Posterior Left Hemisphere Research Articles

2 Rethinking the Neuropsychology of g: Structural and Functional Lesion Network Mapping of General Cognitive Ability

Objective:General cognitive ability (g) is central to our understanding of human cognition, as it accounts for nearly half of individual differences in performances on diverse cognitive tests. There is growing interest in the brain networks necessary for g because such knowledge could elucidate neural mechanisms of g. Prior work highlighted the association between g and frontoparietal functional networks. However, the specificity of this relationship has been questioned. Moreover, no studies have compared the relative importance of structural and functional networks for g, and most studies have relied on data from neurologically healthy individuals, which limits causal brain-behavior inference. Lesion network mapping (LNM) can overcome such limitations. LNM integrates lesion location and structural and functional brain network data, and allows for inference upon networks necessary for cognitive functions. Here, we used data from three cohorts of patients with focal brain lesions to perform a large-scale LNM study of g. We also compared the relative value of lesion-behavior mapping, and structural and functional LNM, for predicting g across cohorts.Participants and Methods:Using data from 402 individuals with chronic, focal brain lesions from the Iowa Neurological Patient Registry, we created a bifactor model to estimate g from the shared variance across neuropsychological tests. To create “cognitive comparisons,” we also estimated the unique aspects of domain-specific abilities (visuospatial processing, memory, and processing speed) by removing domain-general variance from each. Next, we used multivariate lesion-behavior mapping to create statistically weighted maps linking deficits in g and domain-specific abilities to regions of focal brain damage. To perform LNM, the local maxima of the lesion-behavior maps were used as seeds for structural and functional connectivity analyses based on normative diffusion-weighted imaging and resting-state functional connectivity data, respectively. The resulting maps were collapsed using principal components analysis (PCA). We quantified the overlap between each map and the lesion volumes of patients from two validation cohorts (n = 101, n = 100). We used these scores to predict observed g in the validation cohorts while controlling for lesion volume. We also compared the relative predictive value of the lesion-behavior maps, and the structural and functional LNMs.Results:Lesion-behavior mapping indicated that lesions of left frontal white matter, bilateral frontal operculum/insula, and a region of white matter in the posterior left hemisphere were associated with impairments in g. Across all lesion-behavior mapping and LNM results, only two of the structural LNM maps linked to g were statistically significantly predictive of g in both validation cohorts: a map corresponding to the anterior thalamic radiation, and another corresponding to left frontal pyramidal projections. Both added value beyond lesion-behavior mapping and functional LNM.Conclusions:The results are notable in several respects: they highlight the importance of structural networks for g, de-emphasize the relevance of functional networks for g, and suggest novel brain circuitry involved in g. Our findings are consistent with animal studies implicating anterior thalamic nuclei in working memory, a cognitive function central to g. Clinically, our study highlights the importance of considering domain-general deficits and the effects of focal lesions on distributed cognitive networks.

496: REVERSIBLE MALIGNANT CEREBRAL EDEMA FOLLOWING CRANIOPLASTY

Introduction: Cranioplasty is a low-risk procedure and is performed for improving hydrocephalus and cerebral protection after decompressive craniectomy. Until recently, a complication that received little attention despite the devastating consequences is malignant cerebral swelling occurring after cranioplasty. There is limited knowledge regarding the pathophysiology or prevention of this condition. We present a novel case wherein a patient developed malignant cerebral swelling and fully recovered from the event. Description: 44-year-old female initially hospitalized in January 2021 for a right MCA occlusion; she received Alteplase and thrombectomy was performed. Hospital course was complicated by post procedure CT head showing midline shift and mass effect for which she was taken for right sided hemicraniectomy and right temporal lobectomy. She underwent tracheostomy, PEG and was discharged. She presented back in August 2021 for an elective right sided cranioplasty. The operative course was uneventful, a hemovac was placed with a subgaleal drain and a postoperative CT head showed cranioplasty in good position. That evening, the patient became increasingly lethargic, and was intubated. She was given hyperosmotic therapy and a repeat CT head showed newly evolving right PCA infarct, cerebellar infarcts with edema, worsening subdural hematoma and left MCA infarcts. While obtaining the repeat CT head, the patient developed seizures with progression to status epilepticus and was started on a midazolam infusion. CEEG showed epileptiform potentials in the right posterior quadrant and left hemisphere, without seizures. Two days later, on a repeat CT head there were no new findings. Patient began to improve clinically, and MRI brain on day 3 didn’t show new infarct or lesion other than encephalomalacia. She was transferred out of the ICU on day 6, a stability CT head three weeks later was stable, and she was discharged to acute rehab. Discussion: Transient malignant swelling followed cranioplasty is a high risk complication and possibly related to severe TBI, SSFS and vacuum suction drainage. Our patient is the first reported survivor from this. Further research and investigation of other cases should be identified to assess for commonalities and interventions to provide the best chance of recovery.

