Inter-identity amnesia in dissociative identity disorder resolved: A behavioural and neurobiological study.

INTRODUCTION: Dissociative identity disorder (DID) is characterised by, among others, subjectively reported inter-identity amnesia, reflecting compromised information transfer between dissociative identity states. Studies have found conflicting results regarding memory transfer between dissociative identity states. Here, we investigated inter-identity amnesia in individuals with DID using self-relevant, subject specific stimuli, and behavioural and neural measures. METHODS: Data of 46 matched participants were included; 14 individuals with DID in a trauma-avoidant state, 16 trauma-avoiding DID simulators, and 16 healthy controls. Reaction times and neural activation patterns related to three types of subject specific words were acquired and statistically analysed, namely non-self-relevant trauma-related words (NSt), self-relevant trauma-related words from a trauma-avoidant identity state (St), and trauma-related words from a trauma-related identity state (XSt). RESULTS: We found no differences in reaction times between XSt and St words and faster reaction times for XSt over NSt. Reaction times of the diagnosed DID group were the longest. Increased brain activation to XSt words was found in the frontal and parietal regions, while decreased brain activity was found in the anterior cingulate cortex in the diagnosed DID group. DISCUSSION: The current study reproduces and amalgamates previous behavioural reports as well as brain activation patterns. Our finding of increased cognitive control over self-relevant trauma-related knowledge processing has important clinical implications and calls for the redefinition of "inter-identity amnesia" to "inter-identity avoidance".

Neural correlates of transfer of learning in motor coordination tasks: role of inhibitory and excitatory neurometabolites.

We aimed to investigate transfer of learning, whereby previously acquired skills impact new task learning. While it has been debated whether such transfer may yield positive, negative, or no effects on performance, very little is known about the underlying neural mechanisms, especially concerning the role of inhibitory (GABA) and excitatory (Glu) (measured as Glu + glutamine (Glx)) neurometabolites, as measured by magnetic resonance spectroscopy (MRS). Participants practiced a bimanual coordination task across four days. The Experimental group trained a task variant with the right hand moving faster than the left (Task A) for three days and then switched to the opposite variant (Task B) on Day4. The control group trained Task B across four days. MRS data were collected before, during, and after task performance on Day4 in the somatosensory (S1) and visual (MT/V5) cortex. Results showed that both groups improved performance consistently across three days. On Day4, the Experimental group experienced performance decline due to negative task transfer while the control group continuously improved. GABA and Glx concentrations obtained during task performance showed no significant group-level changes. However, individual Glx levels during task performance correlated with better (less negative) transfer performance. These findings provide a first window into the neurochemical mechanisms underlying task transfer.

Baseline GABA+ levels in areas associated with sensorimotor control predict initial and long-term motor learning progress.

Synaptic plasticity relies on the balance between excitation and inhibition in the brain. As the primary inhibitory and excitatory neurotransmitters, gamma-aminobutyric acid (GABA) and glutamate (Glu), play critical roles in synaptic plasticity and learning. However, the role of these neurometabolites in motor learning is still unclear. Furthermore, it remains to be investigated which neurometabolite levels from the regions composing the sensorimotor network predict future learning outcome. Here, we studied the role of baseline neurometabolite levels in four task-related brain areas during different stages of motor skill learning under two different feedback (FB) conditions. Fifty-one healthy participants were trained on a bimanual motor task over 5 days while receiving either concurrent augmented visual FB (CA-VFB group, N = 25) or terminal intrinsic visual FB (TA-VFB group, N = 26) of their performance. Additionally, MRS-measured baseline GABA+ (GABA + macromolecules) and Glx (Glu + glutamine) levels were measured in the primary motor cortex (M1), primary somatosensory cortex (S1), dorsolateral prefrontal cortex (DLPFC), and medial temporal cortex (MT/V5). Behaviorally, our results revealed that the CA-VFB group outperformed the TA-VFB group during task performance in the presence of augmented VFB, while the TA-VFB group outperformed the CA-VFB group in the absence of augmented FB. Moreover, baseline M1 GABA+ levels positively predicted and DLPFC GABA+ levels negatively predicted both initial and long-term motor learning progress in the TA-VFB group. In contrast, baseline S1 GABA+ levels positively predicted initial and long-term motor learning progress in the CA-VFB group. Glx levels did not predict learning progress. Together, these findings suggest that baseline GABA+ levels predict motor learning capability, yet depending on the FB training conditions afforded to the participants.

