Investigation of alternative RF power limit control methods for 0.5T, 1.5T, and 3T parallel transmission cardiac imaging: A simulation study.

PURPOSE: To investigate safety and performance aspects of parallel-transmit (pTx) RF control-modes for a body coil at B 0 ≤ 3 T $$ {B}_0\le 3\mathrm{T} $$ . METHODS: Electromagnetic simulations of 11 human voxel models in cardiac imaging position were conducted for B 0 = 0.5 T $$ {B}_0=0.5\mathrm{T} $$ , 1.5 T $$ 1.5\mathrm{T} $$ and 3 T $$ 3\mathrm{T} $$ and a body coil with a configurable number of transmit channels (1, 2, 4, 8, 16). Three safety modes were considered: the 'SAR-controlled mode' (SCM), where specific absorption rate (SAR) is limited directly, a 'phase agnostic SAR-controlled mode' (PASCM), where phase information is neglected, and a 'power-controlled mode' (PCM), where the voltage amplitude for each channel is limited. For either mode, safety limits were established based on a set of 'anchor' simulations and then evaluated in 'target' simulations on previously unseen models. The comparison allowed to derive safety factors accounting for varying patient anatomies. All control modes were compared in terms of the B 1 + $$ {B}_1^{+} $$ amplitude and homogeneity they permit under their respective safety requirements. RESULTS: Large safety factors (approximately five) are needed if only one or two anchor models are investigated but they shrink with increasing number of anchors. The achievable B 1 + $$ {B}_1^{+} $$ is highest for SCM but this advantage is reduced when the safety factor is included. PCM appears to be more robust against variations of subjects. PASCM performance is mostly in between SCM and PCM. Compared to standard circularly polarized (CP) excitation, pTx offers minor B 1 + $$ {B}_1^{+} $$ improvements if local SAR limits are always enforced. CONCLUSION: PTx body coils can safely be used at B 0 ≤ 3 T $$ {B}_0\le 3\mathrm{T} $$ . Uncertainties in patient anatomy must be accounted for, however, by simulating many models.

Dopamine differentially modulates medial temporal lobe activity and behavior during spatial navigation in young and older adults.

Aging is associated with changes in spatial navigation behavior. In addition to an overall performance decline, older adults tend to rely more on proximal location cue information than on environmental boundary information during spatial navigation compared to young adults. The fact that older adults are more susceptible to errors during spatial navigation might be partly attributed to deficient dopaminergic modulation of hippocampal and striatal functioning. Hence, elevating dopamine levels might differentially modulate spatial navigation and memory performance in young and older adults. In this work, we administered levodopa (L-DOPA) in a double-blind within-subject, placebo-controlled design and recorded functional neuroimaging while young and older adults performed a 3D spatial navigation task in which boundary geometry or the position of a location cue were systematically manipulated. An age by intervention interaction on the neural level revealed an upregulation of brain responses in older adults and a downregulation of responses in young adults within the medial temporal lobe (including hippocampus and parahippocampus) and brainstem, during memory retrieval. Behaviorally, L-DOPA had no effect on older adults' overall memory performance; however, older adults whose spatial memory improved under L-DOPA also showed a shift towards more boundary processing under L-DOPA. In young adults, L-DOPA induced a decline in spatial memory performance in task-naïve participants. These results are consistent with the inverted-U-shaped hypothesis of dopamine signaling and cognitive function and suggest that increasing dopamine availability improves hippocampus-dependent place learning in some older adults.

Wirelessly interfacing sensor-equipped implants and MR scanners for improved safety and imaging.

PURPOSE: To investigate a novel reduced RF heating method for imaging in the presence of active implanted medical devices (AIMDs) which employs a sensor-equipped implant that provides wireless feedback. METHODS: The implant, consisting of a generator case and a lead, measures RF-induced E $$ E $$ -fields at the implant tip using a simple sensor in the generator case and transmits these values wirelessly to the MR scanner. Based on the sensor signal alone, parallel transmission (pTx) excitation vectors were calculated to suppress tip heating and maintain image quality. A sensor-based imaging metric was introduced to assess the image quality. The methodology was studied at 7T in testbed experiments, and at a 3T scanner in an ASTM phantom containing AIMDs instrumented with six realistic deep brain stimulation (DBS) lead configurations adapted from patients. RESULTS: The implant successfully measured RF-induced E $$ E $$ -fields (Pearson correlation coefficient squared [R2 ] = 0.93) and temperature rises (R2 = 0.95) at the implant tip. The implant acquired the relevant data needed to calculate the pTx excitation vectors and transmitted them wirelessly to the MR scanner within a single shot RF sequence (<60 ms). Temperature rises for six realistic DBS lead configurations were reduced to 0.03-0.14 K for heating suppression modes compared to 0.52-3.33 K for the worst-case heating, while imaging quality remained comparable (five of six lead imaging scores were ≥0.80/1.00) to conventional circular polarization (CP) images. CONCLUSION: Implants with sensors that can communicate with an MR scanner can substantially improve safety for patients in a fast and automated manner, easing the current burden for MR personnel.

