; amplitude 3-5 µV; the index in the frontal regions can reach 100%; the absence of beta activity is not a sign of pathology.
In a healthy adult who is in a state of passive wakefulness, theta and delta rhythms are not recorded; they are observed only in a state of sleep or anesthesia.
With a well-defined norm, the alpha rhythm dominates in the EEG. In the frontal parts of the brain and at the junctions of the alpha rhythm spindles, low-frequency beta activity is recorded, and in the posterior parts of the brain, rare, not exceeding the alpha rhythm, bursts of the theta rhythm of 2-4 waves are observed, multiples of the alpha rhythm in frequency, with an amplitude not exceeding the background rhythm. Rare single scattered low-amplitude delta waves are also recorded here.
Disturbances of a functional or morphological nature affect primarily the parameters of the alpha rhythm. The criteria for pathology when assessing alpha rhythm are as follows:
1) the constant presence of an alpha rhythm (index more than 50%) in the frontal regions of the brain during bipolar recording from electrodes placed along sagittal lines with small interelectrode distances;
2) amplitude interhemispheric asymmetry more than 30%;
3) frequency asymmetry more than 1 oscillation/s;
4) image disturbance: lack of modulation, the appearance of paroxysmal, arch-shaped alpha rhythm, disturbance of sinusoidality of waves;
5) changes in quantitative parameters: lack of stability in frequency; a decrease in amplitude below 20 μV or an increase above 90 μV, a decrease in the alpha rhythm index below 50% up to its complete absence.
Certain changes in the beta-rime band also indicate the presence of a pathological process. The criteria for pathology are:
1) dominance of the low-frequency beta rhythm throughout the convexital surface of the brain;
2) paroxysmal discharges of the beta rhythm;
3) focal localization of the beta rhythm, especially with an increase in its amplitude;
4) gross interhemispheric asymmetry in amplitude (more than 50%);
5) acquisition by the beta rhythm of an alpha-like rhythmic sinusoidal pattern;
6) an increase in the amplitude of the beta rhythm over 7 μV.
Pathological manifestations on the EEG include the appearance of slow rhythms: theta and delta. The lower their frequency and higher the amplitude, the more pronounced the pathological process. The appearance of slow-wave activity is usually associated with dystrophic processes, demyelinating and degenerative lesions of the brain, compression of brain tissue, hypertension, as well as the presence of some inhibition, deactivation phenomena, and a decrease in the activating influences of the brain stem. Typically, unilateral localized slow-wave activity is a sign of localized cortical damage. Outbursts and paroxysms of generalized slow-wave activity in waking adults appear as a result of pathological changes in the deep structures of the brain.
The presence of high-frequency rhythms (beta-1, beta-2, gamma rhythm) is also a criterion for pathology, the more pronounced the more the frequency is shifted towards high frequencies and the more the amplitude of the high-frequency rhythm is increased. The high-frequency component is usually associated with the phenomena of irritation of brain structures.
Polymorphic slow activity with an amplitude below 25 μV is sometimes considered as a possible activity of a healthy brain. However, if its index is more than 30% and its occurrence is not a consequence of successive indicative reactions, as is the case in the absence of a soundproof chamber, then its presence in the EEG indicates a pathological process involving deep brain structures. The dominance of low-amplitude polymorphic slow activity (LPSA) may be a manifestation of activation of the cerebral cortex, but it may also be a manifestation of deactivation of cortical structures. These conditions can only be differentiated using functional loads.
The dominance of flat EEG may also be associated with phenomena of increased activation of the cortex or its deactivation. These conditions can also be differentiated only with the help of functional loads.
High-frequency asynchronous low-amplitude activity is a consequence of either processes of irritation of the cortex, or the result of an increase in activating influences from the reticular activating system. Differentiation of these states is also carried out using functional loads.
Pathological images of the electroencephalogram - spike, peak, slow spike, sharp waves, complexes are a manifestation of synchronous discharges of huge masses of neurons in epilepsy.
2.2. Signs of normality and pathology when assessing functional loads and their significance for medical and labor examination. Due to the fact that recording a resting EEG (background electroencephalogram) in many cases is not able to detect pathological changes in the bioelectrical activity of the brain, recording a reactive EEG is mandatory (Appendix 1).
In this case, a mandatory set of functional loads and additional loads are used, which are used to diagnose epilepsy. Mandatory functional loads include a load that allows one to evaluate the EEG component of the orienting reaction - orienting load, rhythmic photostimulation (RPS) and trigger photostimulation (TPS). Additional loads include hyperventilation, a test with bemegride (megimide), and aminazine test. Signs of normality and pathology when assessing the estimated load.
Normally, in response to a single flash of light from a standard photostimulator (Appendix 1), a clear, simultaneous depression of the alpha rhythm occurs in all leads, which lasts 3-4 s, after which it is restored. Repetition of the stimulus is used to assess extinction of the orienting response. Normally, upon presentation of the 4th-5th flash of light, the indicative reaction completely fades away, i.e., depression of the alpha rhythm does not occur.
Criteria for pathology when assessing the indicative reaction.
1) Incomplete depression of the alpha rhythm (the amplitude of the alpha rhythm decreases, but it does not disappear).
2) Areactivity (the amplitude of the alpha rhythm or other dominant rhythm does not change).
