Prefrontal cortex neural compensation during an operant devaluation task

Deficits in goal-directed action are reported in multiple neuropsychiatric conditions, including schizophrenia. However, dysfunction is not always apparent in early stages of schizophrenia, possibly due to neural compensation. We designed a novel devaluation task in which goal-directed action could be guided by stimulus-outcome (S-O) [presumably orbitofrontal cortex (OFC)-mediated] or response-outcome (R-O) associations [presumably prelimbic cortex (PL)-mediated]. We previously found suggestive evidence that OFC and PL could compensate for each other in this task, and we more directly assessed this potential compensation here. In Experiment 1, rats received OFC, PL, combined OFC+PL, or sham lesions and then completed our devaluation task. The OFC+PL lesion group exhibited impaired devaluation. In Experiment 2, rats received cholera-toxin-b (CTb) into OFC and either neurotoxic or sham PL lesions. Rats were then sacrificed on the last training day to double-label for Arc and CTb. We found increased Arc+CTb in mediodorsal thalamus (MD) and increased Arc+ neurons in OFC when PL was lesioned, suggesting that PL lesions lead to a compensatory increased activation of the MD->OFC circuit. Our results suggest that our devaluation task can model neural compensation between OFC and PL and this compensation may be regulated by MD.

Brain activity during walking in older adults: Implications for compensatory versus dysfunctional accounts.

A prominent trend in the functional brain imaging literature is that older adults exhibit increased brain activity compared to young adults to perform a given task. This phenomenon has been extensively studied for cognitive tasks, with the field converging on interpretations described in two alternative accounts. One account interprets over-activation in older adults as reflecting neural dysfunction, whereas another interprets it as neural compensation. Here we review studies that have recorded brain activity and walking measurements in older adults, and we categorize their findings as reflecting either neural dysfunction or neural compensation. Based on this synthesis, we recommend including multiple task difficulty levels in future work to help differentiate if and when compensation fails as the locomotion task becomes more difficult. Using multiple task difficulty levels with neuroimaging will lead to a more advanced understanding of how age-related changes in locomotor brain activity fit with existing accounts of brain aging and support the development of targeted neural rehabilitation techniques.

Layer-specific Loss and Compensation of Parvocellular Response in Subcortical Pathways of Adult Human Amblyopia

Abnormal visual experience in critical period causes amblyopia or lazy eye, reducing visual abilities even with corrected optics. A long-standing question is where in the human visual system does the amblyopic deficit arise. In particular, whether amblyopia induces selective deficits of the magnocellular (M) or the parvocellular (P) geniculostriate pathways, and whether the more ancient retinotectal pathway is also affected. Technical limitations to non-invasively measure layer-specific activity in human lateral geniculate nucleus (LGN) and superior colliculus (SC) hampered efforts in addressing these questions. In the current study, using lamina-resolved 3T and 7T fMRI and visual stimuli selectively activating the M and P pathways, we investigated layer-specific response properties of the LGN and the SC of amblyopia patients and normal controls. With stimuli presented to the amblyopic eye, there was a stronger response loss in the P layers than in the M layers of the LGN. Compared to normal controls, amblyopic eye’s response to the P stimulus was selectively reduced in the superficial SC, while the fellow eye’s response was robustly increased in the deep SC. Selective P response deficits of amblyopia were also observed in the visual pulvinar, early visual cortex, and ventral but not dorsal visual streams. These results provide strong in vivo evidence in adult amblyopic patients for selective deficits of parvocellular functions in the visual thalamus, and additionally reveal response deficits to the amblyopic eye and neural compensation to the fellow eye in the retinotectal pathway.HighlightsParvocellular response loss in the LGN P layers, visual pulvinar and ventral visual streamSelective amblyopic deficits of the parvocellular pathwayAmblyopic eye’s response decreased in the superficial SCFellow eye’s response increased in the deep SCAmblyopic deficits and neural compensation in the retinotectal pathway

Investigating Age-Related Neural Compensation During Emotion Perception Using Electroencephalography