Towards an integrated radiofrequency safety concept for implant carriers in MRI based on sensor-equipped implants and parallel transmission.

To protect implant carriers in MRI from excessive radiofrequency (RF) heating it has previously been suggested to assess that hazard via sensors on the implant. Other work recommended parallel transmission (pTx) to actively mitigate implant-related heating. Here, both ideas are integrated into one comprehensive safety concept where native pTx safety (without implant) is ensured by state-of-the-art field simulations and the implant-specific hazard is quantified in situ using physical sensors. The concept is demonstrated by electromagnetic simulations performed on a human voxel model with a simplified spinal-cord implant in an eight-channel pTx body coil at 3 T . To integrate implant and native safety, the sensor signal must be calibrated in terms of an established safety metric (e.g., specific absorption rate [SAR]). Virtual experiments show that E -field and implant-current sensors are well suited for this purpose, while temperature sensors require some caution, and B 1 probes are inadequate. Based on an implant sensor matrix Q s , constructed in situ from sensor readings, and precomputed native SAR limits, a vector space of safe RF excitations is determined where both global (native) and local (implant-related) safety requirements are satisfied. Within this safe-excitation subspace, the solution with the best image quality in terms of B 1 + magnitude and homogeneity is then found by a straightforward optimization algorithm. In the investigated example, the optimized pTx shim provides a 3-fold higher mean B 1 + magnitude compared with circularly polarized excitation for a maximum implant-related temperature increase ∆ T imp ≤ 1 K . To date, sensor-equipped implants interfaced to a pTx scanner exist as demonstrator items in research labs, but commercial devices are not yet within sight. This paper aims to demonstrate the significant benefits of such an approach and how this could impact implant-related RF safety in MRI. Today, the responsibility for safe implant scanning lies with the implant manufacturer and the MRI operator; within the sensor concept, the MRI manufacturer would assume much of the operator's current responsibility.

L-DOPA enhances neural direction signals in younger and older adults.

Previous studies indicate a role of dopamine in spatial navigation. Although neural representations of direction are an important aspect of spatial cognition, it is not well understood whether dopamine directly affects these representations, or only impacts other aspects of spatial brain function. Moreover, both dopamine and spatial cognition decline sharply during age, raising the question which effect dopamine has on directional signals in the brain of older adults. To investigate these questions, we used a double-blind cross-over L-DOPA/Placebo intervention design in which 43 younger and 37 older adults navigated in a virtual spatial environment while undergoing functional magnetic resonance imaging (fMRI). We studied the effect of L-DOPA, a dopamine precursor, on fMRI activation patterns that encode spatial walking directions that have previously been shown to lose specificity with age. This was done in predefined regions of interest, including the early visual cortex, retrosplenial cortex, and hippocampus. Classification of brain activation patterns associated with different walking directions was improved across all regions following L-DOPA administration, suggesting that dopamine broadly enhances neural representations of direction. No evidence for differences between regions was found. In the hippocampus these results were found in both age groups, while in the retrosplenial cortex they were only observed in younger adults. Taken together, our study provides evidence for a link between dopamine and the specificity of neural responses during spatial navigation. SIGNIFICANCE STATEMENT: The sense of direction is an important aspect of spatial navigation, and neural representations of direction can be found throughout a large network of space-related brain regions. But what influences how well these representations track someone's true direction? Using a double-blind cross-over L-DOPA/Placebo intervention design, we find causal evidence that the neurotransmitter dopamine impacts the fidelity of direction selective neural representations in the human hippocampus and retrosplenial cortex. Interestingly, the effect of L-DOPA was either equally present or even smaller in older adults, despite the well-known age related decline of dopamine. These results provide novel insights into how dopamine shapes the neural representations that underlie spatial navigation.

