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Resistance to pharmacological treatment poses a notable challenge for psychiatry. Such cases are usually treated with brain stimulation techniques, including repetitive transcranial magnetic stimulation (rTMS) and electroconvulsive therapy (ECT). Empirical evidence links treatment resistance to insufficient brain plasticity and chronic inflammation. Therefore, this study encompasses analysis of neurotrophic and inflammatory factors in psychiatric patients undergoing rTMS and ECT in order to refine the selection of patients and predict clinical outcomes. This study enrolled 25 drug-resistant depressive patients undergoing rTMS and 31 drug-resistant schizophrenia patients undergoing ECT. Clinical efficacy of brain stimulation therapies was gauged using MADRS and HAM-D scales in the depression group and PANSS scale in the schizophrenia group. Blood-derived BDNF, VEGF, and TNFα were analysed during the treatment course. For reference, 19 healthy control subjects were also enrolled. After statistical analysis, no significant differences were detected in BDNF, VEGF, and TNFα concentrations among healthy, depressive, and schizophrenic subject groups before the treatment. However, depressive patient treatment with rTMS has increased BDNF concentration, while schizophrenic patient treatment with ECT has lowered the concentration of TNFα. Our findings suggest that a lower initial TNFα concentration could be a marker for treatment success in depressed patients undergoing rTMS, whereas in schizophrenic patient group treated with ECT, a higher concentration of VEGF correlates to milder symptoms post-treatment, especially in the negative scale.

The 40 Hz auditory steady-state response (ASSR) impairment is suggested as an electrophysiological biomarker of schizophrenia, however, existing data also points to the deficiency of low and high frequency ASSR responses. In order to obtain the full picture of potential impairment in schizophrenia, it is important to test responses at different frequencies. The current study aims to evaluate a wide frequency range (1&ndash, 120 Hz) in response to brief low-frequency carrier chirp-modulated tones in a group of patients with schizophrenia. The EEG-derived envelope following responses (EFRs) were obtained in a group of male patients with schizophrenia (N = 18) and matched controls (N = 18). While subjects were watching silent movies, 440 Hz carrier chirp-modulated at 1&ndash, 120 Hz tones were presented. Phase-locking index and evoked amplitude in response to stimulation were assessed and compared on point-to-point basis. The peak frequency of the low gamma response was estimated. Measures were correlated with psychopathology&mdash, positive, negative, total scores of the Positive and Negative Syndrome Scale (PANSS), and hallucination subscale scores. In comparison to controls, patients showed (1) reduced power of theta-beta (4&ndash, 18 Hz) responses, (2) intact but slower low gamma (30&ndash, 60 Hz), and (3) reduced high gamma (95&ndash, 120 Hz) responses. No correlation survived the Bonferroni correction, but a sign of positive association between low gamma phase-locking and the prevalence of hallucinations, and a sign of negative association between high gamma phase-locking and the total PANSS scores were observed. Brain networks showed impaired capabilities to generate EFRs at different frequencies in schizophrenia, moreover, even when responses of patients did not significantly differ from controls on the group level, they still showed potentially clinically relevant variability.

Repetitive transcranial magnetic stimulation (rTMS) is a popular and effective treatment for drug resistant depression. However, there is considerable variability in clinical outcomes, in previous studies and between patients. Because of high requirements for the use of fMRI based neuronavigation, many practitioners of rTMS still choose to use a standard 5 cm rule for rTMS coil placement which leads to large variations in which brain regions are being stimulated. We decided to test the possibilities of a MNI based MR‑less neuronavigation system in rTMS depression treatment, by comparing the physiological effects and clinical outcomes of 3 distinct stimulation targets. Forty‑six patients (thirty‑three female, thirteen male) from the Republican Vilnius psychiatric hospital, all with drug resistant depressive disorder, participated in the study. All patients received high frequency (10 Hz) stimulation for 10 to 15 daily rTMS sessions. However, before the treatment they were randomly sorted into 3 groups according to stimulation target in MNI map: Group 1 received rTMS at point ‑40; 48; 35; Group 2 received rTMS at point ‑46; 45; 38; Group 3 received rTMS at point ‑38; 44; 26. Electroencephalography (EEG) recordings and clinical tests were obtained the day before the rTMS course and after the last session. There were some notable differences in physiological changes between the groups, with the largest EEG band spectral power increases found in Group 1 patients and the lowest in Group 2 patients. There was a significantly larger decrease of the Hamilton Depression Rating Scale (HAM-D) scores in the Group 3 (66.94%) compared to Group 1 (57.52%) and Group 2 (56.02%). This suggests it is possible to achieve higher clinical efficacy and less physiological impact on the brain when using different targets in a neuronavigated MNI based MR‑less rTMS system.

