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Intermittent Theta Burst Stimulation of the Prefrontal Cortex in Cocaine Use Disorder: A Pilot Study
Transcranial Magnetic Stimulation (TMS) is earning a role in the therapeutic arsenal of cocaine use disorder (CUD). A widespread and still growing number of studies have reported beneficial use of repeated TMS (rTMS) in reduction of craving, intake and cue-induced craving in cocaine addicts. In spite of these encouraging findings, many issues are still unresolved such as brain area to be stimulated, laterality of the effects, coil geometry and stimulation protocols/parameters. Intermittent theta burst stimulation (iTBS) is a more tolerable protocol administered at lower intensities and shorter intervals than conventional rTMS protocols. Yet, its effects on cocaine craving and length of abstinence in comparison with standard high frequency (10-15 Hz) protocols have never been evaluated so far. In the present paper, we describe the effect of the bilateral iTBS of the prefrontal cortex (PFC) in a population (
= 25) of treatment-seeking cocaine addicts, in an outpatient setting, and compare them with 15 Hz stimulation of the same brain area (
= 22). The results indicate that iTBS produces effects on cocaine consumption and cocaine craving virtually superimposable to the 15 Hz rTMS group. Both treatments had low numbers of dropouts and similar side-effects, safety and tolerability profiles. While larger studies are warranted to confirm these observations, iTBS appears to be a valid approach to be considered in treatment-seeking cocaine addicts, especially in light of its brief duration (3 min) vs. 15 Hz stimulation (15 min). The use of iTBS would allow increasing the number of patients treated per day with current rTMS devices, thus reducing patient discomfort and hopefully reducing drop-out rates without compromising clinical effectiveness.
Journal Article
Quantitative Characterization of Gait Patterns in Individuals with Spinocerebellar Ataxia 38
Spinocerebellar ataxia 38 (SCA 38) is a rare autosomal neurological disease whose clinical features include, among others, severe gait disturbances that have not yet been fully characterized. In this study, we employed a computerized 3D gait analysis to obtain spatio-temporal parameters of gait and the kinematics in the sagittal plane in the hip, knee, and ankle joints of seven individuals with SCA 38, which were then compared with those of twenty unaffected individuals matched for age, sex, and anthropometric features. The results show that, in comparison with unaffected individuals, those with SCA 38 are characterized by a significantly reduced speed, stride length, and duration of the swing phase, as well as an increased step width and stance and double support phase durations. The point-by-point comparison of the angular trends at the hip, knee, and ankle joints revealed significant alterations during most part of the stance phase for hip joint and at pre-swing/swing phases for knee and ankle joints. For these latter joints, a significantly reduced dynamic range of motion was also found. Such findings provide some new insights into hip and knee kinematics for this specific form of ataxia and may be useful for monitoring the disease’s progression and designing specific, tailored rehabilitative interventions.
Journal Article
Therapeutic Use of Cerebellar Intermittent Theta Burst Stimulation (iTBS) in a Sardinian Family Affected by Spinocerebellar Ataxia 38 (SCA 38)
Spinocerebellar ataxia 38 (SCA 38) is an autosomal dominant disorder caused by conventional mutations in the ELOVL5 gene which encodes an enzyme involved in the synthesis of very long fatty acids, with a specific expression in cerebellar Purkinje cells. Three Italian families carrying the mutation, one of which is of Sardinian descent, have been identified and characterized. One session of cerebellar intermittent theta burst stimulation (iTBS) was applied to 6 affected members of the Sardinian family to probe motor cortex excitability measured by motor-evoked potentials (MEPs). Afterwards, patients were exposed to ten sessions of cerebellar real and sham iTBS in a cross-over study and clinical symptoms were evaluated before and after treatment by Modified International Cooperative Ataxia Rating Scale (MICARS). Moreover, serum BDNF levels were evaluated before and after real and sham cerebellar iTBS and the role of BDNF Val66Met polymorphism in influencing iTBS effect was explored. Present data show that one session of cerebellar iTBS was able to increase MEPs in all tested patients, suggesting an enhancement of the cerebello-thalamo-cortical pathway in SCA 38. MICARS scores were reduced after ten sessions of real cerebellar iTBS showing an improvement in clinical symptoms. Finally, although serum BDNF levels were not affected by cerebellar iTBS when considering all samples, segregating for genotype a difference was found between Val66Val and Val66Met carriers. These preliminary data suggest a potential therapeutic use of cerebellar iTBS in improving motor symptoms of SCA38.
