Cerebral cortex activation and functional connectivity during low-load resistance training with blood flow restriction: An fNIRS study.

Despite accumulating evidence that blood flow restriction (BFR) training promotes muscle hypertrophy and strength gain, the underlying neurophysiological mechanisms have rarely been explored. The primary goal of this study is to investigate characteristics of cerebral cortex activity during BFR training under different pressure intensities. 24 males participated in 30% 1RM squat exercise, changes in oxygenated hemoglobin concentration (HbO) in the primary motor cortex (M1), pre-motor cortex (PMC), supplementary motor area (SMA), and dorsolateral prefrontal cortex (DLPFC), were measured by fNIRS. The results showed that HbO increased from 0 mmHg (non-BFR) to 250 mmHg but dropped sharply under 350 mmHg pressure intensity. In addition, HbO and functional connectivity were higher in M1 and PMC-SMA than in DLPFC. Moreover, the significant interaction effect between pressure intensity and ROI for HbO revealed that the regulation of cerebral cortex during BFR training was more pronounced in M1 and PMC-SMA than in DLPFC. In conclusion, low-load resistance training with BFR triggers acute responses in the cerebral cortex, and moderate pressure intensity achieves optimal neural benefits in enhancing cortical activation. M1 and PMC-SMA play crucial roles during BFR training through activation and functional connectivity regulation.

Bilateral Prefrontal Cortex Blood Flow Dynamics during Silent and Oral Reading Using Near-Infrared Spectroscopy.

This study aimed to investigate blood flow dynamics in the bilateral prefrontal cortex during silent and oral reading using near-infrared spectroscopy (NIRS). The subjects were 40 right-handed university students (20.5±1.8 years old, 20 men and 20 women). After completing the NIRS measurements, the subjects were asked to rate their level of proficiency in silent and oral reading, using a 5-point Likert scale. During oral reading, the left lateral prefrontal cortex (Broca's area) was significantly more active than the right side. During silent reading, prefrontal cortex activity was lower than that during oral reading, and there was no significant difference between both sides of the brain. A significant negative correlation was found between the change in oxy-hemoglobin (oxy-Hb) concentration in the left and right lateral prefrontal cortex during silent reading and silent reading speed. In addition, students with lower self-reported reading proficiency had significantly greater changes in oxy-Hb concentrations in the left and right lateral prefrontal cortex during silent/oral reading than did students with higher self-reported reading proficiency. Reading task assessment using NIRS may be useful for identifying language lateralization and Broca's area. The results demonstrate that NIRS is useful for assessing effortful reading and may be used to diagnose developmental dyslexia in children. J. Med. Invest. 71 : 92-101, February, 2024.

Vascular and blood-brain barrier-related changes underlie stress responses and resilience in female mice and depression in human tissue.

Prevalence, symptoms, and treatment of depression suggest that major depressive disorders (MDD) present sex differences. Social stress-induced neurovascular pathology is associated with depressive symptoms in male mice; however, this association is unclear in females. Here, we report that chronic social and subchronic variable stress promotes blood-brain barrier (BBB) alterations in mood-related brain regions of female mice. Targeted disruption of the BBB in the female prefrontal cortex (PFC) induces anxiety- and depression-like behaviours. By comparing the endothelium cell-specific transcriptomic profiling of the mouse male and female PFC, we identify several pathways and genes involved in maladaptive stress responses and resilience to stress. Furthermore, we confirm that the BBB in the PFC of stressed female mice is leaky. Then, we identify circulating vascular biomarkers of chronic stress, such as soluble E-selectin. Similar changes in circulating soluble E-selectin, BBB gene expression and morphology can be found in blood serum and postmortem brain samples from women diagnosed with MDD. Altogether, we propose that BBB dysfunction plays an important role in modulating stress responses in female mice and possibly MDD.

The cholinergic system modulates negative BOLD responses in the prefrontal cortex once electrical perforant pathway stimulation triggers neuronal afterdischarges in the hippocampus.