3) Paradoxical reaction (the amplitude of the alpha rhythm increases).
4) The appearance of rhythms and complexes of a pathological series (beta rhythm, spikes, peaks, etc.).
5) Non-simultaneous depression of the alpha rhythm in various parts of the brain.
6) Lengthening the area of alpha rhythm desynchronization.
7) Delay or lack of extinction of the orienting reaction.
Acceleration of extinction of the indicative reaction - extinction by 1-2 flashes of light.
Signs of normality and pathology when assessing rhythmic photostimulation (RPS) Brain responses to rhythmic photostimulation:
1) rhythm assimilation - the appearance of a rhythm equal to the frequency of light flickers (rhythm assimilation reaction - RUR;
2) harmonics - the appearance of rhythms that are multiples of the frequency of light flickers and exceed the original by 2, 3, etc.;
3) subharmonics - transformation of rhythms towards low frequencies, multiples of the frequency of light flashes;
4) the appearance of a rhythm that is not a multiple of the flash frequency.
In healthy people, a reaction of rhythm assimilation is observed in the range from 8 to 25 Hz, i.e., in the band of natural frequencies of the electroencephalogram. There may be harmonics or subharmonics that do not exceed the natural frequency band of the EEG. Lack of rhythm acquisition is not a pathology.
Pathology criteria for assessing RFS.
1) Expanding the range of rhythm assimilation towards high frequencies, towards low frequencies or towards low and high frequencies.
2) Assimilation of rhythm in the frontal regions of the brain.
3) Asymmetry of rhythm reproduction in symmetrical leads of the right and left hemispheres, if the difference in amplitude reaches 50%.
4) Excitation of subharmonics with a frequency below 8 oscillations/s.
5) Excitation of harmonics with a frequency of over 25 oscillations/s.
6) Excitation of rhythms that are not a multiple of the frequency of light flashes (beta, theta, delta, etc.), as well as the appearance of waves or spike-wave complexes, etc. Signs of pathology when assessing trigger photostimulation (TPS).
TPS is most effective for identifying latent brain pathology, especially deep structures. The response to TPS is more clearly detected from the occipital electrodes along the median (vertex) line or from the area of the focus of the process. Trigger stimulation - stimulation in the rhythm of oscillations of brain potentials. The stimulation rhythms are controlled through a special feedback device by applying potential oscillations to it and converting them into a control signal for the photostimulator. Stimulation is carried out in series. The duration of the series is 10-15 s when the irritating stimulus is delayed from the moment the wave transitions from minus to plus through the zero line at 300, 250, 200, 150, 100, 80, 50, 20, 10 and 0 ms. Delays of 300, 250, 200 ms excite delta activity, delays of 200, 150 and 100 ms excite theta activity, delays of 100, 80 and 50 ms excite alpha rhythm, delays of 20, 10 and 0 ms excite high frequencies, as well as delta. - and theta rhythm.
Signs of pathology during hyperventilation (HV).
GV - intense deep breathing with a frequency of 20 breaths per minute for three minutes (i.e., for 180 s, which is 18 EEG frames of 10 s) or until the appearance of epileptic activity, which may appear earlier.
GV in healthy people does not cause significant changes in the EEG - only depression of the alpha rhythm or an increase in its amplitude and the appearance of slow activity are observed.
Excitation of slow-wave activity with a gradual slowdown in its frequency and a gradual increase in its amplitude is considered as a failure of vascular regulation of brainstem structures and, in connection with this, a decrease in the level of general activation.
The appearance of spikes, peaks, spike-wave complexes or paroxysms of slow-wave activity with an amplitude of up to 200 μV against the background of alpha rhythm or theta activity indicates the presence of an epileptic focus. If the epileptic focus is not detected, then after a 3-minute break the subject is given 1-2 therapeutic doses of nitroglycerin and the GV is repeated. Signs of pathology when assessing pharmacological loads.
a) Test with bemegride (syn. megimid).
During continuous EEG recording, a 0.5% solution of bemegride is administered intravenously every 15 s at the rate of 1 mg per 10 kg of body weight of the subject with each injection. The total dose should not exceed 150 mg. The appearance of spikes, peaks, spike-wave complexes or paroxysms of slow-wave activity with an amplitude of up to 200 μV against the background of alpha rhythm or theta activity indicates the presence of an epileptic focus.
b) Test with chlorpromazine. 25-50 mg of aminazine is administered intramuscularly or intravenously and the EEG is recorded for 30 minutes for 30-40 seconds at intervals of 3-5 minutes.
2.3. Dynamics of the process of changes in the electroencephalogram in diseases that are of greatest importance for medical and labor examination
EEGs do not have nosological specificity, since it does not record the pathological process itself, but only the local and general reaction of brain tissue to it. EEG with brain damage is a reflection of local disturbances caused by the pathological focus. In addition, it reflects changes in the activity of structures functionally associated with the affected substrate, as well as general functional rearrangements that arise due to dysregulation of brain mechanisms.
The presence of many factors leads to the fact that with similar lesions different patterns of bioelectrical activity can develop, and, conversely, with different lesions the same. Therefore, clinical electroencephalography, like any other additional research method, cannot have independent significance outside of combination with the clinical picture of the disease. For example, even the presence of undeniable epileptic activity on the EEG does not indicate epilepsy, but only the presence of an epileptic focus or increased convulsive readiness. In combination with clinical data, the results of EEG studies acquire enormous differential diagnostic significance. It is always necessary to take into account that pathological changes in the EEG may be the first sign of an incipient disease.