The impact of respiratory motion on electromagnetic fields and specific absorption rate in cardiac imaging at 7T.

PURPOSE: To present electromagnetic simulation setups for detailed analyses of respiration's impact on B 1 + $$ {B}_1^{+} $$ and E-fields, local specific absorption rate (SAR) and associated safety-limits for 7T cardiac imaging. METHODS: Finite-difference time-domain electromagnetic field simulations were performed at five respiratory states using a breathing body model and a 16-element 7T body transceiver RF-coil array. B 1 + $$ {B}_1^{+} $$ and SAR are analyzed for fixed and moving coil configurations. SAR variations are investigated using phase/amplitude shimming considering (i) a local SAR-controlled mode (here SAR calculations consider RF amplitudes and phases) and (ii) a channel-wise power-controlled mode (SAR boundary calculation is independent of the channels' phases, only dependent on the channels' maximum amplitude). RESULTS: Respiration-induced variations of both B 1 + $$ {B}_1^{+} $$ amplitude and phase are observed. The flip angle homogeneity depends on the respiratory state used for B 1 + $$ {B}_1^{+} $$ shimming; best results were achieved for shimming on inhale and exhale simultaneously ( | Δ C V | < 35 % $$ \mid \Delta CV\mid <35\% $$ ). The results reflect that respiration impacts position and amplitude of the local SAR maximum. With the local-SAR-control mode, a safety factor of up to 1.4 is needed to accommodate for respiratory variations while the power control mode appears respiration-robust when the coil moves with respiration (SAR peak decrease: 9% exhale→inhale). Instead, a spatially fixed coil setup yields higher SAR variations with respiration. CONCLUSION: Respiratory motion does not only affect the B 1 + $$ {B}_1^{+} $$ distribution and hence the image contrast, but also location and magnitude of the peak spatial SAR. Therefore, respiration effects may need to be included in safety analyses of RF coils applied to the human thorax.

Rapid safety assessment and mitigation of radiofrequency induced implant heating using small root mean square sensors and the sensor matrix Qs.

PURPOSE: Rapid detection and mitigation of radiofrequency (RF)-induced implant heating during MRI based on small and low-cost embedded sensors. THEORY AND METHODS: A diode and a thermistor are embedded at the tip of an elongated mock implant. RF-induced voltages or temperature change measured by these root mean square (RMS) sensors are used to construct the sensor Q-Matrix (QS ). Hazard prediction, monitoring and parallel transmit (pTx)-based mitigation using these sensors is demonstrated in benchtop measurements at 300 MHz and within a 3T MRI. RESULTS: QS acquisition and mitigation can be performed in <20 ms demonstrating real-time capability. The acquisitions can be performed using safe low powers (<3 W) due to the high reading precision of the diode (126 µV) and thermistor (26 µK). The orthogonal projection method used for pTx mitigation was able to reduce the induced signals and temperatures in all 155 investigated locations. Using the QS approach in a pTx capable 3T MRI with either a two-channel body coil or an eight-channel head coil, RF-induced heating was successfully assessed, monitored and mitigated while the image quality outside the implant region was preserved. CONCLUSION: Small (<1.5 mm3 ) and low-cost (<1 €) RMS sensors embedded in an implant can provide all relevant information to predict, monitor and mitigate RF-induced heating in implants, while preserving image quality. The proposed pTx-based QS approach is independent of simulations or in vitro testing and therefore complements these existing safety assessments.

Cortical thickness and related depressive symptoms in early abstinence from chronic methamphetamine use.