Journal Article
Comparison of Two Therapeutic Approaches of Cerebellar Transcranial Direct Current Stimulation in a Sardinian Family Affected by Spinocerebellar Ataxia 38: a Clinical and Computerized 3D Gait Analysis Study
Spinocerebellar ataxia 38 (SCA 38) is a very rare autosomal dominant inherited disorder caused by a mutation in
ELOV5
gene, specifically expressed in cerebellar Purkinje cells, encoding an enzyme involved in the synthesis of fatty acids. Seven symptomatic SCA 38 patients of a Sardinian family were administered 15 sessions of cerebellar anodal transcranial direct current stimulation (tDCS) in a cross-over study, employing deltoid cerebellar-only (C-tDCS) and cerebello-spinal (CS-tDCS) cathodal montage. Clinical evaluation was performed at baseline (T0), after 15 sessions of tDCS (T1) and after 1 month of follow-up (T2). Modified International Cooperative Ataxia Rating Scale (MICARS) and the Robertson dysarthria profile were used to rate ataxic and dysarthric symptoms, respectively. Alertness and split attention tests from Zimmermann test battery for attentional performance were employed to rate attentive functions. Moreover, 3D computerized gait analysis was employed to obtain a quantitative measure of efficacy of tDCS on motor symptoms. While clinical data showed that both CS and C-tDCS improved motor, dysarthric, and cognitive scores, the quantitative analysis of gait revealed significant improvement in spatio-temporal parameters only for C-tDCS treatment. Present findings, yet preliminary and limited by the small size of the tested sample, confirm the therapeutic potential of cerebellar tDCS in improving motor and cognitive symptoms in spinocerebellar ataxias and underline the need to obtain quantitative and objective measures to monitor the efficacy of a therapeutic treatment and to design tailored rehabilitative interventions.
ClinicalTrials.gov
identifier: NCT05951010
Journal Article
Haloperidol, but not clozapine, produces dramatic catalepsy in Δ9‐THC‐treated rats: possible clinical implications
The effect on rat catalepsy induced by Δ9‐tetrahydrocannabinol (Δ9‐THC) in association with haloperidol (HP) or clozapine (CLOZ) administration was investigated. Δ9‐THC dose‐dependently increased HP (0.05–1 mg kg−1, s.c.)‐induced rat catalepsy, while no catalepsy was observed after CLOZ (1–20 mg kg−1, s.c.) or Δ9‐THC+CLOZ administration. The CB1 antagonist SR141716A (0.5–5 mg kg−1, i.p.) reversed the increase mediated by Δ9‐THC on HP‐induced catalepsy. The D2 agonist quinpirole completely reversed the catalepsy induced by both HP and HP+Δ9‐THC; however, higher doses of quinpirole were needed in the presence of Δ9‐THC. The M1 antagonist scopolamine and α2 antagonist yohimbine were able to reduce the catalepsy induced by HP and HP+Δ9‐THC in a similar manner. CLOZ and the 5‐HT2A/2C antagonists ritanserin, RS102221 and SB242084 were more effective in antagonizing HP than HP+Δ9‐THC‐induced catalepsy. HP and CLOZ failed to inhibit in vitro [3H]CP‐55,940 binding, while Δ9‐THC and SR141716A did not show an appreciable affinity for the D2 receptor. It was suggested that the different effects on rat catalepsy induced by Δ9‐THC following HP or CLOZ administration may depend on the receptor‐binding profiles of the two antipsychotics. The preferential use of CLOZ rather than HP in the treatment of psychotic symptoms in cannabis abusers was discussed. British Journal of Pharmacology (2003) 140, 520–526. doi:10.1038/sj.bjp.0705478
Journal Article
Haloperidol, but not clozapine, produces dramatic catalepsy in Delta9-THC-treated rats: possible clinical implications
The effect on rat catalepsy induced by Delta9-tetrahydrocannabinol (Delta9-THC) in association with haloperidol (HP) or clozapine (CLOZ) administration was investigated. Delta9-THC dose-dependently increased HP (0.05-1 mg kg-1, s.c.)-induced rat catalepsy, while no catalepsy was observed after CLOZ (1-20 mg kg-1, s.c.) or Delta9-THC+CLOZ administration. The CB1 antagonist SR141716A (0.5-5 mg kg-1, i.p.) reversed the increase mediated by Delta9-THC on HP-induced catalepsy. The D2 agonist quinpirole completely reversed the catalepsy induced by both HP and HP+Delta9-THC; however, higher doses of quinpirole were needed in the presence of Delta9-THC. The M1 antagonist scopolamine and alpha2 antagonist yohimbine were able to reduce the catalepsy induced by HP and HP+Delta9-THC in a similar manner. CLOZ and the 5-HT2A/2C antagonists ritanserin, RS102221 and SB242084 were more effective in antagonizing HP than HP+Delta9-THC-induced catalepsy.7 HP and CLOZ failed to inhibit in vitro [3H]CP-55,940 binding, while Delta9-THC and SR141716A did not show an appreciable affinity for the D2 receptor. It was suggested that the different effects on rat catalepsy induced by Delta9-THC following HP or CLOZ administration may depend on the receptor-binding profiles of the two antipsychotics. The preferential use of CLOZ rather than HP in the treatment of psychotic symptoms in cannabis abusers was discussed.