It has been established that in a number of diseases, especially when certain structures of the brain are affected, for example, the brain stem, hypothalamus and some others, certain disturbances in the general functional state of the brain may develop. Thus, with certain diseases or with damage to certain brain structures, certain mosaics of bioelectrical signs characteristic of each level of damage can develop. Despite the fact that the display of functional patterns in the bioelectric picture has certain areas of overlap, the dynamics of changes in background activity and, especially the nuances of the EEG when applying functional loads, make it possible in most cases to differentiate these conditions, despite the identity of the clinical manifestations. In these cases, EEG, if the specific focus of the study is observed, becomes a valuable method that allows the doctor to quickly make a differential diagnosis. When assessing the general functional state of the brain and its dynamic changes, EEG data are of decisive importance.
Using clinical methods, a doctor can only take into account the aggregate data of the entire system, but not the state of its intermediate links, which is especially important for a medical expert, since when assessing a patient’s ability to work, both the general functional state and the determination of individual functional capabilities are one of the leading factors.
To assess the EEG reflection of the severity of damage to the brain substrate, it is necessary to use the following provisions.
1. In the event of death of brain elements (formation of a glial scar, volumetric process, etc.), bioelectrical activity is not generated in this place. However, registration of a flat EEG from any part of the brain cannot indicate the absence of its bioelectric activity (the so-called “bioelectric silence”), but only indicates the absence of a potential difference between the two electrodes. This position is easily verified by monopolar EEG recording with an averaged electrode or an indifferent electrode located on the cheek.
2. Severe focal lesions are indicated by high-amplitude waves of the delta and theta rhythm, expressed as a dominant component. It is usually believed that the higher its amplitude and the higher the index, the more severe the pathological changes. At the same time, it is necessary to take into account the fact that when nerve elements die, their electrical activity disappears, i.e., a decrease in slow bioelectrical activity when observed over time and with an unfavorable course of the disease and worsening symptoms does not yet indicate normalization of the process.
3. Focal disturbances of moderate severity usually correlate with slow-wave activity superimposed on the alpha rhythm. The preservation of the alpha rhythm in these cases indicates the presence of structures with normal metabolic processes. To the same extent, a process of moderate severity is indicated by pronounced irritation activity in the form of a high-frequency beta rhythm or gamma rhythm. And the higher the frequency and amplitude of this activity, as well as its regularity, the deeper the pathological changes.
4. Moderately pronounced focal shifts are characterized by the preservation of the alpha rhythm, against the background of which there are bursts of slow activity of low amplitude, the presence in certain local areas of polymorphic slow activity, as well as bursts of high-frequency asynchronous low-amplitude activity. Dynamic observations in all these cases make it possible to assess the direction in the development of the pathological process.
When using EEG, the localization of the pathological process fits into the following scheme.
1. The presence of persistent, clear changes on the convexital surface with limited localization only in the area of several electrodes indicates the localization of the process in the structures of the cortex.
2. Changes affecting one hemisphere or simultaneously observed to a lesser extent in the symmetrical leads of the other hemisphere indicate a deeper localization of the process. The same occurs when the alpha rhythm is preserved with pathological rhythms superimposed on it.
3. Localization of the focus in the area of the median (vertex) line in deep structures causes the appearance of bilateral synchronous activity in the form of paroxysms of various rhythms.
4. The anterior parts of the diencephalic region often produce changes in the frontal parts and are less pronounced in other parts of the brain.
5. Changes in the EEG in the parieto-occipital region are more associated with pathological processes of mesencephalic localization.
6. A shift in the focus of pathological bioelectrical activity towards one of the hemispheres indicates a shift in the pathological focus in deep structures in the same direction.
7. The appearance of a regular alpha-like low-frequency beta rhythm in the EEG is associated with damage to the bottom of the third ventricle.
8. Lesions of the caudal part of the trunk usually give generalized symptoms in the form of paroxysms of slow activity, widely covering the entire convexital surface.
It should be borne in mind that the above diagram should be treated with some caution. The fact is that the nature of the pathological focus, its size, the malignancy of the process, the presence of concomitant hypertension - all these factors have a significant impact on the severity of bioelectrical manifestations.
The use of various loads, determination of the correlation of background and evoked shifts in bioelectrical activity, the severity of changes with various recording methods (i.e., when recording EEG on various wiring diagrams), as well as comparison with clinical data allow the specialist to carry out fairly accurate topical diagnostics.
When assessing the general functional state of the brain using the EEG method, the following must be kept in mind.
1. Bioelectrical activity recorded on the EEG characterizes the functional state of the entire brain or its individual parts that are located under the electrodes.
2. Normal EEG or pathological bioelectrical activity, characterized by a sign of constancy, stability of the electroencephalogram pattern, indicates the presence of a stable functional state of the brain.
3. Frequent changes in the EEG pattern - frequent transition from a well-defined alpha rhythm to its spontaneous desynchronization, frequent appearance of bursts of slow-wave activity with suppression of the dominant rhythm, frequent transition from one dominant rhythm to another - all this indicates instability of the functional state of the brain.