Methamphetamine use is surging globally as a cause of morbidity and mortality. Treatment is typically sought in early abstinence, when craving and depressive symptoms are intense, contributing to relapse and poor outcomes. To advance an understanding of this problem and identify therapeutic targets, we conducted a retrospective analysis of brain structure in 89 adults with Methamphetamine Use Disorder who were in early abstinence and 89 healthy controls. Unlike most prior research, the participants did not significantly differ in age, sex and recent use of alcohol and tobacco (p-values ≥ 0.400). We analysed thickness across the entire cerebral cortex by fitting a general linear model to identify differences between groups. Follow-up regressions were performed to determine whether cortical thickness in regions showing group differences was related to craving, measured on a visual analogue scale, or to the Beck Depression Inventory score. Participants in early methamphetamine abstinence (M ± SD = 22.1 ± 25.6 days) exhibited thinner cortex in clusters within bilateral frontal, parietal, temporal, insular, and right cingulate cortices relative to controls (p-values < 0.001, corrected for multiple comparisons). Unlike craving (ß = 0.007, p = 0.947), depressive symptoms were positively correlated with cortical thickness across clusters (ß = 0.239, p = 0.030) and with thickness in the anterior cingulate cluster (ß = 0.246, p = 0.027) in the methamphetamine-dependent group. Inasmuch as anterior cingulate pathology predicts response to antidepressants for Major Depressive Disorder, cingulate structure may also identify patients with Methamphetamine Use Disorder who can benefit from antidepressant medication.

Effects of moderate alcohol levels on default mode network connectivity in heavy drinkers.

BACKGROUND: It is well established that even moderate levels of alcohol affect cognitive functions such as memory, self-related information processing, and response inhibition. Nevertheless, the neural mechanisms underlying these alcohol-induced changes are still unclear, especially on the network level. The default mode network (DMN) plays an important role in memory and self-initiated mental activities; hence, studying functional interactions of the DMN may provide new insights into the neural mechanisms underlying alcohol-related changes. METHODS: We investigated resting-state functional connectivity (rsFC) of the DMN in a cohort of 37 heavy drinkers at a breath alcohol concentration of 0.8 g/kg. Alcohol and saline were infused in a single-blind crossover design. RESULTS: Intranetwork connectivity analyses revealed that participants showed significantly decreased rsFC of the right hippocampus and right middle temporal gyrus during acute alcohol exposure. Moreover, follow-up analyses revealed that these rsFC decreases were more pronounced in participants who reported stronger craving for alcohol. Exploratory internetwork connectivity analyses of the DMN with other resting-state networks showed no significant alcohol-induced changes, but suffered from low statistical power. CONCLUSIONS: Our results indicate that acute alcohol exposure affects rsFC within the DMN. Functionally, this finding may be associated with impairments in memory encoding and self-referential processes commonly observed during alcohol intoxication. Future resting-state functional magnetic resonance imaging studies might therefore also investigate memory function and test whether DMN-related connectivity changes are associated with alcohol-induced impairments or craving.

Parallel transmission medical implant safety testbed: Real-time mitigation of RF induced tip heating using time-domain E-field sensors.

PURPOSE: To implement a modular, flexible, open-source hardware configuration for parallel transmission (pTx) experiments on medical implant safety and to demonstrate real-time mitigation strategies for radio frequency (RF) induced implant heating based on sensor measurements. METHODS: The hardware comprises a home-built 8-channel pTx system (scalable to 32-channels), wideband power amplifiers and a positioning system with submillimeter precision. The orthogonal projection (OP) method is used to mitigate RF induced tip heating and to maintain sufficient B1+ for imaging. Experiments are performed at 297MHz and inside a clinical 3T MRI using 8-channel pTx RF coils, a guidewire substitute inside a phantom with attached thermistor and time-domain E-field probes. RESULTS: Repeatability and precision are ~3% for E-field measurements including guidewire repositioning, ~3% for temperature slopes and an ~6% root-mean-square deviation between B1+ measurements and simulations. Real-time pTx mitigation with the OP mode reduces the E-fields everywhere within the investigated area with a maximum reduction factor of 26 compared to the circularly polarized mode. Tip heating was measured with ~100 µK resolution and ~14 Hz sampling frequency and showed substantial reduction for the OP vs CP mode. CONCLUSION: The pTx medical implant safety testbed presents a much-needed flexible and modular hardware configuration for the in-vitro assessment of implant safety, covering all field strengths from 0.5-7 T. Sensor based real-time mitigation strategies utilizing pTx and the OP method allow to substantially reduce RF induced implant heating while maintaining sufficient image quality without the need for a priori knowledge based on simulations or in-vitro testing.

[Update - Lithium in the Long-Term Treatment of Bipolar Disorders]. / Update ­ Lithium in der Phasenprophylaxe Bipolarer Störungen.

