Left Hemisphere Areas Research Articles

The neural substrates of inferential and referential semantic processing

IntroductionA distinction has been proposed, on theoretical grounds, between referential and inferential semantic abilities. The former account for the relationship of words to the world, the latter for the relationship of words among themselves. The hypothesis of, at least partially, different neurological underpinnings for this distinction has been supported by the presence of double dissociations in neurological patients between tasks that can be considered to tap the cognitive processes involving these two different classes of semantic knowledge, such as, for example, picture naming (referential) and naming to a verbal definition (inferential). MethodsWe report here the results of a functional magnetic resonance experiment, contrasting the pattern of brain activity associated with, respectively, “referential” (picture naming, word-to-picture matching) and “inferential” (naming to definition, word-to-word matching) tasks. ResultsAll tasks activate an extensive set of brain areas involving both hemispheres, corresponding to the “common semantic network”. In addition, left hemispheric temporal areas are selectively engaged by the inferential tasks. Conversely, a specific activation of the right fusiform gyrus is associated with the referential tasks. ConclusionsThese findings suggest that while inferential tasks, as compared with referential tasks, engage additional processing resources subserved by left hemispheric language areas involved in lexical retrieval, referential tasks (as compared with inferential tasks) recruit right hemispheric areas generally associated with nonverbal conceptual and structural object processing. These findings are compatible with the double dissociations reported in neurological patients.

Auditory verbal hallucinations in schizophrenia as aberrant lateralized speech perception: Evidence from dichotic listening

We report evidence that auditory verbal hallucinations (AVH) in schizophrenia patients are perceptual distortions lateralized to the left hemisphere. We used a dichotic listening task with repeated presentations of consonant–vowel syllables, a different syllable in the right and left ear. This task produces more correct reports for the right ear syllable in healthy individuals, indicative of left hemisphere speech processing focus. If AVHs are lateralized to the left hemisphere language receptive areas, then this should interfere with correct right ear reports in the dichotic task, which would result in significant negative correlations with severity of AVHs. We correlated the right and left ear correct reports with the PANSS hallucination symptom, and a randomly selected negative symptom, in addition to the sum total of the positive and negative symptoms, in 160 patients with schizophrenia. The results confirmed the predictions with significant negative correlations for the right ear scores with the PANSS hallucination item, and for the sum total of positive symptoms, while all other correlations were close to zero. The results are unambiguous evidence for AVHs as aberrant speech perceptions originating in the left hemisphere.

Whose side are you on: Does serotonin preferentially activate the right hemisphere and norepinephrine the left?

Serotonin (5-HT) and norepinephrine (NE) innervate both the left and right hemispheres of the brain, but whether they affect lateralization of function is unknown. This paper concisely examines evidence that these two neurotransmitters differentially affect the two hemispheres, and puts forth the novel hypothesis 5-HT preferentially activates the right hemisphere (RH) and NE the left hemisphere (LH). The principal lines of evidence comprise studies of: (1) 5-HT and NE level measurement, (2) receptor binding, (3) functional brain imaging, (4) dichotic listening, and (5) electroencephalography and evoked potentials. In assessing these 5 lines, emphasis is placed on studies of pharmaceutical drugs that affect the 5-HT and NE systems. While all of the data do not support the hypothesis, they are generally consistent with it, or a variant of the hypothesis that there is a bias toward 5-HT preferentially activating a majority of brain areas or functions in the RH, and NE a majority of LH areas or functions. If this hypothesis, or a variant of it, is correct, it may be relevant to understanding the physiological basis of neuropsychiatric disorders that could involve dysfunction in brain monoaminergic systems, as well as understanding potential lateralization of the effects of drugs that act on these systems.