Role of Left Hemisphere Language Areas in Visuospatial Working Memory

Role of Left Hemisphere Language Areas in Visuospatial Working Memory

Arterial spin labelling shows functional depression of non-lesion tissue in chronic Wernicke's aphasia

Behavioural impairment post-stroke is a consequence of structural damage and altered functional network dynamics. Hypoperfusion of intact neural tissue is frequently observed in acute stroke, indicating reduced functional capacity of regions outside the lesion. However, cerebral blood flow (CBF) is rarely investigated in chronic stroke. This study investigated CBF in individuals with chronic Wernicke's aphasia (WA) and examined the relationship between lesion, CBF and neuropsychological impairment.Arterial spin labelling CBF imaging and structural MRIs were collected in 12 individuals with chronic WA and 13 age-matched control participants. Joint independent component analysis (jICA) investigated the relationship between structural lesion and hypoperfusion. Partial correlations explored the relationship between lesion, hypoperfusion and language measures.Joint ICA revealed significant differences between the control and WA groups reflecting a large area of structural lesion in the left posterior hemisphere and an associated area of hypoperfusion extending into grey matter surrounding the lesion. Small regions of remote cortical hypoperfusion were observed, ipsilateral and contralateral to the lesion. Significant correlations were observed between the neuropsychological measures (naming, repetition, reading and semantic association) and the jICA component of interest in the WA group. Additional ROI analyses found a relationship between perfusion surrounding the core lesion and the same neuropsychological measures.This study found that core language impairments in chronic WA are associated with a combination of structural lesion and abnormal perfusion in non-lesioned tissue. This indicates that post-stroke impairments are due to a wider disruption of neural function than observable on structural T1w MRI.

Neuroimaging of the bilingual brain: Structural brain correlates of listening and speaking in a second language

Diffusion tensor imaging was used to compare white matter structure between American monolingual and Spanish-English bilingual adults living in the United States. In the bilingual group, relationships between white matter structure and naturalistic immersive experience in listening to and speaking English were additionally explored. White matter structural differences between groups were found to be bilateral and widespread. In the bilingual group, experience in listening to English was more robustly correlated with decreases in radial and mean diffusivity in anterior white matter regions of the left hemisphere, whereas experience in speaking English was more robustly correlated with increases in fractional anisotropy in more posterior left hemisphere white matter regions. The findings suggest that (a) foreign language immersion induces neuroplasticity in the adult brain, (b) the degree of alteration is proportional to language experience, and (c) the modes of immersive language experience have more robust effects on different brain regions and on different structural features.

Right hemisphere dominance for language in a woman with schizophrenia and a porencephalic cyst of the left hemisphere

ABSTRACTA large left hemisphere porencephalic cyst was incidentally found in a 48-year-old woman (MS) with a Diagnostic and Statistical Manual (DSM)-5 diagnosis of schizophrenia. The encephaloclastic characteristics of the cyst indicated that it was acquired between the 22nd and 24th gestational weeks, after the major waves of neuronal migration had tapered off. The cyst destroyed the left temporal and occipital lobes, and the inferior parietal lobule. Surprisingly, MS had no evidence of aphasia, alexia, agraphia, or ideational apraxia; in contrast, cognitive functions dependent on the integrity of the right hemisphere were severely impaired. To test the hypothesis that the development of language in MS took place at the expense of functions that are normally carried out by the right hemisphere, we investigated MS’s correlates of oral comprehension with fMRI as a proxy for auditory comprehension and other cognitive functions strongly lateralized to the posterior left hemisphere, such as ideational praxis and reading. Comprehension of spoken language engaged the homologous of Wernicke’s area in the right planum temporale. Porencephaly may represent a natural model of neuroplasticity supervening at predictable epochs of prenatal development.