Identity state-dependent self-relevance and emotional intensity ratings of words in dissociative identity disorder: A controlled longitudinal study.

INTRODUCTION: Dissociative identity disorder (DID) is characterized by, among others, amnesic episodes and the recurrence of different dissociative identity states. While consistently observed in clinical settings, to our knowledge, no controlled research study has shown the degree to which different identity states report autobiographical knowledge over time. Hence, the current study investigates self-relevance and emotional intensity ratings of words longitudinally. METHODS: Data of 46 participants were included: 13 individuals with DID, 11 DID-simulating actors, and a control group of 22 paired individuals. Individuals with DID and DID simulators participated once in the neutral identity state (NIS) and once in the trauma-related dissociative identity state (TIS). The control group paired 11 healthy controls with 11 participants with posttraumatic stress disorder (PTSD) as a NIS-TIS pair. Self-relevance ratings of different word types were collected in a baseline and a follow-up session, on average 6 weeks apart. A mixed ANOVA design was used to assess the effects of group, session, word type, and dissociative identity state. RESULTS: All participants in TIS and individuals with DID in NIS rated self-relevant trauma-related words more negatively. In the NIS, the control group rated self-relevant trauma-related words as less negative, whereas the ratings of simulating actors were intermediate. There was no group-dependent longitudinal effect for intensity ratings. CONCLUSIONS: This study was the first to confirm clinical observations that self-relevant and emotional processing are different between individuals with DID and controls, but consistent over time. Actors were unable to perfectly simulate DID. The finding that ratings of self-relevant trauma-related words differ between subgroups as included in the study is in line with clinical observations.

White matter and neurochemical mechanisms underlying age-related differences in motor processing speed.

Aging is associated with changes in the central nervous system and leads to reduced life quality. Here, we investigated the age-related differences in the CNS underlying motor performance deficits using magnetic resonance spectroscopy and diffusion MRI. MRS measured N-acetyl aspartate (NAA), choline (Cho), and creatine (Cr) concentrations in the sensorimotor and occipital cortex, whereas dMRI quantified apparent fiber density (FD) in the same voxels to evaluate white matter microstructural organization. We found that aging was associated with increased reaction time and reduced FD and NAA concentration in the sensorimotor voxel. Both FD and NAA mediated the association between age and reaction time. The NAA concentration was found to mediate the association between age and FD in the sensorimotor voxel. We propose that the age-related decrease in NAA concentration may result in reduced axonal fiber density in the sensorimotor cortex which may ultimately account for the response slowness of older participants.

A neurostructural biomarker of dissociative amnesia: a hippocampal study in dissociative identity disorder.

