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The ability to read minds has long been a fascination of science fiction, but revolutionary new brain-imaging methods are bringing it closer to scientific reality. The New Mind Readers provides a compelling look at the origins, development, and future of these extraordinary tools, revealing how they are increasingly being used to decode our thoughts and experiences--and how this raises sometimes troubling questions about their application in domains such as marketing, politics, and the law. Russell Poldrack takes readers on a journey of scientific discovery, telling the stories of the visionaries behind these breakthroughs. Along the way, he gives an insider's perspective on what is perhaps the single most important technology in cognitive neuroscience today--functional magnetic resonance imaging, or fMRI, which is providing astonishing new insights into the contents and workings of the mind. He highlights both the amazing power and major limitations of these techniques and describes how applications outside the lab often exceed the bounds of responsible science. Poldrack also details the unique and sometimes disorienting experience of having his own brain scanned more than a hundred times as part of a landmark study of how human brain function changes over time. Written by one of the world's leading pioneers in the field, The New Mind Readers cuts through the hype and misperceptions surrounding these emerging new methods, offering needed perspective on what they can and cannot do--and demonstrating how they can provide new answers to age-old questions about the nature of consciousness and what it means to be human. -- Inside jacket flap.

Disruption in reciprocal connectivity between the right anterior insula and the left dorsolateral prefrontal cortex is associated with depression and may be a target for neuromodulation. In a five-center, parallel, double-blind, randomized controlled trial we personalized resting-state functional magnetic resonance imaging neuronavigated connectivity-guided intermittent theta burst stimulation (cgiTBS) at a site based on effective connectivity from the right anterior insula to the left dorsolateral prefrontal cortex. We tested its efficacy in reducing the primary outcome depression symptoms measured by the GRID Hamilton Depression Rating Scale 17-item over 8, 16 and 26 weeks, compared with structural magnetic resonance imaging (MRI) neuronavigated repetitive transcranial magnetic stimulation (rTMS) delivered at the standard stimulation site (F3) in patients with ‘treatment-resistant depression’. Participants were randomly assigned to 20 sessions over 4–6 weeks of either cgiTBS ( n  = 128) or rTMS ( n  = 127) with resting-state functional MRI at baseline and 16 weeks. Persistent decreases in depressive symptoms were seen over 26 weeks, with no differences between arms on the primary outcome GRID Hamilton Depression Rating Scale 17-item score (intention-to-treat adjusted mean, −0.31, 95% confidence interval (CI) −1.87, 1.24, P  = 0.689). Two serious adverse events were possibly related to TMS (mania and psychosis). MRI-neuronavigated cgiTBS and rTMS were equally effective in patients with treatment-resistant depression over 26 weeks (trial registration no. ISRCTN19674644). A randomized controlled trial found that functional connectivity-guided approaches to intermittent theta burst stimulation and repetitive transcranial magnetic stimulation both reduced depressive symptoms in patients with moderate to severe treatment-resistant depression over 26 weeks.

High-frequency (HF) transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC) is widely used in Major Depressive Episode (MDE). Optimization of its efficacy with a neuro-navigation system has been proposed based on a small randomized controlled trial (RCT) supporting a large effect. This evaluator- and patient-blind, multicenter RCT assessed the superiority in terms of efficacy of 10 HF rTMS sessions of the left DLPFC targeted with MRI based neuro-navigation versus similar sessions targeted by the standard 5 cm technique. The study was conducted between January 2013 and April 2017, at 4 hospitals centers in France where both in- and out- patients with MDE were included. Randomization was computer-generated (1:1), with allocation concealment implemented within the e-CRF. The main outcome measure was the percentage of responders 44 days (D44) after the rTMS session. Secondary outcomes were percentage of remitters, Beck Depression Inventory and psychomotor retardation assessed with Salpêtrière retardation rating scale (SRRS) for depression at D14 and D44. The results are presented along with their 95% confidence intervals. 105 patients were randomized and 92 were evaluable with respectively 45 patients in the neuronavigation group and 47 in the standard group. A treatment response was observed for 14 (31.8%) of 44 patients analyzed in the intervention group, and for 16 (35.6%) of 45 patients analyzed in the control group with no statistical difference (relative risk 0.89; 95% confidence interval, [0.50;1.61]). No difference was evidenced for secondary outcomes at D44 whether it concerns remission at D44 (relative risk, 0.82; 95% CI, 0.36 to 1.88), or BDI results (difference in means, 0,01; 95% CI, -3.06 to 3.26), or SRRS results (difference in means, 0.11; 95% CI, -2.42 to 5.02). Similar results were observed at D14. Rates of adverse events were similar in both groups with 23 (47.9%) and 1 (2.1%) of adverse events and serious adverse events in the neuro-navigation group versus 20 (40.8%) and 0 (0%) in the standard group. This study failed to reproduce previous findings supporting the use of neuro-navigation system to optimize rTMS efficacy. Limitations of this study includes a small sample size and a number of rTMS sessions that may appear substandard in 2025. NCT01677078.