Repeated high-frequency pulse-burst stimulations of the rat perforant pathway elicited positive BOLD responses in the right hippocampus, septum and prefrontal cortex. However, when the first stimulation period also triggered neuronal afterdischarges in the hippocampus, then a delayed negative BOLD response in the prefrontal cortex was generated. While neuronal activity and cerebral blood volume (CBV) increased in the hippocampus during the period of hippocampal neuronal afterdischarges (h-nAD), CBV decreased in the prefrontal cortex, although neuronal activity did not decrease. Only after termination of h-nAD did CBV in the prefrontal cortex increase again. Thus, h-nAD triggered neuronal activity in the prefrontal cortex that counteracted the usual neuronal activity-related functional hyperemia. This process was significantly enhanced by pilocarpine, a mACh receptor agonist, and completely blocked when pilocarpine was co-administered with scopolamine, a mACh receptor antagonist. Scopolamine did not prevent the formation of the negative BOLD response, thus mACh receptors modulate the strength of the negative BOLD response.

Ventrolateral prefrontal hemodynamic responses in autism spectrum disorder with and without depression.

In clinical settings, autism spectrum disorder (ASD) with comorbid depression is often difficult to diagnose, and should be considered in treatment. However, to our knowledge, no functional imaging study has examined the difference between ASD adolescents with and without comorbid depression. We aimed to compare the characteristics and prefrontal brain function of ASD with and without depression in order to identify a biological marker that can be used to detect the difference. Twenty-eight drug-naïve adolescents with ASD (14 ASD with and 14 ASD without depression) and 14 age- and gender-matched adolescents with typical development were evaluated using several variables. These included intelligence quotient, autism quotient, depression severity using the Beck Depression Inventory 2nd edition (BDI-II), and level of social functioning using the Social Adaptation Self-evaluation Scale (SASS). In addition, frontotemporal hemodynamic responses during a verbal fluency task (VFT) were measured using functional near-infrared spectroscopy (fNIRS). The ASD group, including both of the ASD with and ASD without depression groups, showed smaller hemodynamic responses than the typical development group in portions of the left dorsolateral prefrontal cortex (DLPFC), bilateral ventrolateral prefrontal cortex (VLPFC) and anterior part of the temporal cortex (aTC) during the VFT. Moreover, the smaller hemodynamic responses in the right VLPFC during the VFT in the ASD group were associated with the worse BDI-II and SASS scores. Furthermore, the ASD with depression group showed smaller hemodynamic responses in the right VLPFC during the VFT than the ASD without depression group in a direct comparison. Adolescents with ASD showed reduced activation in broad frontotemporal regions during a cognitive task compared with those with typical development. More specifically, the right VLPFC activation reflected the level of self-estimated depression and social functioning in the ASD subjects, and could be used to discriminate between ASD adolescents with and without depression.

Central command-related increases in blood velocity of anterior cerebral artery and prefrontal oxygenation at the onset of voluntary tapping.

