Cerebrovascular reactivity during visual stimulation: Does hypnotizability matter?

Hypnotizability is a trait associated with several physiological correlates including cardiovascular control. The present study aimed to investigate the posterior cerebral artery flow velocity (PCAv) in basal closed eyes (B) and during visual stimulation (VS) conditions in med-highs and med-lows. Twenty-four healthy volunteers were submitted to the hypnotic assessment through the Stanford Hypnotic Susceptibility Scale, form A which classified 13 low-to-medium (med-lows) and 10 high-to-medium (med-highs) hypnotizable participants. One subject scoring 6 out of 12 was excluded from the comparisons between groups. Arterial blood pressure, heart rate, and partial pressure of end-tidal CO2 were monitored during both B and VS conditions. Simultaneously, PCAv was assessed by transcranial Doppler. Cerebrovascular Reactivity (CVR) was computed as a percentage of the PCAv change occurring during VS with respect to B (ΔPCAv). During VS both groups increased their PCAv (mean ± SD: 7.9 ± 5.2 %) significantly with no significant group difference. However, among med-highs, CVR was negatively correlated with hypnotizability scores. Thus, higher hypnotizability may be associated with lower metabolic demand in response to VS only within med-highs hypnotizable participants.

Cerebral hemodynamics in children with sickle cell disease in India: An observational cohort study.

India has the second highest number of cases of sickle cell disease (SCD) and affects the most socioeconomically disadvantaged communities living in a horizontal belt from Gujarat to Odisha state. Despite high prevalence, information about cerebral hemodynamics among children with SCD in India remains scarcely described. We performed transcranial Doppler (TCD) to assess cerebral hemodynamics among Indian children with SCD and evaluated their association with clinical and hematological parameters. Children aged 3-18years, diagnosed with SCD living in Raipur in Chhattisgarh and Ahmedabad in Gujarat state were recruited. TCD was performed to obtain flow velocities from middle cerebral (MCA), intracranial internal carotid (ICA) and basilar artery. Associations were evaluated between timed-average-mean-maximum velocities (TAMMV) and various clinical and hematological parameters. Our prospective study included 62 consecutive children with known SCD. Mean ± SD age of the study population was 9.8 ± 3.9 years and 31 (50%) were male. Mean ± SD hemoglobin was 8.64 ± 1.34 Gm/dL while the mean HbSS ± SD was 70.25 ± 15.27%. While 6 (9.6%) children had suffered from stroke during previous 2 years, 7 (11%) demonstrated abnormal TAMMV. Higher HbSS level along with history of iron chelation therapy, blood transfusion and/or stroke showed a trend towards having higher TAMMV. Stroke and cerebral hemodynamic alterations are common among Indian children with SCD. Larger studies with detailed neuroimaging and genetic evaluations are needed for better understanding, characterization, risk stratification as well as optimization of the timing of blood transfusion to reduce physical disabilities among Indian children with SCD.

Transcranial ultrasound stimulation in humans is associated with an auditory confound that can be effectively masked.

BACKGROUND: Transcranial ultrasound stimulation (TUS) is emerging as a potentially powerful, non-invasive technique for focal brain stimulation. Recent animal work suggests, however, that TUS effects may be confounded by indirect stimulation of early auditory pathways. OBJECTIVE: We aimed to investigate in human participants whether TUS elicits audible sounds and if these can be masked by an audio signal. METHODS: In 18 healthy participants, T1-weighted magnetic resonance brain imaging was acquired for 3D ultrasound simulations to determine optimal transducer placements and source amplitudes. Thermal simulations ensured that temperature rises were <0.5 °C at the target and <3 °C in the skull. To test for non-specific auditory activation, TUS (500 kHz, 300 ms burst, modulated at 1 kHz with 50% duty cycle) was applied to primary visual cortex and participants were asked to distinguish stimulation from non-stimulation trials. EEG was recorded throughout the task. Furthermore, ex-vivo skull experiments tested for the presence of skull vibrations during TUS. RESULTS: We found that participants can hear sound during TUS and can distinguish between stimulation and non-stimulation trials. This was corroborated by EEG recordings indicating auditory activation associated with TUS. Delivering an audio waveform to participants through earphones while TUS was applied reduced detection rates to chance level and abolished the TUS-induced auditory EEG signal. Ex vivo skull experiments demonstrated that sound is conducted through the skull at the pulse repetition frequency of the ultrasound. CONCLUSION: Future studies using TUS in humans need to take this auditory confound into account and mask stimulation appropriately.

