Functional neuroanatomy of time-to-passage perception

The time until an approaching object passes the observer is referred to as time-to-passage (TTP). Accurate judgment of TTP is critical for visually guided navigation, such as when walking, riding a bicycle, or driving a car. Previous research has shown that observers are able to make TTP judgments in the absence of information about local retinal object expansion. In this paper we combine psychophysics and functional MRI (fMRI) to investigate the neural substrate of TTP processing. In a previous psychophysical study, we demonstrated that when local retinal expansion cues are not available, observers take advantage of multiple sources of information to judge TTP, such as optic flow and object retinal velocities, and integrate these cues through a flexible and economic strategy. To induce strategy changes, we introduced trials with motion but without coherent optic flow (0% coherence of the background), and trials with coherent, but noisy, optic flow (75% coherence of the background). In a functional magnetic resonance imaging (fMRI) study we found that coherent optic flow cues resulted in better behavioral performance as well as higher and broader cortical activations across the visual motion processing pathway. Blood oxygen-level-dependent (BOLD) signal changes showed significant involvement of optic flow processing in the precentral sulcus (PreCS), postcentral sulcus (PostCS) and middle temporal gyrus (MTG) across all conditions. Not only highly activated during motion processing, bilateral hMT areas also showed a complex pattern in TTP judgment processing, which reflected a flexible TTP response strategy.Accepted manuscrip

Integration Mechanisms for Heading Perception

Previous studies of heading perception suggest that human observers employ spatiotemporal pooling to accommodate noise in optic flow stimuli. Here, we investigated how spatial and temporal integration mechanisms are used for judgments of heading through a psychophysical experiment involving three different types of noise. Furthermore, we developed two ideal observer models to study the components of the spatial information used by observers when performing the heading task. In the psychophysical experiment, we applied three types of direction noise to optic flow stimuli to differentiate the involvement of spatial and temporal integration mechanisms. The results indicate that temporal integration mechanisms play a role in heading perception, though their contribution is weaker than that of the spatial integration mechanisms. To elucidate how observers process spatial information to extract heading from a noisy optic flow field, we compared psychophysical performance in response to random-walk direction noise with that of two ideal observer models (IOMs). One model relied on 2D screen-projected flow information (2D-IOM), while the other used environmental, i.e., 3D, flow information (3D-IOM). The results suggest that human observers compensate for the loss of information during the 2D retinal projection of the visual scene for modest amounts of noise. This suggests the likelihood of a 3D reconstruction during heading perception, which breaks down under extreme levels of noise

Global Flow Impacts Time-to-passage Judgments Based on Local Motion Cues

We assessed the effect of the coherence of optic flow on time-to-passage judgments in order to investigate the strategies that observers use when local expansion information is reduced or lacking. In the standard display, we presented a cloud of dots whose image expanded consistent with constant observer motion. The dots themselves, however, did not expand and were thus devoid of object expansion cues. Only the separations between the dots expanded. Subjects had to judge which of two colored target dots, presented at different simulated depths and lateral displacements would pass them first. Image velocities of the target dots were chosen so as to correlate with time-to-passage only some of the time. When optic flow was mainly incoherent, subjects’ responses were biased and relied on image velocities rather than on global flow analysis. However, the bias induced by misleading image velocity cues diminished as a function of the coherence of the optic flow. We discuss the results in the context of a global tau mechanism and settle a debate whether local expansion cues or optic flow analysis are the basis for time-to-passage estimation

Disrupted Resting-State Functional Connectivity in Medication-free Women with Postpartum Depression

Background: Women are at increased risk of developing depression in the postpartum, a time of gonadal steroid flux. Abnormalities of gonadal steroids have been identified in some depressed women at times of reproductive flux. Gonadal steroids modulate corticocortical and corticolimbic functional connectivity (FC) in healthy, non-puerperal subjects; however there are no published studies of FC in postpartum depression (PPD). Methods: Healthy comparison (HCS) (n=9) and medication-free subjects with unipolar PPD (n=8) were scanned at 3-9 weeks postpartum (using 3T Philips MRI) while ‘at rest’ with eyes open. Data analysis was carried out using SPM-8 and Data Processing Assistant for Resting-State fMRI (DPARSF) to perform seed based resting-state functional connectivity (rs-FC) analysis. Seeds were placed at bilateral anterior cingulate (ACC) and dorsolateral prefrontal cortices (DLPFC), hippocampi (HIPP) and amygdalae (AMYG). Correlation coefficients obtained from individual subject analysis were used in performing two-sample t-test to compare the two cohorts. Results: Functional connectivity maps revealed a more distributed pattern of connectivity with each seed (i.e. ACC, DLPFX, HIPP, and AMYG) for HCS than PPD. In PPD subjects as compared to HCS, there was attenuation of rs-FC between corticocortical and corticolimbic areas. Conclusions: In the early postpartum period, rs-FC patterns are disrupted in women with PPD in brain regions important for cognition, affect and the stress response. Larger studies are necessary to elucidate the role of disrupted neural connections in the pathophysiology of PPD and the potential modulatory role of gonadal steroids in women