Aim The objective of this work was to study the impact of Transcranial Magnetic Stimulation (TMS) on brain asymmetry in patients with depression using different stimulation protocols, i.e. 1 Hz repetitive TMS over the right dorsolateral prefrontal cortex (DLPFC) (protocol G1), 10 Hz repetitive TMS over the left DLPFC (G2), and intermittent theta burst stimulation (iTBS) consisting of three 50 Hz burst bundle repeated at 5 Hz frequency (G3). Methods EEG analysis was performed using Directed Transfer Function (DTF) and four brain asymmetry measures. The Spearman correlations between the asymmetry measures and the scores of four psychiatric tests were calculated. Results The left hemisphere activity decreased in lower frequency bands (i.e., theta and alpha) for G1 and also in higher frequency bands (i.e., beta and gamma) for G3. Moreover, frontal lobe activity decreased in theta, alpha, beta and gamma bands for G1, but increased in delta, theta, and alpha bands for G2. The highest correlations were found between the frontal-posterior asymmetry measure and the HAM-D test independently on the frequency band when the iTBS protocol was applied, whereas the application of 1 Hz rTMS protocol caused the changes in the hemispheric asymmetry in theta and alpha bands. Conclusions Four brain asymmetry measures derived from DTF allowed for differentiation between conditions (i.e., before and after TMS) as well as between TMS protocols. Significance The asymmetry measures allow for evaluation of the therapeutic effect of TMS and for the choice of the most appropriate stimulation protocol.

Auditory steady-state response (ASSR) at 40Hz has been proposed as a potential biomarker for schizophrenia. The ASSR studies in patients have used click stimulation or amplitude-modulated tones. However, the sensitivity of 40Hz ASSRs to different stimulation types in the same group of patients has not been previously evaluated. Two stimulation types for ASSRs were tested in this study: (1) 40Hz clicks and (2) flutter-amplitude modulated tones. The mean phase-locking index, evoked amplitude and event-related spectral perturbation values were compared between schizophrenia patients (n=26) and healthy controls (n=20). Both stimulation types resulted in the observation of impaired phase-locking and power measures of late (200-500ms) 40Hz ASSR in patients compared to healthy controls. The early-latency (0-100ms) 40Hz ASSR part was diminished in the schizophrenia group in response to clicks only. The late-latency 40Hz ASSR parameters obtained through different stimulation types correlated in healthy subjects but not in patients. We conclude that flutter amplitude-modulated tone stimulation, due to its potential to reveal late-latency entrainment deficits, is suitable for use in clinical populations. Careful consideration of experimental stimulation settings can contribute to the interpretation of ASSR deficits and utilization as a potential biomarker.

Introduction Pathological imitative behavior (ehopraxia) is occasionally observed in schizophrenia patients. However, only a severe form of echopraxia can be detected with the help of a direct observation. Therefore, our goal was to study a latent form of pathological imitative behavior in this disorder, which is indicated by an increase of imitative tendencies. Method In our study, 14 schizophrenia patients and 15 healthy subjects were employed in two tasks: (a) in an imitative task they had to copy a hand action seen on a screen; (b) in a counter-imitative task they had to make a different movement (which involves an inhibition of prepotent imitative tendency that is impaired in case of pathological imitative behavior). Imitative tendencies were assessed by an interference score - a difference between counter-imitative and imitative response parameters. We also studied a response preparation in both groups by employing precueing probabilistic information. Results Our results revealed that schizophrenia patients were able to employ probabilistic information to prepare properly not only the imitative, but also the counter-imitative responses, the same as the healthy subjects did. Nevertheless, we detected increased prepotent imitative tendencies in schizophrenia patients, what indicates the latent pathological imitative behavior in case of this disorder. Conclusions The obtained results suggest that in the case of schizophrenia problems with pathological imitative behavior more likely occurred in executive rather than in the preparatory stage of response. Our findings can help to detect a latent echopraxia in schizophrenia patients that cannot be revealed by direct observation.