Gray matter atrophy in patients with mild cognitive impairment/Alzheimer's disease over the course of developing delusions.

We conducted a neuroimaging analysis to understand the neuroanatomical correlates of gray matter loss in a group of mild cognitive impairment and early Alzheimer's disease patients who developed delusions. With data collected as part of the Alzheimer's Disease Neuroimaging Initiative, we conducted voxel-based morphometry to determine areas of gray matter change in the same Alzheimer's Disease Neuroimaging Initiative participants, before and after they developed delusions. We identified 14 voxel clusters with significant gray matter decrease in patient scans post-delusional onset, correcting for multiple comparisons (false discovery rate, p < 0.05). Major areas of difference included the right and left insulae, left precuneus, the right and left cerebellar culmen, the left superior temporal gyrus, the right posterior cingulate, the right thalamus, and the left parahippocampal gyrus. Although contrary to our initial predictions of enhanced right frontal atrophy, our preliminary work identifies several neuroanatomical areas, including the cerebellum and left posterior hemisphere, which may be involved in delusional development in these patients.

Age-related differences in the automatic processing of single letters: implications for selective attention.

Older adults exhibit diminished ability to inhibit the processing of visual stimuli that are supposed to be ignored. The extent to which age-related changes in early visual processing contribute to impairments in selective attention remains to be determined. Here, 103 adults, 18-85 years of age, completed a color selective attention task in which they were asked to attend to a specified color and respond to designated target letters. An optimal approach would be to initially filter according to color and then process letter forms in the attend color to identify targets. An asymmetric N170 ERP component (larger amplitude over left posterior hemisphere sites) was used as a marker of the early automatic processing of letter forms. Young and middle-aged adults did not generate an asymmetric N170 component. In contrast, young-old and old-old adults produced a larger N170 over the left hemisphere. Furthermore, older adults generated a larger N170 to letter than nonletter stimuli over the left, but not right hemisphere. More asymmetric N170 responses predicted greater allocation of late selection resources to target letters in the ignore color, as indexed by P3b amplitude. These results suggest that unlike their younger counterparts, older adults automatically process stimuli as letters early in the selection process, when it would be more efficient to attend to color only. The inability to ignore letters early in the processing stream helps explain the age-related increase in subsequent processing of target letter forms presented in the ignore color.

Successful therapy for temporomandibular pain alters anterior insula and cerebellar representations of occlusion

Craniomandibular disorders (CMD) are widespread, but we know little about the cerebral representations associated with this pain syndrome and nothing about changes in cerebral representations of occlusion induced by common therapy approaches. In a longitudinal therapy study, we applied functional magnetic resonance imaging (fMRI) in 14 patients with mild CMD during occlusal movements. fMRI, pain scoring, kinematic investigations of occlusal movements, and jaw muscle electromyography (EMG) were measured before and after two weeks of therapy with an individually optimized Michigan splint. The patients' subjective pain ratings decreased, and the symmetry of condylar movements increased over the period of therapy. After therapy, EMG of the jaw muscles demonstrated more relaxed resting conditions and increased activity during maximal occlusion. fMRI during occlusion showed an activation decrease in the right anterior insula and right cerebellum over the course of therapy. Correlation analysis between pain score and fMRI activation decreases identified right anterior insula, left posterior insula and left cerebellar hemisphere. Left cerebellar and right primary motor activation magnitude was negatively associated with symmetry of the condylar movements. Our findings highlight the impact of the anterior insula for the internal monitoring and the anticipation of temporomandibular joint (TMJ) pain. In addition, an increase of symmetry of condylar movements after therapy has been associated with a decrease of activation magnitude in primary motor and cerebellar regions.

