Determination of hemispheric emotional valence in individual subjects: A new approach with research and therapeutic implications

BACKGROUND: Much has been theorized about the emotional properties of the hemispheres. Our review of the dominant hypotheses put forth by Schore, Joseph, Davidson, and Harmon-Jones on hemispheric emotional valences (HEV) shows that none are supported by robust data. Instead, we propose that individual's hemispheres are organized to have differing HEVs that can be lateralized in either direction. METHODS: Probe auditory evoked potentials (AEP) recorded during a neutral and an upsetting memory were used to assess HEV in 28 (20 F) right-handed subjects who were either victims of childhood maltreatment (N = 12) or healthy controls. In a sub-population, we determined HEV by emotional response to lateral visual field stimulation (LVFS), in which vision is limited to one, then the other hemifield. We compare a number of morphometric and functional brain measures between individuals who have right-negative versus left-negative HEV. RESULTS: Using AEPs to determine HEV, we found 62% of controls and 67% of maltreated subjects had right negative HEV. There was a strong interaction between HEV-laterality and gender, which together accounted for 60% of individual variability in total grey matter volume (GMV). HEV-laterality was associated with differences in hippocampal volume, amygdala/hippocampal ratios, and measures of verbal, visual and global memory. HEV-laterality was associated also with different constellations of symptoms comparing maltreated subjects to controls. Emotional response to LVFS provided a convenient and complementary measure of HEV-laterality that correlated significantly with the HEVs determined by AEPs. CONCLUSION: Our findings suggest that HEV-laterality, like handedness or gender, is an important individual difference with significant implications for brain and behavioral research, and for guiding lateralized treatments such as rTMS

Neurobiological mechanisms of repetitive transcranial magnetic stimulation on the underlying neuro circuitry in unipolar depression

For nearly two decades now, transcranial magnetic stimulation (TMS) has been available as a noninvasive clinical tool to treat patients suffering from major depression. In this period, a bulk of animal and human studies examined TMS parameters to improve clinical outcome. However, the neurobiological mechanisms underlying mood changes remain an important focus of research. In addition to having an effect on neuroendocrinological processes, neurotransmitter systems, and neurotrophic factors, TMS may not only affect the stimulated cortical regions, but also those connected to them. Therefore, we will review current human data on possible neurobiological mechanisms of repetitive (r) TMS implicated in the deregulated neurocircuitry present in unipolar depression. Furthermore, as the rTMS application can be considered as a “top-down” neuronal intervention, we will focus on the neuronal pathways linked with the stimulated area and we will present an integrative model of action

White Matter Integrity as a Biomarker for Stroke Recovery: Implications for TMS Treatment

White matter consists of myelinated axons which integrate information across remote brain regions. Following stroke white matter integrity is often compromised leading to functional impairment and disability. Despite its prevalence among stroke patients the role of white matter in development of post-stroke rehabilitation has been largely ignored. Rehabilitation interventions like repetitive transcranial magnetic stimulation (rTMS) are promising but reports on its efficacy have been conflicting. By understanding the role of white matter integrity in post-stroke motor recovery, brain reorganization and TMS efficacy we may be able to improve the development of future interventions. In this dissertation we set out answer these questions by investigating the relationship between white matter integrity and 1) bimanual motor performance following stroke, 2) cortical laterality following stroke and 3) TMS signal propagation (in a group of cocaine users without stroke). We identified white matter integrity of the corpus callosum as a key structure influencing bimanual performance using kinematic measures of hand symmetry (Chapter 2). Second, we found that reduced white matter integrity of corpus callosum was correlated with loss of functional laterality of the primary motor cortex during movement of the affected hand (Chapter 3). Lastly, we found that reduced white matter tract integrity from the site of stimulation to a downstream subcortical target, was correlated to the ability to modulate that target (Chapter 4). Taken together these studies support white matter integrity as a valuable biomarker for future rTMS trials in stroke. To emphasize the implications of these findings, we provide an example of how to incorporate white matter integrity at multiple levels of rTMS study design

Hemispheric asymmetry of motor cortex excitability in mood disorders – Evidence from a systematic review and meta-analysis

Funding Information: Funding: GC was supported by Fundação para a Ciência e Tecnologia (FCT) through a PhD Scholarship (SFRH/BD/130210/2017). AJO-M is supported by grant FCT-PTDC/MEC-PSQ/30302/2017-IC&DT-LIS BOA-01-0145-FEDER, funded by national funds from FCT/MCTES and co-funded by FEDER, under the Partnership Agreement Lisboa 2020 - Programa Operacional Regional de Lisboa. GC and AJO-M are supported by grant FCT-PTDC/MED-NEU/31331/2017, funded by FCT/MCTES. This project was funded by the European Union’s Horizon 2020 research and innovation programme under grant agreement No 777167. AJO-M was national coordinator for Portugal of a noninterventional study (EDMS-ERI-143085581, 4.0) to characterize a Treatment-Resistant Depression Cohort in Europe, sponsored by Janssen-Cilag, Ltd (2019–2020), is recipient of a grant from Schuhfried GmBH for norming and validation of cognitive tests, and is national coordinator for Portugal of trials of psilocybin therapy for treatment-resistant depression, sponsored by Compass Pathways, Ltd (EudraCT number 2017-003288-36 and 2020-001348- 25), and of esketamine for treatment-resistant depression, sponsored by Janssen-Cilag, Ltd (EudraCT NUMBER: 2019-002992-33).Objective: Mood disorders have been associated with lateralized brain dysfunction, on the left-side for depression and right-side for mania. Consistently, asymmetry of cortical excitability, as measured by transcranial magnetic stimulation (TMS) has been reported. Here, we reviewed and summarized work assessing such measures bilaterally in mood disorders. Methods: We performed a systematic review and extracted data to perform meta-analyses of interhemispheric asymmetry of motor cortex excitability, assessed with TMS, across different mood disorders and in healthy subjects. Additionally, potential predictors of interhemispheric asymmetry were explored. Results: Asymmetry of resting motor threshold (MT) among healthy volunteers was significant, favoring lower right relative to left-hemisphere excitability. MT was also significantly asymmetric in major depressive disorder (MDD), but with lower excitability of the left -hemisphere, when compared to the right, no longer observed in recovered patients. Findings on intracortical facilitation were similar. The few trials including bipolar depression revealed similar trends for imbalance, but with lower right hemisphere excitability, relative to the left. Conclusions: There is interhemispheric asymmetry of motor cortical excitability in MDD, with lower excitability on left when compared to right-side. Interhemispheric asymmetry, with lower right relative to left-sided excitability, was found for bipolar depression and was also suggested for healthy volunteers, in a pattern that is clearly distinct from MDD. Significance: Mood disorders display asymmetric motor cortical excitability that is distinct from that found in healthy volunteers, supporting the presence of lateralized brain dysfunction in these disorders.publishersversionpublishe

HF-rTMS treatment decreases psychomotor retardation in medication-resistant melancholic depression

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