Multi-modal approach for investigating brain and behavior changes in an animal model of traumatic brain injury

Utilization of novel approaches in imaging modalities are needed for enhancing diagnostic and therapeutic outcomes of persons suffering a traumatic brain injury (TBI). This study explored the feasibility of using functional magnetic resonance imaging (fMRI) in conjunction with behavioral measures to target dynamic changes in specific neural circuitries in an animal model of traumatic brain injury. Wistar rats were randomly assigned to one of two groups (traumatic brain injury / sham operation). TBI rats were subjected to the closed head injury (CHI) model. Any observable motor deficits and cognitive deficits associated with the injury were measured using Beam Walk and Morris Water Maze tests, respectively. fMRI was performed to assess the underlying post-traumatic cerebral anatomy and function in acute (24 hours after the injury) and chronic (7 and 21 days after the injury) phases. Beam Walk test results detected no significant differences in motor deficits between groups. Morris Water Maze test indicated that cognitive deficits persisted for the first week following injury and to a large extent, recovered thereafter. Resting state functional connectivity (rsFC) analysis detected initially diminished connectivity between cortical areas involved in cognition for the TBI group; however the connectivity patterns normalized at one week and remained so at three weeks post-injury timepoint. Taken together, we have demonstrated an objective in vivo marker for mapping functional brain changes correlated with injury-associated cognitive behavior deficits and offer an animal model for testing potential therapeutic interventions options

Bioenergetic Measurements in Children with Bipolar Disorder: A Pilot 31^{31}P Magnetic Resonance Spectroscopy Study

Background: Research exploring Bipolar Disorder (BD) phenotypes and mitochondrial dysfunction, particularly in younger subjects, has been insufficient to date. Previous studies have found abnormal cerebral pH levels in adults with BD, which may be directly linked to abnormal mitochondrial activity. To date no such studies have been reported in children with BD. Methods: Phosphorus Magnetic Resonance Spectroscopy ($^{31}$P MRS) was used to determine pH, phopshocreatine (PCr) and inorganic phosphate (Pi) levels in 8 subjects with BD and 8 healthy comparison subjects (HCS) ages 11 to 20 years old. Results: There was no significant difference in pH between the patients and HCS. However, frontal pH values for patients with BD increased with age, contrary to studies of HCS and the pH values in the frontal lobe correlated negatively with the YMRS values. Global Pi was significantly lower in subjects with BD compared with HCS. There were no significant differences in PCr between the groups. Global PCr-to-Pi ratio (PCr/Pi) was significantly higher in subjects with BD compared with HCS. Conclusions: The change in Pi levels for the patients with BD coupled with the no difference in PCr levels, suggest an altered mitochondrial phosphorylation. However, our findings require further investigation of the underlying mechanisms with the notion that a mitochondrial dysfunction may manifest itself differently in children than that in adults. Limitations: Further investigations with larger patient populations are necessary to draw further conclusions

The Role of Glutamate and GABA in Autism Spectrum Disorders: Pilot Results from a Proton Magnetic Resonance Spectroscopy Study