4. Since it is important for a medical expert to establish whether the instability of the functional state of the brain is functional or has an organic origin, it should be borne in mind that if, when recording an EEG, a normal, well-defined alpha rhythm is revealed, alternating with areas of desynchronization (with an index alpha rhythm equal to 30%), and the extinction of the orienting reaction is prolonged, then although other signs of pathology are not revealed during its assessment, this indicates instability of the general functional state of the brain of a functional nature. If the instability of the functional state of the brain is caused by damage to certain deep structures that have a local effect on the brain or belong to general regulatory systems, then the EEG shows a frequent change from one type of pathological bioelectrical activity to another. And the more often this change in bioelectrical activity occurs and the more polyrhythmic these activities are, the more pronounced is the disturbance in the functional state of the brain and its individual structures.
For the examination of work ability, assessing the degree of impairment of bioelectrical activity is of great importance. In this case, it is necessary to use the following provisions.
1. A preserved symmetrical alpha rhythm, even in the presence of mild focal disturbances, but with normal responses to stress, indicates the absence of disturbances in the bioelectrical activity of the brain. Such EEGs are regarded as slightly altered or mildly abnormal.
2. The appearance of mild asymmetry of the alpha rhythm, its diffuse distribution with a violation of zoning, rare outbreaks of theta and delta rhythms of moderate amplitude, a decrease in the amplitude of the alpha rhythm to 15-20 μV while maintaining the normal index or an increase to 100 μV, distortion of the alpha rhythm rhythm of diffuse high-frequency low-amplitude (up to 3-5 μV) activity with a normal reactive EEG - indicate mild disturbances in the bioelectrical activity of the brain.
3. The deepening of EEG disturbances during functional loads indicates a lack of compensation for dysfunction, which is directly proportional to the severity of the changes caused.
4. Partial reduction of the alpha rhythm, a decrease in its index to 40-50% with its replacement by polymorphic slow activity or flat EEG, the presence of dysrhythmia of moderate amplitude - indicate the appearance of moderate disturbances in the bioelectrical activity of the brain. Their level of compensation is revealed by the loads.
5. A sharp decrease in the alpha rhythm index (below 10%) or its complete absence, dominance of a flat EEG, polyrhythm with an amplitude of up to 25 µV, dominance of a low-frequency beta rhythm of medium amplitudes (20-25 µV), moderate severity of a high-frequency regular component, an increase in amplitude an alpha rhythm over 100 μV with a decrease in its frequency below 9 Hz with its transition to the spectrum of an alpha-like theta rhythm, as well as with the presence of focal manifestations or bursts of slow rhythms, even with a moderately impaired reactive EEG, can be considered as disorders of moderate severity.
6. Significant shifts towards pathological manifestations when exposed to functional loads, especially trigger photostimulation (TPS), indicate decompensation, a state of subcompensation, instability of compensatory processes and are necessarily indicated in the conclusion.
7. Dominance in the EEG of the theta rhythm (especially alpha-like) with an amplitude of up to 60 μV, the presence of gross focal changes against the background of a reduced alpha rhythm, frequent epileptic paroxysms with a high-amplitude alpha rhythm, dominance of high-amplitude beta rhythms (low-frequency with an amplitude of up to 60 μV or high-frequency with an amplitude of up to 30 μV), the presence of polyrhythmic activity with an amplitude of over 40 μV - refers to significant disturbances in the bioelectrical activity of the brain (even in the absence of deepening of the disturbances when exposed to functional loads).
8. High-amplitude background activity with a regular theta and delta rhythm, the dominance of a high-amplitude polymorphic delta rhythm (50 μV or more), distorted by bursts of high-frequency beta rhythm or epileptic activity, are classified as severe EEG disorders.
Eye opening and closing test
EEG studies should include both eyes-closed and eyes-open regions. In some cases, such as infants who cannot follow a command, passive eye closure may be used.During a routine examination, which lasts 20-30 minutes, a significant part of the procedure takes place with eyes closed, in a state of so-called passive or relaxed wakefulness. In this state, the basic occipital rhythm (alpha rhythm in adults) is best recorded.
The eye opening test allows you to assess the reactivity of the recorded rhythms. When the eyes are opened, the main occipital rhythm is usually suppressed. Eye opening does not have such a significant effect on other rhythms. Therefore, the eye opening test is also a way to identify the rhythm - is it the main occipital rhythm? The fact is that in some patients, especially younger ones, the main occipital rhythm can be represented by oscillations of waves of lower frequency than the alpha rhythm. In such cases, the eye-opening test, showing depression of slow-wave activity in the posterior regions, suggests that this activity is an analogue of the occipital alpha rhythm. And, conversely, rhythms that coincide in frequency with the alpha range, but are not it, will not naturally respond to eye opening with a drop in amplitude. For example, the mu rhythm, also known as the sensorimotor rhythm, typically responds poorly to eye opening. When studying the reactivity of the alpha rhythm, attention is paid to the symmetry of changes. The reactivity of alpha oscillations when opening the eyes on one side may indicate cortical or subcortical pathology - the Bancaud phenomenon.