Histologic safety of transcranial focused ultrasound neuromodulation and magnetic resonance acoustic radiation force imaging in rhesus macaques and sheep.

BACKGROUND: Neuromodulation by transcranial focused ultrasound (FUS) offers the potential to non-invasively treat specific brain regions, with treatment location verified by magnetic resonance acoustic radiation force imaging (MR-ARFI). OBJECTIVE: To investigate the safety of these methods prior to widespread clinical use, we report histologic findings in two large animal models following FUS neuromodulation and MR-ARFI. METHODS: Two rhesus macaques and thirteen Dorset sheep were studied. FUS neuromodulation was targeted to the primary visual cortex in rhesus macaques and to subcortical locations, verified by MR-ARFI, in eleven sheep. Both rhesus macaques and five sheep received a single FUS session, whereas six sheep received repeated sessions three to six days apart. The remaining two control sheep did not receive ultrasound but otherwise underwent the same anesthetic and MRI procedures as the eleven experimental sheep. Hematoxylin and eosin-stained sections of brain tissue (harvested zero to eleven days following FUS) were evaluated for tissue damage at FUS and control locations as well as tissue within the path of the FUS beam. TUNEL staining was used to evaluate for the presence of apoptosis in sheep receiving high dose FUS. RESULTS: No FUS-related pre-mortem histologic findings were observed in the rhesus macaques or in any of the examined sheep. Extravascular red blood cells (RBCs) were present within the meninges of all sheep, regardless of treatment group. Similarly, small aggregates of perivascular RBCs were rarely noted in non-target regions of neural parenchyma of FUS-treated (8/11) and untreated (2/2) sheep. However, no concurrent histologic abnormalities were observed, consistent with RBC extravasation occurring as post-mortem artifact following brain extraction. Sheep within the high dose FUS group were TUNEL-negative at the targeted site of FUS. CONCLUSIONS: The absence of FUS-related histologic findings suggests that the neuromodulation and MR-ARFI protocols evaluated do not cause tissue damage.

Differential influence of vitamin C on the peripheral and cerebral circulation after diving and exposure to hyperoxia.

We examined if the diving-induced vascular changes in the peripheral and cerebral circulation could be prevented by oral antioxidant supplementation. Fourteen divers performed a single scuba dive to eighteen meter sea water for 47 min. Twelve of the divers participated in a follow-up study involving breathing 60% of oxygen at ambient pressure for 47 min. Before both studies, participants ingested vitamin C (2 g/day) or a placebo capsule for 6 days. After a 2-wk washout, the study was repeated with the different condition. Endothelium-dependent vasodilator function of the brachial artery was assessed pre- and postintervention using the flow-mediated dilation (FMD) technique. Transcranial Doppler ultrasound was used to measure intracranial blood velocities pre- and 90 min postintervention. FMD was reduced by ∼32.8% and ∼21.2% postdive in the placebo and vitamin C trial and posthyperoxic condition in the placebo trial by ∼28.2% ( P < 0.05). This reduction in FMD was attenuated by ∼10% following vitamin C supplementation in the hyperoxic study ( P > 0.05). Elevations in intracranial blood velocities 30 min after surfacing from diving were reduced in the vitamin C study compared with the placebo trial ( P < 0.05). O2 breathing had no postintervention effects on intracranial velocities ( P > 0.05). Prophylactic ingestion of vitamin C effectively abrogated peripheral vascular dysfunction following exposure to 60% O2 but did not abolish the postdive decrease in FMD. Transient elevations of intracranial velocities postdive were reduced by vitamin C. These findings highlight the differential influence of vitamin C on peripheral and cerebral circulations following scuba diving, which are only partly mediated via hyperoxia.

A random phased-array for MR-guided transcranial ultrasound neuromodulation in non-human primates.