The amygdala and the hippocampus are two limbic structures that play a critical role in cognition and behavior, however their manual segmentation and that of their smaller nuclei/subfields in multicenter datasets is time consuming and difficult due to the low contrast of standard MRI. Here, we assessed the reliability of the automated segmentation of amygdalar nuclei and hippocampal subfields across sites and vendors using FreeSurfer in two independent cohorts of older and younger healthy adults. Sixty-five healthy older (cohort 1) and 68 younger subjects (cohort 2), from the PharmaCog and CoRR consortia, underwent repeated 3D-T1 MRI (interval 1–90 days). Segmentation was performed using FreeSurfer v6.0. Reliability was assessed using volume reproducibility error (ε) and spatial overlapping coefficient (DICE) between test and retest session. Significant MRI site and vendor effects (p ​< ​.05) were found in a few subfields/nuclei for the ε, while extensive effects were found for the DICE score of most subfields/nuclei. Reliability was strongly influenced by volume, as ε correlated negatively and DICE correlated positively with volume size of structures (absolute value of Spearman’s r correlations >0.43, p ​< ​1.39E-36). In particular, volumes larger than 200 ​mm3 (for amygdalar nuclei) and 300 ​mm3 (for hippocampal subfields, except for molecular layer) had the best test-retest reproducibility (ε ​< ​5% and DICE ​> ​0.80). Our results support the use of volumetric measures of larger amygdalar nuclei and hippocampal subfields in multisite MRI studies. These measures could be useful for disease tracking and assessment of efficacy in drug trials. •Differences in MRI site/vendor had a limited effect on volume reproducibility.•Differences in MRI site/vendor had an extensive effect on spatial accuracy.•Reliability is good for larger amygdalar and hippocampal structures.•Automated volumetry is reliable in multicenter MRI studies.

Repetitive transcranial magnetic stimulation (rTMS) has demonstrated antidepressant efficacy but has limited evidence in depression associated with traumatic brain injury (TBI). Here, we investigate the use of rTMS targeted with individualized resting-state network mapping (RSNM) of dorsal attention network (DAN) and default mode network (DMN) in subjects with treatment-resistant depression associated with concussive or moderate TBI. The planned sample size was 50 with first interim analysis planned at 20, but only 15 were enrolled before the study was terminated for logistical reasons. Subjects were randomized to 20 sessions of bilateral rTMS (4000 left-sided excitatory pulses, 1000 right-sided inhibitory pulses) or sham. Treatment was targeted to the dorsolateral prefrontal cluster with maximal difference between DAN and DMN correlations based on resting-state functional magnetic resonance imaging with individualized RSNM. Mean improvement in the primary outcome, Montgomery-Asberg Depression Rating Scale (MADRS), was 56% ± 14% (n = 9) with active treatment and 27% ± 25% (n = 5) with sham (Cohen's d = 1.43). One subject randomized to sham withdrew before starting treatment. There were no seizures or other significant adverse events. MADRS improvement was inversely correlated with functional connectivity between the right-sided stimulation site and the subgenual anterior cingulate cortex (sgACC; r = -0.68, 95% confidence interval 0.03-0.925). Active treatment led to increased sgACC-DMN connectivity (d = 1.55) and increased sgACC anti-correlation with the left- and right-sided stimulation sites (d = -1.26 and -0.69, respectively). This pilot study provides evidence that RSNM-targeted rTMS is feasible in TBI patients with depression. Given the dearth of existing evidence-based treatments for depression in this patient population, these preliminarily encouraging results indicate that larger controlled trials are warranted.