In some patients, closing the eyes can trigger short-lived epileptiform activity, a symptom of photosensitivity known as eye-closure sensitivity. In this case, the activity often initially has the character of high-frequency oscillations, which gradually slow down and transform into a normal alpha rhythm. In children, when closing their eyes, slow oscillations of the delta range may appear in the occipital-parietal-temporal regions, which last 2-3 seconds and should not be regarded as epileptiform activity. A rare variant of photosensitivity is scotosensitivity - when epileptiform activity is not only provoked by closing the eyes, but also continues as long as the eyes are closed. Unlike classical photosensitivity to closing the eyes, epileptiform activity with scotosensitivity is also recorded in complete darkness.
EEG artifacts that appear during tests with closing and opening the eyes reflect the movements of the eyeballs and are recorded mainly in the frontal regions. Oculomotor potentials are recorded due to the fact that, from an electrical point of view, the eyeball is a dipole - the positivity of the cornea compared to the negative charge of the retina. When the eyes are closed, the eyeball reflexively moves upward (Bell's phenomenon), which creates a positive potential in the frontopolar leads (Fp1 and Fp2). Accordingly, when the eyes are moved to the sides, the greatest fluctuations will be observed under the lower frontal electrodes F7 and F8.
Prepared by A.G. Brutyan
Cognitive impairment in depression
The article discusses the causes and clinical symptoms of cognitive dysfunction in depression. It is noted that cognitive impairment has an adverse effect on the quality of life of patients and their daily activities. Methods for diagnosing and treating cognitive impairment in depression are discussed in detail. Cognitive disorders may persist after achieving remission and regression of emotional disorders, therefore, in patients with depression, it is necessary to carefully examine the cognitive sphere and take its condition into account when choosing therapeutic tactics.
Table 1. Diagnostic criteria for depression according to the International Classification of Diseases, 10th revision
Drawing. Mechanisms of formation of cognitive dysfunction in depression
Table 2. “Cold” and “hot” symptoms of depression
Table 3. Methods for studying cognitive functions in depression
Introduction
Depression is one of the most common mental disorders, which is found in the practice of not only psychiatrists, but also neurologists, therapists and doctors of other specialties. According to epidemiological studies, the risk of developing depression during life is up to 10% in men and up to 20% in women [1, 2].
Among neurological and medical patients, the prevalence of depression is significantly higher than in the general population. Thus, according to the Russian epidemiological program COMPASS (2004), the frequency of depressive disorders in general medical practice varies from 24 to 64% [3–5]. Moreover, in approximately half of the cases depression reaches significant severity.
In neurological practice, depression usually accompanies chronic pain syndromes (headache, back pain), vascular diseases of the brain, neurodegenerative diseases with predominant damage to the subcortical basal ganglia, multiple sclerosis, epilepsy, etc. It should be noted: to achieve significant success in the treatment of the underlying neurological disease almost impossible without correction of comorbid emotional disorders.
Depression has an extremely negative impact on all aspects of the lives of patients and often their immediate family. The quality of life suffers the most, since any person perceives everyday reality exclusively through the prism of his own emotions. The presence of emotional disturbances inevitably leads to loss or reduction of ability to work.
Due to its high prevalence and negative impact on work ability, depression is one of the most costly diseases for society. Thus, according to pharmacoeconomic studies, in the United States the annual cost of depression is estimated at approximately $83 billion [6], and in the European Union – at 75 billion euros [7]. The greatest economic losses are caused by the patient’s absence from the workplace (absenteeism) or a decrease in labor productivity due to depression despite the formal presence of the employee (presenteeism) [6, 7]. Depression causes an average of 27 workdays lost per worker per year. Of these, 18 days (two thirds) are due to presenteeism and only nine days (one third) are due to absenteeism [6]. It is hypothesized that decreased productivity in the workplace is primarily due to cognitive problems. This is stated by the patients themselves, who point to a decrease in mental abilities as the main reason for the decrease in labor productivity. Similar results were obtained in a European study of 21,000 patients from six countries. According to respondents, decreased attention and mental performance account for up to 25% of the total negative impact of depression on psychosocial functions [9].
Prevalence of cognitive impairment in depression
Depression is a mental disorder characterized by a triad of symptoms (Kraepelin’s triad): depressed mood or melancholy, ideational and motor retardation [10]. As can be seen from this definition, the cognitive component makes a significant contribution to the overall picture of depression, which is reflected in the description of clinical symptoms and diagnostic criteria for depression (Table 1).
In recent years, the cognitive aspect of depression has received special attention. It has been shown that correction of cognitive disorders is of paramount importance for normalizing the daily functioning of patients when achieving remission, in particular for restoring impaired working capacity [8].
According to a survey of patients diagnosed with depression, they experience difficulty concentrating and decreased mental performance almost all the time. And even despite the normalization of the emotional state during remission, patients often continue to experience cognitive difficulties, which interferes with work and everyday life [8]. These data confirm the autonomy of cognitive disorders, which must be taken into account when choosing treatment tactics for depression. Thus, achieving a satisfactory level of daily functioning is impossible without restoring the patient’s normal level of mental performance, that is, without additional impact on the cognitive component.
According to the first Russian laboratory of memory disorders based at the Clinic of Nervous Diseases named after. AND I. Kozhevnikov, anxiety and depression are the third cause of moderate cognitive impairment in the Russian population after cerebrovascular pathology and neurodegenerative process, being responsible for 5% of cases of this syndrome [11].