Transcranial focused ultrasound (FUS) is a non-invasive technique for therapy and study of brain neural activation. Here we report on the design and characterization of a new MR-guided FUS transducer for neuromodulation in non-human primates at 650 kHz. The array is randomized with 128 elements 6.6 mm in diameter, radius of curvature 7.2 cm, opening diameter 10.3 cm (focal ratio 0.7), and 46% coverage. Simulations were used to optimize transducer geometry with respect to focus size, grating lobes, and directivity. Focus size and grating lobes during electronic steering were quantified using hydrophone measurements in water and a three-axis stage. A novel combination of optical tracking and acoustic mapping enabled measurement of the 3D pressure distribution in the cortical region of an ex vivo skull to within ~3.5 mm of the surface, and allowed accurate modelling of the experiment via non-homogeneous 3D acoustic simulations. The data demonstrates acoustic focusing beyond the skull bone, with the focus slightly broadened and shifted proximal to the skull. The fabricated design is capable of targeting regions within the S1 sensorimotor cortex of macaques.

Neuromodulation with single-element transcranial focused ultrasound in human thalamus.

Transcranial focused ultrasound (tFUS) has proven capable of stimulating cortical tissue in humans. tFUS confers high spatial resolutions with deep focal lengths and as such, has the potential to noninvasively modulate neural targets deep to the cortex in humans. We test the ability of single-element tFUS to noninvasively modulate unilateral thalamus in humans. Participants (N = 40) underwent either tFUS or sham neuromodulation targeted at the unilateral sensory thalamus that contains the ventro-posterior lateral (VPL) nucleus of thalamus. Somatosensory evoked potentials (SEPs) were recorded from scalp electrodes contralateral to median nerve stimulation. Activity of the unilateral sensory thalamus was indexed by the P14 SEP generated in the VPL nucleus and cortical somatosensory activity by subsequent inflexions of the SEP and through time/frequency analysis. Participants also under went tactile behavioral assessment during either the tFUS or sham condition in a separate experiment. A detailed acoustic model using computed tomography (CT) and magnetic resonance imaging (MRI) is also presented to assess the effect of individual skull morphology for single-element deep brain neuromodulation in humans. tFUS targeted at unilateral sensory thalamus inhibited the amplitude of the P14 SEP as compared to sham. There is evidence of translation of this effect to time windows of the EEG commensurate with SI and SII activities. These results were accompanied by alpha and beta power attenuation as well as time-locked gamma power inhibition. Furthermore, participants performed significantly worse than chance on a discrimination task during tFUS stimulation.

Cerebrovascular Hemodynamics During the Practice of Bhramari Pranayama, Kapalbhati and Bahir-Kumbhaka: An Exploratory Study.

Various pranayama techniques are known to produce different physiological effects. We evaluated the effect of three-different pranayama techniques on cerebrovascular hemodynamics. Eighteen healthy volunteers with the mean ± standard deviation age of 23.78 ± 2.96 years were performed three-different pranayama techniques: (1) Bhramari, (2) Kapalbhati and (3) Bahir-Kumbhaka in three-different orders. Continuous transcranial Doppler (TCD) monitoring was performed before, during and after the pranayama techniques. TCD parameters such as peak systolic velocity, end diastolic velocity (EDV), mean flow velocity (MFV) and pulsatility index (PI) of right middle cerebral artery were recorded. Practice of Kapalbhati showed significant reductions in EDV and MFV with significant increase in PI while, Bahir-Kumbhaka showed significant increase in EDV and MFV with significant reduction in PI. However, no such significant changes were observed in Bhramari pranayama. Various types of pranayama techniques produce different cerebrovascular hemodynamic changes in healthy volunteers.

Numerical evaluation of the skull for human neuromodulation with transcranial focused ultrasound.