BACKGROUND: Little is known about the neural correlates of dissociative amnesia, a transdiagnostic symptom mostly present in the dissociative disorders and core characteristic of dissociative identity disorder (DID). Given the vital role of the hippocampus in memory, a prime candidate for investigation is whether total and/or subfield hippocampal volume can serve as biological markers of dissociative amnesia. METHODS: A total of 75 women, 32 with DID and 43 matched healthy controls (HC), underwent structural magnetic resonance imaging (MRI). Using Freesurfer (version 6.0), volumes were extracted for bilateral global hippocampus, cornu ammonis (CA) 1-4, the granule cell molecular layer of the dentate gyrus (GC-ML-DG), fimbria, hippocampal-amygdaloid transition area (HATA), parasubiculum, presubiculum and subiculum. Analyses of covariance showed volumetric differences between DID and HC. Partial correlations exhibited relationships between the three factors of the dissociative experience scale scores (dissociative amnesia, absorption, depersonalisation/derealisation) and traumatisation measures with hippocampal global and subfield volumes. RESULTS: Hippocampal volumes were found to be smaller in DID as compared with HC in bilateral global hippocampus and bilateral CA1, right CA4, right GC-ML-DG, and left presubiculum. Dissociative amnesia was the only dissociative symptom that correlated uniquely and significantly with reduced bilateral hippocampal CA1 subfield volumes. Regarding traumatisation, only emotional neglect correlated negatively with bilateral global hippocampus, bilateral CA1, CA4 and GC-ML-DG, and right CA3. CONCLUSION: We propose decreased CA1 volume as a biomarker for dissociative amnesia. We also propose that traumatisation, specifically emotional neglect, is interlinked with dissociative amnesia in having a detrimental effect on hippocampal volume.

Bridging cognition and action: executive functioning mediates the relationship between white matter fiber density and complex motor abilities in older adults.

Aging may be associated with motor decline that is attributed to deteriorating white matter microstructure of the corpus callosum (CC), among other brain-related factors. Similar to motor functioning, executive functioning (EF) typically declines during aging, with age-associated changes in EF likewise being linked to altered white matter connectivity in the CC. Given that both motor and executive functions rely on white matter connectivity via the CC, and that bimanual control is thought to rely on EF, the question arises whether EF can at least party account for the proposed link between CC-connectivity and motor control in older adults. To address this, diffusion magnetic resonance imaging data were obtained from 84 older adults. A fiber-specific approach was used to obtain fiber density (FD), fiber cross-section (FC), and a combination of both metrics in eight transcallosal white matter tracts. Motor control was assessed using a bimanual coordination task. EF was determined by a domain-general latent EF-factor extracted from multiple EF tasks, based on a comprehensive test battery. FD of transcallosal prefrontal fibers was associated with cognitive and motor performance. EF partly accounted for the relationship between FD of prefrontal transcallosal pathways and motor control. Our results underscore the multidimensional interrelations between callosal white matter connectivity (especially in prefrontal brain regions), EF across multiple domains, and motor control in the older population. They also highlight the importance of considering EF when investigating brain-motor behavior associations in older adults.

The interaction between endogenous GABA, functional connectivity, and behavioral flexibility is critically altered with advanced age.

The flexible adjustment of ongoing behavior challenges the nervous system's dynamic control mechanisms and has shown to be specifically susceptible to age-related decline. Previous work links endogenous gamma-aminobutyric acid (GABA) with behavioral efficiency across perceptual and cognitive domains, with potentially the strongest impact on those behaviors that require a high level of dynamic control. Our analysis integrated behavior and modulation of interhemispheric phase-based connectivity during dynamic motor-state transitions with endogenous GABA concentration in adult human volunteers. We provide converging evidence for age-related differences in the preferred state of endogenous GABA concentration for more flexible behavior. We suggest that the increased interhemispheric connectivity observed in the older participants represents a compensatory neural mechanism caused by phase-entrainment in homotopic motor cortices. This mechanism appears to be most relevant in the presence of a less optimal tuning of the inhibitory tone as observed during healthy aging to uphold the required flexibility of behavioral action. Future work needs to validate the relevance of this interplay between neural connectivity and GABAergic inhibition for other domains of flexible human behavior.

Dissociative identity state-dependent working memory in dissociative identity disorder: a controlled functional magnetic resonance imaging study.

