Biomedical subjects

Mikhail Lomarev

Publications and source records attributed to Mikhail Lomarev.

9 recordsLinked to original sources

PubMed2007

Serial vagus nerve stimulation functional MRI in treatment-resistant depression.

Vagus nerve stimulation (VNS) therapy has shown antidepressant effects in open acute and long-term studies of treatment-resistant major depression. Mechanisms of action are not fully understood, although clinical data suggest slower onset therapeutic benefit than conventional psychotropic interventions. We set out to map brain systems activated by VNS and to identify serial brain functional correlates of antidepressant treatment and symptomatic response. Nine adults, satisfying DSM-IV criteria for unipolar or bipolar disorder, severe depressed type, were implanted with adjunctive VNS therapy (MRI-compatible technique) and enrolled in a 3-month, double-blind, placebo-controlled, serial-interleaved VNS/functional MRI (fMRI) study and open 20-month follow-up. A multiple regression mixed model with blood oxygenation level dependent (BOLD) signal as the dependent variable revealed that over time, VNS therapy was associated with ventro-medial prefrontal cortex deactivation. Controlling for other variables, acute VNS produced greater right insula activation among the participants with a greater degree of depression. These results suggest that similar to other antidepressant treatments, BOLD deactivation in the ventro-medial prefrontal cortex correlates with the antidepressant response to VNS therapy. The increased acute VNS insula effects among actively depressed participants may also account for the lower dosing observed in VNS clinical trials of depression compared with epilepsy. Future interleaved VNS/fMRI studies to confirm these findings and further clarify the regional neurobiological effects of VNS.

Adult↗

PubMed2006

Modeling the current distribution during transcranial direct current stimulation.

OBJECTIVE: To investigate the spatial distribution of the magnitude and direction of the current density in the human head during transcranial direct current stimulation (tDCS). METHODS: The current density distribution was calculated using a numerical method to implement a standard spherical head model into which current was injected by means of large electrodes. The model was positioned in 'MNI space' to facilitate the interpretation of spatial coordinates. RESULTS: The magnitude and direction of the current density vector are illustrated in selected brain slices for four different electrode montages. Approximately half of the current injected during tDCS is shunted through the scalp, depending on electrode dimension and position. Using stimulating currents of 2.0 mA, the magnitude of the current density in relevant regions of the brain is of the order of 0.1 A/m2, corresponding to an electric field of 0.22 V/m. CONCLUSIONS: Calculations based on a spherical model of the head can provide useful information about the magnitude and direction of the current density vector in the brain during tDCS, taking into account the geometry and position of the electrodes. Despite the inherent limitations of the spherical head model, the calculated values are comparable to those used in the most recent in vitro studies on modulation of neuronal activity. SIGNIFICANCE: The methodology presented in this paper may be used to assess the current distribution during tDCS using new electrode montages, to help optimize montages that target a specific region of the brain or to preliminarily investigate compliance with safety guidelines.

Brain↗

PubMed2005

Short-latency afferent inhibition during selective finger movement.

During individual finger movement, two opposite phenomena occur at the level of the central nervous system that could affect other intrinsic hand muscle representations, unintentional co-activation, and surround inhibition (SI). At rest, excitability in the motor cortex (M1) is inhibited at about 20 ms after electric stimulation of a peripheral nerve [short-latency afferent inhibition (SAI)]. We sought to determine whether SAI changes during selective index finger movement. Effects were measured by the response to transcranial magnetic stimulation in two functionally distinct target muscles of the hand [abductor digiti minimi muscle (ADM), first dorsal interosseus muscle (FDI)]. An increase in SAI in the ADM during index finger movement compared to at rest could help explain the genesis of SI. Electrical stimulation was applied to either the little finger (homotopic for ADM, heterotopic for FDI) or the index finger (heterotopic for ADM, homotopic for FDI). During index finger movement, homotopic SAI was present only in the ADM, and the effect of peripheral stimulation was greater when there was less co-activation. Heterotopic SAI found at rest disappeared with movement. We conclude that during movement, homotopic SAI on the muscle in the surround of the intended movement may contribute to SI.

Adult↗

PubMed2005

Long-latency afferent inhibition during selective finger movement.