The anterior cerebral artery (ACA) supplies blood predominantly to the frontal lobe including the prefrontal cortex. Our laboratory reported that prefrontal oxygenated-hemoglobin concentration (Oxy-Hb) increased before and at exercise onset, as long as exercise is arbitrarily started. Moreover, the increased prefrontal oxygenation seems independent of both exercise intensity and muscle mass. If so, mean blood velocity of the ACA (ACABV) should increase with "very light motor effort," concomitantly with the preexercise and initial increase in prefrontal Oxy-Hb. This study aimed to examine the responses in ACABV and vascular conductance index (ACAVCI) of the ACA as well as prefrontal Oxy-Hb during arbitrary or cued finger tapping in 12 subjects, an activity with a Borg scale perceived exertion rating of 7 (median). With arbitrary start, ACABV increased at tapping onset (14 ± 9%) via an elevation in ACAVCI. Likewise, prefrontal Oxy-Hb increased at the onset of tapping with a time course resembling that of ACABV. A positive cross correlation between the initial changes in ACABV and prefrontal Oxy-Hb was found significant in 67% of subjects, having a time lag of 2 s, whereas a positive linear regression between them was significant in 75% of subjects. When tapping was forced to start by cue, the initial increases in ACABV, ACAVCI, and prefrontal Oxy-Hb were delayed and blunted as compared with an arbitrary start. Thus, active vasodilatation of the ACA vascular bed occurs at tapping onset, as long as tapping is arbitrarily started, and contributes to immediate increases in blood flow and prefrontal oxygenation.NEW & NOTEWORTHY Anterior cerebral artery blood velocity and vascular conductance index along with prefrontal oxygenated-hemoglobin concentration all increased at the onset of finger tapping, peaking immediately after tapping onset, as long as tapping was arbitrarily started. Positive cross correlation and linear regression between the increases in ACABV and prefrontal Oxy-Hb were significant in 67%-75% of subjects. Active vasodilatation of the ACA vascular bed occurs with arbitrary tapping onset and contributes to increased ACABV and prefrontal oxygenation.

Brain Function Changes Induced by Intermittent Sequential Pneumatic Compression in Patients With Stroke as Assessed by Functional Near-Infrared Spectroscopy.

OBJECTIVE: Intermittent sequential pneumatic compression (ISPC) can effectively promote cerebral perfusion and collateral blood supply in patients with stroke. However, the effects of ISPC on cerebral oscillations are still unclear. METHODS: The tissue concentration of oxyhemoglobin and deoxyhemoglobin oscillations were measured by functional near-infrared spectroscopy under resting and ISPC conditions in 27 right-handed adult patients with stroke. Five characteristic frequency signals (I, 0.6-2 Hz; II, 0.145-0.6 Hz; III, 0.052-0.145 Hz; IV, 0.021-0.052 Hz; and V, 0.0095-0.021 Hz) were identified using the wavelet method. The wavelet amplitude (WA) and laterality index (LI) were calculated to describe the frequency-specific cortical activities. RESULTS: The ISPC state of patients with ischemic stroke showed significantly increased WA values of the ipsilesional motor cortex (MC) in the frequency intervals III (F37 = 8.017), IV (F37 = 6.347), and V (F37 = 5.538). There was no significant difference in the WA values in the ISPC state compared with the resting state in patients with hemorrhagic stroke. Also, the LI values of the prefrontal cortex and MC in patients decreased more obviously in the ISPC state than in the resting state despite no significant difference. CONCLUSION: The significantly increased WA values in the frequency intervals III, IV, and V in the MC of patients with ischemic stroke might be related to cortical activity in the MC in addition to increased cerebral perfusion. The decreased LI values in the prefrontal cortex and MC indicated that the ISPC may have had a positive effect on the functional rehabilitation of these regions. IMPACT: This study provides a method for assessing the effects of ISPC on cerebral oscillations, and the results benefit the optimization of ISPC parameters in personalized treatment for the functional recovery of patients with stroke.

Increased cognitive workload evokes greater neurovascular coupling responses in healthy young adults.

