Mathematics Meets Science in the Brain.

Our ability to perform a variety of difficult tasks everything from reasoning about the best chess move, to shooting a free throw, or finely dicing an onion is due to the coordinated activity of populations of neurons throughout the nervoussystem. And yet, we lack an understanding of how the brain generates the activity appropriate for achieving something as simple as pressing an elevator button. In part, this is because we do not know which neural activity patterns the brain is capable of generating, nor how that activity will change with experience. By exploring the structure and constraints on the activity patterns the brain can express, we move closer to understanding how the brain can generate the activity supportive of such a rich variety of behaviors and adaptations. Presently, in studies of arm or eye movements, we typically don't know the causal relationship between neural activity and behavior. Here we use a brain-computer interface (BCI) paradigm to study learning, because the exact relationship between neural activity and behavior is controlled by the experimenter. To generate proficient behavior, the animal must change the activity of the neurons currently being recorded. This provides us with the means to causally relate any observed structure in neural population activity with animals' performance at the task. The focus of this thesis is to characterize the structure and time course of neural population activity during learning. In the first part of this thesis, we note that just as there is more than one way to win a game of chess, the brain has many differentpatterns of neural activity it can produce to drive the same behavior. Which of these redundant options does the brain prefer? We find that the frequency with which animals used different patterns of neural population activity was remarkably similar before and after learning. This suggests that the brain's ability to take advantage of redundancy may be somewhat limited, at least within the span of a few hours. In the second part of this thesis, we asked how internal states such as our arousal, attention, and motivation interact with how we learn new tasks. We identified large, abrupt fluctuations in neural population activity in motor cortex indicative of arousal-like internal state changes, which we term \neural engagement. We find that stereotyped changes in neural engagement during learning were unrelated to goal-seeking behavior, but nevertheless influenced how quickly different tasks were learned. Overall, this thesis characterizes a variety of different constraints and influences on how populations of neurons change their activity during learning.

Traumatic brain injury (TBI) is a leading cause of disability and death and survivors often suffer from long-lasting motor impairment, cognitive deficits, anxiety disorders and epilepsy. Few experimental studies have investigated long-term sequelae after TBI and relations between behavioral changes and neural activity patterns remain elusive. We examined these issues in a murine model of TBI combining histology, behavioral analyses and single-photon emission computed tomography (SPECT) imaging of regional cerebral blood flow (CBF) as a proxy for neural activity. Adult C57Bl/6N mice were subjected to unilateral cortical impact injury and investigated at early (15-57days after lesion, dal) and late (184-225 dal) post-traumatic time points. TBI caused pronounced tissue loss of the parietal cortex and subcortical structures and enduring neurological deficits. Marked perilesional astro- and microgliosis was found at 57 dal and declined at 225 dal. Motor and gait pattern deficits occurred at early time points after TBI and improved over the time. In contrast, impaired performance in the Morris water maze test and decreased anxiety-like behavior persisted together with an increased susceptibility to pentylenetetrazole-induced seizures suggesting alterations in neural activity patterns. Accordingly, SPECT imaging of CBF indicated asymmetric hemispheric baseline neural activity patterns. In the ipsilateral hemisphere, increased baseline neural activity was found in the amygdala. In the contralateral hemisphere, homotopic to the structural brain damage, the hippocampus and distinct cortex regions displayed increased baseline neural activity. Thus, regionally elevated CBF along with behavioral alterations indicate that increased neural activity is critically involved in the long-lasting consequences of TBI.

A novel method of recording neural activity from the rodent medial prefrontal cortex reveals that the medial prefrontal cortex is composed of functionally distinct subregions that process economic decision information differentially along a dorso-ventral gradient.

Associations Between Parenting Behavior and Neural Processing of Adolescent Faces in Mothers With and Without Depression

BackgroundNew daily persistent headache (NDPH) is a rare but debilitating primary headache disorder that poses a significant burden on individuals and society. Despite its clinical importance, the underlying pathophysiological mechanisms of NDPH remain unclear. In this study, we aimed to investigate the brain structural changes and neural activity patterns in patients with NDPH using multimodal brain imaging analysis of structural magnetic resonance imaging (sMRI) combined with magnetoencephalography (MEG).MethodsTwenty-eight patients with NDPH and 37 healthy controls (HCs) were recruited for this study, and their structural and resting-state data were collected by 3.0 Tesla MRI and MEG. We analyzed the brain morphology using voxel-based morphometry and source-based morphometry. In each brain region, MEG sensor signals from 1 to 200 Hz were analyzed using an adapted version of Welch's method. MEG source localization was conducted using the dynamic statistical parametric mapping, and the difference of source distribution between patients with NDPH and HCs was examined.ResultsOur results revealed significant differences in the regional grey matter volume, cortical thickness, and cortical surface area between the two groups. Specifically, compared with HCs, patients with NDPH showed a significant decrease in cortical thickness of the left rostral cortex in the middle frontal gyrus, decreased cortical surface area of the left fusiform gyrus, decreased grey matter volume of the left superior frontal gyrus and the left middle frontal gyrus, and increased grey matter volume of the left calcarine. Furthermore, the power of the whole brain, bilateral frontal lobes, and right temporal lobe in the NDPH group were higher than that in HCs in the ripple frequency band (80-200 Hz). Functional and structural analysis suggested that there were structural changes and abnormal high frequency cortical activity in both frontal and temporal lobes in patients with NDPH.ConclusionOur findings indicated that patients with NDPH have abnormalities in brain morphology, such as cortical area, cortical thickness, and grey matter volume, accompanied by abnormal cortical neural activity. Brain structural changes in the frontotemporal cortex and abnormalities in cortical ripple activity may be involved in the pathogenesis of NDPH.

