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Primary and secondary process mentation: Two modes of acting and thinking from Freud to modern neurosciences The purpose of this study is to return to Freud’s original descriptions of the primary and secondary processes in the light of modern neurosciences. In his Project for a Scientific Psychology, Freud draws the axes of the architecture of a mental apparatus: on a horizontal plane, the primary process transfers the excitation by impinging stimuli over a sequence of analogous states towards their discharge; thus, the primary process is essentially characterized by its associative tendency. On a vertical plane, the secondary process opposes the primary bottom-up pressure by a top-down inhibition with its origins in the purposive idea: the secondary process is essentially characterized by its inhibitory interventions. Freud later proposed that the primary and secondary process are seeking for perceptual, respectively thought identity. These different elements are coherent with the dynamics of the ventral and dorsal brain pathways respectively. Moreover, the dorsal pathway has an inhibitory influence upon the ventral pathway, much like the secondary has upon the primary. This influence is exerted thanks to what Freud called the “indications of reality.” We propose to equate these indications with the efference copies in modern neurosciences since they proceed from the same physiology and have the same function, besides originating from the same Helmholtzian source. Finally, even if both primary and secondary processes serve the death drive through the pleasure and the reality principle respectively, only the secondary process, requiring the bearing of an accumulation of excitations, also serves the life drive.

Cleaning up the Brickyard: How Theory and Methodology Shape Experiments in Cognitive Neuroscience of Language The capacity for language is a defining property of our species, yet despite decades of research, evidence on its neural basis is still mixed and a generalized consensus is difficult to achieve. We suggest that this is partly caused by researchers defining “language” in different ways, with focus on a wide range of phenomena, properties, and levels of investigation. Accordingly, there is very little agreement among cognitive neuroscientists of language on the operationalization of fundamental concepts to be investigated in neuroscientific experiments. Here, we review chains of derivation in the cognitive neuroscience of language, focusing on how the hypothesis under consideration is defined by a combination of theoretical and methodological assumptions. We first attempt to disentangle the complex relationship between linguistics, psychology, and neuroscience in the field. Next, we focus on how conclusions that can be drawn from any experiment are inherently constrained by auxiliary assumptions, both theoretical and methodological, on which the validity of conclusions drawn rests. These issues are discussed in the context of classical experimental manipulations as well as study designs that employ novel approaches such as naturalistic stimuli and computational modeling. We conclude by proposing that a highly interdisciplinary field such as the cognitive neuroscience of language requires researchers to form explicit statements concerning the theoretical definitions, methodological choices, and other constraining factors involved in their work.

Language comprehenders are sensitive to multiple states of semantically similar objects The present research shows that language comprehenders are sensitive to multiple states of target and semantically related objects. In Experiments 1 to 2B, participants (total N = 273) read sentences that either implied a minimal change of an object’s state (e.g., “Jane chose a mango”) or a substantial change (e.g., “Jane stepped on a mango”) and then verified whether a subsequently pictured object was mentioned in the sentence. Crucially, the picture either showed the original/modified state of an object that was mentioned in the sentence (e.g., “mango” in Experiment 1) or not (e.g., “banana” in Experiments 2A and 2B). The results of Experiment 1 demonstrated that the objects in a modified state were verified faster when a sentence implied a substantial state-change rather than a minimal state-change. In contrast, the reverse was true for the objects in the original state. Importantly, verification latencies of pictures depicting original and modified states of an object in the substantial state-change condition were approximately similar, thus suggesting that language comprehenders maintain multiple representations of an object in different states. The results of Experiments 2A and 2B revealed that when participants had to indicate that a pictured object (e.g., banana) was not mentioned in the sentence, their verification latencies were slowed down when the sentence contained a semantically related item (e.g., mango) and described this item as being changed substantially by the action. However, these verification latencies varied continuously with the degree of change: the more dissimilar the states of a semantically related item, the less time participants needed to verify a pictured object. The results are discussed through the prism of theories emphasizing dynamic views of event cognition.

Interpreting Rhythm as Parsing: Syntactic-Processing Operations Predict the Migration of Visual Flashes as Perceived During Listening to Musical Rhythms Music can be interpreted by attributing syntactic relationships to sequential musical events, and, computationally, such musical interpretation represents an analogous combinatorial task to syntactic processing in language. While this perspective has been primarily addressed in the domain of harmony, we focus here on rhythm in the Western tonal idiom, and we propose for the first time a framework for modeling the moment-by-moment execution of processing operations involved in the interpretation of music. Our approach is based on (1) a music-theoretically motivated grammar formalizing the competence of rhythmic interpretation in terms of three basic types of dependency (preparation, syncopation, and split; Rohrmeier, 2020), and (2) psychologically plausible predictions about the complexity of structural integration and memory storage operations, necessary for parsing hierarchical dependencies, derived from the dependency locality theory (Gibson, 2000). With a behavioral experiment, we exemplify an empirical implementation of the proposed theoretical framework. One hundred listeners were asked to reproduce the location of a visual flash presented while listening to three rhythmic excerpts, each exemplifying a different interpretation under the formal grammar. The hypothesized execution of syntactic-processing operations was found to be a significant predictor of the observed displacement between the reported and the objective location of the flashes. Overall, this study presents a theoretical approach and a first empirical proof-of-concept for modeling the cognitive process resulting in such interpretation as a form of syntactic parsing with algorithmic similarities to its linguistic counterpart. Results from the present small-scale experiment should not be read as a final test of the theory, but they are consistent with the theoretical predictions after controlling for several possible confounding factors and may form the basis for further large-scale and ecological testing.