“The archeologist's career ended in ruins”: Hemispheric differences in pun comprehension in autism

Appropriate interpretation of figurative language involves inferring the speaker's intent by integrating word meaning with context. In disorders like autism, understanding intended and contextual meanings in language may pose a challenge. Such difficulties are prevalent even when individuals exhibit otherwise fluent language ability (Szatmari et al., 1990). A pun is a rhetorical technique in which a speaker deliberately invokes multiple meanings through a word or phrase likely resulting in a joke. Comprehending puns may involve identifying multiple meanings of a word, embedding it in right contexts, and understanding the underlying humor. This fMRI study investigated the brain responses associated with figures of speech like puns. In the fMRI scanner, participants read sentences containing puns (e.g. To write with a broken pencil is pointless) and control sentences (literal meaning) presented in a blocked design format. The participants' task was to silently read and understand one meaning (in the literal condition) or two meanings (in the pun condition). Participants with autism, relative to typical controls, showed an increase in overall activation while comprehending sentences containing puns, particularly within the right hemisphere as well as in relatively posterior brain areas. Overall, there was reduced response in left hemisphere areas, reduced response to humor, and more distributed recruitment of regions in autism relative to control participants. We also examined the relationship between symptom severity in autism and verbal ability with brain responses to pun comprehension finding negative and positive correlations respectively. Overall, the results from the present study suggest that individuals with autism resort to altered neural routes in comprehending language in general, and figurative language in particular.

A crucial role for the cortico-striato-cortical loop in the pathogenesis of stroke-related neurogenic stuttering

Neurogenic stuttering is an acquired speech disorder characterized by the occurrence of stuttering-like dysfluencies following brain damage. Because the onset of stuttering in these patients is associated with brain lesions, this condition provides a unique opportunity to study the neural processes underlying speech dysfluencies. Lesion localizations of 20 stroke subjects with neurogenic stuttering and 17 control subjects were compared using voxel-based lesion symptom mapping. The results showed nine left-hemisphere areas associated with the presence of neurogenic stuttering. These areas were largely overlapping with the cortico-basal ganglia-cortical network comprising the inferior frontal cortex, superior temporal cortex, intraparietal cortex, basal ganglia, and their white matter interconnections through the superior longitudinal fasciculus and internal capsule. These results indicated that stroke-induced neurogenic stuttering is not associated with neural dysfunction in one specific brain area but can occur following one or more lesion throughout the cortico-basal ganglia-cortical network. It is suggested that the onset of neurogenic stuttering in stroke subjects results from a disintegration of neural functions necessary for fluent speech.

Sturge-Weber syndrome: A rare entity

A 10-year-old boy presented with focal seizure involving right angle of mouth and arm followed by generalized seizures, which were controlled with valproic acid. The majority of seizures were focal seizures, which were confirmed by the electroencephalography. Initiallywe started on 15mg/kg and then gradually over 3 mo seizures got control with 25 mg/kg/day and he is now seizure free over last 15 mo. He had normal developmental milestones except for his school performance which was slightly lesser than his peers. On physical examination, head circumference was within 2 standard deviations for his age. He had facial angiomas and soft tissue hypertrophy on left side (Fig. 1). Opthalmological examination was normal. In our case, there were presence of both facial and leptomeningeal angiomas, therefore he belongs to type I. Cranial computerized tomography revealed calcifications in left frontotemporo-parietal region (Fig. 2). Cranial magnetic resonance imaging revealed presence of cortical atrophy in left hemisphere and patchy areas of mild contrast enhancement suggesting presence of venous angiomas (Fig. 3). The Sturge-Weber syndrome (SWS) is also called encephalotrigeminal angiomatosis. It is a neurocutaneous disorder with angiomas involving the leptomeninges (leptomeningeal angiomas [LA]) and skin of the face, typically in the ophthalmic (V1) and maxillary (V2) distributions of the trigeminal nerve. The cutaneous

Influence of area 5 on interhemispheric inhibition

Brodmann's area 5 is implicated in the sensorimotor control of hand movement in humans and nonhuman primates. However, little is known about the influence of area 5 on the neural circuitry within the primary motor cortex that underpins hand control. The present study investigated the neural circuitry of interhemispheric inhibition (IHI) that exists between homologous muscle representations in the motor cortex. Using paired-pulse transcranial magnetic stimulation, IHI was probed from the left-to-right hemisphere and vice versa for the first dorsal interosseous muscle of the hand at short (10 ms) and long (40 ms) latencies before and for up to 1 h after continuous θ-burst stimulation over left hemisphere area 5. The results indicate that continuous θ-burst over area 5 increases IHI at short latencies in the left hand (left-to-right inhibition) from 5-20 and 45-60 min after stimulation. Short latency inhibition in the right hand and bilateral long latency inhibition remain unaltered. The data indicate that area 5 influences the IHI that exists between the representations of the hand muscles. This effect occurs ipsilateral to the left area 5, suggesting that effects are mediated through changes in the excitability of transcallosal neurons originating in the left motor cortex.