To behave more efficiently the human brain must anticipate future events with different probabilities and prepare appropriate responses. Previous studies demonstrated that participants react faster to more probable stimuli. It has been shown that this effect in reaction time reduction is related to the response preparation process. However it is still unknown what the minimum difference in stimulus probabilities is that is sufficient to elicit response preparation as measured with the EEG. Intra-individual reaction time variability indicates the stability of an individual's response performance and provides useful information about cognitive functioning. It's use has become prevalent in recent clinical studies. In order to extend understanding of cognitive and neural mechanisms of response stability we hypothesized that intra-individual reaction time variability relates to the response preparation process. Specifically, we hypothesized that response preparation to more probable stimuli would result in not only faster reaction time but also in a reduction of response variability. To verify this hypothesis, we tested 14 healthy subjects using reaction time and EEG as dependent measures. Two different stimuli with probabilities of 33.3% and 66.6% were assigned to two counterbalanced responses. The results of our study showed that stimulus probabilities of 66.6% and 33.3% were sufficient to elicit response preparation. Our data also revealed that response preparation to more probable stimuli speeds RT and reduces RT variability.

We aimed to evaluate the effect of arousal level in healthy subjects on P50 potential, as the variation in the level of arousal may be a source of variance in the recordings as well as it may provide additional information about the pathology under study. Eleven healthy volunteers participated in the study. A standard auditory P50 potential paradigm was applied. Two stimulation conditions were selected: eyes-open, i.e., high arousal level condition and eyes-closed, i.e., low arousal level condition. P50 component amplitudes in response to both the first (S1) and second stimulus (S2) of the pair, their ratio and difference were evaluated. P50 amplitude in response to S1 was significantly higher during the low arousal closed eyes condition as compared to high arousal open eyes condition. There was no P50 amplitude difference in response to S2 and no arousal effect on gating measures. This prompts for more careful evaluation of patients' arousal level when performing P50 studies and interpreting the results.

10 Hz rTMS over the left prefrontal cortex may be useful in the treatment of depressive disorders. However, the effects of 10 Hz rTMS applied in potentially effective doses on electroencephalographic activity are not well studied. Using EEG, we aimed to investigate the neurobiological effects of the 10 Hz rTMS set of parameters currently used for depression treatment in a sample of healthy subjects. In 18 healthy subjects, either 10 Hz real rTMS or sham stimulation were given in a crossover design. Real rTMS stimulation was carried out with an intensity of 110% of motor threshold (MT) over the left dorsolateral prefrontal cortex. For the sham condition, the coil was angled over a parietotemporal position and the intensity was reduced to 90% of MT. EEG recordings were taken before and after a single rTMS session. EEG power spectrum was extracted using the complex demodulation method and changes in power were evaluated statistically. Real 10 Hz rTMS induced an overall increase in delta power. This increase prevailed throughout the sample, whereas effects on the power of the alpha, beta and theta EEG bands were highly variable. Sham stimulation had no substantial effects on the EEG power spectrum. Furthermore, no changes in EEG asymmetry were detected. Real 10 Hz rTMS applied at 2000 stimuli and 110% intensity may induce significant changes in resting EEG in healthy subjects.