Causes of cognitive dysfunction in depression
The development of cognitive dysfunction in depression has both psychological and biological (neurochemical, morphological, pathophysiological) prerequisites.
Cognitive difficulties in patients with depression may be associated with the negative impact of the emotional state on the ability to correctly distribute attention (impaired selectivity of attention). Thus, a patient with depression can be completely absorbed in his emotional experience, which dominates him, occupying a central position in his thoughts, while the perception, processing, analysis and memorization of other information that is not related to the content of the patient’s emotional experiences is naturally impaired. Likewise, healthy people perceive and remember information that is unimportant to them significantly worse compared to the perception and memory of significant and emotionally charged information.
A decrease in motivation, which naturally develops in patients with depression, has a negative impact on cognitive processes. A decrease in motivation inevitably entails a decrease in the activity of cognitive activity, which ultimately negatively affects the overall effectiveness of solving cognitive problems [12].
Depression is accompanied by a decrease in the synthesis and activity of cerebral neurotransmitters, which is considered today to be the key neurochemical mechanism for the formation of emotional disorders (monoamine hypothesis of depression) (figure). A decrease in the synthesis and activity in the brain of such mediators as serotonin, norepinephrine, and dopamine is described. These changes, of course, can lead not only to emotional, but also to cognitive dysfunction. In particular, the dopaminergic systems of the brain (mesocortical dopaminergic pathway) play an important role in the distribution and switching of attention and the implementation of cognitive control over the implementation of the intended program (the so-called executive functions of the brain). Activation of the noradrenergic system is necessary for more efficient memory of information coming from the senses. The serotonergic system of the brain is involved in the formation of motivation for cognitive activity. Thus, the decrease in the synthesis and activity of dopamine, norepinephrine and serotonin, observed in depression, can be considered as a neurochemical substrate for the formation of cognitive syndrome [13].
In addition, depression promotes activation of the hypothalamic-pituitary-adrenal axis, which leads to increased activity of steroid hormones. The latter negatively affects the processes of neurogenesis and neuroplasticity of the brain and promotes the activation of age-related cerebral atrophic changes [7, 14]. Indeed, a number of studies using morphometric methods have shown that depression is often associated with more pronounced atrophic changes in the medial temporal region and hippocampus [15]. These changes may underlie the decreased ability to remember new information, which is observed in patients with depression [12–15].
Modern studies using functional neuroimaging methods (positron emission and functional magnetic resonance imaging) indicate that cognitive symptoms of depression are accompanied by metabolic changes in structures integrated into closed frontal-subcortical functional systems (frontostriatal circuits). Changes are recorded in the orbital and dorsolateral parts of the frontal cortex, striatum, amygdala nuclei, etc. The data presented bring together the pathophysiology of cognitive disorders in depression and the so-called subcortical dementias (Parkinson's disease, vascular brain damage associated with leukoaraiosis, etc.). It should be noted: phenomenologically, there is a significant similarity between cognitive dysfunction in depression and diseases with predominant damage to the subcortical basal ganglia or white matter of the brain [16–19].
Particularly noteworthy is the fact that some changes in the metabolism of critical cerebral structures (striatum, amygdaloid nucleus) were also noted in clinically healthy individuals genetically predisposed to the development of recurrent depression. This once again emphasizes the independence of the emotional and cognitive axes of depression from each other, which should be taken into account when planning therapy in each specific case [20].
A characteristic complication of depression is sleep disturbance. Secondary, that is, associated with an emotional disorder, insomnia can also contribute to the formation of cognitive dysfunction in depression, since sleep completes the process of processing and consolidating in memory information received during the day. Lack of sleep leads to a decrease in activation of the cerebral cortex from the brainstem-subcortical structures. Clinically, this will be manifested by a decrease in concentration, activity and rate of cognitive activity, which, as mentioned above, is very characteristic of depression [21].
Clinical manifestations of cognitive dysfunction in depression
Currently, it is customary to distinguish between “cold” and “hot” cognitive symptoms of depression (Table 2) [22]. “Cold” symptoms include cognitive impairment when working with emotionally indifferent information. At the same time, there is a decrease in the activity and speed of cognitive activity: all cognitive processes (perception, processing, analysis, transformation, transmission of information) are carried out at a slow pace [23–27]. Patients become slow, any mnestic, intellectual and motor activity requires them more time than normal. They develop fatigue more quickly, which is often reflected in complaints of increased fatigue during mental work.
Another common complaint is difficulty concentrating or difficulty maintaining an appropriate level of attention for the required amount of time. Objectively, a neuropsychological study reveals a disturbance in the neurodynamics of cognitive processes. According to A.R. Luria, the term “neurodynamics” refers to the degree of activation of the cerebral cortex from the brainstem-subcortical structures [28, 29]. A decrease in neurodynamics is manifested by an increase in reaction time to external stimuli, a decrease in concentration and increased distractibility from ongoing intellectual work. To diagnose neurodynamic disorders, methods are used that take into account the time it takes to complete intellectual tasks. The study of literal associations (name as many words as possible starting with the letter C in a minute), the Schulte test, and the number-letter connection test, part A [30] are widely used.