BACKGROUND: Memory function is at the core of the psychopathology of dissociative identity disorder (DID), but little is known about its psychobiological correlates. AIMS: This study aims to investigate whether memory function in DID differs between dissociative identity states. METHOD: Behavioural data and neural activation patterns were assessed in 92 sessions during an n-back working memory task. Participants were people with genuine diagnosed DID (n = 14), DID-simulating controls (n = 16) and a paired control group (post-traumatic stress disorder (n = 16), healthy controls (n = 16)). Both DID groups participated as authentic or simulated neutral and trauma-related identity states. Reaction times and errors of omission were analysed with repeated measures ANOVA. Working memory neural activation (main working memory and linear load) was investigated for effects of identity state, participant group and their interaction. RESULTS: Identity state-dependent behavioural performance and neural activation was found. DID simulators made fewer errors of omission than those with genuine DID. Regarding the prefrontal parietal network, main working memory in the left frontal pole and ventrolateral prefrontal cortex (Brodmann area 44) was activated in all three simulated neutral states, and in trauma-related identity states of DID simulators, but not those with genuine DID or post-traumatic stress disorder; for linear load, trauma-related identity states of those with genuine DID did not engage the parietal regions. CONCLUSIONS: Behavioural performance and neural activation patterns related to working memory in DID are dependent on the dissociative identities involved. The narrowed consciousness of trauma-related identity states, with a proneness to re-experiencing traumatising events, may relate to poorer working memory functioning.

Normal amygdala morphology in dissociative identity disorder.

Studies investigating the structure of the amygdala in relation to dissociation in psychiatric disorders are limited and have reported normal or preserved, increased or decreased global volumes. Thus, a more detailed investigation of the amygdala is warranted. Amygdala global and subregional volumes were compared between individuals with dissociative identity disorder (DID: n = 32) and healthy controls (n = 42). Analyses of covariance did not show volumetric differences between the DID and control groups. Although several unknowns make it challenging to interpret our findings, we propose that the finding of normal amygdala volume is a genuine finding because other studies using this data-set have presented robust morphological aberrations in relation to the diagnosis of DID.

The role of MRS-assessed GABA in human behavioral performance.

Understanding the neurophysiological mechanisms that drive human behavior has been a long-standing focus of cognitive neuroscience. One well-known neuro-metabolite involved in the creation of optimal behavioral repertoires is GABA, the main inhibitory neurochemical in the human brain. Converging evidence from both animal and human studies indicates that individual variations in GABAergic function are associated with behavioral performance. In humans, one increasingly used in vivo approach to measuring GABA levels is through Magnetic Resonance Spectroscopy (MRS). However, the implications of MRS measures of GABA for behavior remain poorly understood. In this respect, it is yet to be determined how GABA levels within distinct task-related brain regions of interest account for differences in behavioral performance. This review summarizes findings from cross-sectional studies that determined baseline MRS-assessed GABA levels and examined their associations with performance on various behaviors representing the perceptual, motor and cognitive domains, with a particular focus on healthy participants across the lifespan. Overall, the results indicate that MRS-assessed GABA levels play a pivotal role in various domains of behavior. Even though some converging patterns emerge, it is challenging to draw comprehensive conclusions due to differences in behavioral task paradigms, targeted brain regions of interest, implemented MRS techniques and reference compounds used. Across all studies, the effects of GABA levels on behavioral performance point to generic and partially independent functions that refer to distinctiveness, interference suppression and cognitive flexibility. On one hand, higher baseline GABA levels may support the distinctiveness of neural representations during task performance and better coping with interference and suppression of preferred response tendencies. On the other hand, lower baseline GABA levels may support a reduction of inhibition, leading to higher cognitive flexibility. These effects are task-dependent and appear to be mediated by age. Nonetheless, additional studies using emerging advanced methods are required to further clarify the role of MRS-assessed GABA in behavioral performance.

No Self Without Salience: Affective and Self-relevance Ratings of 552 Emotionally Valenced and Neutral Dutch Words.