Klausos sukelti potencialai (KSP) yra elektroencefalogramos pokyciai, kuriuos sukelia sensoriniai klausos dirgikliai. Jų registracija leidžia neinvaziniu būdu gauti neurofiziologinės informacijos apie žmogaus galvos smegenų aktyvumą, susijusį su informacijos apdorojimo procesais. Retų reiksmingų klausos dirgiklių (garso tonų) atpažinimas dažnų nereiksmingų dirgiklių eilėje sukelia KSP bangas N2 ir P300 – vadinamąjį kognityvinį kompleksą. Sių bangų parametrai – latencija ir amplitudė – atspindi laiką, reikalingą įvertinti reiksmingą dirgiklį. P300 amplitudė siejama su galvos smegenų neuroninių isteklių paskirstymu, o N2 amplitudė gali būti susijusi su reiksmingų dirgiklių atpažinimo procesais.Buvo aptikta, kad pacientų, turincių sizofrenijos spektro sutrikimų, N2 ir P300 bangų amplitudės mažesnės. Tai rodo klausos informacijos apdorojimo procesų sutrikimus sergant sizofrenija. Taciau klinikinis KSP taikymas susiduria su tam tikromis problemomis (didelis tarpasmeninis rezultatų issibarstymas), kurioms spresti nutarėme pasitelkti naujus papildomus KSP kognityvinio komplekso parametrus.Sio tyrimo tikslas buvo įvertinti naujus P300 bangos parametrus ir palyginti jų patikimumą su įprastiniais P300 bangos parametrais (amplitude ir latencija), tiriant pacientus, turincius sizofrenijos spektro sutrikimų. Buvo istirti 56 sveiki asmenys ir 22 pacientai, turintys sizofrenijos spektro sutrikimų. KSP buvo registruojami taikant atsitiktinio įvykio (angl. odd-ball) paradigmą – tarp dažnų nereiksmingų dirgiklių atsitiktine tvarka buvo pateikiami retesni reiksmingi dirgikliai, kuriuos tiriamieji turėjo suskaiciuoti. Greta įprastinių parametrų matavome siuos naujus parametrus: latencijos (LP300) ir amplitudės (AP300) santykį, atpažinimo laiką (IT), kognityvinio komplekso statumą (SCC), P300 bangos energiją, P300 bangos nusileidžianciosios dalies greitį (SDS) bei greicio parametrus A ir B. Taip pat matavome tuos pacius isskaiciuotos bangos (gaunama is atsako į nereiksmingus dirgiklius kreivės skaitmeniniu būdu atimant atsako į reiksmingus dirgiklius kreive) parametrus, žymimus sSDS, sA ir sB. Tyrimo metu paaiskėjo, kad kai kurie naujai pasiūlyti parametrai yra statistiskai patikimesni, lyginant pacientų ir kontroline grupes, negu tradiciniai parametrai (amplitudė ir latencija). Daroma isvada, kad siūlomi nauji parametrai gali būti naudingi padedant įvertinti kognityvinių funkcijų pakitimus, esant sizofrenijos spektro sutrikimams, bei atskirti jų potipius. Taip pat skaitmeniniu būdu isskaiciuotos bangos parametrai gali būti naudingesni negu užrasytos tyrimo metu.