Stimulation of a peripheral nerve of a hand at rest modulates excitability in the motor cortex and, in particular, leads to inhibition when applied at an interval of approximately 200 ms (long-latency afferent inhibition; LAI). Surround inhibition (SI) is the process that inhibits neighboring muscles not involved in a particular task. The neuronal mechanisms of SI are not known, and it is possible that LAI might contribute to it. Using transcranial magnetic stimulation (TMS) with and without movement of the index finger, the motor-evoked potentials (MEPs) were measured of two functionally distinct target muscles of the hand (abductor digiti minimi muscle = ADM, 1st dorsal interosseus muscle = FDI). Electrical stimulation was applied 180 ms before TMS to either the fifth finger or the index finger. Both homotopic and heterotopic finger stimulation resulted in LAI without movement. With index finger movement, motor output further decreased with homo- and heterotopic stimulation in the ADM. In the moving FDI, however, there was no change with either homo- or heterotopic stimulation. Additionally, in the unstimulated movement trials, LAI increased with the amount of unintentional co-activation that occurred despite attempts to maintain the ADM at rest. However, with finger stimulation added, there were almost no increased MEPs despite co-activation. These findings suggest that LAI increases during movement and can enhance SI.

Adult↗

PubMed2005

Cortical and subcortical brain effects of transcranial magnetic stimulation (TMS)-induced movement: an interleaved TMS/functional magnetic resonance imaging study.

BACKGROUND: To date, interleaved transcranial magnetic stimulation and functional magnetic resonance imaging (TMS/fMRI) studies of motor activation have not recorded whole brain patterns. We hypothesized that TMS would activate known motor circuitry with some additional regions plus some areas dropping out. METHODS: We used interleaved TMS/fMRI (11 subjects, three scans each) to elucidate whole brain activation patterns from 1-Hz TMS over left primary motor cortex. RESULTS: Both TMS (110% motor threshold) and volitional movement of the same muscles excited by TMS caused blood oxygen level-dependent (BOLD) patterns encompassing known motor circuitry. Additional activation was observed bilaterally in superior temporal auditory areas. Decreases in BOLD signal with unexpected post-task "rebounds" were observed for both tasks in the right motor area, right superior parietal lobe, and in occipital regions. Paired t test of parametric contrast maps failed to detect significant differences between TMS- and volition-induced effects. Differences were detectable, however, in primary data time-intensity profiles. CONCLUSIONS: Using this interleaved TMS/fMRI technique, TMS over primary motor cortex produces a whole brain pattern of BOLD activation similar to known motor circuitry, without detectable differences from mimicked volitional movement. Some differences may exist between time courses of BOLD intensity during TMS circuit activation and volitional circuit activation.

Adult↗

PubMed2004

Acute vagus nerve stimulation using different pulse widths produces varying brain effects.

BACKGROUND: Vagus nerve stimulation (VNS) is an approved treatment for epilepsy and has been investigated in clinical trials of depression. Little is known about the relationship of VNS parameters to brain function. Using the interleaved VNS /functional magnetic resonance imaging (fMRI) technique, we tested whether variations of VNS pulse width (PW) would produce different immediate brain activation in a manner consistent with single neuron PW studies. METHODS: Twelve adult patients with major depression, treated with VNS, underwent three consecutive VNS/fMRI scans, each randomly using one of three PWs (130 micros, 250 micros, or 500 micros). The data were analyzed with SPM2. RESULTS: Global activations induced by PWs 250 and 500 were both significantly greater than that induced by PW 130 but not significantly different from each other. For global deactivation, PWs 130 and 250 were both significantly greater than PW 500 but not significantly different from each other. Regional similarities and differences were also seen with the various PWs. CONCLUSIONS: The data confirm our hypothesis that VNS at PW 500 globally produces no more activation than does PW 250, and PW 130 is insufficient for activation of some regions. These data suggest that PW is an important variable in producing VNS brain effects.

Adult↗

PubMed2004

A high resolution assessment of the repeatability of relative location and intensity of transcranial magnetic stimulation-induced and volitionally induced blood oxygen level-dependent response in the motor cortex.