Understanding how the brain allocates resources to match the demands of active neurons under physiological conditions is critically important. Increased metabolic demands of active brain regions are matched with hemodynamic responses known as neurovascular coupling (NVC). Several methods that allow noninvasive assessment of brain activity in humans detect NVC and early detection of NVC impairment may serve as an early marker of cognitive impairment. Therefore, non-invasive NVC assessments may serve as a valuable tool to detect early signs of cognitive impairment and dementia. Working memory tasks are routinely employed in the evaluation of cognitive task-evoked NVC responses. However, recent attempts that utilized functional near-infrared spectroscopy (fNIRS) or transcranial Doppler sonography (TCD) while using a similar working memory paradigm did not provide convincing evidence for the correlation of the hemodynamic variables measured by these two methods. In the current study, we aimed to compare fNIRS and TCD in their performance of differentiating NVC responses evoked by different levels of working memory workload during the same working memory task used as cognitive stimulation. Fourteen healthy young individuals were recruited for this study and performed an n-back cognitive test during TCD and fNIRS monitoring. During TCD monitoring, the middle cerebral artery (MCA) flow was bilaterally increased during the task associated with greater cognitive effort. fNIRS also detected significantly increased activation during a more challenging task in the left dorsolateral prefrontal cortex (DLPFC), and in addition, widespread activation of the medial prefrontal cortex (mPFC) was also revealed. Robust changes in prefrontal cortex hemodynamics may explain the profound change in MCA blood flow during the same cognitive task. Overall, our data support our hypothesis that both TCD and fNIRS methods can discriminate NVC evoked by higher demand tasks compared to baseline or lower demand tasks.

Theta burst stimulation over the prefrontal cortex: Effects on cerebral oximetry and cardiovascular measures in healthy humans.

Theta Burst Stimulation (TBS) is a non-invasive neurophysiological technique, able to induce changes in synaptic activity. Research suggests that TBS may induce changes in cerebral oxygenation, cerebral blood flow, blood pressure and heart rate but there are conflicting results across studies. Thus, the objective of our sham-controlled study is to evaluate if TBS applied to the dorsolateral prefrontal cortex (DLPFC) of healthy volunteers produces changes in cerebral oximetry, heart rate and blood pressure. Forty-nine volunteers of both sexes were randomly allocated to one of five stimulation groups. Before and after real TBS or sham stimulation, blood pressure, heart rate, and cerebral oxygenation of the volunteers were measured. Cerebral oxygenation values were obtained with a near infra-red spectroscopy system. We found a significant reduction in left cortex oximetry after continuous TBS (cTBS) over the left DLPFC (p = 0.039) and a non-significant reduction in right cortex oximetry (p = 0.052). Right hemisphere inhibition (using cTBS) seemed to originate a significant reduction of 8 mmHg in systolic arterial pressure. No other changes were seen in oximetry, cardiac frequency and diastolic arterial pressure. In our group of normal subjects, cTBS applied to the left DLPFC was able to reduce oxygenation in the left cortex. Right hemisphere inhibition was associated with a significant reduction in systolic pressure.

The Association Between Generalized Anxiety Disorder and Resting-State Prefrontal Cortex Oxygenation Is Modified by Self-Reported Physical Activity: Results From The Irish Longitudinal Study on Ageing.

Individuals with anxiety disorders exhibit lower intrinsic functional connectivity between prefrontal cortical areas and subcortical regions. The prefrontal cortex (PFC) is sensitive to the acute and chronic effects of physical activity (PA), while the anxiolytic effects of PA are well known. The current study examined the association of generalized anxiety disorder (GAD) and its interaction with PA, with resting-state, left PFC oxygenation. This cross-sectional study used data from participants (N = 2444) from The Irish Longitudinal Study on Ageing, a nationally representative prospective study of community-living adults aged 50 and older in Ireland. The Composite International Diagnostic Interview Short-Form determined fulfillment of criteria for GAD. The short-form International Physical Activity Questionnaire determined adherence to the World Health Organization PA guidelines. Resting-state, left PFC oxygenation was continuously measured via a Portalite. Tissue saturation index (TSI) was calculated as the ratio of oxygenated hemoglobin to total tissue hemoglobin (expressed as a percentage) for the final minute of a 5-minute supine-rest period. Multivariable linear regression quantified associations of GAD with TSI in the total population and population stratified by PA status. Participants with GAD had lower TSI (b = -1.416, p = .008) compared to those without GAD. However, this association was modified by PA. Among participants who met the PA guidelines, TSI did not differ according to GAD status (b = -0.800, p = .398). For participants who did not meet the guidelines, TSI was significantly lower among those with GAD (b = -1.758, p = .004). These findings suggest that PA may help to protect brain health among older adults with GAD.