Previous research suggests declines in emotion perception in older as compared to younger adults, but the underlying neural mechanisms remain unclear. Here, we address this by investigating how “face-age” and “face emotion intensity” affect both younger and older participants’ behavioural and neural responses using event-related potentials (ERPs). Sixteen young and fifteen older adults viewed and judged the emotion type of facial images with old or young face-age and with high- or low- emotion intensities while EEG was recorded. The ERP results revealed that young and older participants exhibited significant ERP differences in two neural clusters: the left frontal and centromedial regions (100–200 ms stimulus onset) and frontal region (250–900 ms) when perceiving neutral faces. Older participants also exhibited significantly higher ERPs within these two neural clusters during anger and happiness emotion perceptual tasks. However, while this pattern of activity supported neutral emotion processing, it was not sufficient to support the effective processing of facial expressions of anger and happiness as older adults showed reductions in performance when perceiving these emotions. These age-related changes are consistent with theoretical models of age-related changes in neurocognitive abilities and may reflect a general age-related cognitive neural compensation in older adults, rather than a specific emotion-processing neural compensation.

Neural Compensation Mechanisms of Siblings of Schizophrenia Patients as Revealed by High-Density EEG

Visual backward masking (VBM) deficits are candidate endophenotypes of schizophrenia indexing genetic liability of the disorder. In VBM, a target is followed by a mask that deteriorates target perception. Schizophrenia patients and, to a lesser extent, their unaffected relatives show strong and reproducible VBM deficits. In patients, VBM deficits are associated with strongly decreased amplitudes in the evoked-related potentials (ERPs). Here, to unveil the neural mechanisms of VBM in schizophrenia, circumventing illness-specific confounds, we investigated the electroencephalogram correlates of VBM in unaffected siblings of schizophrenia patients. We tested 110 schizophrenia patients, 60 siblings, and 83 healthy controls. As in previous studies, patients showed strong behavioral deficits and decreased ERP amplitudes compared to controls. Surprisingly, the ERP amplitudes of siblings were even higher than the ones of controls, while their performances were similar. ERP amplitudes in siblings were found to correlate with performance. These results suggest that VBM is deteriorated in patients and siblings. However, siblings, unlike patients, can partially compensate for the deficits by over-activating a network of brain regions.

B-03 Neurocognitive Outcome from Anaplastic Astrocytoma: A Case Study of Neural Compensation

Objective Anaplastic astrocytoma is a rare malignant brain tumor occurring in adults aged 30 to 50, with an incidence of 5 to 8 people per 100,000. Cognitive dysfunction is a complication after tumor resection, resulting from neurotrauma of surgery, chemotherapy, and radiation treatment. Neural compensation and neuroplasticity can allow intact cognitive functioning after brain resection in brain areas expected to be impacted by the neurotrauma. Method The current case study is a 45-year-old female post -resection for dendritic cell vaccine clinical trial followed by adjuvant radiation of an anaplastic astrocytoma of the frontal lobe. MRI of the brain post right frontal craniotomy was indicative of extra-axial fluid communicating with the anterior aspect of the right lateral ventricle, hemosiderin along the medial resection margin, and T2/FLAIR signal abnormality in the left medial and right inferior frontal lobes. Results Test data revealed intact global cognitive functioning (WAIS-IV; FSIQ = 101 SS), with below expected performance on verbal comprehension (WAIS-IV; VCI = 98 SS). Consistent with the area of resection, she had impairments in visuoconstruction and executive functioning specific to mental generativity. However, performances with regard to math achievement were intact (WIAT; Math Problem Solving = 110 SS; Numerical Operations = 104 SS), despite significant neurotrauma to the prefrontal cortex. She also produced left lateralized fine motor weakness. Conclusions Accommodations for work, outpatient therapies, and psychotherapy were recommended. This case enhances the understanding of neurocognitive performance after neurotrauma involving tumor resection and radiation treatment in rare malignant brain tumor, and highlights the impact of neural compensation after resection.