OBJECTIVE: Using functional magnetic resonance imaging, we assessed variation in location and intensity of blood oxygen level-dependent contrast associated with movements induced by transcranial magnetic stimulation or volition. BACKGROUND: Anatomic location and within-subject repeatability of blood oxygen level-dependent responses induced by transcranial magnetic stimulation comprise critical information to the use of interleaved transcranial magnetic stimulation/functional magnetic resonance imaging as a neuroscience tool. METHODS: Eleven healthy adults were scanned 3 times each at 1.5 T. Interleaved with functional magnetic resonance imaging, 1-Hz transcranial magnetic stimulation was applied over motor cortex. VOL was alternated with transcranial magnetic stimulation over the scans. RESULTS: Intra-subject standard deviations in blood oxygen level-dependent locations ranged between 3 and 6 millimeters, allowing localization to subregions of the motor strip. Coil placement relative to blood oxygen level-dependent location varied more than blood oxygen level-dependent location (sdx = 9.5mm, sdy = 8.7 mm, sdz = 9.0mm) with consistent anterior displacement (dy = 21.8 mm, P = <0.025). Analysis of variance did not detect significant differences between transcranial magnetic stimulation and VOL blood oxygen level-dependent locations or intensities, in contrast to significant intensity differences detected in auditory blood oxygen level dependence. CONCLUSION: The high repeatability of location of transcranial magnetic stimulation-induced blood oxygen level-dependent activation suggests that transcranial magnetic stimulation/functional magnetic resonance imaging stimulation can be used as a precise tool in investigation of cortical mechanisms. The similarity between VOL and transcranial magnetic stimulation suggests that transcranial magnetic stimulation may act through natural brain movement circuits.

Adult↗

PubMedDate not supplied

Vagus nerve stimulation (VNS) synchronized BOLD fMRI suggests that VNS in depressed adults has frequency/dose dependent effects.

Stimulation of the vagus nerve in the neck can reduce seizures in epilepsy patients, and may be helpful in treating depression. PET studies have shown that vagus nerve stimulation (VNS) in epilepsy patients causes acute dose (intensity) dependent changes in regional cerebral blood flow. We sought to use the newly developed VNS synchronized fMRI technique to examine whether VNS BOLD signal changes depend on the frequency of stimulation. Six adults with recurrent depression were scanned inside a 1.5 T MR scanner. Data were acquired at rest, with the VNS device on for 7 s, and also, for comparison, while the patient listened to a tone for 7 s. In two separate back-to-back sessions, the VNS stimulation frequency was set to either 5 or 20 Hz. Data were transformed into Talairach space and then compared by condition. Compared to 5 Hz, 20 Hz VNS produced more acute activity changes from rest in regions similar to our initial VNS synchronized fMRI feasibility study in depression. Brain regions activated by hearing a tone were also greater when VNS was intermittently being applied at 20 Hz than at 5 Hz. In depressed adults, left cervical VNS causes regional brain activity changes that depend on the frequency of stimulation or total dose, or both. In addition to the acute immediate effects of VNS on regional brain activity, this study suggests further that VNS at different frequencies likely has frequency or dose dependent modulatory effects on other brain activities (e.g. hearing a tone).

Adult↗

PubMedDate not supplied

A review of functional neuroimaging studies of vagus nerve stimulation (VNS).

Vagus nerve stimulation (VNS) is a new method for preventing and treating seizures, and shows promise as a potential new antidepressant. The mechanisms of action of VNS are still unknown, although the afferent direct and secondary connections of the vagus nerve are well established and are the most likely route of VNS brain effects. Over the past several years, many groups have used functional brain imaging to better understand VNS effects on the brain. Since these studies differ somewhat in their methodologies, findings and conclusions, at first glance, this literature may appear inconsistent. Although disagreement exists regarding the specific locations and the direction of brain activation, the differences across studies are largely due to different methods, and the results are not entirely inconsistent. We provide an overview of these functional imaging studies of VNS. PET (positron emission tomography) and SPECT (single photon emission computed tomography) studies have implicated several brain areas affected by VNS, without being able to define the key structures consistently and immediately activated by VNS. BOLD (blood oxygen level dependent) fMRI (functional magnetic resonance imaging), with its relatively high spatio-temporal resolution, performed during VNS, can reveal the location and level of the brain's immediate response to VNS. As a whole, these studies demonstrate that VNS causes immediate and longer-term changes in brain regions with vagus innervations and which have been implicated in neuropsychiatric disorders. These include the thalamus, cerebellum, orbitofrontal cortex, limbic system, hypothalamus, and medulla. Functional neuroimaging studies have the potential to provide greater insight into the brain circuitry behind the activity of VNS.

Brain↗