Su įvykiais susije potencialai (SĮSP) gali padėti objektyvizuoti daugelį psichologinių tyrimų. Vienas dažniausiai pastaruoju metu taikomų SĮSP yra P300 potencialas. Jis gali padėti nustatyti kognityvinius sutrikimus pacientams, sergantiems sizofrenija, depresija, esant demencijai, taip pat vertinant gydymo efektyvumą. Taciau P300 parametrų pokyciai (latencijos pailgėjimas arba amplitudės sumažėjimas) nėra pakankamai specifiski kai kuriems psichikos sutrikimams. Sio tyrimo tikslas buvo tikslesnių ir specifiskesnių P300 parametrų paieska. Is viso istyrėme 86 sveikus žmones (60 moterų, 26 vyrus, amžiaus vidurkis 45,9 metų). P300 potencialas buvo registruojamas naudojant klasikinį "atsitiktinio įvykio" metodą. Tiriamasis buvo prasomas nekreipti dėmesio į nereiksmingus ir suskaiciuoti reiksmingus garso signalus, pateikiamus per ausines. Garso signalai skyrėsi savo savybėmis: reiksmingo dažnis 2000 Hz, pasirodymo tikimybė 20 proc., nereiksmingo -1000 Hz, tikimybė - 80 proc. Abiejų dirgiklių garso stiprumas - 60 dB. P300 potencialas buvo registruojamas Cz elektrodo (remiantis tarptautine "10-20" sistema) vietoje. Analizės periodas - 1000 ms. Įvertine naujus P300 bangos parametrus gavome siuos rezultatus: Is desimties naujų istirtų parametrų statistiskai reiksminga koreliacija su amžiumi buvo sesių: P3 energijos (EP3), amplitudžių santykio (AS), latencijos ir amplitudės santykio (LAS), kognityvinio komplekso kritimo statumo (KKKS), atpažinimo trukmės (AT) ir kognityvinio komplekso trukmės galios (KKTG). Jie gali būti siūlomi naudoti bendram kognityvinių procesų įvertinimui. Is visų istirtų parametrų geriausiai su amžiumi koreliavo kognityvinio komplekso trukmės galia (KKTG) ir P3 smailės latencija (L(P3)) P3 ir N2 latencijų santykis (LS) buvo labai pastovus rodiklis, todėl gali būti taikomas P300 įvertinti, ypac pacientams, turintiems įvairių psichikos sutrikimų. Reikia istirtų P300 potencialo įvertinimo parametrų efektyvumo tyrimų kai kurių sutrikimų (sizofrenija, demencija, epilepsija) atvejais. Siems tyrimams siūlomi P3 energija (E(P3)), amplitudžių santykis (As), latencijos ir amplitudės santykis (LAS), kognityvinio komplekso kritimo statumas (KKKS), atpažinimo tukmė (AT), kognityvinio komplekso trukmės galia (KKTG), P3 smailės latencija (L(P3)) ir latencijų santykis (LS). THE SEARCH FOR NEW PARAMETERS ON EVALUATION OF P300 POTENTIAL Milena Korostenskaja, Kastytis Dapsys, Valentinas Maciulis, Osvaldas Ruksėnas Summary ERPs could be helpful in the objectification of many psychological measures. One of the most commonly used ERPs in the last decades is P300 potential. It may be used in differentiation of cognitive dysfunction in patients suffering from schizophrenia, dementia, depression, and also could be successfully applied in treatment monitoring. Nevertheless, changes of P300 parameters (prolongation of latency or reduction of amplitude) are not highly specific for certain kinds of diagnosis. In this study we searched for more strict and specific P300 characteristics, which would be selective for different kinds of disorders. 86 healthy subjects were studied during the study. Ten new P300 measures were considered. Main results of the study are as follows: Overall six out of ten new considered measures had significant correlation with age: P3 energy (EP3), amplitude ratio (AS), latency and amplitude ratio (LAS), steepness of cognitive complex (KKKS), identification time (AT) and the global power of cognitive complex (KKTG). All these parameters could be considered to differentiate cognitive processing in general. From all studied parameters the best correlation with age demonstrated global power of cognitive complex (KKTG) and latency of P3 (L(P3)). Latency ratio (LS) is very stable parameter and therefore could be used in psychiatric diagnostic. The next step in search of selective P300 measures would be evaluation of effectiveness of the described P300 potential parameters in patients with schizophrenia, depression, dementia, epilepsy and other psychiatric disorders. For this purpose these parameters are considered: P3 energy (E(P3)), amplitude ratio (AS), latency and amplitude ratio (LAS), steepness of cognitive complex (KKKS), identification time (AT), latency of N2 (L(N2)), global power of cognitive complex (KKTG), latency of P3 (L(P3)) and latency ratio (LS). Keywords: early Greek philosophy, Sophists, being, knowledge, man-measure, rhetoric.

Auditory steady-state responses (ASSRs) are widely applied to test brain ability to follow external stimulation and this appeared to be a promising method in neuropsychiatric disorders. Nevertheless, there is no established conclusion on the way aging affects phase-locking measures of ASSRs in healthy subjects. We aimed to identify the effects of aging on phaselocking measures of 40 Hz ASSR. The effect of aging was tested in a sample of 46 healthy male subjects (20-58 years old) during eyes open condition. Stimuli were 500 ms trains, consisting of 20 identical clicks (1.5 ms burst of white noise) delivered binaurally. Time-frequency analysis of the data was performed and phase-locking index, evoked amplitude and total intensity measures were extracted and decomposed by non-negative multi-way factorization. As shown by curve-fitting analyses, phase-locking index and evoked amplitudes were diminishing with age in the linear manner. This was also proven by ANOVA testing when sample was divided into age groups. No effect of age on the total intensity was found. The complexity of the factors modulating the 40 Hz ASSR is not entirely solved; nevertheless, the current results suggest that the ability to synchronize to high frequency external stimulation diminishes with age. This should be taken into account, particularly when ASSRs are used in clinical practice, comparing patients and healthy subjects.

