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Arithmetic is a cornerstone of scientifically and technologically advanced human culture, but its neuronal mechanisms are poorly understood. Calculating with numbers requires temporary maintenance and manipulation of numerical information according to arithmetic rules. We explored the brain mechanisms involved in simple arithmetic operations by recording single-neuron activity from the medial temporal lobe of human subjects performing additions and subtractions. We found abstract and notation-independent codes for addition and subtraction in neuronal populations. The neuronal codes of arithmetic in different brain areas differed drastically. Decoders applied to time-resolved recordings demonstrate a static code in hippocampus based on persistently rule-selective neurons, in contrast to a dynamic code in parahippocampal cortex originating from neurons carrying rapidly changing rule information. The implementation of abstract arithmetic codes suggests different cognitive functions for medial temporal lobe regions in arithmetic. [Display omitted] • Single neurons in the human MTL show abstract codes for addition and subtraction • Time-resolved decoding analysis shows a dynamic code in the parahippocampal cortex • The hippocampus shows a static code based on persistently rule-selective neurons • Different codes suggest different cognitive functions of MTL regions in arithmetic Kutter et al. demonstrate abstract and notation-independent codes for addition and subtraction in neuronal populations in the human medial temporal lobe (MTL). A dynamic code in the parahippocampal cortex contrasts with a static code in the hippocampus, suggesting different cognitive functions for these MTL regions in arithmetic. [ABSTRACT FROM AUTHOR]

Summary Our human-specific symbolic number skills that underpin science and technology spring from nonsymbolic set size representations. Despite the significance of numerical competence, its single-neuron mechanisms in the human brain are unknown. We therefore recorded from single neurons in the medial temporal lobe of neurosurgical patients that performed a calculation task. We found that distinct groups of neurons represented either nonsymbolic or symbolic number, but not both number formats simultaneously. Numerical information could be decoded robustly from the population of neurons tuned to nonsymbolic number and with lower accuracy also from the population of neurons selective to number symbols. The tuning characteristics of selective neurons may explain why set size is represented only approximately in behavior, whereas number symbols allow exact assessments of numerical values. Our results suggest number neurons as neuronal basis of human number representations that ultimately give rise to number theory and mathematics. Highlights • Single neurons in the human medial temporal lobe (MTL) encode numerical information • Numerosity and abstract numerals are encoded by distinct neuronal populations • Numerosity representation shows a distance effect; numerals are encoded categorically • Representation of symbolic numerals may evolve from numerosity representations Kutter et al. show how nonsymbolic and symbolic numerical quantity is encoded in the human brain by neurons of the medial temporal lobe. The data support the hypothesis that high-level human numerical abilities are rooted in biologically determined mechanisms. [ABSTRACT FROM AUTHOR]

Summary Neural representations of specific stimuli rely on activity patterns in distributed neural assemblies [ 1–4 ]. According to one influential view, these assemblies are characterized by synchronized gamma-band activity (GBA) [ 5–11 ] that reflects stimulus-specific representations [ 12–14 ]. However, recent studies have shown that GBA is closely correlated with the overall amount of cellular activity and may be detrimental for precise representations of specific stimuli [ 15, 16 ]. Until now, the role of GBA for the formation of dynamically changing representations has been unknown. Here, we applied representational similarity analysis (RSA) [ 17 ] to intracranial electroencephalogram (iEEG) data from ten presurgical epilepsy patients to identify stimulus-specific neural representations. Patients first learned and then retrieved their paths through virtual houses. Dynamic representations were identified by the rapidly changing distributions of frequency-specific global (spatial) activity patterns across the brain. We found that GBA patterns during successful (but not unsuccessful) retrieval of one sequence were more similar to activity during encoding of that same sequence compared to other sequences. The contribution of individual electrodes to these global representations was correlated with local similarity in individual electrodes (i.e., with RSA across time). Moreover, time-resolved RSA values were negatively correlated with the magnitude of iEEG gamma power: RSA values were higher at time points when gamma power was reduced. Both global and local representations relied on a small proportion of electrodes. These results show that behaviorally relevant neural representations of specific dynamically changing stimuli can be tracked by iEEG recordings and that they are associated with reductions of gamma power. [ABSTRACT FROM AUTHOR]

