Exploring the role of task performance and learning style on prefrontal hemodynamics during a working memory task.

BackgroundPrevious epidemiological studies have reported associations of pesticide exposure with poor cognitive function and behavioral problems. However, these findings have relied primarily on neuropsychological assessments. Questions remain about the neurobiological effects of pesticide exposure, specifically where in the brain pesticides exert their effects and whether compensatory mechanisms in the brain may have masked pesticide-related associations in studies that relied purely on neuropsychological measures. MethodsWe conducted a functional neuroimaging study in 48 farmworkers from Zarcero County, Costa Rica, in 2016. We measured concentrations of 13 insecticide, fungicide, or herbicide metabolites or parent compounds in urine samples collected during two study visits (approximately 3–5 weeks apart). We assessed cortical brain activation in the prefrontal cortex during tasks of working memory, attention, and cognitive flexibility using functional near-infrared spectroscopy (fNIRS). We estimated associations of pesticide exposure with cortical brain activation using multivariable linear regression models adjusted for age and education level. ResultsWe found that higher concentrations of insecticide metabolites were associated with reduced activation in the prefrontal cortex during a working memory task. For example, 3,5,6-trichloro-2-pyridinol (TCPy; a metabolite of the organophosphate chlorpyrifos) was associated with reduced activation in the left dorsolateral prefrontal cortex (β = −2.3; 95% CI: −3.9, −0.7 per two-fold increase in TCPy). Similarly, 3-phenoxybenzoic acid (3-PBA; a metabolite of pyrethroid insecticides) was associated with bilateral reduced activation in the dorsolateral prefrontal cortices (β = −3.1; 95% CI: −5.0, −1.2 and −2.3; 95% CI: −4.5, −0.2 per two-fold increase in 3-PBA for left and right cortices, respectively). These associations were similar, though weaker, for the attention and cognitive flexibility tasks. We observed null associations of fungicide and herbicide biomarker concentrations with cortical brain activation during the three tasks that were administered. ConclusionOur findings suggest that organophosphate and pyrethroid insecticides may impact cortical brain activation in the prefrontal cortex – neural dynamics that could potentially underlie previously reported associations with cognitive and behavioral function. Furthermore, our study demonstrates the feasibility and utility of fNIRS in epidemiological field studies.

Patients with schizophrenia exhibit impairments in working memory that often appear in attenuated form in persons at high risk for the illness. The authors hypothesized that deviations in task-related brain activation and deactivation would occur in persons with an at-risk mental state performing a working memory task that entailed the maintenance and manipulation of letters. Participants at ultra high risk for developing psychosis (N=60), identified using the Comprehensive Assessment of At-Risk Mental States, and healthy comparison subjects (N=38) 14 to 29 years of age underwent functional MRI while performing a verbal working memory task. Group differences in brain activation were identified using analysis of covariance. The two groups did not show significant differences in speed or accuracy of performance, even after accounting for differences in education. Irrespective of task condition, at-risk participants exhibited significantly less activation than healthy comparison subjects in the left anterior insula. During letter manipulation, at-risk persons exhibited greater task-related deactivation within the default-mode network than comparison subjects. Region-of-interest analysis in the at-risk group revealed significantly greater right dorsolateral prefrontal cortex activation during manipulation of letters. Despite comparable behavioral performance, at-risk participants performing a verbal working memory task exhibited altered brain activation compared with healthy subjects. These findings demonstrate an altered pattern of brain activation in at-risk persons that contains elements of reduced function as well as compensation.

Altered brain activation in dorsolateral prefrontal cortex in adolescents and young adults at genetic risk for schizophrenia: An fMRI study of working memory

<bold>Objective</bold> The contractions of abdominal muscle during voluntary urination is a motor control task, Which aims to explore the central activity characteristics of this action with functional near-infrared spectroscopy (fNIRS). <bold>Methods</bold> A total of 19 healthy subjects aged 18 years or older were recruited to undergo fNIRS testing twice, performing repetitive abdominal muscle contractions in the no-urine and strong-urine states. Brain activity under the corresponding no-abdominal muscle-contraction task was used as a baseline to analyze the cortical activities specific to abdominal muscle contractions in these two different states. <bold>Results</bold> Abdominal muscle contractions during the strong desire to urinate primarily activated the bilateral pre-motor/supplementary motor area (BA6), bilateral dorsolateral prefrontal cortex (BA9/46), bilateral frontal pole area (BA10), the anterior portion of the right inferior frontal gyrus (BA47), the right middle temporal gyrus (BA21), the right primary motor cortex (BA4), and the left primary somatosensory cortex (BA1/2/3) in conjunction with the left inferior frontal of pars triangularis Broca's area (BA45) (<italic>P</italic>&lt;0.05). In contrast, abdominal muscle contractions with no desire to urinate primarily activated the bilateral pre-motor/supplementary motor area (BA6) (<italic>P</italic>&lt;0.05), the right primary motor cortex (BA4), the right primary somatosensory cortex (BA1/2/3), the right inferior frontal of pars triangularis Broca's area (BA45), and the right supramarginal gyrus part of Wernicke's area (BA40) (<italic>P</italic>&lt;0.05). Compared to the strong urination state, stronger activation of the bilateral premotor/assistive motor area (BA6) was present in the non-urination state (<italic>P</italic>&lt;0.05). Compared to the non-urination state, stronger activation of the left dorsolateral prefrontal cortex (BA46) was present in the strong urination state (<italic>P</italic>&lt;0.05). <bold>Conclusion</bold> The primary somatosensory cortex, primary motor cortex, and pre-motor/supplementary motor area are jointly involved in the regulation of voluntary urination-associated random abdominal muscle contractions. And further activation of the prefrontal cortex can be induced during abdominal muscle contractions in the strong urination state, suggesting that the prefrontal cortex plays a positive role in facilitating abdominal muscle movements and initiating urination following the perception of urinary awareness.