Perivascular space (PVS) burden is an emerging, poorly understood, magnetic resonance imaging marker of cerebral small vessel disease, a leading cause of stroke and dementia. Genome-wide association studies in up to 40,095 participants (18 population-based cohorts, 66.3 ± 8.6 yr, 96.9% European ancestry) revealed 24 genome-wide significant PVS risk loci, mainly in the white matter. These were associated with white matter PVS already in young adults ( N  = 1,748; 22.1 ± 2.3 yr) and were enriched in early-onset leukodystrophy genes and genes expressed in fetal brain endothelial cells, suggesting early-life mechanisms. In total, 53% of white matter PVS risk loci showed nominally significant associations (27% after multiple-testing correction) in a Japanese population-based cohort ( N  = 2,862; 68.3 ± 5.3 yr). Mendelian randomization supported causal associations of high blood pressure with basal ganglia and hippocampal PVS, and of basal ganglia PVS and hippocampal PVS with stroke, accounting for blood pressure. Our findings provide insight into the biology of PVS and cerebral small vessel disease, pointing to pathways involving extracellular matrix, membrane transport and developmental processes, and the potential for genetically informed prioritization of drug targets. Genomic analyses of large population-based cohorts uncover the genetic determinants of perivascular space burden, an MRI marker of cerebral small vessel disease, across the lifespan, and reveal potential pathways implicated in the etiology of stroke and dementia.

Abstract Background and Hypothesis Schizophrenia manifests with marked heterogeneity in both clinical presentation and underlying biology. Modeling individual differences within clinical cohorts is critical to translate knowledge reliably into clinical practice. We hypothesized that individualized brain atrophy in patients with schizophrenia may explain the heterogeneous outcomes of repetitive transcranial magnetic stimulation (rTMS). Study Design The magnetic resonance imaging (MRI) data of 797 healthy subjects and 91 schizophrenia patients (between January 1, 2015, and December 31, 2020) were retrospectively selected from our hospital database. The healthy subjects were used to establish normative reference ranges for cortical thickness as a function of age and sex. Then, a schizophrenia patient’s personalized atrophy map was computed as vertex-wise deviations from the normative model. Each patient’s atrophy network was mapped using resting-state functional connectivity MRI from a subgroup of healthy subjects (n = 652). In total 52 of the 91 schizophrenia patients received rTMS in a randomized clinical trial (RCT). Their longitudinal symptom changes were adopted to test the clinical utility of the personalized atrophy map. Results The personalized atrophy maps were highly heterogeneous across patients, but functionally converged to a putative schizophrenia network that comprised regions implicated by previous group-level findings. More importantly, retrospective analysis of rTMS-RCT data indicated that functional connectivity of the personalized atrophy maps with rTMS targets was significantly associated with the symptom outcomes of schizophrenia patients. Conclusions Normative modeling can aid in mapping the personalized atrophy network associated with treatment outcomes of patients with schizophrenia.

BackgroundBreast cancer remains a leading cause of death in women and novel imaging biomarkers are urgently required. Here, we demonstrate the diagnostic and treatment-monitoring potential of non-invasive sodium (23Na) MRI in preclinical models of breast cancer.MethodsFemale Rag2−/−Il2rg−/− and Balb/c mice bearing orthotopic breast tumours (MDA-MB-231, EMT6 and 4T1) underwent MRI as part of a randomised, controlled, interventional study. Tumour biology was probed using ex vivo fluorescence microscopy and electrophysiology.Results23Na MRI revealed elevated sodium concentration ([Na+]) in tumours vs non-tumour regions. Complementary proton-based diffusion-weighted imaging (DWI) linked elevated tumour [Na+] to increased cellularity. Combining 23Na MRI and DWI measurements enabled superior classification accuracy of tumour vs non-tumour regions compared with either parameter alone. Ex vivo assessment of isolated tumour slices confirmed elevated intracellular [Na+] ([Na+]i); extracellular [Na+] ([Na+]e) remained unchanged. Treatment with specific inward Na+ conductance inhibitors (cariporide, eslicarbazepine acetate) did not affect tumour [Na+]. Nonetheless, effective treatment with docetaxel reduced tumour [Na+], whereas DWI measures were unchanged.ConclusionsOrthotopic breast cancer models exhibit elevated tumour [Na+] that is driven by aberrantly elevated [Na+]i. Moreover, 23Na MRI enhances the diagnostic capability of DWI and represents a novel, non-invasive biomarker of treatment response with superior sensitivity compared to DWI alone.