Cortical hemodynamics as a function of handgrip strength and cognitive performance: a cross-sectional fNIRS study in younger adults.

BACKGROUND: There is growing evidence for a positive correlation between measures of muscular strength and cognitive abilities. However, the neurophysiological correlates of this relationship are not well understood so far. The aim of this study was to investigate cortical hemodynamics [i.e., changes in concentrations of oxygenated (oxyHb) and deoxygenated hemoglobin (deoxyHb)] as a possible link between measures of muscular strength and cognitive performance. METHODS: In a cohort of younger adults (n = 39, 18-30 years), we assessed (i) handgrip strength by a handhold dynamometer, (ii) short-term working memory performance by using error rates and reaction times in the Sternberg task, and (iii) cortical hemodynamics of the prefrontal cortex (PFC) via functional near-infrared spectroscopy (fNIRS). RESULTS: We observed low to moderate negative correlations (rp = ~ - 0.38 to - 0.51; p < 0.05) between reaction time and levels of oxyHb in specific parts of the PFC. Furthermore, we noticed low to moderate positive correlations (rp = ~ 0.34 to 0.45; p < 0.05) between reaction times and levels of deoxyHb in distinct parts of the PFC. Additionally, higher levels of oxyHb (rp (35) = 0.401; p = 0.014) and lower levels of deoxyHb (rp (34) = - 0.338; p = 0.043) in specific parts of the PFC were linked to higher percentage of correct answers. We also found low to moderate correlations (p < 0.05) between measures of handgrip strength and levels of oxyHb (rp = ~ 0.35; p < 0.05) and levels of deoxyHb (rp = ~ - 0.25 to - 0.49; p < 0.05) in specific parts of the PFC. However, there was neither a correlation between cognitive performance and handgrip strength nor did cortical hemodynamics in the PFC mediate the relationship between handgrip strength and cognitive performance (p > 0.05). CONCLUSION: The present study provides evidence for a positive neurobehavioral relationship between cortical hemodynamics and cognitive performance. Our findings further imply that in younger adults higher levels of handgrip strength positively influence cortical hemodynamics although the latter did not necessarily culminate in better cognitive performance. Future research should examine whether the present findings can be generalized to other cohorts (e.g., older adults).

Cortical hemodynamic mapping of subthalamic nucleus deep brain stimulation in Parkinsonian patients, using high-density functional near-infrared spectroscopy.

Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment for idiopathic Parkinson's disease. Despite recent progress, the mechanisms responsible for the technique's effectiveness have yet to be fully elucidated. The purpose of the present study was to gain new insights into the interactions between STN-DBS and cortical network activity. We therefore combined high-resolution functional near-infrared spectroscopy with low-resolution electroencephalography in seven Parkinsonian patients on STN-DBS, and measured cortical haemodynamic changes at rest and during hand movement in the presence and absence of stimulation (the ON-stim and OFF-stim conditions, respectively) in the off-drug condition. The relative changes in oxyhaemoglobin [HbO], deoxyhaemoglobin [HbR], and total haemoglobin [HbT] levels were analyzed continuously. At rest, the [HbO], [HbR], and [HbT] over the bilateral sensorimotor (SM), premotor (PM) and dorsolateral prefrontal (DLPF) cortices decreased steadily throughout the duration of stimulation, relative to the OFF-stim condition. During hand movement in the OFF-stim condition, [HbO] increased and [HbR] decreased concomitantly over the contralateral SM cortex (as a result of neurovascular coupling), and [HbO], [HbR], and [HbT] increased concomitantly in the dorsolateral prefrontal cortex (DLPFC)-suggesting an increase in blood volume in this brain area. During hand movement with STN-DBS, the increase in [HbO] was over the contralateral SM and PM cortices was significantly lower than in the OFF-stim condition, as was the decrease in [HbO] and [HbT] in the DLPFC. Our results indicate that STN-DBS is associated with a reduction in blood volume over the SM, PM and DLPF cortices, regardless of whether or not the patient is performing a task. This particular effect on cortical networks might explain not only STN-DBS's clinical effectiveness but also some of the associated adverse effects.