Distributed Coding of Actual and Hypothetical Outcomes in the Orbital and Dorsolateral Prefrontal Cortex

Disclosure: G. Scozia: None. D. Menghini: None. D. Fintini: None. S. Cianfarani: None. V. Russo: None. M. Mainardi: None. N. Gianni: None. G. Furini: None. G. Scabia: None. M. Maffei: None. M. Manco: None.Background: In pediatric obesity, altered energy regulation and impaired inhibitory control over food intake are linked to dysfunction in the dorsolateral prefrontal cortex (DLPFC). Lifestyle interventions can potentially restore these brain-metabolic pathways. Leptin, brain-derived neurotrophic factor (BDNF), and eotaxin (CCL11), a chemokine involved in immune signaling, may modulate neural responses to metabolic challenges. Objective: To assess the impact of an 8-week intensive health behavioral treatment (IHBT) on DLPFC activation during oral glucose tolerance testing (OGTT), and to explore the relationship with insulin sensitivity and circulating levels of leptin, BDNF and eotaxin in children with obesity. Methods: Twenty-seven children with obesity (mean age 11 years) underwent functional near-infrared spectroscopy (fNIRS) during OGTT at baseline (T0) and post-IHBT (T1). The IHBT included healthy diet, structured physical activity, and cognitive training. Changes in cerebral blood flow (total Hb, tHb) and oxygenated hemoglobin (O₂Hb) were measured in the DLPFC. Insulin sensitivity was assessed via the Matsuda Index and HOMA-IR; serum eotaxin, leptin, and BDNF levels were also measured by commercial assays. Results: After IHBT, there was a significant increase in bilateral DLPFC activation during OGTT:Left DLPFC: ΔO₂Hb ↑, p < 0.01Right DLPFC: ΔO₂Hb ↑, p < 0.05ΔtHb bilateral ↑, indicating enhanced cortical perfusionImprovement in DLPFC activity correlated with metabolic indices:Positive correlation with Matsuda Index (r = 0.54, p < 0.01)Negative correlation with HOMA-IR (r = -0.47, p < 0.05)Left DLPFC activation at T1 showed sex-related differences, with greater increase in males (p < 0.05)Baseline eotaxin levels were positively associated with DLPFC activation changes at T1 (r = 0.41, p < 0.05), while leptin and BDNF showed no significant associations. Conclusion: An 8-week lifestyle intervention significantly enhanced DLPFC activation during glucose challenge, suggesting improved neural regulation of food-related behavior in children with obesity. The association with eotaxin implicates a potential neuroimmune mechanism whereby inflammatory signaling may influence prefrontal responsiveness to metabolic inputs. Eotaxin may serve as a biomarker of neuroplastic adaptation to behavioral interventions targeting obesity.Presentation: Monday, July 14, 2025