Functional and anatomical connectivity predict brain stimulation’s mnemonic effects Closed-loop direct brain stimulation is a promising tool for modulating neural activity and behavior. However, it remains unclear how to optimally target stimulation to modulate brain activity in particular brain networks that underlie particular cognitive functions. Here, we test the hypothesis that stimulation’s behavioral and physiological effects depend on the stimulation target’s anatomical and functional network properties. We delivered closed-loop stimulation as 47 neurosurgical patients studied and recalled word lists. Multivariate classifiers, trained to predict momentary lapses in memory function, triggered the stimulation of the lateral temporal cortex (LTC) during the study phase of the task. We found that LTC stimulation specifically improved memory when delivered to targets near white matter pathways. Memory improvement was largest for targets near white matter that also showed high functional connectivity to the brain’s memory network. These targets also reduced low-frequency activity in this network, an established marker of successful memory encoding. These data reveal how anatomical and functional networks mediate stimulation’s behavioral and physiological effects, provide further evidence that closed-loop LTC stimulation can improve episodic memory, and suggest a method for optimizing neuromodulation through improved stimulation targeting.

Decoding motor plans using a closed-loop ultrasonic brain–machine interface Brain–machine interfaces (BMIs) enable people living with chronic paralysis to control computers, robots and more with nothing but thought. Existing BMIs have trade-offs across invasiveness, performance, spatial coverage and spatiotemporal resolution. Functional ultrasound (fUS) neuroimaging is an emerging technology that balances these attributes and may complement existing BMI recording technologies. In this study, we use fUS to demonstrate a successful implementation of a closed-loop ultrasonic BMI. We streamed fUS data from the posterior parietal cortex of two rhesus macaque monkeys while they performed eye and hand movements. After training, the monkeys controlled up to eight movement directions using the BMI. We also developed a method for pretraining the BMI using data from previous sessions. This enabled immediate control on subsequent days, even those that occurred months apart, without requiring extensive recalibration. These findings establish the feasibility of ultrasonic BMIs, paving the way for a new class of less-invasive (epidural) interfaces that generalize across extended time periods and promise to restore function to people with neurological impairments.

Motor Activity-Induced White Matter Repair in White Matter Stroke Subcortical white matter stroke (WMS) is a progressive disorder which is demarcated by the formation of small ischemic lesions along white matter tracts in the CNS. As lesions accumulate, patients begin to experience severe motor and cognitive decline. Despite its high rate of incidence in the human population, our understanding of the cause and outcome of WMS is extremely limited. As such, viable therapies for WMS remain to be seen. This study characterizes myelin recovery following stroke and motor learning-based rehabilitation in a mouse model of subcortical WMS. Following WMS, a transient increase in differentiating oligodendrocytes occurs within the peri-infarct in young male adult mice, which is completely abolished in male aged mice. Compound action potential recording demonstrates a decrease in conduction velocity of myelinated axons at the peri-infarct. Animals were then tested on one of three distinct motor learning-based rehabilitation strategies (skilled reach, restricted access to a complex running wheel, and unrestricted access to a complex running wheel) for their capacity to induce repair. These studies determined that unrestricted access to a complex running wheel alone increases the density of differentiating oligodendrocytes in infarcted white matter in young adult male mice, which is abolished in aged male mice. Unrestricted access to a complex running wheel was also able to enhance conduction velocity of myelinated axons at the peri-infarct to a speed comparable to naive controls suggesting functional recovery. However, there was no evidence of motor rehabilitation-induced remyelination or myelin protection.

Ca2+ regulation of glutamate release from inner hair cells of hearing mice In our hearing organ, sound is encoded at ribbon synapses formed by inner hair cells (IHCs) and spiral ganglion neurons (SGNs). How the underlying synaptic vesicle (SV) release is controlled by Ca2+ in IHCs of hearing animals remained to be investigated. Here, we performed patch-clamp SGN recordings of the initial rate of release evoked by brief IHC Ca2+-influx in an ex vivo cochlear preparation from hearing mice. We aimed to closely mimic physiological conditions by perforated-patch recordings from IHCs kept at the physiological resting potential and at body temperature. We found release to relate supralinearly to Ca2+-influx (power, m: 4.3) when manipulating the [Ca2+] available for SV release by Zn2+-flicker-blocking of the single Ca2+-channel current. In contrast, a near linear Ca2+ dependence (m: 1.2 to 1.5) was observed when varying the number of open Ca2+-channels during deactivating Ca2+-currents and by dihydropyridine channel-inhibition. Concurrent changes of number and current of open Ca2+-channels over the range of physiological depolarizations revealed m: 1.8. These findings indicate that SV release requires ~4 Ca2+-ions to bind to their Ca2+-sensor of fusion. We interpret the near linear Ca2+-dependence of release during manipulations that change the number of open Ca2+-channels to reflect control of SV release by the high [Ca2+] in the Ca2+-nanodomain of one or few nearby Ca2+-channels. We propose that a combination of Ca2+ nanodomain control and supralinear intrinsic Ca2+-dependence of fusion optimally links SV release to the timing and amplitude of the IHC receptor potential and separates it from other IHC Ca2+-signals unrelated to afferent synaptic transmission.