Journal Article
Haloperidol, but not clozapine, produces dramatic catalepsy in delta9-THC-treated rats: possible clinical implications
The effect on rat catalepsy induced by Delta9-tetrahydrocannabinol (Delta9-THC) in association with haloperidol (HP) or clozapine (CLOZ) administration was investigated. Delta9-THC dose-dependently increased HP (0.05-1 mg kg-1, s.c.)-induced rat catalepsy, while no catalepsy was observed after CLOZ (1-20 mg kg-1, s.c.) or Delta9-THC+CLOZ administration. The CB1 antagonist SR141716A (0.5-5 mg kg-1, i.p.) reversed the increase mediated by Delta9-THC on HP-induced catalepsy. The D2 agonist quinpirole completely reversed the catalepsy induced by both HP and HP+Delta9-THC; however, higher doses of quinpirole were needed in the presence of Delta9-THC. The M1 antagonist scopolamine and alpha2 antagonist yohimbine were able to reduce the catalepsy induced by HP and HP+Delta9-THC in a similar manner. CLOZ and the 5-HT2A/2C antagonists ritanserin, RS102221 and SB242084 were more effective in antagonizing HP than HP+Delta9-THC-induced catalepsy.7 HP and CLOZ failed to inhibit in vitro [3H]CP-55,940 binding, while Delta9-THC and SR141716A did not show an appreciable affinity for the D2 receptor. It was suggested that the different effects on rat catalepsy induced by Delta9-THC following HP or CLOZ administration may depend on the receptor-binding profiles of the two antipsychotics. The preferential use of CLOZ rather than HP in the treatment of psychotic symptoms in cannabis abusers was discussed.
Journal Article
Role of the Hydroxyl Radical-Generating System in the Estimation of the Antioxidant Activity of Plant Extracts by Electron Paramagnetic Resonance (EPR)
The scavenging activity of hydroxyl radicals, produced by the Fenton reaction, is commonly used to quantify the antioxidant capacity of plant extracts. In this study, three Fenton systems (Fe/phosphate buffer, Fe/quinolinic acid and Fe/phosphate buffer/quinolinic acid) and the thermal degradation of peroxydisulfate were used to produce hydroxyl radicals; the hydroxyl radical scavenging activity of plant extracts (ginger, blueberry juices and green tea infusion) and chemical compounds (EGCG and GA) was estimated by spin trapping with DMPO (5,5-dimethyl-1-pyrroline N-oxide) and EPR (Electron Paramagnetic Resonance) spectroscopy. Phosphate buffer was used to mimic the physiological pH of cellular systems, while quinolinic acid (pyridine-2,3-dicarboxylic acid) facilitates the experimental procedure by hindering the spontaneous oxidation of Fe(II). The EC50 (the concentration of chemical compounds or plant extracts which halves the intensity of the DMPO–OH adduct) values were determined in all the systems. The results show that, for both the chemical compounds and the plant extracts, there is not a well-defined order for the EC50 values determined in the four hydroxyl radical generating systems. The interactions of phosphate buffer and quinolinic acid with the antioxidants and with potential iron-coordinating ligands present in the plant extracts can justify the observed differences.
Journal Article
Electron Paramagnetic Resonance Spectroscopy to Evaluate the Oxidative Stability of Beer, Wine, and Oils
Oxidative stability plays an important role in determining the quality of oxidation-sensitive foods and beverages such as beer, wine, and edible oils. Oxidation occurs through radical chain reactions producing off-flavors and leading to deterioration and decrease in the quality and nutritional value of food and beverages. In this context, electron paramagnetic resonance (EPR) spectroscopy has emerged as a powerful and selective technique for investigating reactions involving paramagnetic species, particularly free radicals and transition metal ions. This review provides a critical overview of the applications of EPR spectroscopy in the study of the oxidative stability and antioxidant activity of the above-mentioned matrices. It highlights the main methodological approaches that this technique can offer to gain insight into oxidative processes. Furthermore, current advances in low-cost and portable EPR instrumentation are discussed, along with their implications for broader adoption in both research and industry settings. The aim is to provide an up-to-date literature survey on the application of EPR spectroscopy for studying the oxidative stability and antioxidant activity of beer, wine, and edible oils, providing a methodological tool for academic and food industry researchers interested in monitoring, improving, and extending food shelf life through reliable analytical tools.
Journal Article