It is unknown how self-relevance is dependent on emotional salience. Emotional salience encompasses an individual's degree of attraction or aversion to emotionally-valenced information. The current study investigated the interconnection between self and salience through the evaluation of emotional valence and self-relevance. 56 native Dutch participants completed a questionnaire assessing valence, intensity, and self-relevance of 552 Dutch nouns and verbs. One-way repeated-measures ANCOVA investigated the relationship between valence and self, age and gender. Repeated-measures ANCOVA also tested the relationship between valence and self with intensity ratings and effects of gender and age. Results showed a significant main effect of valence for self-relevant words. Intensity analyses showed a main effect of valence but not of self-relevance. There were no significant effects of gender and age. The most important finding presents that self-relevance is dependent on valence. These findings concerning the relationship between self and salience opens avenues to study an individual's self-definition.

The utility of the Structured Inventory of Malingered Symptomatology for distinguishing individuals with Dissociative Identity Disorder (DID) from DID simulators and healthy controls.

Background: Individuals with dissociative identity disorder (DID) have complex symptoms consistent with severe traumatic reactions. Clinicians and forensic assessors are challenged by distinguishing symptom exaggeration and feigning from genuine symptoms among these individuals. This task may be aided by administering validity measures. Objective: This study aimed to document how individuals with DID score on the Structured Inventory of Malingered Symptomatology (SIMS). The second objective was to compare coached DID simulators and healthy controls to DID patients on the SIMS's total score and subscales. The third objective was to examine the utility rates of the SIMS in distinguishing simulated DID from clinically diagnosed DID. Method: We compared SIMS data gathered from participants from two Dutch sites, one Swiss site and one U.S. site. Sixty-three DID patients were compared to 77 coached DID simulators and 64 healthy controls on the SIMS. A multivariate analysis compared the groups on the SIMS total scores and subscales, and post-hoc Games Howell tests and univariate ANOVAs examined differences between the groups. Utility statistics assessed the accuracy of the SIMS in distinguishing clinical from simulated DID. Results: DID simulators scored significantly higher than DID individuals and healthy controls on every SIMS subscale as well as the total score. The majority (85.7%) of the individuals with DID scored above the cut-off, which is typically interpreted as indicative of possible symptom exaggeration. DID individuals scored higher than the healthy controls on every subscale except Low Intelligence, even after controlling for dissociation. The subscales and items most frequently endorsed by the DID group are consistent with symptoms associated with complex trauma exposure and dissociative reactions. The SIMS total score had a sensitivity of 96% but an unacceptably low specificity of 14%. Conclusions: The findings indicate that the instrument is not accurate in assessing potential symptom exaggeration or feigning in DID.

Antecedentes: Los individuos con trastorno de identidad disociativo (TID) tienen síntomas complejos consistentes con reacciones traumáticas severas. Los clínicos y evaluadores forenses se enfrentan al reto de distinguir la exageración de los síntomas y la simulación de los síntomas genuinos entre estos individuos. Esta tarea puede verse facilitada por la administración de medidas de validez.Objetivo: Este estudio tuvo como objetivo documentar la puntuación de los individuos con TID en el Inventario Estructurado de Sintomatología Simulada (SIMS). El segundo objetivo era comparar los simuladores de TID entrenados y los controles sanos con los pacientes de TID en la puntuación total y las subescalas del SIMS. El tercer objetivo fue examinar los índices de utilidad del SIMS para distinguir el TID simulado del TID diagnosticado clínicamente.Método: Se compararon los datos de la SIMS obtenidos de participantes de dos centros holandeses, un centro suizo y un centro estadounidense. Se compararon 63 pacientes de TID con 77 simuladores de TID entrenados y 64 controles sanos en el SIMS. Un análisis multivariante comparó los grupos en las puntuaciones totales y subescalas de la SIMS, y las pruebas post-hoc de Games Howell y los ANOVAs univariantes examinaron las diferencias entre los grupos. Las estadísticas de utilidad evaluaron la precisión de la SIMS para distinguir el TID clínico del simulado.Resultados: Los simuladores de TID obtuvieron puntuaciones significativamente más altas que los individuos con TID y los controles sanos en cada subescala del SIMS, así como en la puntuación total. La mayoría (85,7%) de los individuos con TID puntuaron por encima del punto de corte, que suele interpretarse como indicativo de una posible exageración de los síntomas. Los individuos con TID puntuaron más alto que los controles sanos en todas las subescalas excepto en Inteligencia baja, incluso después de controlar la disociación. Las subescalas y los ítems más frecuentemente respaldados por el grupo de TID son consistentes con los síntomas asociados con la exposición al trauma complejo y las reacciones disociativas. La puntuación total del SIMS tuvo una sensibilidad del 96% pero una especificidad inaceptablemente baja del 14%.Conclusiones: Los resultados indican que el instrumento no es preciso para evaluar la potencial exageración o simulación de los síntomas en el TID.