Objectives: To measure the levels of glutamate, a major excitatory neurotransmitter; glutamine, a metabolite of glutamate; and γ-aminobutyric acid (GABA), a major inhibitory neurotransmitter; in a pilot study of proton magnetic resonance spectroscopy (1H-MRS) findings in adolescents with Autism Spectrum Disorders (ASD). Methods: The subjects were assessed with the Autism Diagnostic Observation Schedule (ADOS), the Reading the Mind in the Eyes test (RMET) and the Social Responsiveness Scale (SRS). 1H-MRS measures of the anterior cingulate cortex were conducted using a Philips 3.0 T scanner. Results: To date, we have completed the data analysis on 18 subjects, 8 with ASD and 10 healthy control (HC) subjects. There was no significant difference between the combined glutamate + glutamine concentrations as measured by 1H-MRS (ASD = 12.0 ± 0.9 IU, HC = 11.6 ± 0.8 IU, p = 0.37). However, there was a higher than average glutamine level in the ASD group compared to healthy controls (ASD = 2.4 ± 0.2 IU, HC = 1.9 ± 0.3 IU, p = 0.01). This was accompanied by a trend toward lower GABA/Cr levels in the ASD group (ASD = 0.073 ± 0.010, HC = 0.082 ± 0.010, p = 0.06). Glutamine levels in the ACC were correlated positively with deficits of social cognition across groups (higher SRS, lower RMET scores). Those with higher glutamine levels made more errors when identifying emotions in the RMET task (r(10) = -0.77, p = 0.009), and also had more clinically significant scores on the SRS (r(10) = 0.87, p = 0.001). Conclusions: Our results present evidence that glutamine levels measured within the ACC region are higher for adolescent males with ASD than age-matched HC males, and signal that GABA levels may also be decreased in this region. These changes are correlated with deficits in social cognition

Areas of the brain modulated by single-dose methylphenidate treatment in youth with ADHD during task-based fMRI: a systematic review

OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) is a psychiatric disorder affecting 5% of children. Methylphenidate (MPH) is a common medication for ADHD. Studies examining MPH\u27s effect on pediatric ADHD patients\u27 brain function using functional magnetic resonance imaging (fMRI) have not been compiled. The goals of this systematic review were to determine (1) which areas of the brain in pediatric ADHD patients are modulated by a single dose of MPH, (2) whether areas modulated by MPH differ by task type performed during fMRI data acquisition, and (3) whether changes in brain activation due to MPH relate to clinical improvements in ADHD-related symptoms. METHODS: We searched the electronic databases PubMed and PsycINFO (1967-2011) using the following terms: ADHD AND (methylphenidate OR MPH OR ritalin) AND (neuroimaging OR MRI OR fMRI OR BOLD OR event related), and identified 200 abstracts, 9 of which were reviewed based on predefined criteria. RESULTS: In ADHD patients the middle and inferior frontal gyri, basal ganglia, and cerebellum were most often affected by MPH. The middle and inferior frontal gyri were frequently affected by MPH during inhibitory control tasks. Correlation between brain regions and clinical improvement was not possible due to the lack of symptom improvement measures within the included studies. CONCLUSIONS: Throughout nine task-based fMRI studies investigating MPH\u27s effect on the brains of pediatric patients with ADHD, MPH resulted in increased activation within frontal lobes, basal ganglia, and cerebellum. In most cases, this increase normalized activation of at least some brain areas to that seen in typically developing children

Enhancement in cognitive function recovery by granulocyte-colony stimulating factor in a rodent model of traumatic brain injury

Traumatic brain injury (TBI) is characterized by neuronal damage and commonly, secondary cell death, leading to functional and neurological dysfunction. Despite the recent focus of TBI research on developing therapies, affective therapeutic strategies targeting neuronal death associated with TBI remain underexplored. This study explored the efficacy of granulocyte-colony stimulating factor (G-CSF) as an intervention for improving cognitive deficits commonly associated with TBI. Although G-CSF has been studied with histological techniques, to date, its effects on functional outcome remain unknown. To this end, we used a closed head injury (CHI) model in Wistar rats that were randomly assigned to one of four groups (untreated TBI, G-CSF treated TBI, G-CSF treated Control, Control). The treatment groups were administered subcutaneous injections of G-CSF 30 min (120 mug/kg) and 12 h (60 mug/kg) post-trauma. The Morris Water Maze test was used to measure any treatment-associated changes in cognitive deficits observed in TBI animals at days 2-6 post-injury. Our findings demonstrate a significant improvement in cognitive performance in the G-CSF treated TBI animals within a week of injury, compared to untreated TBI, indicative of immediate and beneficial effect of G-CSF on cognitive performance post CHI. Our model suggests that early G-CSF exposure may be a promising therapeutic approach in recovery of cognitive deficits due to TBI