Single pulse TMS induced disruption to right and left parietal cortex on addition and multiplication

Whether or not mathematical operations are dependent on verbal codes in left hemisphere areas - particularly the left intraparietal sulcus - remains an issue of intense debate. Using single pulse transcranial magnetic stimulation directed at horizontal and ventral regions of the left and right intraparietal sulcus, we examined disruption to reaction times in simple addition and multiplication. Results indicate that these two operations differ in the pattern of lateralization across time for the two areas studied. These show that computational efficiency is not specifically dependent on left hemisphere regions and, in particular, that efficiency in multiplication is dependent on the ventral region of the intraparietal sulcus in the right hemisphere considered to be critical for motion representation and automatization.

Characteristics of EEG reactivity changes during the performance of dual tasks in healthy subjects (voluntary postural control and calculation)

Comprehensive EEG and stabilography investigation with separate and simultaneous performance of motor (voluntary postural control) and cognitive (calculation) tasks has been performed in 20 healthy subjects (22 ± 0.7 years). Specific spatial and frequency reactive changes have been found during motor task performance. These included an increase in coherence in the EEG α band for distant derivation pairs in the right hemisphere, as well as in symmetric parietal-occipital areas in both hemispheres. Cognitive task performance was accompanied by an increase in coherence for the slow bands (δ and θ) with a higher activation in the left hemisphere and frontal cortex areas. In performing the dual task, one could observe activation of spatial and frequency changes including both motor and cognitive tasks. In the dual tasks where both components were performed worse as compared to the control, reactive reorganization of EEG coherence was less pronounced than during the performance of separate tasks. A decrease in the coherence of the α1 band in the frontal areas appeared as a zone of “conflict of interest” or interference. In dual tasks with better performance of each component as compared to the control, EEG coherence increased in each specific area, as well as in the areas of “conflict of interests.”

Influence of informational oversaturation on the quality of creative activity and spatial organization of EEG

The features of the spatial organization of bioelectric potentials in the cases of successful and unsuccessful creative imagination (refusal or poor quality of the product) under conditions of informational oversaturation. Two groups of subjects were compared: professionals (23 healthy students of the Department of Graphic Arts) and non-professionals (34 persons whose specialties were not linked with systematic visual imagination). During the experiments, the subjects were asked to mentally create a visual image based on two simple graphic elements, a right angle and a diagonal; after recording the EEG, they had to draw the image on paper and give it a title. The total number of elements exceeded 7 ± 2; hence, information processing at the conscious level was impossible, which caused the necessity of involving the mechanisms of unconscious information processing. The quality of the created product was evaluated with regard to the degree of success of performing the task and the features of spatial EEG organization. The EEG was recorded from 24 scalp sites of a subject using a SIT-EEG portable telemetric device. In the case of the successful performance of the task by professionals, the parameters of spatial organization of bioelectric potentials, i.e., spatial synchronization (linear processes) and spatial disorder (non-linear process) were strengthened compared to the base-line level in the frontal temporal areas of the right hemisphere and parietal occipital areas of the left hemisphere. Conversely, in the nonprofessionals, these parameters increased in the frontal temporal areas of the left hemisphere and parietal occipital areas of the right hemisphere. In the case a task was not successfully performed by the professionals, the spatial disorder of bioelectric potentials increased in all the cortical areas; in the nonprofessionals, only weak changes were observed. In all situations, the groups differed also in the parameters of coherence (Coh), spectral power (Sp) of bioelectric potentials, and informational energy, which reflects the level of expenditure of the brain’s energy for information processing. The evidence obtained is interpreted in terms of electroencephalographic correlates of successful task performance by professionals and nonprofessionals, i.e., their creative imagination under the conditions of informational over-saturation.