Summary: The human brain is adept at anticipating upcoming events, but in a rapidly changing world, it is essential to detect and encode events that violate these expectancies. Unexpected events are more likely to be remembered than predictable events, but the underlying neural mechanisms for these effects remain unclear. We report intracranial EEG recordings from the hippocampus of epilepsy patients, and from the nucleus accumbens of depression patients. We found that unexpected stimuli enhance an early (187 ms) and a late (482 ms) hippocampal potential, and that the late potential is associated with successful memory encoding for these stimuli. Recordings from the nucleus accumbens revealed a late potential (peak at 475 ms), which increases in magnitude during unexpected items, but no subsequent memory effect and no early component. These results are consistent with the hypothesis that activity in a loop involving the hippocampus and the nucleus accumbens promotes encoding of unexpected events. [Copyright &y& Elsevier]

Recently, somatic recombination of human mitochondrial DNA (mtDNA) was discovered in skeletal muscle. To determine whether recombinant mtDNA molecules can be transmitted through the germ line, we investigated two families, each harboring two inherited heteroplasmic mtDNA mutations. Using allele-specific polymerase chain reaction and single-cell and single-molecule mutational analyses, we discovered, in both families, all four possible allelic combinations of the two heteroplasmic mutations (tetraplasmy), the hallmark of mtDNA recombination. We strongly suggest that these recombinant mtDNA molecules were inherited rather than de novo generated somatically, because they (1) are highly abundant and (2) are present in different tissues of maternally related family members, including young individuals. Moreover, the comparison of the complete mtDNA sequence of one of the families with database sequences revealed an irregular, nontreelike pattern of mutations, reminiscent of a reticulation. We therefore propose that certain reticulations of the human mtDNA phylogenetic tree might be explained by recombination of coexisting mtDNA molecules harboring multiple mutations. [ABSTRACT FROM AUTHOR]

The human medial temporal lobe (MTL) has been suggested to play a role in valuation. However, little is known about its role in binary decisions and metacognition. We performed two decision-making tasks while recording from neurons in the human MTL. During a break, subjects consumed their preferred food item to satiation and subsequently repeated both tasks. We identified both a persistent and a transient modulation of the neural activity. Two independent subpopulations of neurons showed a persistent correlation of their firing rates with either decision confidence or reaction times. Importantly, the changes in confidence and reaction time between experimental sets were accompanied by a correlated change in the neural activity, and this correlation lasted as long as it was relevant for the behavioral task. Previous studies have suggested a transient modulation of the neural activity in the human MTL correlated with subjective value. However, in our study, neither subjective value nor unsigned value could explain this transient activity better than the nutritional features of the stimuli, calling into question the role of the human MTL in valuation. • MTL neurons are modulated by confidence and reaction time in decision making • Independent subpopulations of neurons reflect confidence and reaction times • Correlations lasted for as long as they were relevant for the behavioral task • Transient changes in neuronal activity were not explained by value Unruh-Pinheiro et al. demonstrate both a persistent and a transient modulation of the neural activity in the human medial temporal lobe (MTL) during decision making. Persistent activity correlated with decision confidence and reaction time, but transient activity was not explained by value, calling into question the MTL's role in valuation. [ABSTRACT FROM AUTHOR]

Summary The neuronal mechanisms giving rise to conscious perception remain largely elusive [ 1 ]. It is known that the strength of single-neuron activity correlates with conscious perception, especially in anterior regions of the ventral pathway in non-human primates [ 2–4 ] and in the human medial temporal lobe (MTL) [ 5, 6 ]. It is unclear, however, whether single-neuron correlates of conscious perception are characterized solely by the magnitude of neuronal responses, and whether the correlates of perception are equally prominent across different regions of the human MTL. While recording from 2,735 neurons in 21 neurosurgical patients during 40 experimental sessions, we created experimental conditions in which otherwise identical visual stimuli are sometimes seen and sometimes not detected at all by means of the attentional blink, i.e., the phenomenon that the second of two target stimuli in close succession often goes unnoticed to conscious perception [ 7 ]. Remarkably, responses to unseen versus seen stimuli were delayed and temporally more dispersed, in addition to being attenuated in firing rate. This finding suggests precise timing of neuronal responses as a novel candidate physiological marker of conscious perception. In addition, we found modulation of neuronal response timing and strength in response to seen versus unseen stimuli to increase along an anatomical gradient from the posterior to the anterior MTL. Our results thus map out the neuronal correlates of conscious perception in the human MTL both in time and in space. [ABSTRACT FROM AUTHOR]