Effects of Acceleration-Induced Reductions in Retinal and Cerebral Oxygenation on Human Performance.

BACKGROUND: Ischemic hypoxia induced by suprathreshold G-force loading can adversely affect vision, cognition, and lead to loss of consciousness (LOC). The purpose of this study was to determine whether reductions in cerebral oxygenation, caused by subthreshold G-forces (up to 4 Gz and of limited durations that do not lead to LOC), would affect visual perception and working memory performance.METHODS: Sixteen subjects performed visual perception and working memory tasks both before and during Gz exposures (1, 2.2, 3, 4 with leg pressurization, 4 with leg and abdomen pressurization) within a human-use centrifuge.RESULTS: As measured using near-infrared spectroscopy, blood oxygenation over medial prefrontal cortex was similar in the 1 and 2.2 Gz conditions, but was reduced to a similar extent in the 3 and 4 Gz conditions. In parallel, visual perception accuracy was reduced in the 3 and 4 Gz conditions, with no difference between the 3 and 4 Gz conditions. No change in reaction time was seen. Conversely, neither accuracy nor reaction time changes were observed for the visual working memory task.DISCUSSION: These results indicate that although visual working memory is not affected, the ability to visually discriminate between stimuli is reduced at G-forces as low as 3 and 4 Gz. This may have important ramifications for pilots who are routinely subjected to such forces.Croft RJ, Klegrd R, Tribukait A, Taylor NAS, Eiken O. Effects of acceleration-induced reductions in retinal and cerebral oxygenation on human performance. Aerosp Med Hum Perform. 2021; 92(2):7582.

Regional hyperperfusion in older adults with objectively-defined subtle cognitive decline.

Although cerebral blood flow (CBF) alterations are associated with Alzheimer's disease (AD), CBF patterns across prodromal stages of AD remain unclear. Therefore, we investigated patterns of regional CBF in 162 Alzheimer's Disease Neuroimaging Initiative participants characterized as cognitively unimpaired (CU; n = 80), objectively-defined subtle cognitive decline (Obj-SCD; n = 31), or mild cognitive impairment (MCI; n = 51). Arterial spin labeling MRI quantified regional CBF in a priori regions of interest: hippocampus, inferior temporal gyrus, inferior parietal lobe, medial orbitofrontal cortex, and rostral middle frontal gyrus. Obj-SCD participants had increased hippocampal and inferior parietal CBF relative to CU and MCI participants and increased inferior temporal CBF relative to MCI participants. CU and MCI groups did not differ in hippocampal or inferior parietal CBF, but CU participants had increased inferior temporal CBF relative to MCI participants. There were no CBF group differences in the two frontal regions. Thus, we found an inverted-U pattern of CBF signal across prodromal AD stages in regions susceptible to early AD pathology. Hippocampal and inferior parietal hyperperfusion in Obj-SCD may reflect early neurovascular dysregulation, whereby higher CBF is needed to maintain cognitive functioning relative to MCI participants, yet is also reflective of early cognitive inefficiencies that distinguish Obj-SCD from CU participants.

Frontal Hemodynamic Response During Step Initiation Under Cognitive Conflict in Older and Young Healthy People.