The right hemisphere is not unitary in its role in aphasia recovery

Neurologists and aphasiologists have debated for over a century whether right hemisphere recruitment facilitates or impedes recovery from aphasia. Here we present a well-characterized patient with sequential left and right hemisphere strokes whose case substantially informs this debate. A 72-year-old woman with chronic nonfluent aphasia was enrolled in a trial of transcranial magnetic stimulation (TMS). She underwent 10 daily sessions of inhibitory TMS to the right pars triangularis. Brain activity was measured during picture naming using functional magnetic resonance imaging (fMRI) prior to TMS exposure and before and after TMS on the first day of treatment. Language and cognition were tested behaviorally three times prior to treatment, and at 2 and 6 months afterward. Inhibitory TMS to the right pars triangularis induced immediate improvement in naming, which was sustained 2 months later. fMRI confirmed a local reduction in activity at the TMS target, without expected increased activity in corresponding left hemisphere areas. Three months after TMS, the patient suffered a right hemisphere ischemic stroke, resulting in worsening of aphasia without other clinical deficits. Behavioral testing 3 months later confirmed that language function was impacted more than other cognitive domains. The paradoxical effects of inhibitory TMS and the stroke to the right hemisphere demonstrate that even within a single patient, involvement of some right hemisphere areas may support recovery, while others interfere. The behavioral evidence confirms that compensatory reorganization occurred within the right hemisphere after the original stroke. No support is found for interhemispheric inhibition, the theoretical framework on which most therapeutic brain stimulation protocols for aphasia are based.

Changes in maps of language function and the integrity of the arcuate fasciculus after therapy for chronic aphasia

A patient with chronic aphasia secondary to unilateral stroke in the left hemisphere underwent language testing, diffusion tensor imaging (DTI), and functional imaging using magnetoencephalography (MEG) at four time points: 3 weeks prior to, immediately prior to, immediately after, and 3 months after Constraint Induced Language Therapy (CILT). Performance on language tests involving visual naming and repetition of spoken sentences improved between the immediately prior to and immediately after CILT testing sessions, but not between the pre-CILT sessions. MEG activation in putative pre-morbid language areas of the left hemisphere and homotopic areas of the right hemisphere increased immediately after therapy, as did integrity within the arcuate fasciculus bilaterally. These changes were not evident between the two pre-CILT sessions. While some of these functional, neurophysiological and structural changes had regressed 3 months after therapy, all remained at or above baseline levels. Results provide evidence for an association between improvement in functional status and the increased integrity within a white matter tract known to be involved in language function and its contralateral homologue, as well as increased neurophysiological activity in areas that have the potential to subserve language function bilaterally.

Are networks for residual language function and recovery consistent across aphasic patients?

If neuroplastic changes in aphasia are consistent across studies, this would imply relatively stereotyped mechanisms of recovery which could guide the design of more efficient noninvasive brain stimulation treatments. To address this question, we performed a meta-analysis of functional neuroimaging studies of chronic aphasia after stroke. Functional neuroimaging articles using language tasks in patients with chronic aphasia after stroke (n = 105) and control subjects (n = 129) were collected. Activation likelihood estimation meta-analysis determined areas of consistent activity in each group. Functional homology between areas recruited by aphasic patients and controls was assessed by determining whether they activated under the same experimental conditions. Controls consistently activated a network of left hemisphere language areas. Aphasic patients consistently activated some spared left hemisphere language nodes, new left hemisphere areas, and right hemisphere areas homotopic to the control subjects' language network. Patients with left inferior frontal lesions recruited right inferior frontal gyrus more reliably than those without. Some areas, including right dorsal pars opercularis, were functionally homologous with corresponding control areas, while others, including right pars triangularis, were not. The network of brain areas aphasic patients recruit for language functions is largely consistent across studies. Several recruitment mechanisms occur, including persistent function in spared nodes, compensatory recruitment of alternate nodes, and recruitment of areas that may hinder recovery. These findings may guide development of brain stimulation protocols that can be applied across populations of aphasic patients who share common attributes.

Language proficiency modulates the recruitment of non-classical language areas in bilinguals.