Thalamic morphology predicts the onset of freezing of gait in Parkinson's disease.

The onset of freezing of gait (FOG) in Parkinson's disease (PD) is a critical milestone, marked by a higher risk of falls and reduced quality of life. FOG is associated with alterations in subcortical neural circuits, yet no study has assessed whether subcortical morphology can predict the onset of clinical FOG. In this prospective multimodal neuroimaging cohort study, we performed vertex-based analysis of grey matter morphology in fifty-seven individuals with PD at study entry and two years later. We also explored the behavioral correlates and resting-state functional connectivity related to these local volume differences. At study entry, we found that freezers (N = 12) and persons who developed FOG during the course of the study (converters) (N = 9) showed local inflations in bilateral thalamus in contrast to persons who did not (non-converters) (N = 36). Longitudinally, converters (N = 7) also showed local inflation in the left thalamus, as compared to non-converters (N = 36). A model including sex, daily levodopa equivalent dose, and local thalamic inflation predicted conversion with good accuracy (AUC: 0.87, sensitivity: 88.9%, specificity: 77.8%). Exploratory analyses showed that local thalamic inflations were associated with larger medial thalamic sub-nuclei volumes and better cognitive performance. Resting-state analyses further revealed that converters had stronger thalamo-cortical coupling with limbic and cognitive regions pre-conversion, with a marked reduction in coupling over the two years. Finally, validation using the PPMI cohort suggested FOG-specific non-linear evolution of thalamic local volume. These findings provide markers of, and deeper insights into conversion to FOG, which may foster earlier intervention and better mobility for persons with PD.

Age-related GABAergic differences in the primary sensorimotor cortex: A multimodal approach combining PET, MRS and TMS.

Healthy aging is associated with mechanistic changes in gamma-aminobutyric acid (GABA), the most abundant inhibitory neurotransmitter in the human brain. While previous work mainly focused on magnetic resonance spectroscopy (MRS)-based GABA+ levels and transcranial magnetic stimulation (TMS)-based GABAA receptor (GABAAR) activity in the primary sensorimotor (SM1) cortex, the aim of the current study was to identify age-related differences in positron emission tomography (PET)-based GABAAR availability and its relationship with GABA+ levels (i.e. GABA with the contribution of macromolecules) and GABAAR activity. For this purpose, fifteen young (aged 20-28 years) and fifteen older (aged 65-80 years) participants were recruited. PET and MRS images were acquired using simultaneous time-of-flight PET/MR to evaluate age-related differences in GABAAR availability (distribution volume ratio with pons as reference region) and GABA+ levels. TMS was applied to identify age-related differences in GABAAR activity by measuring short-interval intracortical inhibition (SICI). Whereas GABAAR availability was significantly higher in the SM cortex of older as compared to young adults (18.5%), there were neither age-related differences in GABA+ levels nor SICI. A correlation analysis revealed no significant associations between GABAAR availability, GABAAR activity and GABA+ levels. Although the exact mechanisms need to be further elucidated, it is possible that a higher GABAAR availability in older adults is a compensatory mechanism to ensure optimal inhibitory functionality during the aging process.