Objective To investigate the grey matter volume in patients with early adulthood episode (18-25 ages) schizophrenia and the correlations between regional volume and symptom severity. Methods Twenty-one schizophrenia patients with early adulthood episode and twenty-one normal controls matched with age, sex and education were recruited. The diagnosis of schizophrenia was made according to the Diagnostic and Statistical Manual of Mental Disorder the Fourth Edition (DSM-Ⅳ) criteria. Each participant received whole brain MRI scans, then the 3D brain structural MRI images were obtained. The grey matter volume difference between patients and controls was analyzed by using the optimized voxel-based morphometry method (VBM). Symptom severity were assessed using the Positive and Negative Syndrome Scale (PANSS), and the correlation with the grey matter volume were analyzed in the patients. Results Compared to the normal controls, the patients had multiple brain areas abnormal volume. It showed significant decreased grey matter volume in the left orbital gyrus（t=4.88，P<0.001）, left middle frontal gyrus（t=4.50，P<0.001）, left middle teporal gyrus（t=3.95，P<0.001）, right middle temporal gyrus ( t=3.92，P<0.001）, left superior parietal lobule（t=3.71，P<0.001）, left inferior parietal lobule（t=3.93，P<0.001） and right lingual gyrus/cuneus（t=3.65，P<0.001）. Within the patient group, total score of PANSS was positively correlated with grey matter volume of the right superior parietal lobule, but negatively correlated with the left pons/midbrain; and the positive symptom score was negatively related to grey matter volume of the right inferior parietal lobule; and the negative symptom score was positively correlated with grey matter volume of the right superior parietal lobule, bilateral precuneus, but negatively correlated with grey matter of the left pons/ midbrain; and the common score was negatively correlated with grey matter of the right inferior temporal gyrus, right inferior parietal lobule and left pons/midbrain. Conclusions These preliminary findings support that obvious multiple grey volume abnormality are in patients with early adulthood episode schizophrenia, and the gray matter volume of different brain regions are associated with symptoms severity. Key words: Schizophrenia; Magnetic resonance imaging; Grey matter; Voxel-based morphometry

Aging modulates large-scale neural network interactions during speech comprehension.

A method is presented for analyzing cochlear implant stimulations and typical representations used in simulations. Filtered "white-noise" bands are modulated using sinusoids, representing differing stimulation channels. These representations, along with their corresponding envelopes, are used to generate neural activation patterns (NAPs), which represent "normal-hearing" responses In the auditory nerve to these stimuli. Additionally, NAPs are generated to represent the neural activity induced by cochlear implant stimulation strategies, assuming exponential rolloff from the electrodes. The mean squared error is measured between NAPs both directly, and after compensation for perceptual resolution. Results suggest that the noise-band approximation of the CIS implant signal actually has more in common with the original source than with the implant stimulation patterns.

Frontostriatal neuroimaging findings differ in patients with bipolar disorder who have or do not have ADHD comorbidity

Creativity is a multifaceted cognitive process that can be driven by either malevolent or benevolent intentions, leading to divergent social outcomes. There is still uncertainty about the similarities and differences in the underlying neural activities of creativity associated with malevolent and benevolent intentions. This study investigates how intentions shape creative ideation using functional magnetic resonance imaging during malevolent and benevolent creative tasks. Key findings include: (i) overlapping activation in the middle frontal gyrus and superior frontal gyrus across tasks, indicating a shared neural basis for creative thinking; (ii) distinct activation patterns, with the malevolent creative task showing greater activation and reduced functional connectivity in regions such as the right rolandic operculum and supramarginal gyrus compared to the benevolent creative task; (iii) similar neural activity patterns in regions like the middle frontal gyrus and lingual gyrus between the malevolent creative task and benevolent creative task may indicate overlapping cognitive processes. (iv) Correlations between task-specific neural activity and behavioral performance, including malevolence negatively correlating with functional connectivity in the rolandic operculum and middle cingulate cortex during the malevolent creative task, and benevolence correlating with functional connectivity in the parahippocampal gyrus and insula during the benevolent creative task. This study indicated distinct and shared neural correlates linked to malevolent and benevolent creativity.