Lithium is the gold standard in the long-term treatment of bipolar disorders and the only substance with a convincing antisuicidal effect in affective disorders. Under regular monitoring, lithium represents mostly a well-tolerated and safe medication. Balancing risk and benefits shows that lithium can also be an off-label therapeutic option during pregnancy and breast feeding. Lithium may exhibit neuroprotective effects and has been linked to a reduced risk of Alzheimer's disease and stroke. In the future, biomarkers of lithium response may be available that enable development of more personalized therapies.

Structural indices of brain aging in methamphetamine use disorder.

BACKGROUND: Methamphetamine use is surging globally. It has been linked to premature stroke, Parkinsonism, and dementia, suggesting that it may accelerate brain aging. METHODS: We performed a retrospective study to determine if structural indices of brain aging were more prevalent prior to old age (26 - 54 years) in individuals with Methamphetamine Use Disorder (MUD), who were in early abstinence (M ± SD = 22.1 ± 25.6 days) than in healthy control (HC) participants. We compared T1-weighted MRI brain scans in age- and sex-matched groups (n = 89/group) on three structural features of brain aging: the brain volume/cerebrospinal fluid (BV/CSF) index, volume of white matter hypointensities/lesions, and choroid plexus volume. RESULTS: The MUD group had a lower mean BV/CSF index and larger volumes of white matter hypointensities and choroid plexus (p-values < 0.01). Regression analyses showed significant age-by-group effects, indicating different age trajectories of the BV/CSF index and choroid plexus volume, consistent with abnormal global brain atrophy and choroid plexus pathology in the MUD group. Significant age and group main effects reflected a larger volume of white matter hypointensities for older participants across groups and for the MUD group irrespective of age. None of the three measures of brain aging correlated significantly with recent use or duration of recent abstinence from methamphetamine. CONCLUSIONS: Premature brain pathology, which may reflect cerebrovascular damage and dysfunction of the choroid plexus, occurs in people with MUD. Such pathology may affect cognition and thereby efficacy of behavioral treatments for MUD.

[Follow-up Evaluation of a Multimodal Treatment Program for Pregnant Women, Mothers and Fathers who Consume Methamphetamine]. / Verlaufsevaluation eines multimodalen Therapieprogrammes für Methamphetamin-konsumierende Schwangere, Mütter und Väter.

OBJECTIVE: Follow-up evaluation of the addiction therapy part of the multimodal treatment program "Mama Denk an mich" ("Mummy, think of me"), an interdisciplinary cooperation of several departments of the University Hospital Dresden with the local youth welfare offices and addiction counseling centers. METHOD: Description of treatment course and sample of the first 100 patients with a methamphetamine-related disorder and prospective observational study of treatment outcome. RESULTS: Besides a high proportion of first-time treated subjects (51%) and a young mean age (29 years), the sample was notable for precarious socioeconomic conditions and numerous comorbidities. Nevertheless, the comparatively high adherence rate (68%) suggests a good efficacy of the therapeutic methods used. CONCLUSION: Parenthood or pregnancy represent an opportunity to motivate methamphetamine addicts for effective outpatient addiction therapy even in the presence of severe addiction and psychiatric comorbidities.

Value-based decision-making predicts alcohol use and related problems in young men.

BACKGROUND: Alcohol consumption is a leading cause of morbidity and mortality worldwide, disproportionately affecting young men. Heavy episodic drinking is particularly prevalent among men, with this behavior peaking between the ages of 20 and 24. AIMS: We sought to identify dimensions of decision-making in men that would predict the development of hazardous alcohol use through emerging adulthood. METHODS: This prospective observational study profiled value-based decision-making in 198 healthy men at age 18 and assessed their alcohol involvement annually until age 24. Latent growth curve modeling estimated individual variability in trajectories of alcohol involvement and regressed this variability on five choice dimensions. RESULTS: Low loss aversion predicted sustained heavy episodic drinking from age 18 to 24. Both high delay discounting and risk-seeking for gains independently predicted a considerably higher cumulative alcohol use during these 6 years, with high delay discounting indicating escalating consumption from age 21. Risk-seeking for gains additionally predicted meeting more criteria for Alcohol Use Disorder in these 6 years. Risk-seeking for losses was not significantly related to alcohol outcomes. Choice preferences were largely independent of each other but were correlated with choice consistency, with low consistency predicting heavy episodic drinking from age 18 to 24 beyond these associations. CONCLUSIONS: The predictive effects collectively suggest that overvaluing immediate and probabilistic incentives, rather than underestimating harm, drives hazardous drinking in young men. The differential relations of choice preferences and consistency to alcohol involvement through emerging adulthood provide distinct cognitive-behavioral patterns that warrant consideration in the development of harm reduction interventions.