Prefronto-Striatal Structural Connectivity Mediates Adult Age Differences in Action Selection.

In complex everyday environments, action selection is critical for optimal goal-directed behavior. This refers to the process of choosing a proper action from the range of possible alternatives. The neural mechanisms underlying action selection and how these are affected by normal aging remain to be elucidated. In the present cross-sectional study, we studied processes of effector selection during a multilimb reaction time task in a lifespan sample of healthy human adults (N = 89; 20-75 years; 48 males, 41 females). Participants were instructed to react as quickly and accurately as possible to visually cued stimuli representing single-limb or combined upper and/or lower limb motions. Diffusion MRI was used to study structural connectivity between prefrontal and striatal regions as critical nodes for action selection. Behavioral findings revealed that increasing age was associated with slowing of action selection performance. At the neural level, aging had a negative impact on prefronto-striatal connectivity. Importantly, mediation analyses revealed that the negative association between action selection performance and age was mediated by prefronto-striatal connectivity, specifically the connections between left rostral medial frontal gyrus and left nucleus accumbens as well as right frontal pole and left caudate. These results highlight the potential role of prefronto-striatal white matter decline in poorer action selection performance of older adults.SIGNIFICANCE STATEMENT As a result of enhanced life expectancy, researchers have devoted increasing attention to the study of age-related alterations in cognitive and motor functions. Here we study associations between brain structure and behavior to reveal the impact of central neural white matter changes as a function of normal aging on action selection performance. We demonstrate the critical role of a reduction in prefronto-striatal structural connectivity in accounting for action selection performance deficits in healthy older adults. Preserving this cortico-subcortical pathway may be critical for behavioral flexibility and functional independence in older age.

The role of the PMd in task complexity: functional connectivity is modulated by motor learning and age.

The dorsal premotor cortex (PMd) plays a key role in the control and learning of motor tasks, especially when task complexity is high. This study sought to investigate the effect of task complexity on PMd-seeded functional connectivity in the context of aging using psychophysiological interaction analyses. Young and older participants were enrolled in a 3-day training protocol whereby task-related functional magnetic resonance imaging data were acquired. During training, movement was either internally generated or externally generated in the absence or presence of online visual feedback, respectively. Behavioral results indicated that older adults tended to have more difficulties with the complex task variants as compared with young adults. On a neural level, older adults demonstrated difficulties in flexibly adjusting their neural resources dependent on the feedback provided. Furthermore, PMd-seeded connectivity was related to a behavioral task complexity index in both age groups, albeit mediated by age. Together, these results highlight the importance of PMd in adaptability to task complexity and its age-related effects.

Reduced Modulation of Task-Related Connectivity Mediates Age-Related Declines in Bimanual Performance.

Aging is accompanied by marked changes in motor behavior and its neural correlates. At the behavioral level, age-related declines in motor performance manifest, for example, as a reduced capacity to inhibit interference between hands during bimanual movements, particularly when task complexity increases. At the neural level, aging is associated with reduced differentiation between distinct functional systems. Functional connectivity (FC) dedifferentiation is characterized by more homogeneous connectivity patterns across various tasks or task conditions, reflecting a reduced ability of the aging adult to modulate brain activity according to changing task demands. It is currently unknown, however, how whole-brain dedifferentiation interacts with increasing task complexity. In the present study, we investigated age- and task-related FC in a group of 96 human adults across a wide age range (19.9-74.5 years of age) during the performance of a bimanual coordination task of varying complexity. Our findings indicated stronger task complexity-related differentiation between visuomotor- and nonvisuomotor-related networks, though modulation capability decreased with increasing age. Decreased FC modulation mediated larger complexity-related increases in between-hand interference, reflective of worse bimanual coordination. Thus, the ability to maintain high motor performance levels in older adults is related to the capability to properly segregate and modulate functional networks.