Bilingualism provides a unique opportunity for understanding the relative roles of proficiency and order of acquisition in determining how the brain represents language. In a previous study, we combined magnetoencephalography (MEG) and magnetic resonance imaging (MRI) to examine the spatiotemporal dynamics of word processing in a group of Spanish-English bilinguals who were more proficient in their native language. We found that from the earliest stages of lexical processing, words in the second language evoke greater activity in bilateral posterior visual regions, while activity to the native language is largely confined to classical left hemisphere fronto-temporal areas. In the present study, we sought to examine whether these effects relate to language proficiency or order of language acquisition by testing Spanish-English bilingual subjects who had become dominant in their second language. Additionally, we wanted to determine whether activity in bilateral visual regions was related to the presentation of written words in our previous study, so we presented subjects with both written and auditory words. We found greater activity for the less proficient native language in bilateral posterior visual regions for both the visual and auditory modalities, which started during the earliest word encoding stages and continued through lexico-semantic processing. In classical left fronto-temporal regions, the two languages evoked similar activity. Therefore, it is the lack of proficiency rather than secondary acquisition order that determines the recruitment of non-classical areas for word processing.

Increased gray matter volume of left pars opercularis in male orchestral musicians correlate positively with years of musical performance

To compare manual volumetry of gray matter (GM) / white matter (WM) of Broca's area subparts: pars opercularis (POP) and pars triangularis (PTR) in both hemispheres between musicians and nonmusician, as it has been shown that these regions are crucial for musical abilities. A previous voxel-based morphometric (VBM) study conducted in our laboratory reported increased GM density in Broca's area of left hemisphere in male orchestral musicians. Functional segregation of POP/PTR justified separate volumetric analysis of these parts. We used the same cohort for the VBM study. Manual morphometry (stereology) was used to compare volumes between 26/26 right-handed orchestral musicians/nonmusicians. As expected, musicians showed significantly increased GM volume in the Broca's area, specifically in the left POP. No significant results were detected in right POP, left/right PTR GM volumes, and WM volumes for all regions. Results were positively correlated with years of musical performance (r = 0.7, P = 0.0001). This result corroborates the VBM study and is in line with the hypothesis of critical involvement of POP in hearing-action integration being an integral component of frontoparietotemporal mirror neuron network. We hypothesize that increased size of musicians' left POP represent use-dependent structural adaptation in response to intensive audiomotor skill acquisition.

Behavioral patterns and lesion sites associated with impaired processing of lexical and conceptual knowledge of actions

To further investigate the neural substrates of lexical and conceptual knowledge of actions, we administered a battery of six tasks to 226 brain-damaged patients with widely distributed lesions in the left and right cerebral hemispheres. The tasks probed lexical and conceptual knowledge of actions in a variety of verbal and non-verbal ways, including naming, word-picture matching, attribute judgments involving both words and pictures, and associative comparisons involving both words and pictures. Of the 226 patients who were studied, 61 failed one or more of the six tasks, with four patients being impaired on the entire battery, and varied numbers of patients being impaired on varied combinations of tasks. Overall, the 61 patients manifested a complex array of associations and dissociations across the six tasks. The lesion sites of 147 of the 226 patients were also investigated, using formal methods for lesion-deficit statistical mapping and power analysis of lesion overlap maps. Significant effects for all six tasks were found in the following left-hemisphere regions: the inferior frontal gyrus; the ventral precentral gyrus, extending superiorly into what are likely to be hand-related primary motor and premotor areas; and the anterior insula. In addition, significant effects for 4–5 tasks were found in not only the regions just mentioned, but also in several other left-hemisphere areas: the ventral postcentral gyrus; the supramarginal gyrus; and the posterior middle temporal gyrus. These results converge with previous research on the neural underpinnings of action words and concepts. However, the current study goes considerably beyond most previous investigations by providing extensive behavioral and lesion data for an unusually large and diverse sample of brain-damaged patients, and by incorporating multiple measures of verb comprehension. Regarding theoretical implications, the study provides new support for the Embodied Cognition Framework, which maintains that conceptual knowledge is grounded in sensorimotor systems.