<bold>Objective</bold>To explore the cortical control mechanisms of auditory comprehension and verbal expression deficits in post-stroke aphasia (PSA) patients based on a naturalistic paradigm that closely mimics real-world scenarios. <bold>Methods</bold> A total of 26 PSA patients (PSA group) treated in the Second Rehabilitation Hospital of Shanghai from March 2024 and February 2025 were enrolled, along with 21 gender-, age-, and education-matched healthy controls (control group). All participants completed an auditory comprehension-verbal expression task under functional near-infrared spectroscopy (fNIRS) monitoring. A block-task paradigm was designed based on a natural question-answer language model, consisting three phases, including listening to questions embedded in short narratives, thinking, and responding, with the entire paradigm repeated six times. fNIRS monitoring encompassed bilateral temporal, parietal, and prefrontal lobes. The Western Aphasia Battery (WAB) and the Boston Diagnostic Aphasia Examination (BDAE) were used to evaluate language function. The fNIRS system was used to assess cortical activation levels in various channels and brain regions, including the superior temporal gyrus (STG), middle temporal gyrus (MTG), supramarginal gyrus (SMG), fusiform gyrus (FG), angular gyrus (AG), somatosensory association cortex (SAC), primary somatosensory cortex (PSC), primary motor cortex (PMC), pre-motor and supplementary motor cortex (PMSC), pars triangularis of Broca's area (PT), pars opercularis (PO), dorsolateral prefrontal cortex (DLPFC), and frontal eye fields (FEF), during auditory comprehension and verbal expression tasks. To analyze the correlations between WAB auditory comprehension/verbal expression scores, WAB-AQ scores, BDAE scores, and cortical activation levels in the PSA group during auditory comprehension and verbal expression tasks.<bold>Results</bold>In the auditory comprehension task, the control group showed significant bilateral brain activation, with higher activation levels in the right hemisphere than the left, including the superior temporal gyrus (STG) (P=0.041), middle temporal gyrus (MTG) (P=0.002), and supramarginal gyrus (SMG) (P=0.028). In contrast, the PSA group primarily relied on the right-hemisphere homologue of Wernicke's area, including the STG (P=0.030) and MTG (P=0.024), with significantly reduced activation in the left hemisphere (P&lt;0.05). During the verbal expression task, the control group showed pronounced activation in the left Broca's area and related regions, including the PT (P=0.036), PO (P=0.001), and PMC (P=0.002), with symmetrical activation in the right hemisphere. The PSA group demonstrated compensatory activation in the right hemisphere, including the PT (P=0.035), PO (P=0.002), and PMC (P=0.017), while activation in the left hemisphere(particularly Broca's area) decreased significantly(P&lt;0.05). WAB auditory comprehension scores in patients with PSA correlated with the degree of activation in the bilateral DLPFC (r=-0.401, P=0.047), PMSC (r =-0.417, P=0.038), and PMC (r=-0.414, P=0.040). WAB spontaneous speech scores correlated with activation in the left DLPFC (r =-0.423, P=0.035), PMC (r =-0.400, P = 0.048), and PSC (r =-0.481, P = 0.015), as well as with activation in the right STG (r=-0.404, P = 0.045). <bold>Conclusion</bold> The degree of cortical activation during auditory comprehension and verbal expression tasks in PSA patients is significantly correlated with language function impairment scores, emphasizing the crucial role of the right hemisphere in PSA recovery.

Higher dopamine release induced by less rather than more preferred reward during a working memory task in the primate prefrontal cortex

Social anxiety is characterized by an excessive fear of being embarrassed in social interactions or social performance situations. Emotional support can help to decrease or diminish social distress. Such support may play an important role at different points of social interaction. However, it is unclear how the beneficial effects of social support are represented in the brains of socially anxious individuals. To explore this, we used the same paradigm previously used to examine the effects of emotional support on social pain caused by exclusion. Undergraduates (n = 46) showing a wide range of social anxiety scores underwent functional magnetic resonance imaging (fMRI) while participating in a Cyberball game. Participants were initially included and later excluded from the game. In the latter half of the session in which participants were excluded, they were provided with supportive messages. In line with our previous work, we found that social exclusion led to increased anterior cingulate cortex (ACC) activity, whereas emotional support led to increased left dorsolateral prefrontal cortex (DLPFC) activity. Despite validation of the paradigm, social anxiety was not associated with increased ACC activity during social exclusion, or during perceived emotional support. Instead, fear of negative evaluation as assessed by the Brief Fear of Negative Evaluation (BFNE) scale showed positive associations with left DLPFC activation while receiving emotional support, compared to while being socially excluded. The more socially anxious an individual was, the greater was the left DLPFC activity increased during receipt of messages. This suggests that highly socially anxious people still have the ability to perceive social support, but that they are nevertheless susceptible to negative evaluation by others.

The Versatile Wayfinder: Prefrontal Contributions to Spatial Navigation.

Working memory for complex figures: An fMRI comparison of letter and fractal n-back tasks.