OBJECTIVE: Transcranial focused ultrasound is an emerging field for human non-invasive neuromodulation, but its dosing in humans is difficult to know due to the skull. The objective of the present study was to establish modeling methods based on medical images to assess skull differences between individuals on the wave propagation of ultrasound. APPROACH: Computational models of transcranial focused ultrasound were constructed using CT and MR scans to solve for intracranial pressure. We explored the effect of including the skull base in models, different transducer placements on the head, and differences between 250 kHz or 500 kHz acoustic frequency for both female and male models. We further tested these features using linear, nonlinear, and elastic simulations. To better understand inter-subject skull thickness and composition effects we evaluated the intracranial pressure maps between twelve individuals at two different skull sites. MAIN RESULTS: Nonlinear acoustic simulations resulted in virtually identical intracranial pressure maps with linear acoustic simulations. Elastic simulations showed a difference in max pressures and full width half maximum volumes of 15% at most. Ultrasound at an acoustic frequency of 250 kHz resulted in the creation of more prominent intracranial standing waves compared to 500 kHz. Finally, across twelve model human skulls, a significant linear relationship to characterize intracranial pressure maps was not found. SIGNIFICANCE: Despite its appeal, an inherent problem with the use of a noninvasive transcranial ultrasound method is the difficulty of knowing intracranial effects because of the skull. Here we develop detailed computational models derived from medical images of individuals to simulate the propagation of neuromodulatory ultrasound across the skull and solve for intracranial pressure maps. These methods allow for a much better understanding of the intracranial effects of ultrasound for an individual in order to ensure proper targeting and more tightly control dosing.

Evaluation function of transcranial two-dimensional and color Doppler ultrasonography (TCCS) for patients with different degrees of cerebral vasospasm before and after the nimodipine treatment.

OBJECTIVE: To evaluate the changes in cerebral hemodynamics of patients with different degrees of cerebral vasospasm before and after the nimodipine treatment using transcranial two-dimensional and color Doppler ultrasonography (TCCS). PATIENTS AND METHODS: A total of 77 patients with subarachnoid hemorrhage was collected; and the maximum peak systolic velocity (Vs), end diastolic velocity (Vd), time averaged maximum velocity (Vm), pulsatility index (PI) and resistance index (RI) of middle cerebral artery (MCA) were measured by spectral Doppler technique. The standard-dose nimodipine was given for clinical treatment, and changes in blood flow velocity of MCA were monitored by TCCS, and the therapeutic effect was observed. RESULTS: 68 out of 77 patients (88.3%) with subarachnoid hemorrhage were diagnosed as cerebral vasospasm (CVS), including 53 cases (77.9%) of mild spasm, 11 cases (16.2%) of moderate spasm and 4 cases (5.9%) of severe spasm. The sensibility of CVS detected by TCCS after operation was 88.3%. Color Doppler flow imaging (CDFI) showed that the blood flow was multicolored. After the nimodipine treatment, the measured values of MCA-Vs and RI were decreased in different degrees compared with those before treatment. CONCLUSIONS: Nimodipine has improving effects on CVS in different degrees, and TCCS can be used to evaluate the therapeutic effects on CVS.

Transcranial sonography of subcortical structures in patients with multiple sclerosis.

BACKGROUND: Transcranial sonography may be applied to assess the basal ganglia nuclei and brain atrophy by the measurement of the width of the third ventricle. The aim of this study was to assess usefulness of transcranial sonography (TCS) in patients with multiple sclerosis (MS) by examining the echogenicity of subcortical structures and the width of the third ventricle. METHOD: Transcranial sonography evaluation of substantia nigra, brain stem raphe nuclei, diameter of the third ventricle, width of the anterior horn of the lateral ventricle, thalamus, lenticular nucleus, and head of the caudate nucleus in 41 patients with relapsing-remitting MS (RRMS), 23 with secondary progressive MS (SPMS), and 20 healthy controls was compared. A potential link between the patients' age, sex, Expanded Disability Status Scale (EDSS) score, relapse index, and ultrasound parameters was assessed. RESULTS: The following were found in patients with MS, as compared to the control group: a greater area of the substantia nigra, a longer diameter of the third ventricle and wider frontal horns of the lateral ventricles, hypo-echogenicity of the brain stem raphe, and hyperechogenicity of the lenticular nucleus. The study group was found to have a significant correlation between the area of the substantia nigra, and the age of patients, the duration of the illness, EDSS score, and the number of relapses. There was a significant correlation between the diameter of the third ventricle and the age of patients and EDSS score. CONCLUSIONS: Patients with MS reveal ultrasound features of subcortical structure atrophy. Selected TCS findings show a correlation with disease progression and activity.