Several factors may mitigate the efficacy of repetitive transcranial magnetic stimulation (rTMS) over sham rTMS in patients with treatment-resistant depression (TRD). These factors include unilateral stimulation (i.e., treatment of only the left dorsolateral prefrontal cortex [DLPFC]), suboptimal methods of targeting the DLPFC and insufficient stimulation intensity (based on coil-to-cortex distance). We recruited patients with TRD between the ages of 18 and 85 years from a university hospital, and participants were randomized to receive sequential bilateral rTMS (600 pulses at 1 Hz followed by 1500 pulses at 10 Hz), unilateral high-frequency left (HFL)-rTMS (2100 pulses at 10 Hz) or sham rTMS for 3 or 6 weeks depending on treatment response. Stimulation was targeted with MRI localization over the junction of the middle and anterior thirds of the middle frontal gyrus, using 120% of the coil-to-cortex adjusted motor threshold. Our primary outcome of interest was the remission rate. A total of 121 patients participated in this study. The remission rate was significantly higher in the bilateral group than the sham group. The remission rate in the HFL-rTMS group was intermediate and did not differ statistically from the rate in the 2 other groups. There were no significant differences in reduction of depression scores among the 3 groups. The number of pulses used per session in the unilateral group was somewhat lower in our trial than in more recent trials, and the sham condition did not involve active stimulation. Our findings suggest that sequential bilateral rTMS is superior to sham rTMS; however, adjusting for coil-to-cortex distance did not yield enhanced efficacy rates.

IntroductionApproximately, 50% of stroke survivors experience impaired walking ability 6 months after conventional rehabilitation and standard care. However, compared with upper limb motor function, research on lower limbs rehabilitation through non-invasive neuromodulation like repetitive transcranial magnetic stimulation (rTMS) has received less attention. Limited evidence exists regarding the effectiveness of intermittent theta-burst stimulation (iTBS), an optimised rTMS modality, on lower limbs rehabilitation after stroke. This study aims to evaluate the effects of iTBS on gait, balance and lower limbs motor function in stroke recovery while also exploring the underlying neural mechanisms using longitudinal analysis of multimodal neuroimaging data.Methods and analysisIn this double-blinded randomised controlled trial, a total of 46 patients who had a stroke will be randomly assigned in a 1:1 ratio to receive either 15 sessions of leg motor area iTBS consisting of 600 pulses or sham stimulation over the course of 3 weeks. Additionally, conventional rehabilitation therapy will be administered following the (sham) iTBS intervention. The primary outcome measure will be the 10 m walking test. Secondary outcomes include the Fugl-Meyer assessment of the lower extremity, Timed Up and Go Test, Functional Ambulation Category Scale, Berg Balance Scale, modified Barthel Index, Mini-Mental State Examination, montreal cognitive assessment, tecnobody balance assessment encompassing both static and dynamic stability evaluations, surface electromyography recording muscle activation of the lower limbs, three-dimensional gait analysis focusing on temporal and spatial parameters as well as ground reaction force measurements, corticomotor excitability tests including resting motor threshold, motor evoked potential and recruitment curves and multimodal functional MRI scanning. Outcome measures will be collected prior to and after the intervention period with follow-up at 3 weeks.Ethics and disseminationThe study has received approval from the Medical Research Ethics Committee of Wuxi Mental Health Center/Wuxi Central Rehabilitation Hospital (no. WXMHCCIRB2023LLky078). Results will be disseminated through peer-reviewed journals and scientific conferences.Trial registration numberChiCTR2300077431.