Housing Correlates in Pregnant and Parenting Women Using Methamphetamine and Accessing Psychiatric Care.

Background: Integrated care is a promising model for pregnant and parenting women with problems related to methamphetamine use. Yet more research is imperative to guide services for this vulnerable population as methamphetamine use contributes to housing instability, which is associated with heavier use and overdose death. Method: This prospective observational study analyzed how housing at discharge from psychiatric care was related to patient characteristics, program participation, and aftercare in 102 pregnant and/or parenting women. Results: Twelve of 23 women who were unstably housed at admission (three of six homeless) achieved stable housing by discharge from integrated care. Women were more likely unstably housed at discharge when unstably housed at admission, single, living apart from at least one minor, or when the other parent had a substance use disorder (p < 0.05). Unstably housed women at discharge were also more likely to have used social and inpatient services, and to transition to inpatient rehabilitation (p < 0.05). Among baseline characteristics, logistic regression identified unstable housing at admission (OR = 6.07) and being single (OR = 4.01) as the strongest unique contributors to unstable housing at discharge (p < 0.05). Conclusion: Unstably housed women and single women seem particularly at risk of remaining in precarious living conditions despite accessing integrated care for problems associated with methamphetamine use. Future work should investigate whether stronger partnerships with government and community agencies could be a way forward to help these women attain and maintain stable housing.

Mechanistic insights into the size-dependent effects of nanoparticles on inhibiting and accelerating amyloid fibril formation.

The aggregation of peptides into amyloid fibrils has been linked to ageing-related diseases, such as Alzheimer's and type 2 diabetes. Interfaces, particularly those with large nanostructured surfaces, can affect the kinetics of peptide aggregation, which ranges from complete inhibition to strong acceleration. While a number of physiochemical parameters determine interfacial effects, we focus here on the role of nanoparticle (NP) size and curvature. We used thioflavin T (ThT) fluorescence assays to demonstrate the size-dependent effects of NPs on amyloid fibril formation for the peptides Aß40, NNFGAIL, GNNQQNY and VQIYVK. While 5 nm gold NPs (AuNP-5) retarded or inhibited the aggregation of all peptides except NNFGAIL, larger 20 nm gold NPs (AuNP-20) tended to accelerate or not influence peptide aggregation. Differences in the NP effects for the peptides resulted from the different peptide properties (size, tendency to aggregate) and associated surface binding affinities. Additional dynamic light scattering (DLS), electron microscopy, and atomic force microscopy (AFM) experiments with the Aß40 peptide confirmed size-dependent NP effects on peptide aggregation, and also suggested a structural influence on the formed fibrils. NPs can serve as a surface for the adsorption of peptide monomers and enable nucleation to oligomers and fibril formation. However, molecular dynamics (MD) simulations showed that peptide oligomers were less stable at smaller NPs. High surface curvatures destabilized prefibrillar structures, which provides a possible explanation for inhibitory effects on fibril growth, provided that peptide-NP surface binding was relevant for fibril formation. These mechanistic insights can support the design of future nanostructured materials.

Targeting mGlu5 for Methamphetamine Use Disorder.

Methamphetamine abuse leads to devastating consequences, including addiction, crime, and death. Despite decades of research, no medication has been approved by the U.S. Food and Drug Administration for the treatment of Methamphetamine Use Disorder. Thus, there is a need for new therapeutic approaches. Animal studies demonstrate that methamphetamine exposure dysregulates forebrain function involving the Group-I metabotropic glutamate receptor subtype 5 (mGlu5), which is predominantly localized to postsynaptic sites. Allosteric modulators of mGlu5 offer a unique opportunity to modulate glutamatergic neurotransmission selectively, thereby potentially ameliorating methamphetamine-induced disruptions. Negative allosteric modulators of mGlu5 attenuate the effects of methamphetamine, including rewarding/reinforcing properties of the drug across animal models, and have shown promising effects in clinical trials for Anxiety Disorder and Major Depressive Disorder. Preclinical studies have also sparked great interest in mGlu5 positive allosteric modulators, which exhibit antipsychotic and anxiolytic properties, and facilitate extinction learning when access to methamphetamine is removed, possibly via the amelioration of methamphetamine-induced cognitive deficits. Clinical research is now needed to elucidate the mechanisms underlying the mGlu5 receptor-related effects of methamphetamine and the contributions of these effects to addictive behaviors. The growing array of mGlu5 allosteric modulators provides excellent tools for this purpose and may offer the prospect of developing tailored and effective medications for Methamphetamine Use Disorder.