Transcranial Sonography of the Insula: Digitized Image Analysis of Fusion Images with Magnetic Resonance.

Purpose: Transcranial B-mode sonography (TCS) of brain parenchyma is increasingly used as a diagnostic tool for movement disorders. Accordingly, experimental B-Mode Assist software was developed to enable digitized analysis of the echogenicity of predefined brain regions. The aim of the study was to assess the reproducibility of digitized TCS image analysis of the insula. Materials and Methods: A total of 130 patients with an indication for neurosonological examination were screened for participation in the study. The insula was imaged from the right temporal bone window using Virtual Navigator and TCS-MRI (magnetic resonance imaging) fusion imaging. All subjects were examined three times by two experienced sonographers. Corresponding images of the insula in the axial thalamic plane were encoded and digitally analyzed. Interclass correlation coefficient (ICC) and Spearman's rank correlation coefficient were used for the assessment of intra- and inter-reader as well as intra- and inter-investigator reliabilities. Results: TCS images of 114 patients were evaluated (21 patients with TIA, 53 patients with headache, 18 patients with essential tremor, 22 patients with neurodegerative disease). 16 patients were excluded from analysis due to insufficient bone window. The intra-reader, inter-reader, intra-investigator and inter-investigator ICCs/Spearman's rank correlation coefficients were 0.995/0.993, 0.937/0.921, 0.969/0.961 and 0.875/0.858, resp. Conclusion: The present study demonstrates a high reliability to reproduce echogenicity values of the insula using digitized image analysis and TCS-MRI fusion images with almost perfect intra-reader, inter-reader, intra-investigator and inter-investigator agreement.

Image-guided transcranial focused ultrasound stimulates human primary somatosensory cortex.

Focused ultrasound (FUS) has recently been investigated as a new mode of non-invasive brain stimulation, which offers exquisite spatial resolution and depth control. We report on the elicitation of explicit somatosensory sensations as well as accompanying evoked electroencephalographic (EEG) potentials induced by FUS stimulation of the human somatosensory cortex. As guided by individual-specific neuroimage data, FUS was transcranially delivered to the hand somatosensory cortex among healthy volunteers. The sonication elicited transient tactile sensations on the hand area contralateral to the sonicated hemisphere, with anatomical specificity of up to a finger, while EEG recordings revealed the elicitation of sonication-specific evoked potentials. Retrospective numerical simulation of the acoustic propagation through the skull showed that a threshold of acoustic intensity may exist for successful cortical stimulation. The neurological and neuroradiological assessment before and after the sonication, along with strict safety considerations through the individual-specific estimation of effective acoustic intensity in situ and thermal effects, showed promising initial safety profile; however, equal/more rigorous precautionary procedures are advised for future studies. The transient and localized stimulation of the brain using image-guided transcranial FUS may serve as a novel tool for the non-invasive assessment and modification of region-specific brain function.

Transcranial focused ultrasound modulates the activity of primary somatosensory cortex in humans.

Improved methods of noninvasively modulating human brain function are needed. Here we probed the influence of transcranial focused ultrasound (tFUS) targeted to the human primary somatosensory cortex (S1) on sensory-evoked brain activity and sensory discrimination abilities. The lateral and axial spatial resolution of the tFUS beam implemented were 4.9 mm and 18 mm, respectively. Electroencephalographic recordings showed that tFUS significantly attenuated the amplitudes of somatosensory evoked potentials elicited by median nerve stimulation. We also found that tFUS significantly modulated the spectral content of sensory-evoked brain oscillations. The changes produced by tFUS on sensory-evoked brain activity were abolished when the acoustic beam was focused 1 cm anterior or posterior to S1. Behavioral investigations showed that tFUS targeted to S1 enhanced performance on sensory discrimination tasks without affecting task attention or response bias. We conclude that tFUS can be used to focally modulate human cortical function.

Physical exercise might influence the risk of oxygen-induced acute neurotoxicity.