We aimed to evaluate the effect of changing attentional demands towards stimulation in healthy subjects on P50 potential-related high-frequency beta and gamma oscillatory responses, P50 and N100 peak amplitudes and their gating measures. There are no data showing effect of attention on P50 potential-related beta and gamma oscillatory responses and previous results of attention effects on P50 and N100 amplitudes and gating measures are inconclusive. Nevertheless the variation in the level of attention may be a source of variance in the recordings as well as it may provide additional information about the pathology under study. Nine healthy volunteers participated in the study. A standard paired stimuli auditory P50 potential paradigm was applied. Four stimulation conditions were selected: focused attention (stimuli pair counting), unfocused attention (sitting with open eyes), easy distraction (reading a magazine article), and difficult distraction (searching for Landolt rings with appropriate gap orientation). Time-frequency responses to both S1 and S2 were evaluated in slow beta (13-16 Hz, 45-175 ms window); fast beta (20-30 Hz, 45-105 ms window) and gamma (32-46 Hz, 45-65 ms window) ranges. P50 and N100 peak amplitudes in response to both S1 and S2 and their ratio were evaluated. The phase-locked P50 potential-associated gamma activity was attenuated during distraction tasks as compared to focused attention and an unfocused attention condition. The amplitudes and gating measures of P50 and N100 waves and beta activity were not sensitive to the competing distraction task performance. The use of a distraction task is not favorable when phase-locked gamma range activity is a key interest in auditory potential studies.

The 40-Hz auditory steady-state responses (ASSRs) of 14 medicated schizophrenic patients were recorded in eyes-open and eyes-closed conditions as previously done in healthy volunteers. Patients show significantly increased precision of the evoked response with eyes closed, and a significant increase of broad-band noise activity when eyes are open.

Transcranial magnetic stimulation is a noninvasive method for stimulation of brain that is based on the ability of magnetic field to penetrate skull and brain meninges, subsequently inducing electric current in the brain tissues that produces neuronal depolarization and generation of action potentials. Moreover, transcranial magnetic stimulation has effects on neurochemical and synaptic processes in neurons. Due to its easy use and relatively fair side effects, nowadays, transcranial magnetic stimulation is widely used in neurosciences and medicine. The main areas of transcranial magnetic stimulation application are: 1) the investigation of cortical and spinal excitability, 2) the investigation of neuronal plasticity, 3) the investigation of neuronal connectivity, 4) functional mapping, and 5) the treatment of some neurological and psychiatric disorders. Transcranial magnetic stimulation alone or in combination with other noninvasive neuroimaging (PET--positron emission topography, MRI--magnetic resonance imaging) and neurofunctional (EEG--electroencephalography, ERP--event-related potentials, fMRI--functional magnetic resonance imaging) methods allows conducting research on brain functions. Thus, transcranial magnetic stimulation is suitable as a diagnostic tool in neurologic and neuropsychiatric brain research.

Electroconvulsive therapy (ECT), as a treatment tool for psychiatric disorders, is believed to be safe and effective. Nevertheless, it has a negative impact on cognitive functioning, especially on memory, causing both retrograde and anterograde amnesia. However, ECT effects on more subtle stages of information processing are not studied enough. Event-related potentials, and especially P300, are thought to reflect physiology of cognition. Thus, we aimed to evaluate the effects of ECT treatment on parameters of endogenous components (N2, P3) of the P300 potential. Seventeen patients suffering from schizophrenia, schizoaffective disorder and recurrent depressive disorder participated at the study. After the course of ECT, significant increase of N2 amplitude in parietal midline region and prolongation of P3 latency in frontal midline region, of which the magnitude positively correlated with the number of ECT procedures, have been obtained.

ERPs could be helpful in the objectification of many psychological measures. In the last few decades one of the most commonly used ERPs has been the mismatch negativity (MMN) potential. It may be used to detect cognitive dysfunction in patients suffering from schizophrenia, dementia, depression, and can also be successfully applied in treatment monitoring. Nevertheless, changes of MMN parameters (prolongation of latency or reduction of amplitude) are not sufficiently specific to help to diagnose particular diseases. In this study we looked for more strict and specific MMN characteristics selective for schizophrenia. Fifteen healthy human subjects and twelve suffering from schizophrenia spectrum disorders were studied. Two new parameters were considered: the speed of ascending part of MMN slope (SAS) and the half area of the MMN wave. These two measures could differentiate the early stages of cognitive processing disturbances in schizophrenia spectrum disorders.