Biology subjects

Gera, R.

Publications and source records attributed to Gera, R..

5 recordsLinked to original sources

bioRxiv2025

Distributed activity in the human posterior putamen distinguishes goal-directed from habitual control in humans

How do some individuals rapidly form habits while others maintain flexible, goal-directed control? Using multivariate fMRI decoding in 199 participants, we show that distributed neural activity patterns in the left posterior putamen during initial learning predict individual behavioral strategy on a subsequent outcome devaluation test. This prediction generalized across two independent cohorts of healthy adults and psychiatric patients with heterogeneous diagnoses and was anatomically specific to the posterior putamen. Critically, predictive neural signatures were present during training, before strategy expression after devaluation, enabling prospective classification of habitual versus goal-directed behavior. These findings demonstrate that stable individual differences in behavioral control are reflected in circumscribed brain activity during learning, highlighting the posterior putamen as a candidate neural marker of habit propensity with potential clinical relevance.

neuroscience↗

bioRxiv2022

Characterizing habit learning in the human brain at the individual and group levels: a multi-modal MRI study

The dual-process theory of action control postulates that there are two competitive and complementary mechanisms that control our behavior: a goal-directed system that executes deliberate actions, explicitly aimed toward a particular outcome, and a habitual system that autonomously execute well-learned actions, typically following an encounter with a previously associated cue. In line with dual-process theory, animal studies have provided convincing evidence for dissociable neural mechanisms, mainly manifested in cortico-striatal regions, involved in goal-directed and habitual action control. While substantial progress has been made in characterizing the neural mechanism underlying habit learning in animals, we still lack knowledge on how habits are formed and maintained in the human brain. Thus far only one study, conducted more than a decade ago by Tricomi et al. (2009), has been able to induce habitual behavior in humans via extensive training. This study also implicated the posterior putamen in the process, using functional magnetic resonance imaging (fMRI). However, recent attempts to replicate the behavioral results of this study were not successful. This leaves the research of human habits, and particularly the research of their formation through extensive repetition, as well as their neural basis, limited and far behind the animal research in the field. This motivated us to (1) attempt to replicate the behavioral and imaging main findings of Tricomi et al., (2) identify further functional and microstructural neural modifications associated with habit formation and manifestation, and (3) investigate the relationships between functional and structural plasticity and individual differences in habit expression. To this end, in this registered report we used Tricomi et al.s free-operant task along with multi-modal MRI methods in a well-powered sample (n=123). In this task participants sensitivity to outcome devaluation (an index of goal-directed/habitual action control) is tested following either short or extensive training. In contrast to our hypothesis, we were not able to demonstrate habit formation as a function of training duration nor were we able to relate any functional or microstructural plasticity in the putamen with individual habit expression. We found that a pattern of increased activations in the left head of caudate that re-occurred across each days training is associated with goal directed behavior and that increased processing of devalued cues in low-level visual regions was indicative of goal-directed behavior (and vice versa). In a follow-up exploratory analysis comparing habitual and goal-directed subgroups within each experimental group, we found that elevated activations in frontoparietal regions during early stages of training, as well as increased reactivity towards still-valued cues in somatosensory and superior parietal regions were found in individuals that were more inclined to perform goal-directed behavior (compared with more habitual individuals). Taken together, regions commonly implicated in goal-directed behavior were most predictive of individual habit expression. Finally, we also found that differential patterns of training-related microstructural plasticity, as measured with diffusion MRI, in midbrain dopaminergic regions were associated with habit expression. This work provides new insights into the neural dynamics involved in individual habit formation/expression and encourages the development and testing of new, more sensitive, procedures for experimental habit induction in humans.

neuroscience↗

bioRxiv2020

Brain volumetric changes in the general population following the COVID-19 outbreak and lockdown

The COVID-19 outbreak introduced unprecedented health-risks, as well as pressure on the financial, social, and psychological well-being due to the response to the outbreak. Here, we examined the manifestations of the COVID-19 outbreak on the brain structure in the healthy population, following the initial phase of the pandemic in Israel. We pre-registered our hypothesis that the intense experience of the outbreak potentially induced stress-related brain modifications. Volumetric changes in n = 50 participants who were scanned before and after the COVID-19 outbreak and lockdown, were compared with n = 50 control participants who were scanned twice prior to the pandemic. The pandemic provided a rare opportunity to examine brain plasticity in a natural experiment. We found volumetric increases in bilateral amygdalae, putamen, and the anterior temporal cortices. Changes in the amygdalae diminished as time elapsed from lockdown relief, suggesting that the intense experience associated with the pandemic outbreak induced transient volumetric changes in brain regions commonly associated with stress and anxiety.

