Maternal Parenting Distress Associated With Offspring Altered Dentate Gyrus Microstructure, Dentate Gyrus-Orbitofrontal Functional Connectivity and Decreased Cognitive Flexibility

Cognitive flexibility, the ability to appropriately adjust behavior in a changing environment, has been challenging to operationalize and validate in cognitive neuroscience studies. Here, we investigate neural activation and directed functional connectivity underlying cognitive flexibility using an fMRI-adapted version of the Flexible Item Selection Task (FIST) in adults ( n = 32, ages 19–46 years). The fMRI-adapted FIST was reliable, showed comparable performance to the computer-based version of the task, and produced robust activation in frontoparietal, anterior cingulate, insular, and subcortical regions. During flexibility trials, participants directly engaged the left inferior frontal junction, which influenced activity in other cortical and subcortical regions. The strength of intrinsic functional connectivity between select brain regions was related to individual differences in performance on the FIST, but there was also significant individual variability in functional network topography supporting cognitive flexibility. Taken together, these results suggest that the FIST is a valid measure of cognitive flexibility, which relies on computations within a broad corticosubcortical network driven by inferior frontal junction engagement.

Download Full-text

Cortical and thalamic influences on striatal involvement in instructed, serial reversal learning; implications for the organisation of flexible behaviour.

10.1101/2021.12.20.472804 ◽

2021 ◽

Author(s):

Brendan Williams ◽

Anastasia Christakou

Keyword(s):

Functional Connectivity ◽

Cognitive Flexibility ◽

Reversal Learning ◽

Orbitofrontal Cortex ◽

Dorsal Striatum ◽

Response Strategy ◽

Flexible Control ◽

The Right ◽

Serial Reversal

Cognitive flexibility is essential for enabling an individual to respond adaptively to changes in their environment. Evidence from human and animal research suggests that the control of cognitive flexibility is dependent on an array of neural architecture. Cortico-basal ganglia circuits have long been implicated in cognitive flexibility. In particular, the role of the striatum is pivotal, acting as an integrative hub for inputs from the prefrontal cortex and thalamus, and modulation by dopamine and acetylcholine. Striatal cholinergic modulation has been implicated in the flexible control of behaviour, driven by input from the centromedian-parafascicular nuclei of the thalamus. However, the role of this system in humans is not clearly defined as much of the current literature is based on animal work. Here, we aim to investigate the roles corticostriatal and thalamostriatal connectivity in serial reversal learning. Functional connectivity between the left centromedian-parafascicular nuclei and the associative dorsal striatum was significantly increased for negative feedback compared to positive feedback. Similar differences in functional connectivity were observed for the right lateral orbitofrontal cortex, but these were localised to when participants switched to using an alternate response strategy following reversal. These findings suggest that connectivity between the centromedian-parafascicular nuclei and the striatum may be used to generally identify potential changes in context based on negative outcomes, and the effect of this signal on striatal output may be influenced by connectivity between the lateral orbitofrontal cortex and the striatum.

Download Full-text

P04.56 Brain tumor patients with impaired cognitive flexibility do not efficiently update functional connectivity within the fronto-parietal network

Neuro-Oncology ◽

10.1093/neuonc/noy139.290 ◽

2018 ◽

Vol 20 (suppl_3) ◽

pp. iii292-iii292

Author(s):

W de Baene ◽

J M Jansma ◽

G Rutten ◽

M M Sitskoorn

Keyword(s):

Brain Tumor ◽

Functional Connectivity ◽

Cognitive Flexibility ◽

Tumor Patients

Download Full-text

Vangl2, a core component of the WNT/PCP pathway, regulates adult hippocampal neurogenesis and age-related decline in cognitive flexibility

10.1101/2021.01.05.425435 ◽

2021 ◽

Author(s):

M Koehl ◽

E Ladevèze ◽

M Montcouquiol ◽

DN Abrous

Keyword(s):

Episodic Memory ◽

Dentate Gyrus ◽

Cognitive Flexibility ◽

Adult Neurogenesis ◽

Continuous Production ◽

Hippocampal Neurogenesis ◽

Adult Hippocampal Neurogenesis ◽

Core Component ◽

Dominant Negative Mutation ◽

Age Related

AbstractDecline in episodic memory is one of the hallmarks of aging and represents one of the most important health problems facing western societies. A key structure in episodic memory is the hippocampal formation and the dentate gyrus in particular, as the continuous production of new dentate granule neurons in this brain region was found to play a crucial role in memory and in age-related decline in memory. As such, understanding the molecular processes that regulate the relationship between adult neurogenesis and aging of memory function holds great therapeutic potential. Recently, we found that Vang-gogh like 2 (Vangl2), a core component of the planar cell polarity signaling pathway, is enriched in the dentate gyrus of adult mice. In this context, we sought to evaluate the involvement of this effector of the Wnt/PCP pathway in both adult neurogenesis and memory abilities in adult and middle-aged mice. Using a heterozygous mouse model carrying a dominant negative mutation in Vangl2 gene, we show that alteration in Vangl2 expression decreases the survival of adult-born granule cells and advances the onset of decrease in cognitive flexibility. Inability of mutant mice to erase old irrelevant information to the benefit of new relevant ones highlights a key role of Vangl2 in interference-based forgetting. Taken together, our findings show for the first that Vangl2 activity may constitute an interesting target to prevent age-related decline in hippocampal plasticity and memory.