OBJECTIVE: Hyperoxia can induce acute neurotoxicity with generalized seizures. Hyperoxia-induced reduction in cerebral blood flow velocity (CBFV) might be protective. It is unclear whether dynamic exercise during hyperoxia can overcome CBFV-reduction and thus possibly increase the risk of neurotoxicity. METHODS: We studied CBFV with both-sided transcranial Doppler with fixed transducer-position and heart rate under increasing hyperoxic conditions in nine professional military oxygen divers. The divers performed dynamic exercise on a bicycle-ergometer in a hyperbaric chamber (ergometries I-III, 21kPa, 100kPa, 150kPa pO2), with continuous blood pressure (ergometries I, II), end-tidal CO2 (PetCO2; ergometry I) being measured. RESULTS: Systolic (CBFVsyst) and diastolic CBFV (CBFVdiast) readings at rest decreased with increasing pO2. During exercise, CBFVsyst and CBFVdiast significantly increased in parallel with increasing pO2, despite reduced flow velocities at rest. ERGOMETRY I: CBFVsyst increased from 65.0 +/- 11.3 cm/second at rest to 80.2 +/- 23.4cm/s during maximum workload (n.s.), diastolic from 14.5 +/- 4.1 cm/second to 15.6 +/- 7.5 cm/s (n.s.). PetCO2 increased from 43.4 +/- 7.8mmHg to 50.0 +/- 7.5mmHg. ERGOMETRY II: CBFVsyst increased from 58.2 +/- 16.5 cm/second to 99.7 +/- 17.0 cm/s (p<0.001), diastolic from 14.0 +/- 10.7 cm/second to 29.4 +/- 11.1 cm/second (p<0.01). ERGOMETRY III: CBFVsyst increased from 54.4 +/-15.0cm/second to 109.4 +/- 22.3cm/s (p<0.001), diastolic from 14.7 +/- 10.4 cm/second to 35.5 +/- 9.3 cm/second (p<0.01). INTERPRETATION: Physical exercise overrules the decrease in CBFV during hyperoxia and leads to even higher CBFV-increases with increasing pO2. A tendency towards CO2 retainment with elevated PetCOz may be causative and thus heighten the risk of oxygen-induced neurotoxicity.

Effects of active, passive and motor imagery paradigms on cerebral and peripheral hemodynamics in older volunteers: a functional TCD study.

This study aimed to compare the response of metabolic-induced cerebral hemodynamic changes measured using transcranial Doppler (TCD) ultrasonography during passive, active and motor imagery paradigms, and associated peripheral hemodynamic responses. Continuous recordings of bilateral cerebral blood flow velocity (CBFv), blood pressure, heart rate and end-tidal CO(2) were performed in 12 right-handed subjects (aged ≥45 y) before, during and after 60 s of active, passive and mental-imagined paradigms. The results revealed no significant difference in CBFv responses between the paradigms and, furthermore, the temporal patterns of the hemodynamic responses showed some degree of similarity. Moreover, significant changes were seen in cerebral and peripheral hemodynamic responses for all paradigms. Our results suggest that active, passive and motor imagery paradigms can be used interchangeably to assess hemodynamic responses. This will enable more detailed noninvasive assessment in patients, where voluntary movement is not possible, but where abnormalities of cerebral hemodynamic control mechanisms can be anticipated.

Brazilian Guidelines for transcranial doppler in children and adolescents with sickle cell disease

BACKGROUND: Sickle cell disease is the most common monogenic hereditary disease in Brazil. Although strokes are one of the main causes of morbidity and mortality in these patients, the use of transcranial Doppler to identify children at risk is not universally used. OBJECTIVE: To develop Brazilian guidelines for the use of transcranial Doppler in sickle cell disease children and adolescents, so that related health policies can be expanded, and thus contribute to reduce morbidity and mortality. METHODS: The guidelines were formulated in a consensus meeting of experts in transcranial Doppler and sickle cell disease. The issues discussed were previously formulated and scientific articles in databases (MEDLINE, SciELO and Cochrane) were carefully analyzed. The consensus for each question was obtained by a vote of experts on the specific theme. RESULTS: Recommendations were made, including indications for the use of transcranial Doppler according to the sickle cell disease genotype and patients age; the necessary conditions to perform the exam and its periodicity depending on exam results; the criteria for the indication of blood transfusions and iron chelation therapy; the indication of hydroxyurea; and the therapeutic approach in cases of conditional transcranial Doppler. CONCLUSION: The Brazilian guidelines on the use of transcranial doppler in sickle cell disease patients may reduce the risk of strokes, and thus reduce the morbidity and mortality and improve the quality of life of sickle cell disease patients.