neuroscience↗

bioRxiv2019

Cross-Sectional and Longitudinal Validation of Serum Neurofilament Light Chain (NfL) as a Biomarker of Parkinson’s Disease Progression

ObjectiveTo assess neurofilament light chain (NfL), as a biomarker for Parkinsons disease (PD). MethodsWe quantified NfL in (1) longitudinal CSF samples from PD, other cognate/neurodegenerative disorders (OND), and healthy controls (HC); (2) a cross-sectional cohort with paired CSF and serum samples from participants with PD, OND, and HC, and (3) a large longitudinal validation cohort with serum samples from PD, OND, HC, prodromal conditions, and mutation carriers. ResultsIn the longitudinal discovery cohort (1) NfL in CSF was highest in OND and higher in PD vs. HC across all visits (p<0.05) but did not change longitudinally. In the cross-sectional cohort (2) paired CSF and serum NfL samples were highly correlated (Spearmans rank [Formula]; p<10^-6). In the large validation cohort (3) mean baseline serum NfL was higher in PD (13{+/-}7.2pg/ml) vs. HC (12{+/-}6.7pg/ml; p=0.0336) and was highest in OND (18{+/-}7pg/ml; p=0.0351). Serum NfL increased longitudinally in PD vs. HC (p<0.01). Longitudinal motor scores were positively longitudinally associated with NfL, whereas some cognitive scores showed a negative longitudinal association with NfL. ConclusionsNfL levels in serum samples are increased in PD vs. HC, increase significantly over time, and correlate with clinical measures of PD severity. Although the specificity of NfL in PD is low and more specific biomarkers are needed, serum NfL is the first blood-based biomarker candidate that could support disease stratification (PD vs. OND), track clinical progression, and possibly assess responsiveness to neuroprotective treatments. NfL as a biomarker of response to neuroprotective interventions remains to be determined. Funding sources for studyPPMI is sponsored by the Michael J. Fox Foundation for Parkinsons Research (MJFF) and is co-funded by MJFF, Abbvie, Avid Radiopharmaceuticals, Biogen Idec, Bristol-Myers Squibb, Covance, Eli Lilly & Co., F. Hoffman-La Roche, Ltd., GE Healthcare, Genentech, GlaxoSmithKline, Lundbeck, Merck, MesoScale, Piramal, Pfizer and UCB. The funders had no role in the design and conduct of the study, in the collection, management, analysis, and interpretation of the data, in the preparation, review, or approval of the manuscript or in the decision to submit the manuscript for publication. Financial Disclosure/Conflict of Interest concerning the research related to the manuscriptBrit Mollenhauer, Douglas Galasko, Tatiana Foroud, Lana M. Chahine, Christopher S. Coffey, Andrew B. Singleton, Tanya Simuni, Daniel Weintraub, John Seibyl, Arthur W. Toga, and Caroline M. Tanner received funding from The Michael J. Fox Foundation for Parkinsons Research. Mohammed Dakna, Tzu-Ying Liu, Henrik Zetterberg, Sebastian Schade, Roland G. Gera, Wenting Wang, Feng Gao, Niels Kruse, Mark Frasier, Jesse M. Cedarbaum, Samantha J. Hutten, Claudia Trenkwalder, and Danielle Graham report no disclosures.

neuroscience↗

bioRxiv2018

A retrieval-counterconditioning procedure diminishes reinstatement of appetitive memories in humans

Appetitive memories play a crucial role in learning and behavior but under certain circumstances become maladaptive and play a vital part in addiction and other psychopathologies. In recent years, scientific research demonstrated the ability of memories to be modified following their reactivation through memory retrieval, in a process termed memory reconsolidation. Several non-pharmacological behavioral manipulations yielded mixed results in their capacity to alter maladaptive memories in humans. Here, aiming to translate promising findings observed in rodents to humans, we constructed a novel three-day procedure to test the efficacy of aversive counterconditioning to alter appetitive memories when given following memory retrieval. On Day1 we used appetitive conditioning to form appetitive memories. On Day2, we retrieved these appetitive memories for half of the participants (Retrieval group). Subsequently, all participants underwent counterconditioning. On Day3, we tried to reinstate Day1 appetitive memories. We observed a significant reduction in the reinstatement of the original appetitive memory when counterconditioning was induced following memory retrieval. We provide here a novel human paradigm that models several memory processes, and demonstrate memory attenuation when counterconditioned after its retrieval. This paradigm can be used to study complex appetitive memory dynamics, e.g., memory reconsolidation, and their underlying brain mechanisms.

neuroscience↗