Background and ObjectivesObesity is emerging as the most significant health concern of the twenty-first century. A wealth of neuroimaging data suggest that weight gain might be related to aberrant brain function, particularly in prefrontal cortical regions modulating mesolimbic addictive responses to food. Nevertheless, food addiction is currently a model hotly debated. Here, we conduct a meta-analysis of neuroimaging data, examining the most common functional differences between normal-weight and obese participants in response to food stimuli.Data SourceWe conducted a search using several journal databases and adhered to the ‘Preferred Reporting Items for Systematic Reviews and Meta-analyses’ (PRISMA) method. To this aim, 10 studies were found with a total of 126 obese participants, 129 healthy controls, equaling 184 foci (146 increased, 38 decreased activation) using the Activation Likelihood Estimation (ALE) technique. Out of the 10 studies, 7 investigated neural responses to food versus non-food images.ResultsIn response to food images, obese in comparison to healthy weight subjects had increased activation in the left dorsomedial prefrontal cortex, right parahippocampal gyrus, right precentral gyrus and right anterior cingulate cortex, and reduced activation in the left dorsolateral prefrontal cortex and left insular cortex.ConclusionsPrefrontal cortex areas linked to cognitive evaluation processes, such as evaluation of rewarding stimuli, as well as explicit memory regions, appear most consistently activated in response to images of food in those who are obese. Conversely, a reduced activation in brain regions associated with cognitive control and interoceptive awareness of sensations in the body might indicate a weakened control system, combined with hypo-sensitivity to satiety and discomfort signals after eating in those who are prone to overeat.

ObjectiveWe aimed to study the neural processing of emotion-denoting words based on a circumplex model of affect, which posits that all emotions can be described as a linear combination of two neurophysiological dimensions, valence and arousal. Based on the circumplex model, we predicted a linear relationship between neural activity and incremental changes in these two affective dimensions.MethodsUsing functional magnetic resonance imaging, we assessed in 10 subjects the correlations of BOLD (blood oxygen level dependent) signal with ratings of valence and arousal during the presentation of emotion-denoting words.ResultsValence ratings correlated positively with neural activity in the left insular cortex and inversely with neural activity in the right dorsolateral prefrontal and precuneus cortices. The absolute value of valence ratings (reflecting the positive and negative extremes of valence) correlated positively with neural activity in the left dorsolateral and medial pre-frontal cortex (PFC), dorsal anterior cingulate cortex, posterior cingulate cortex, and right dorsal PFC, and inversely with neural activity in the left medial temporal cortex and right amygdala. Arousal ratings and neural activity correlated positively in the left parahippocampus and dorsal anterior cingulate cortex, and inversely in the left dorsolateral PFC and dorsal cerebellum.ConclusionWe found evidence for two neural networks subserving the affective dimensions of valence and arousal. These findings clarify inconsistencies from prior imaging studies of affect by suggesting that two underlying neurophysiological systems, valence and arousal, may subserve the processing of affective stimuli, consistent with the circumplex model of affect.

We previously found that a 10-min bout of moderate-intensity exercise (50% maximal oxygen uptake) under normobaric and hypoxic conditions (fraction of inspired oxygen [{{text{F}}_text{IO}}_{_{2}}] = 0.135) reduced executive performance and neural activity in the left dorsolateral prefrontal cortex (DLPFC). To examine whether this cognitive fatigue is due to a decrease in SpO2 during exercise, we compared executive performance and related prefrontal activation between two experimental conditions, in which the participants inhaled normobaric hypoxic gas ({{text{F}}_text{IO}}_{_{2}}= 0.135) (hypoxic exercise [HE]) or hypoxic gas adjusted so that SpO2 during exercise remained at the resting level (milder hypoxic exercise [ME]). ME condition showed that reaction time in executive performance decreased (t[13] = 2.228, P < 0.05, d = 0.34, paired t-test) and left DLPFC activity increased (t[13] = -2.376, P < 0.05, d = 0.63, paired t-test) after exercise compared with HE condition. These results showed that the HE-induced reductions in the left DLPFC activity and executive performance were both suppressed in the ME condition, supporting the hypothesis that exercise-induced cognitive fatigue under hypoxic environment is due to hypoxemia during exercise. This may lead to the development of a method of coping with cognitive fatigue due to exercise that causes hypoxemia.

Self-harm is a potentially lethal symptom of borderline personality disorder (BPD) that often improves with dialectical behavior therapy (DBT). While DBT is effective for reducing self-harm in many patients with BPD, a small but significant number of patients either does not improve in treatment or ends treatment prematurely. Accordingly, it is crucial to identify factors that may prospectively predict which patients are most likely to benefit from and remain in treatment. In the present preliminary study, 29 actively self-harming patients with BPD completed brain-imaging procedures probing activation of the prefrontal cortex (PFC) during impulse control prior to beginning DBT and after 7 months of treatment. Patients that reduced their frequency of self-harm the most over treatment displayed lower levels of neural activation in the bilateral dorsolateral prefrontal cortex (DLPFC) prior to beginning treatment, and they showed the greatest increases in activity within this region after 7 months of treatment. Prior to starting DBT, treatment non-completers demonstrated greater activation than treatment-completers in the medial PFC and right inferior frontal gyrus. Reductions in self-harm over the treatment period were associated with increases in activity in right DLPFC even after accounting for improvements in depression, mania, and BPD symptom severity. These findings suggest that pre-treatment patterns of activation in the PFC underlying impulse control may be prospectively associated with improvements in self-harm and treatment attrition for patients with BPD treated with DBT.