Another typical “cold” cognitive symptom of depression is deficits in the executive functions of the frontal lobes of the brain [23–27, 31]. Executive functions include the ability to plan and control cognitive activity and one’s own behavior (synonyms: regulatory functions, executive functions, regulation of voluntary activity). With depression, the ability to plan is more likely to suffer. The ability to switch attention from the current stage of the cognitive process to the next stage is also impaired (decreased mobility of cognitive processes, inertia). Because of this, the pace of cognitive processes may decrease, but mainly only in situations where it is necessary to change the usual paradigm of activity. Perseverations may be noted. It is believed that the basis for the decrease in the mobility of cognitive processes is dysfunction of the dorsolateral frontal cortex. One of the best neuropsychological techniques for identifying cognitive inertia is the number-letter connection test. The execution time of the first and second parts of this test (part A and part B) is compared. A proportional increase in the time for performing both parts of the test is characteristic of a decrease in the neurodynamics of cognitive processes (dysfunction of brainstem-subcortical structures), and a disproportionate increase in the time for performing the second part of the test (Part B) indicates the inertia of cognitive processes (dysfunction of the dorsolateral frontal cortex) [30].
The “cold” manifestations of cognitive dysfunction in depression also include memory impairment. Patients complain of increased forgetfulness, which can interfere with work, daily household activities, and education. According to neuropsychological research methods, memory impairment in depression is based on insufficient reproduction with relative safety of memorization and storage of information. This is evidenced by the relative mildness of mnestic disorders, which almost never extend to current or distant life events, the effectiveness of hints during reproduction, and the preserved ability to recognize previously received information in tests where the patient is given multiple choice [23–27].
Cognitive disorders in depression can be both objective and predominantly subjective. Objective cognitive impairment refers to disorders that are confirmed by abnormal neuropsychological test results. Predominantly subjective cognitive disorders are spoken of in cases where patients present cognitive complaints (increased forgetfulness, difficulty concentrating, increased fatigue during mental work), but the results of neuropsychological tests remain within the normal range for a given age and level of education. It should be emphasized: predominantly subjective cognitive disorders are no less important than objective ones, since they reduce the quality of life of patients and, at least in some cases, affect the efficiency of their functioning at work and in the social sphere. The reason for the predominantly subjective nature of cognitive impairment may be the patient’s high premorbid intellectual level. In this case, he may be aware of his cognitive decline compared to what was before, while remaining formally within the average age and educational norm. In other cases, subjective cognitive impairment is explained by the increased anxiety that often accompanies depression: the patient may experience significant anxiety about the slight forgetfulness inherent in the vast majority of people (for example, “I came into the room, I don’t remember why,” “I don’t remember what I put where,” “I forget the names and surnames of distant acquaintances”) [30, 32, 33].
“Hot” cognitive symptoms of depression include a predominant redistribution of the patient’s attention to negative or negatively emotionally charged information [22]. Thus, if the patient is asked to identify the emotional expression of a face in a drawing, he will more quickly recognize a sad expression compared to a cheerful or neutral expression. In addition, a sad face will attract the patient's attention for a longer period of time. Similarly, negative information is remembered by depressed patients much better than positive or neutral information [34–36]. According to some observations, elements of “hot” cognitive disorders are observed in clinically healthy (i.e., without depression) individuals genetically predisposed to recurrent affective disorder [19]. These data suggest that changes in the cognitive sphere may not only be a complication of depression or a parallel symptom, but also the cause of depression (the patient notices and remembers only negative information, and is therefore prone to developing depressive reactions).
Diagnosis and differential diagnosis of cognitive impairment in depression
Given the importance of cognitive impairment for patients' daily functioning and quality of life, the presence of depression is an indication for an objective study of cognitive functions. At the same time, we are talking about depression not only at the time of medical consultation, but also in the anamnesis, since changes in the cognitive sphere can persist in such patients, despite achieving remission in the emotional sphere.
The only method for objective assessment of cognitive function is neuropsychological testing. Based on the clinical characteristics of cognitive depression syndrome, the preferred neuropsychological methods are the literal association test, the Symbols and Numbers test, the number-letter connection test, tests for memorizing and reproducing verbal and visual material (Table 3) [30].
Cognitive impairment in a patient with depression may be associated with a concomitant disease, which is especially likely in elderly and senile patients. As is known, the most common cause of cognitive impairment in old age is Alzheimer's disease in the initial stages in the vast majority of cases accompanied by anxiety and depression. However, the clinical features of cognitive disorders in this case will be fundamentally different. Already in the initial stages of Alzheimer's disease, memory impairments caused by insufficient memorization come to the fore. At the same time, mnestic disorders are expressed to a much greater extent than in primary depression, and are characterized by the ineffectiveness of hints during reproduction, impaired recognition of information in multiple choice tests (the so-called hippocampal type of memory impairment). Memory for current and recent events in these cases suffers to a greater extent than memory for distant events [37–39].
It is much more difficult to carry out a differential diagnosis of cognitive disorders in the structure of depression and in the structure of diseases with the clinic of “subcortical” cognitive disorders (diseases with damage to the subcortical basal ganglia, dyscirculatory encephalopathy, multiple sclerosis). As mentioned above, there are no phenomenological differences between the cognitive syndrome of depression and “subcortical” cognitive disorders, since both are based on a common substrate - dysfunction of the frontostriatal circuits. At the same time, diseases with a clinical picture of “subcortical” cognitive impairment are almost obligately accompanied by depression or apathy [40, 41]. However, from a practical point of view, the differential diagnosis between cognitive disorders within depression and diseases with damage to subcortical structures is not of fundamental importance: in all cases, treatment of both depression and cognitive dysfunction is required. At the same time, eliminating depression does not automatically lead to a complete regression of cognitive disorders, even in patients with primary depression.