Gait initiation is a daily challenge even for healthy individuals as it requires the timely coupling between the automatic anticipatory postural adjustment (APA) and the voluntary step according to the context. Modulation of this motor event has been thought to involve higher level brain control, including cognitive inhibitory circuitries. Despite the known participation of the supplementary motor area (SMA) in the modulation of some parameters of APA, the participation of areas controlling inhibition during gait initiation still needs to be investigated. In this study, the hemodynamic responses of the SMA and dorsolateral prefrontal cortex (DLPFC) were assessed using functional near-infrared spectroscopy (fNIRS) during a gait initiation task under cognitive conflict to select the foot to step (congruent [CON] and incongruent [INC] conditions). The older group (OG) showed worse inhibitory control than the young group (YG) along with more impairments in APA parameters. OG also had a lower amplitude of hemodynamic responses in both areas than YG in the INC. The INC increased the correlation between SMA and DLPFC only in the YG. Aging seems to impair the interaction between the hemodynamic responses of SMA and DLPFC, which influences APA performance in gait initiation under cognitive conflict.

The feasibility of fNIRS as a diagnostic tool for pediatric TBI: A pilot study.

BACKGROUND: Functional near-infrared spectroscopy (fNIRS) enables assessment of prefrontal hemodynamic response. This study explored the feasibility of fNIRS in determining hemodynamic changes related to cognitive task performance in pediatric traumatic brain injury (TBI) in order to assess its potential as a diagnostic tool. METHODS: We measured changes in oxygenated hemoglobin [O2Hb] during a verbal fluency task (VFT), which activates frontal brain regions involved in working memory, in 15 TBI patients and 21 healthy controls using a 3-channel fNIRS system. Baseline and absolute changes in [O2Hb] during the VFT were compared to the rest condition to obtain effect-scores. Patients were tested in the acute phase and six weeks after injury. Task-related fNIRS responses were categorized into positive, negative, and no response. RESULTS: For patients and controls, a positive response was observed in 61% (n = 22), a negative response in 19% (n = 7), and no response in 19% (n = 7). Patients showed a mean [O2Hb] effect-score of 2.18 compared to 2.52 in the control group (p = 0.743) in the acute phase after injury. Follow-up effect-scores did not differ significantly (p = 0.721). Decreased task performance was associated with a higher effect-score in controls compared to decreased task performance with lower effect-score in the patient group. DISCUSSION: Our study shows that it is feasible to assess hemodynamic response with fNIRS in pediatric TBI patients. A trend of reduced prefrontal hemodynamic response in patients in the acute phase after injury was found suggesting impairment in cognitive performance that warrants further study.

Stereotactic radiosurgery for orbital cavernous venous malformation: a single center's experience for 15 years.

BACKGROUND: Stereotactic radiosurgery such as Gamma Knife radiosurgery (GKRS) has been shown to have a good treatment effect for orbital cavernous venous malformation (CVM). However, radiation-induced retinopathy or optic neuropathy is a vision-threatening complication of orbital irradiation. Predicting the post-treatment visual outcome is critical. METHODS: Clinical and radiological outcomes were investigated in 30 patients who underwent GKRS for orbital CVM between July 2005 and February 2020. Measurement of peripapillary retinal nerve fiber layer (pRNFL) thickness using optical coherence tomography (OCT) was obtained in 14 patients. RESULTS: The median clinical and radiological follow-up periods were 46.6 months (range, 15.9-105.8) and 27.5 months (range, 15.4-105.8), respectively. Twenty-eight patients underwent multisession (4 fractions) GKRS. The median cumulative marginal dose was 20 Gy (range, 16-24). Two patients underwent single-session GKRS. Marginal doses were 15 Gy and 10.5 Gy in each patient. The volume of CVM decreased in 29 (97%) patients. Visual acuity was improved in 6 (20%) patients and was stable in 22 (73%) patients. Visual field defect and exophthalmos were improved in all patients. Serial investigation of OCT showed no statistically significant difference in pRNFL thickness after GKRS. Patients with normal average pRNFL thickness showed better visual recovery than patients with thin average pRNFL thickness. CONCLUSIONS: GKRS is an effective and safe treatment option for orbital CVM. The pRNFL thickness before GKRS can be a prognostic indicator for visual recovery in orbital CVM after GKRS.

Dynamic response of cerebral blood flow to insulin-induced hypoglycemia.