Functional coupling of cortical areas during problem-solving task: Analysis of θ rhythm coherence

We analyzed the EEG theta rhythm coherence in adult subjects who performed visual object classification task in the condition of uncertainty. The coherence function was estimated for the EEG segment following a feedback signal. It was shown that the functional coupling of cortical areas was stronger in the process of strategy discovering as comparing to the final period when the strategy is already found. The theta-related functional links are characterized by a specific topographical pattern: they converge to the foci located in the polar frontal cortex and reflect the interaction between the latter and the anterior associative cortices of the left hemisphere and occipital areas of both hemispheres. This pattern of functional connectivity may reflect an interaction between limbic structures and the frontal cortex in the process of strategy formation.

Functional connectivity from area 5 to primary motor cortex via paired-pulse transcranial magnetic stimulation

In non-human primates area 5 is dominated by the representation of the hand and forelimb, and has direct connectivity with primary motor cortex (M1) implicating its role in the control of hand movements. To date, few studies have investigated the function of area 5 in humans or its connectivity with M1. Using paired-pulse TMS, the present study investigates the functional connectivity between putative area 5 within the medial superior parietal lobule and ispilateral M1 in humans. Specifically, the motor evoked potential (MEP) from the first dorsal interosseous muscle of the right hand was quantified with and without conditioning TMS stimuli applied to left-hemisphere area 5. The timecourse of functional connectivity was examined during cutaneous stimulation applied to the thumb and index finger and also during rest whereby no somatosensory processing demands were imposed. Results indicate that area 5 facilitates and inhibits the MEP at 6 and 40 ms, respectively, during somatosensory processing. No net influence of area 5 on M1 output was observed during rest. We conclude that area 5 has a task-dependent and temporally specific influence on M1 output, and suggest that the interaction between these areas presents a novel path with which to alter the motor output, and possibly movement of hand muscles.

Neural plasticity and treatment-induced recovery of sentence processing in agrammatism

This study examined patterns of neural activation associated with treatment-induced improvement of complex sentence production (and comprehension) in six individuals with stroke-induced agrammatic aphasia, taking into account possible alterations in blood flow often associated with stroke, including delayed time-to-peak of the hemodynamic response function (HRF) and hypoperfused tissue. Aphasic participants performed an auditory verification fMRI task, processing object cleft, subject cleft, and simple active sentences, prior to and following a course of Treatment of Underlying Forms (TUF; Thompson et al., 2003), a linguistically based approach for treating aphasic sentence deficits, which targeted object relative clause constructions. The patients also were scanned in a long-trials task to examine HRFs, to account for any local deviations resulting from stroke, and perfusion images were obtained to evaluate regions of hypoperfused tissue. Region-of-interest (ROI) analyses were conducted (bilaterally), modeling participant-specific local HRFs in left hemisphere areas activated by 12 healthy age-matched volunteers performing the same task, including the middle and inferior frontal gyri, precentral gyrus, middle and superior temporal gyri, and insula, and additional regions associated with complex syntactic processing, including the posterior perisylvian and superior parietal cortices. Results showed that, despite individual variation in activation differences from pre- to post-treatment scans in the aphasic participants, main-effects analyses revealed a general shift from left superior temporal activation to more posterior temporoparietal areas, bilaterally. Time-to-peak of these responses correlated negatively with blood flow, as measured with perfusion imaging.

Neural changes after phonological treatment for anomia: An fMRI study

Functional magnetic resonance imaging (fMRI) was used to investigate the neural processing characteristics associated with word retrieval abilities after a phonologically-based treatment for anomia in two stroke patients with aphasia. Neural activity associated with a phonological and a semantic task was compared before and after treatment with fMRI. In addition to the two patients who received treatment, two patients with aphasia who did not receive treatment and 10 healthy controls were also scanned twice. In the two patients who received treatment, both of whose naming improved after treatment, results showed that activation patterns changed after treatment on the semantic task in areas that would have been expected (e.g., left hemisphere frontal and temporal areas). For one control patient, there were no significant changes in brain activation at the second scan; a second control patient showed changes in brain activation at the second scan, on the semantic task, however, these changes were not accompanied with improved performance in naming. In addition, there appeared to be bilateral, or even more right than left hemisphere brain areas activated in this patient than in the treated patients. The healthy control group showed no changes in activation at the second scan. These findings are discussed with reference to the literature on the neural underpinnings of recovery after treatment for anomia in aphasia.