Journal: Nature neuroscience
Dopamine signaling is implicated in reinforcement learning, but the neural substrates targeted by dopamine are poorly understood. We bypassed dopamine signaling itself and tested how optogenetic activation of dopamine D1 or D2 receptor–expressing striatal projection neurons influenced reinforcement learning in mice. Stimulating D1 receptor–expressing neurons induced persistent reinforcement, whereas stimulating D2 receptor–expressing neurons induced transient punishment, indicating that activation of these circuits is sufficient to modify the probability of performing future actions.
Pregnancy involves radical hormone surges and biological adaptations. However, the effects of pregnancy on the human brain are virtually unknown. Here we show, using a prospective (‘pre’-‘post’ pregnancy) study involving first-time mothers and fathers and nulliparous control groups, that pregnancy renders substantial changes in brain structure, primarily reductions in gray matter (GM) volume in regions subserving social cognition. The changes were selective for the mothers and highly consistent, correctly classifying all women as having undergone pregnancy or not in-between sessions. Interestingly, the volume reductions showed a substantial overlap with brain regions responding to the women’s babies postpartum. Furthermore, the GM volume changes of pregnancy predicted measures of postpartum maternal attachment, suggestive of an adaptive process serving the transition into motherhood. Another follow-up session showed that the GM reductions endured for at least 2 years post-pregnancy. Our data provide the first evidence that pregnancy confers long-lasting changes in a woman’s brain.
It is currently not known whether caffeine has an enhancing effect on long-term memory in humans. We used post-study caffeine administration to test its effect on memory consolidation using a behavioral discrimination task. Caffeine enhanced performance 24 h after administration according to an inverted U-shaped dose-response curve; this effect was specific to consolidation and not retrieval. We conclude that caffeine enhanced consolidation of long-term memories in humans.
Dishonesty is an integral part of our social world, influencing domains ranging from finance and politics to personal relationships. Anecdotally, digressions from a moral code are often described as a series of small breaches that grow over time. Here we provide empirical evidence for a gradual escalation of self-serving dishonesty and reveal a neural mechanism supporting it. Behaviorally, we show that the extent to which participants engage in self-serving dishonesty increases with repetition. Using functional MRI, we show that signal reduction in the amygdala is sensitive to the history of dishonest behavior, consistent with adaptation. Critically, the extent of reduced amygdala sensitivity to dishonesty on a present decision relative to the previous one predicts the magnitude of escalation of self-serving dishonesty on the next decision. The findings uncover a biological mechanism that supports a ‘slippery slope’: what begins as small acts of dishonesty can escalate into larger transgressions.
Understanding normal brain aging and developing methods to maintain or improve cognition in older adults are major goals of fundamental and translational neuroscience. Here we show a core feature of cognitive decline-working-memory deficits-emerges from disconnected local and long-range circuits instantiated by theta-gamma phase-amplitude coupling in temporal cortex and theta phase synchronization across frontotemporal cortex. We developed a noninvasive stimulation procedure for modulating long-range theta interactions in adults aged 60-76 years. After 25 min of stimulation, frequency-tuned to individual brain network dynamics, we observed a preferential increase in neural synchronization patterns and the return of sender-receiver relationships of information flow within and between frontotemporal regions. The end result was rapid improvement in working-memory performance that outlasted a 50 min post-stimulation period. The results provide insight into the physiological foundations of age-related cognitive impairment and contribute to groundwork for future non-pharmacological interventions targeting aspects of cognitive decline.
Recent findings link fronto-temporal gamma electroencephalographic (EEG) activity to conscious awareness in dreams, but a causal relationship has not yet been established. We found that current stimulation in the lower gamma band during REM sleep influences ongoing brain activity and induces self-reflective awareness in dreams. Other stimulation frequencies were not effective, suggesting that higher order consciousness is indeed related to synchronous oscillations around 25 and 40 Hz.
The dentate gyrus (DG) is a region in the hippocampal formation whose function declines in association with human aging and is therefore considered to be a possible source of age-related memory decline. Causal evidence is needed, however, to show that DG-associated memory decline in otherwise healthy elders can be improved by interventions that enhance DG function. We addressed this issue by first using a high-resolution variant of functional magnetic resonance imaging (fMRI) to map the precise site of age-related DG dysfunction and to develop a cognitive task whose function localized to this anatomical site. Then, in a controlled randomized trial, we applied these tools to study healthy 50-69-year-old subjects who consumed either a high or low cocoa-containing diet for 3 months. A high-flavanol intervention was found to enhance DG function, as measured by fMRI and by cognitive testing. Our findings establish that DG dysfunction is a driver of age-related cognitive decline and suggest non-pharmacological means for its amelioration.
A decade after speech was first decoded from human brain signals, accuracy and speed remain far below that of natural speech. Here we show how to decode the electrocorticogram with high accuracy and at natural-speech rates. Taking a cue from recent advances in machine translation, we train a recurrent neural network to encode each sentence-length sequence of neural activity into an abstract representation, and then to decode this representation, word by word, into an English sentence. For each participant, data consist of several spoken repeats of a set of 30-50 sentences, along with the contemporaneous signals from ~250 electrodes distributed over peri-Sylvian cortices. Average word error rates across a held-out repeat set are as low as 3%. Finally, we show how decoding with limited data can be improved with transfer learning, by training certain layers of the network under multiple participants' data.
Using olfactory molecular specificity, we examined the inheritance of parental traumatic exposure, a phenomenon that has been frequently observed, but not understood. We subjected F0 mice to odor fear conditioning before conception and found that subsequently conceived F1 and F2 generations had an increased behavioral sensitivity to the F0-conditioned odor, but not to other odors. When an odor (acetophenone) that activates a known odorant receptor (Olfr151) was used to condition F0 mice, the behavioral sensitivity of the F1 and F2 generations to acetophenone was complemented by an enhanced neuroanatomical representation of the Olfr151 pathway. Bisulfite sequencing of sperm DNA from conditioned F0 males and F1 naive offspring revealed CpG hypomethylation in the Olfr151 gene. In addition, in vitro fertilization, F2 inheritance and cross-fostering revealed that these transgenerational effects are inherited via parental gametes. Our findings provide a framework for addressing how environmental information may be inherited transgenerationally at behavioral, neuroanatomical and epigenetic levels.
We describe convergent evidence from transcriptomics, morphology, and physiology for a specialized GABAergic neuron subtype in human cortex. Using unbiased single-nucleus RNA sequencing, we identify ten GABAergic interneuron subtypes with combinatorial gene signatures in human cortical layer 1 and characterize a group of human interneurons with anatomical features never described in rodents, having large ‘rosehip’-like axonal boutons and compact arborization. These rosehip cells show an immunohistochemical profile (GAD1+CCK+, CNR1-SST-CALB2-PVALB-) matching a single transcriptomically defined cell type whose specific molecular marker signature is not seen in mouse cortex. Rosehip cells in layer 1 make homotypic gap junctions, predominantly target apical dendritic shafts of layer 3 pyramidal neurons, and inhibit backpropagating pyramidal action potentials in microdomains of the dendritic tuft. These cells are therefore positioned for potent local control of distal dendritic computation in cortical pyramidal neurons.