Treatment of cognitive impairment in depression
Taking into account the results of recent studies, the traditional recommendation to “treat depression first” for comorbid cognitive and emotional disorders should be considered outdated. The tactics of simultaneous treatment of both cognitive and emotional disorders are more justified. If depression is not the sole or primary cause of cognitive impairment (for example, in patients with incipient Alzheimer's disease or chronic cerebrovascular pathology), antidepressants and acetylcholinergic and/or glutamatergic drugs should be prescribed in parallel. If cognitive dysfunction is associated primarily with depression, then there is no need for simultaneous administration of an antidepressant and drugs that improve cognitive function. However, when choosing an antidepressant, its effect on the cognitive sphere should be taken into account.
Tricyclic antidepressants (amitriptyline, imipramine, nortriptyline) are known to have a pronounced anticholinergic effect and therefore can cause cognitive dysfunction or intensify existing cognitive impairment. In this regard, it is undesirable to prescribe drugs from this pharmacological group to patients with depression and severe cognitive dysfunction and elderly patients, regardless of the presence and severity of cognitive symptoms.
This effect is somewhat less pronounced in tetracyclic antidepressants (for example, mianserin). However, in patients with depression and cognitive impairment, selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors are preferable. These drugs not only do not increase cognitive disorders, but, on the contrary, help reduce their severity. At the same time, the so-called “hot” cognitive symptoms of depression (primarily focusing attention on negatively emotionally charged information) respond to antidepressant therapy faster and to a greater extent. According to some observations, positive dynamics in the area of “hot” cognitive symptoms precedes regression of emotional disorders themselves [42]. This fact also indirectly indicates the role of cognitive dysfunction in the formation of depression in general.
The most promising in patients with depression and cognitive disorders are antidepressants with a multimodal mechanism, which act simultaneously on several pharmacological targets. That is why great hopes for practical use are currently associated with a drug from the new group of multimodal antidepressants vortioxetine (Brintellix) (has received approval in Europe and the USA, but has not yet been registered in Russia).
Brintellix not only inhibits the reuptake of serotonin in brain structures, but also has a direct effect on postsynaptic serotonin receptors. This action is multidirectional in relation to different types of receptors. Brintellix is an antagonist of 5-HT3, 5-HT7 and 5-HT1D receptors, an agonist of 5-HT-1A receptors and a partial antagonist of 5-HT-1B receptors. Brintellix's ability to modulate the activity of other neurotransmitter systems is associated with its effect on postsynaptic serotonin receptors. It has been shown that its use increases the extracellular content of neurotransmitters such as acetylcholine, norepinephrine, dopamine and histamine [43–46]. This effect likely underlies the beneficial effects of Brintellix on cognitive function. In addition, the experiment showed activation during the use of Brintellix of the synthesis of neuronal RNA and proteins, which underlie the processes of neuroplasticity [47]. The use of Brintellix also helps to modulate the activity of GABAergic and glutamatergic activity of the brain, which determines the anxiolytic effect of the drug [48].
The positive effect of Brintellix on cognitive functions has been shown in both experimental [49–52] and clinical studies [53–54]. Thus, in a large double-blind randomized study (n = 301), when Brintellix was administered at a dose of 5 mg/day to elderly patients with depression, a significant improvement in concentration and memory was recorded compared with placebo [53].
In another large study (n = 591), also conducted according to all the principles of evidence-based medicine, improvements in memory, concentration and frontal executive functions were demonstrated with the use of Brintellix. This study examined two dosing regimens: 10 and 20 mg/day. Both dosages were superior to placebo on cognitive outcomes. Moreover, the positive dynamics in the mnestic sphere were more pronounced when using a lower dose of the drug (10 mg/day) [54].
Another study compared the effectiveness of Brintellix and duloxetine in patients with depression and cognitive complaints (n = 392). Therapy with both drugs had an advantage over placebo in terms of subjective awareness of cognitive disorders: the severity of cognitive complaints significantly regressed during antidepressant therapy. However, objective indicators of cognitive functions underwent positive dynamics only with the use of Brintellix (at a dose of 10–20 mg/day) [55].
Important advantages of Brintellix are the safety of its use, including in elderly patients, and good tolerability. The most common side effect of therapy was nausea: it was observed in a small proportion of patients, was mild or moderate in severity and was transient, not requiring interruption or discontinuation of therapy.
In terms of its main (antidepressive) effect, Brintellix is not inferior to other drugs from the group of selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors, as evidenced by the results of eight double-blind, placebo-controlled randomized studies, which involved a total of 4186 patients [56].
Conclusion
Impaired cognitive functions, an important component of the clinical picture of depression, have an adverse effect on the quality of life of patients and their daily activities, including work activities. There are no direct correlations between the severity of cognitive and emotional disorders. Cognitive disorders may remain after remission and regression of the emotional disorders themselves have been achieved. In this regard, in patients with depression it is necessary to carefully examine the cognitive sphere and take its condition into account when choosing therapeutic tactics.