How low can you go: Spatial frequency sensitivity in a patient with pure alexia

Pure alexia is a selective deficit in reading, following lesions to the posterior left hemisphere. Writing and other language functions remain intact in these patients. Whether pure alexia is caused by a primary problem in visual perception is highly debated. A recent hypothesis suggests that a low level deficit – reduced sensitivity to particular spatial frequencies – is the underlying cause. We tested this hypothesis in a pure alexic patient (LK), using a sensitive psychophysical paradigm to examine her performance with simple patterns of different spatial frequency. We find that both in a detection and a classification task, LK’s contrast sensitivity is comparable to normal controls for all spatial frequencies. Thus, reduced spatial frequency sensitivity does not constitute a general explanation for pure alexia, suggesting that the core deficit in this disorder is at a higher level in the visual processing stream.

Investigation of Whole-Brain White Matter Identifies Altered Water Mobility in the Pathogenesis of High-Altitude Headache

Elevated brain water is a common finding in individuals with severe forms of altitude illness. However, the location, nature, and a causative link between brain edema and symptoms of acute mountain sickness such as headache remains unknown. We examined indices of brain white matter water mobility in 13 participants after 2 and 10 hours in normoxia (21% O2) and hypoxia (12% O2) using magnetic resonance imaging. Using a whole-brain analysis (tract-based spatial statistics (TBSS)), mean diffusivity was reduced in the left posterior hemisphere after 2 hours and globally reduced throughout cerebral white matter by 10 hours in hypoxia. However, no changes in T2 relaxation time (T2) or fractional anisotropy were observed. The TBSS identified an association between changes in mean diffusivity, fractional anisotropy, and T2 both supra and subtentorially after 2 and 10 hours, with headache score after 10 hours in hypoxia. Region of interest-based analyses generally confirmed these results. These data indicate that acute periods of hypoxemia cause a shift of water into the intracellular space within the cerebral white matter, whereas no evidence of brain edema (a volumetric enlargement) is identifiable. Furthermore, these changes in brain water mobility are related to the intensity of high-altitude headache.

Understanding the time variant connectivity of the language network in developmental dyslexia: new insights using Granger causality

The reading process takes place in a neuronal network comprising the inferior frontal, posterior dorsal and posterior ventral brain areas. It is suggested that developmental dyslexia is caused by a disruption of the two posterior network areas. What remains debatable is whether these areas are affected in their functionality or whether the neuronal networking (connectivity) of these areas suffer from a disturbed information transfer. Thus, it is of major interest to investigate the time flow of the directed information transfer (time variant connectivity) within the neuronal reading network of dyslexic subjects. We investigated adolescents with dyslexia and normal-reading controls with functional magnetic resonance imaging and electroencephalography (EEG) with a paradigm addressing basic visual, orthographic and phonological processing. EEG data were analyzed with the time variant Granger causality index (tvGCI) to investigate the temporal order of the directed information transfer (time variant causal connectivity: which network node passes when information to which network node) during reading in dyslexic readers. Results show that the reading network of dyslexic readers comprises the same brain areas as identified in normal-reading subjects. The tvGCI analysis of the network profiles of dyslexic readers indicates that dyslexics show a difference in timing and localization of connectivity within this reading network compared to normal readers. Dyslexic readers use right hemisphere language areas to counterbalance posterior left hemisphere processing deficits. The compensatory involvement of homologue right hemisphere brain areas for the reading process may be the neurobiological background for the significantly longer reading times by dyslexics.

The right-hemisphere and valence hypotheses: could they both be right (and sometimes left)?

The two halves of the brain are believed to play different roles in emotional processing, but the specific contribution of each hemisphere continues to be debated. The right-hemisphere hypothesis suggests that the right cerebrum is dominant for processing all emotions regardless of affective valence, whereas the valence specific hypothesis posits that the left hemisphere is specialized for processing positive affect while the right hemisphere is specialized for negative affect. Here, healthy participants viewed two split visual-field facial affect perception tasks during functional magnetic resonance imaging, one presenting chimeric happy faces (i.e. half happy/half neutral) and the other presenting identical sad chimera (i.e. half sad/half neutral), each masked immediately by a neutral face. Results suggest that the posterior right hemisphere is generically activated during non-conscious emotional face perception regardless of affective valence, although greater activation is produced by negative facial cues. The posterior left hemisphere was generally less activated by emotional faces, but also appeared to recruit bilateral anterior brain regions in a valence-specific manner. Findings suggest simultaneous operation of aspects of both hypotheses, suggesting that these two rival theories may not actually be in opposition, but may instead reflect different facets of a complex distributed emotion processing system.