The dynamics of cerebral blood flow (CBF) at the onset of hypoglycemia may play a key role in hypoglycemia unawareness; however, there is currently a paucity of techniques that can monitor adult CBF with high temporal resolution. Herein, we investigated the use of diffuse correlation spectroscopy (DCS) to monitor the dynamics of CBF during insulin-induced hypoglycemia in adults. Plasma glucose concentrations, cortisol levels, and changes in CBF were measured before and during hypoglycemia in 8 healthy subjects. Cerebral blood flow increased by 42% following insulin injection with a delay of 17 ± 10 min, while the onset of hypoglycemia symptoms was delayed by 24 ± 11 min. The findings suggest that the onset of CBF increments precedes the appearance of hypoglycemia symptoms in nondiabetic subjects with normal awareness to hypoglycemia, and DCS could be a valuable tool for investigating the role of CBF in hypoglycemia unawareness.

Roles of the prefrontal cortex in learning to time the onset of pre-existing motor programs.

The prefrontal cortex (PFC) is involved in cognitive control of motor activities and timing of future intensions. This study investigated the cognitive control of balance recovery in response to unpredictable gait perturbations and the role of PFC subregions in learning by repetition. Bilateral dorsolateral (DLPFC), ventrolateral (VLPFC), frontopolar (FPFC) and orbitofrontal (OFC) cortex hemodynamic changes induced by unpredictable slips were analyzed as a function of successive trials in ten healthy young adults. Slips were induced by the acceleration of one belt as the participant walked on a split-belt treadmill. A portable functional near-infrared spectroscope monitored PFC activities quantified by oxyhemoglobin (ΔO2Hb) and deoxyhemoglobin (ΔHbR) during the consecutive trial phases: standing, walking, slip-recovery. During the first 3 trials, the average oxyhemoglobin (ΔO2Hbavg) in the DLPFC, VLPFC, FPFC, and OFC cortex was significantly higher during slip-recovery than unperturbed walking or the standing baseline. Then, ΔO2Hbavg decreased progressively from trial-to-trial in the DLPFC, VLPFC, and FPFC, but increased and then remained constant in the OFC. The average deoxyhemoglobin (ΔHbRavg) presented mirror patterns. These changes after the third trial were paralleled by the progressive improvement of recovery revealed by kinematic variables. The results corroborate our previous hypothesis that only timing of the onset of a "good enough recovery motor program" is learned with practice. They also strongly support the assumption that the PFC contributes to the recall of pre-existing motor programs whose onset timing is adjusted by the OFC. Hence, learning is clearly divided into two steps delineated by the switch in activity of the OFC. Additionally, motor processes appear to share the working memory as well as decisional and predictive resources of the cognitive system.

Shedding light on the frontal hemodynamics of spatial working memory using functional near-infrared spectroscopy.

The dorsolateral prefrontal cortex has been shown to be a key functional network within the middle frontal gyrus in regards to working memory processing. A commonly used paradigm in this line of research is the n-back task. The standard variant of the task requires participants to state whether the current item has been presented n trials prior (or not). Two possible strategies could be used to complete the task. Participants may either actively uphold the last n items in working memory or they may use item familiarity as basis for a decision. Previous functional near infrared spectroscopy studies using this paradigm have reported differing load dependent patterns of middle frontal gyrus activation which might at least in part be attributed to these different strategies. We used a spatial variant of the n-back task in which participants had to reproduce a pattern of locations n trials after presentation. We could thus eliminate the possibility of relying on familiarity for successful task completion. In line with previous functional magnetic resonance imaging studies we found a rise in middle frontal gyrus activity with rising working memory load. This was mainly reflected by a decrease in concentration of deoxygenated blood in this area. In line with previous research utilizing spatial paradigms, we found a lateralization of activity to the right hemisphere. We propose that the forced recall version of the n-back task is a valid alternative to the standard paradigm and can eliminate unwanted variance due to differing strategies, especially in high load conditions.