Integrated Care for Pregnant Women and Parents With Methamphetamine-Related Mental Disorders.

Background: Methamphetamine use is a rapidly increasing cause of morbidity and mortality. Pregnant women and new parents who consume methamphetamine are at high risk since they seldom seek health services despite having multiple needs. We addressed this care gap by implementing an easily accessible program that pools resources from psychiatric, obstetric, and pediatric departments as well as community and government agencies. Method: This real-life observational study evaluated an integrated care program in 27 expecting parents and 57 parents of minors. The outcome criteria were treatment retention, psychosocial functioning, and abstinence. We compared participant demographics according to outcome and applied ordinal logistic regression to predict treatment success. Results: Patients received integrated care for almost 7 months on average. Nearly half achieved stable abstinence and functional recovery. Only one pregnant woman dropped out before a care plan could be implemented, and all women who gave birth during treatment completed it successfully. Three-fourths of patients had psychiatric comorbidities. Patients with depressive disorders were almost 5 times less likely to succeed with treatment. Attention-deficit hyperactivity disorder (ADHD) was diagnosed in nearly 30% of patients who dropped out of a care plan, which was about 4 times more often than in the successful outcome group. Conclusion: Our program engaged pregnant women and parents in treatment and helped them recover from methamphetamine-related mental disorders. Management of comorbid ADHD and depression should be an integral part of care initiatives to counter the methamphetamine crisis that affects parents and children across the globe.

Neurocognitive Dysfunctions and Their Therapeutic Modulation in Patients With Methamphetamine Dependence: A Pilot Study.

AIM: Methamphetamine (MA) abuse and dependence are increasing worldwide and are commonly associated with cognitive deficits. Some studies indicate that such impairments can improve if users become abstinent, but overall results remain inconclusive. Hence, we have performed a longitudinal case-control study investigating key surrogates for attention and impulsive decision-making before and after treatment. METHODS: Thirty patients with MA dependence and 24 non-substance-abusing control participants were recruited. Groups were matched on age, sex and education. All subjects performed a baseline assessment to obtain neurocognitive measures of sustained attention and delay discounting. Patients subsequently participated in an MA-specific relapse prevention program including repeated monitoring of relapse status. After 3 months, participants of both groups were reevaluated for neurocognitive performance. RESULTS: At baseline, MA patients showed a significantly higher number of omissions compared to controls, indicative of lower sustained attention. Interestingly, we observed a steep decrease of omissions in MA patients to control-group level post treatment. On the other hand, MA patients discounted delayed rewards significantly stronger than controls, indicating a more impulsive choice behavior both before and after treatment. LIMITATION: The results should be interpreted with care because of the small sample and short follow-up period. CONCLUSION: Our data support earlier findings on partial recovery of cognitive deficits in MA patients. They also strengthen the indication for recently recommended psychotherapeutic interventions and may provide a behavioral monitoring tool to inform treatment progress.

Probabilistic Reversal Learning Deficits in Patients With Methamphetamine Use Disorder-A Longitudinal Pilot Study.

Methamphetamine use disorder (MUD) is increasing worldwide and commonly associated with learning deficits. Little is known the about underlying trajectories, i.e., how the affected higher-order cognitive functions develop over time and with respect to abstinence and relapse. A probabilistic reversal learning (PRL) paradigm was implemented to uncover the microstructure of impulsive choice and maladaptive learning strategies in 23 patients with MUD in comparison with 24 controls. Baseline data revealed fewer optimal choices and a pattern of altered learning behavior from negative and positive feedback in patients suggesting impairments in flexibly-adapting behavior to changes of reward contingencies. Integrating longitudinal data from a follow-up assessment after 3 months of specific treatment revealed a group-by-time interaction indicating a normalization of these cognitive impairments in patients with MUD. In summary, our study demonstrates behavioral correlates of maladaptive decision-making processes in patients with MUD, which may recover after 3 months of MUD-specific therapy paving the way for further learning-based interventions. Limited by a small sample size, the results of this pilot study warrant replication in larger populations.