Variability of fMRI activation during a phonological and semantic language task in healthy subjects.

Assessing inter-individual variability of functional activations is of practical importance in the use of functional magnetic resonance imaging (fMRI) in a clinical context. In this fMRI study we addressed this issue in 30 right-handed, healthy subjects using rhyme detection (phonologic) and semantic categorization tasks. Significant activations, found mainly in the left hemisphere, concerned the inferior frontal gyrus, the superior/middle temporal gyri, the prefrontal cortex, the inferior parietal lobe, the superior parietal lobule/superior occipital gyrus, the pre-central gyrus, and the supplementary motor area. Intensity/spatial analysis comparing activations in both tasks revealed an increased involvement of frontal regions in the semantic task and of temporo-parietal regions in the phonologic task. The frequency of activation analyzed in nine regional subdivisions revealed a high inter-subject variability but showed that the most frequently activated regions were the inferior frontal gyrus and the prefrontal cortex. Laterality indices, strongly lateralizing in both tasks, were slightly higher in the semantic (0.76 +/- 0.19) than the phonologic task (0.66 +/- 0.27). Frontal dominance indices (a measure of frontal vs. posterior left hemisphere dominance) indicated more robust frontal activations in the semantic than the phonologic task. Our study allowed the characterization of the most frequently involved foci in two language tasks and showed that the combination of these tasks constitutes a suitable tool for determining language lateralization and for mapping major language areas.

The role of the cerebral hemispheres in specific versus abstract priming

The present study examined specific and abstract priming for pictures in unilateral brain‐damaged patients using a picture fragment identification task. Participants were 10 posterior right hemisphere (RH) damaged patients, 11 posterior left hemisphere (LH) damaged patients, and 30 healthy normal controls. Results reveal that RH patients perform specific priming tasks significantly worse than healthy participants (p <. 005). There was a trend (p <. 1) towards worse abstract priming in LH patients when compared to healthy participants. These results are additional evidence that specific priming depends on normal functioning of the posterior right cerebral hemisphere, while abstract priming depends on normal functioning of the posterior left cerebral hemisphere, and extend this finding from verbal to non‐verbal stimuli.

Event-Related Potentials for Category-Specific Information During Passive Viewing of Faces and Objects

Normal subjects passively viewed an upright or inverted face or objects during recording of event-related potentials. Face inversion augmented N170 amplitude and latency in the temporal region, but on ly the latency in the parietal region. The same manipulation slowed down the on set of the P220 and caused disappearance of the N300, whereas none of these effects was seen after object inversion. Item-specific processing of objects was observed, namely disappearance of the N190 and the appearance of a P170 wave in the left posterior hemisphere to on e object but not the other. These results are concordant with the hypothesis of category-specific processing during the recognition of faces and objects.

Temporal patterns of human cortical activity reflect tone sequence structure.

Despite growing interest in temporal aspects of auditory neural processing, little is known about large-scale timing patterns of brain activity during the perception of auditory sequences. This is partly because it has not been possible to distinguish stimulus-related activity from other, endogenous brain signals recorded by electrical or magnetic sensors. Here we use amplitude modulation of unfamiliar, approximately 1-minute-long tone sequences to label stimulus-related magnetoencephalographic neural activity in human subjects. We show that temporal patterns of activity recorded over particular brain regions track the pitch contour of tone sequences, with the accuracy of tracking increasing as tone sequences become more predictable in structure. In contrast, temporal synchronization between recording locations, particularly between sites over the left posterior hemisphere and the rest of the brain, is greatest when sequences have melody-like statistical properties, which may reflect the perceptual integration of local and global pitch patterns in melody-like sequences. This method is particularly well suited to studying temporal neural correlates of complex auditory sequences (such as speech or music) which engage multiple brain areas as perception unfolds in time.