Neuroimaging studies on Parkinson's disease (PD) mainly focus on static neural activity. However, the dynamic pattern of regional brain activity in early-stage cognitively normal PD has rarely been elucidated. To identify altered dynamic amplitude of low-frequency fluctuation (dALFF) in PD before the onset of cognitive impairment and verify its differentiating ability between patients with PD and healthy controls (HC). dALFF and static ALFF (sALFF) derived from functional magnetic resonance imaging data of 51 patients with PD and 50 matched HCs were analyzed. The correlations between aberrant regions and clinical performance were investigated using Spearman correlation analysis. Multivariate pattern analysis was conducted to detect the differentiating ability of both ALFF features. Compared with HCs, patients with PD demonstrated reduced dALFF variance in bilateral lingual gyrus, left middle occipital gyrus, left postcentral gyrus (PcG), and right supplementary motor area (SMA); and increased dALFF variability in bilateral parahippocampal gyrus. Besides overlapping with these distributions of altered dALFF, the aberrant regions of sALFF were more extensive with decreased sALFF in the right middle temporal gyrus and right PcG, and increased sALFF in the left inferior temporal gyrus and left thalamus were observed in patients with PD. dALFF values in right SMA and left PcG were correlated with UPDRS-III scores (ρ = -0.29, P = 0.041; ρ = -0.33, P = 0.018, respectively). This study provides novel insights into the neural basis underlying PD as well as the potential role of dynamic neural activity in the diagnosis and prediction of the disease.

The bidirectional selection of high and low anxiety-like behavior is a valuable tool for understanding the neurocircuits that are responsible for anxiety disorders. Our group developed two breeding lines of rats, known as Carioca High- and Low-conditioned Freezing (CHF and CLF), based on defensive freezing in the contextual fear conditioning paradigm. A random selected line was employed as a control (CTL) comparison group for both CHF and CLF lines of animals. The present study performed Fos immunochemistry to investigate changes in neural activity in different brain structures among CHF and CLF rats when they were exposed to contextual cues that were previously associated with footshock. The study indicated that CHF rats expressed high Fos expression in the locus coeruleus, periventricular nucleus of the hypothalamus (PVN), and lateral portion of the septal area and low Fos expression in the medial portion of the septal area, dentate gyrus, and prelimbic cortex (PL) compared to CTL animals. CLF rats exhibited a decrease in Fos expression in the PVN, PL, and basolateral nucleus of the amygdala and increase in the cingulate and perirhinal cortices compared to CTL animals. Both CHF and CLF rats displayed Fos expression changes key regions of the anxiety brain circuitry. The two bidirectional lines exhibit different pattern of neural activation and inhibition with opposing influences on the PVN, the main structure involved in regulating the hypothalamic-pituitary-adrenal neuroendocrine responses observed in anxiety disorders.

Maternal love, which may be the core of maternal behavior, is essential for the mother–infant attachment relationship and is important for an infant’s development and mental health. Therefore, maternal love can be considered a vital human emotion. Using video clips, we examined patterns of maternal brain activation in response to infant cues. We performed functional magnetic resonance imaging (fMRI) measurements while 13 mothers viewed video clips of their own infants and other infants (all approximately 16 months of age) who demonstrated two different attachment behaviors. We found that a limited number of the mother’s brain areas were specifically involved in maternal love, namely orbitofrontal cortex (OFC), striatum, anterior insula, and periaqueductal gray (PAG). Then, we proposed a schematic model of maternal love, based on integration of the two systems in the OFC: the dopamine reward system (OFC, striatum) and the interoceptive information processing system (OFC, insula, PAG). Additionally, we found a strong and specific brain response in a mother viewing her distressed infant. The neural activation pattern was found in the dorsal OFC (dOFC), the dorsolateral prefrontal cortex (DLPFC), ventrolateral prefrontal cortex (VLPFC), dorsomedial prefrontal cortex (DMPFC), dorsal anterior cingulate cortex (dACC), posterior cingulate cortex (PCC), caudate nucleus, supplementary motor area (SMA), and posterior superior temporal sulcus/temporoparietal junction (pSTS/TPJ). These results showed a highly elaborate neural mechanism, based on the above neural basis of maternal love, mediating the diverse and complex maternal behaviors that mothers engage in when raising and protecting their own infants.

Different activity patterns for action and language within their shared neural areas: An fMRI study on action observation and language phonology

Analgesics are commonly used by older adults, raising the question of whether their use might contribute to dementia risk and neuropathologic changes of Alzheimer's disease (AD). The Adult Changes in Thought (ACT) study is a population-based study of brain aging and incident dementia among people 65 years or older who are community dwelling and not demented at entry. Amyloid-β (Aβ)42 and phospho-tau were quantified using Histelide in regions of cerebral cortex from 420 brain autopsies. Total standard daily doses of prescription opioid and non-aspirin nonsteroidal anti-inflammatory drug (NSAID) exposure during a defined 10-year exposure window were identified using automated pharmacy dispensing data and used to classify people as having no/low, intermediate, or high exposure. People with high NSAID exposure had significantly greater Aβ42 concentration in middle frontal gyrus and superior and middle temporal gyri, but not inferior parietal lobule; no Aβ42 regional concentration was associated with prescription opioid usage. People with high opioid usage had significantly greater concentration of phospho-tau in middle frontal gyrus than people with little-to-no opioid usage. Consistent with our previous studies, findings suggest that high levels of NSAID use in older individuals may promote Aβ42 accumulation in cerebral cortex.