Self-regulation of cerebral blood flow by means of transcranial Doppler sonography biofeedback.

BACKGROUND: Transcranial Doppler sonography (TCD) allows the continuous non-invasive assessment of intracranial blood flow velocities with high temporal resolution. It may therefore prove suitable for biofeedback of cerebral perfusion. PURPOSE: The study explored whether healthy individuals can successfully be trained in self-regulation of cerebral blood flow using TCD biofeedback. METHODS: Twenty-two subjects received visual feedback of flow velocities in the middle cerebral arteries of both hemispheres. They were randomly assigned to two groups, one of which attempted to increase, the other to decrease the signal within eight training sessions. Heart rate and respiratory frequency were also monitored. RESULTS: Both groups achieved significant changes in flow velocities in the expected directions. Modulations in heart rate and respiratory frequency during biofeedback did not account for these effects. CONCLUSIONS: TCD biofeedback enables efficient self-regulation of cerebral blood flow. It is promising in applications such as the treatment of migraine and post-stroke rehabilitation.

Basal ganglia hyperechogenicity does not distinguish between patients with primary dystonia and healthy individuals.

Transcranial sonography (TCS) of the basal ganglia is a non-invasive tool to study movement disorders. Very few studies have addressed the question of whether TCS may detect specific echofeatures in patients with primary dystonia. The basal ganglia including the substantia nigra (SN) and the ventricular system were investigated by TCS in 84 primary dystonia patients and 43 neurologically healthy controls. Any hyperechogenicity of the lenticular nucleus was present in 57.5% of the patients and in 50.0% of the controls (p = 0.453). While marked hyperechogenicity was more frequently present in the patients (17.8 vs. 7.9%), this difference was not significant (p = 0.227). No differences in the occurrence of hyperechogenicity were detectable either in the caudate nucleus (21.6 vs. 39.5%, p = 0.122) or the thalamus (4.1 vs. 0%, p = 0.199). Marked hyperechogenicity of the caudate nucleus was rare in dystonia (4.1%) and absent in controls. There was no relationship between the side of basal ganglia hyperechogenicity and the clinically affected side of cervical dystonia. The area of SN echogenicity was similar in patients and controls (0.19 ± 0.14 vs. 0.20 ± 0.13 cm(2)), but correlated negatively with increasing disease duration in the dystonia patients (ρ = -0.257, p = 0.028). Width of the third ventricle correlated with increasing age (ρ = 0.511, p = 0.000) and, in patients, with disease duration (ρ = 0.244, p = 0.034) and severity of cervical dystonia (ρ = 0.281, p = 0.038). No characteristic abnormalities were found in the basal ganglia of primary dystonia patients. It remains to be explored whether this is due to a true absence of signal alterations in the basal ganglia of dystonia patients or to limitations of the current technology used.

Diagnostic transcranial ultrasound perfusion-imaging at 2.5 MHz does not affect the blood-brain barrier.

The purpose was to assess whether standard ultrasound (US) perfusion-imaging by means of contrast-enhanced transcranial color-coded sonography (TCCS) affects the blood-brain barrier (BBB) in patients with small-vessel disease (SVD). One week after a screening MRI to exclude a preexisting BBB disruption, unilateral TCCS phase inversion harmonic imaging (PIHI) was performed in an axial diencephalic plane after intravenous bolus application of 2.5 mL SonoVue (IGEA, Bracco, Italy). Magnetic resonance imaging (MRI) was performed immediately after US. In five patients, PIHI was performed applying a mean mechanical index (MI) of 0.7 +/- 0.1 for a time period of 2.5 min. MRI was started 12 +/- 2 min after US contrast injection. Comparisons of initial and post-US MRI by four blinded readers did not show any signs of BBB disruption. It is concluded that standard contrast-enhanced US perfusion imaging in patients with SVD did not lead to MRI-detectable BBB changes. This gives further evidence for safety of diagnostic US. Future investigations with larger sample sizes and higher-field MRI might give further insights into potential bioeffects of diagnostic, as well as therapeutic, contrast-enhanced transcranial US.