A Case of Prosopagnosia Following Moderate Closed Head Injury with Left Hemisphere Focal Lesion

This study describes a left handed woman with prosopagnosia following traumatic brain injury with a focal lesion confined to the left-posterior hemisphere. Few cases of prosopagnosia following unilateral left hemisphere lesions have previously been reported in the literature. Corrected visual acuity was 20/70 (binocular), color vision was intact on screening, and shape detection was borderline. Impairments in higher order visual perception were evident to varying degrees on nonfacial tasks. Matching of unfamiliar faces was very slow but accurate. A marked impairment in the ability to recognize familiar faces and learn new face-name associations was evident on experimental tasks relative to the performance of healthy control subjects. In contrast, identification of characteristics of faces (gender, age) and identification and matching of facial expressions were relatively preserved. We discuss the cognitive processing stages that appear to be disrupted using Bruce and Young's (1986) model of facial recognition and perception as a framework.

EEG power changes during a multiple level memory retention task

EEG changes related to the amount of information held in memory during a 4-s retention period were studied. The predictability of the amount of information held in memory was varied. In the weighted condition, 60% of the trials contained only one item and the remaining 40% of the trials were evenly distributed between trials containing 3, 5, 7, or 8 items. In the random condition, the levels were equally represented and randomly presented. In the blocked condition the levels were equally represented but presented in five blocks containing only items from one of the levels. Initial widespread decreases in alpha band power were followed by increased activity in all three conditions. The more difficult of the five levels produced decreased alpha activity in more localized posterior left hemisphere sites. This suggests two alpha mechanisms, one associated with task engagement and the other related to the cognitive demands regardless of the presentation context. Theta band power increased over frontal scalp, and to a lesser extent over left parietal and temporal areas and bilateral occipital sites, during only the weighted condition. These changes were uniform over the entire retention period. Beta 2 activity was also influenced by the task difficulty and the time course of the retention period in the two conditions. Beta 2 activity resembled both alpha and theta in that in levels 1, 2 and 3 it acted like alpha with increasing power over time at numerous widespread sites while the higher difficulty levels showed higher power at the beginning of the retention period and then decreased.

Enhancement of anticancer drug delivery to the brain by microwave induced hyperthermia

Methotrexate (MTX) is a widely prescribed antifolate in cancer chemotherapy for a variety of neoplasms. Like many useful, hydrophilic antitumor drugs, MTX is excluded from the brain after systemic administration due to its inability to cross the blood–brain barrier (BBB). The blood–brain barrier functions as a differential filter which permits the selective passage of substance from blood to extracellular brain spaces. It maintains the physical and chemical environments of the brain within certain narrow limits. We have studied enhanced uptake of MTX in brains of male rats (10-week old Wistar, 500 g, three per group) subjected to selective microwave hyperthermia of the left hemisphere. The rat was anesthetized using 40 mg/kg of sodium pentobarbital, IP and was placed in a stereotaxic head holder. Microwave energy (2450 MHz, 2.6 W/cm 2, 208 W/kg, CW) was applied for 20 min. The body temperature was kept at 37.8±0.4°C. The brain temperature recorded in a similar group of rats using a carbon filament probe (Vitek) was 42.7±0.4°C. Three different MTX dosages, 50, 100, and 200 mg/kg, were injected intravenously immediately following microwave irradiation into the rat in 1.5, 3 and 6 min, respectively. The drug was allowed to circulate for 5 min before brains were removed for analysis. Standard HPLC assays were applied to samples from the anterior and posterior left hemisphere of the cerebrum, and the cerebellum. Samples from the right hemisphere were used for controls. The average uptake at the posterior left hemisphere was found to be 2.25±0.43, 10.40±2.59, and 17.23±1.13 μg of MTX per g of brain tissue for 50, 100, and 200 mg/kg doses, respectively. In another series of experiments, MTX bolus was not injected until 15 or 45 min after cessation of microwave irradiation. Brains of rats injected 45 min after irradiation were free of MTX. Animals euthanized 15 min post-irradiation had an average midbrain MTX concentration of 2.5±0.46 μg/g of tissue. These results indicate that MTX uptake is significantly increased in rat brains subjected to noninvasive microwave hyperthermia treatment. Furthermore, the increase is reversible within 45 min post-irradiation.