Download Full-text

Rapid stimulation of human dentate gyrus function with acute mild exercise

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1805668115 ◽

2018 ◽

Vol 115 (41) ◽

pp. 10487-10492 ◽

Cited By ~ 38

Author(s):

Kazuya Suwabe ◽

Kyeongho Byun ◽

Kazuki Hyodo ◽

Zachariah M. Reagh ◽

Jared M. Roberts ◽

...

Keyword(s):

Functional Connectivity ◽

Dentate Gyrus ◽

Acute Exercise ◽

Memory Performance ◽

Memory Function ◽

Pattern Separation ◽

Treadmill Running ◽

Intensity Level ◽

Individual Subject ◽

The Impact

Physical exercise has beneficial effects on neurocognitive function, including hippocampus-dependent episodic memory. Exercise intensity level can be assessed according to whether it induces a stress response; the most effective exercise for improving hippocampal function remains unclear. Our prior work using a special treadmill running model in animals has shown that stress-free mild exercise increases hippocampal neuronal activity and promotes adult neurogenesis in the dentate gyrus (DG) of the hippocampus, improving spatial memory performance. However, the rapid modification, from mild exercise, on hippocampal memory function and the exact mechanisms for these changes, in particular the impact on pattern separation acting in the DG and CA3 regions, are yet to be elucidated. To this end, we adopted an acute-exercise design in humans, coupled with high-resolution functional MRI techniques, capable of resolving hippocampal subfields. A single 10-min bout of very light-intensity exercise (30%V˙O2peak) results in rapid enhancement in pattern separation and an increase in functional connectivity between hippocampal DG/CA3 and cortical regions (i.e., parahippocampal, angular, and fusiform gyri). Importantly, the magnitude of the enhanced functional connectivity predicted the extent of memory improvement at an individual subject level. These results suggest that brief, very light exercise rapidly enhances hippocampal memory function, possibly by increasing DG/CA3−neocortical functional connectivity.

Download Full-text

Adult-born neurons promote cognitive flexibility by improving memory precision and indexing

10.1101/2020.08.10.242966 ◽

2020 ◽

Author(s):

Gabriel Berdugo-Vega ◽

Chi-Chieh Lee ◽

Alexander Garthe ◽

Gerd Kempermann ◽

Federico Calegari

Keyword(s):

Stem Cells ◽

Dentate Gyrus ◽

Cognitive Flexibility ◽

Spatial Information ◽

Differential Regulation ◽

Memory Representations ◽

Adult Born Neurons ◽

Navigational Learning ◽

Memory Precision

SUMMARYThe dentate gyrus (DG) of the hippocampus is fundamental for cognitive flexibility and has the extraordinary ability to generate new neurons throughout life. Recent evidence suggested that adult-born neurons differentially modulate input to the DG during the processing of spatial information and novelty. However, how this differential regulation by neurogenesis is translated into different aspects contributing cognitive flexibility is unclear. Here, we increased adult-born neurons by a genetic expansion of neural stem cells and studied their influence during navigational learning. We found that increased neurogenesis improved memory precision, indexing and retention and that each of these gains was associated with a differential activation of specific DG compartments and better separation of memory representations in the DG-CA3 network. Our results highlight the role of adult-born neurons in promoting memory precision in the infrapyramidal and indexing in the suprapyramidal blade of the DG and together contributing to cognitive flexibility.One sentence summaryNeurogenesis improves memory precision and indexing.

Download Full-text

Fronto-striatal circuits for cognitive flexibility in far from onset Huntington’s disease: evidence from the Young Adult Study

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2020-324104 ◽

2020 ◽

pp. jnnp-2020-324104 ◽

Cited By ~ 1

Author(s):

Christelle Langley ◽

Sarah Gregory ◽

Katie Osborne-Crowley ◽

Claire O'Callaghan ◽

Paul Zeun ◽

...

Keyword(s):

Young Adult ◽

Functional Connectivity ◽

Huntington's Disease ◽

Huntington’S Disease ◽

Cognitive Flexibility ◽

Study Cohort ◽

Set Shifting ◽

Attentional Set ◽

Adult Study ◽

Attentional Set Shifting

ObjectivesCognitive flexibility, which is key for adaptive decision-making, engages prefrontal cortex (PFC)-striatal circuitry and is impaired in both manifest and premanifest Huntington’s disease (pre-HD). The aim of this study was to examine cognitive flexibility in a far from onset pre-HD cohort to determine whether an early impairment exists and if so, whether fronto-striatal circuits were associated with this deficit.MethodsIn the present study, we examined performance of 51 pre-HD participants (mean age=29.22 (SD=5.71) years) from the HD Young Adult Study cohort and 53 controls matched for age, sex and IQ, on the Cambridge Neuropsychological Test Automated Battery (CANTAB) Intra-Extra Dimensional Set-Shift (IED) task. This cohort is unique as it is the furthest from disease onset comprehensively studied to date (mean years=23.89 (SD=5.96) years). The IED task measures visual discrimination learning, cognitive flexibility and specifically attentional set-shifting. We used resting-state functional MRI to examine whether the functional connectivity between specific fronto-striatal circuits was dysfunctional in pre-HD, compared with controls, and whether these circuits were associated with performance on the critical extradimensional shift stage.ResultsOur results demonstrated that the CANTAB IED task detects a mild early impairment in cognitive flexibility in a pre-HD group far from onset. Attentional set-shifting was significantly related to functional connectivity between the ventrolateral PFC and ventral striatum in healthy controls and to functional connectivity between the dorsolateral PFC and caudate in pre-HD participants.ConclusionWe postulate that this incipient impairment of cognitive flexibility may be associated with intrinsically abnormal functional connectivity of fronto-striatal circuitry in pre-HD.

Download Full-text