The study of autism as a distributed disorder

Past autism research has often been dedicated to tracing the causes of the disorder to a localized neurological abnormality, a single functional network, or a single cognitive-behavioral domain. In this review, I argue that autism is a "distributed disorder" on various levels of study (genetic, neuroanatomical, neurofunctional, behavioral). "Localizing" models are therefore not promising. The large array of potential genetic risk factors suggests that multiple (or all) emerging functional brain networks are affected during early development. This is supported by widespread growth abnormalities throughout the brain. Interactions during development between affected functional networks and atypical experiential effects (associated with atypical behavior) in children with autism further complicate the neurological bases of the disorder, resulting in an "exponentially distributed" profile. Promising approaches to a better characterization of neural endophenotypes in autism are provided by techniques investigating white matter and connectivity, such as MR spectroscopy, diffusion-tensor imaging (DTI), and functional connectivity MRI. According to a recent hypothesis, the autistic brain is generally characterized by "underconnectivity." However, not all findings are consistent with this view. The concepts and methodology of functional connectivity need to be refined and results need to be corroborated by anatomical studies (such as DTI tractography) before definitive conclusions can be drawn.     

Recall of grammatical relations within clause-containing sentences

Two major findings were obtained in a study of college students' recall of meaningful grammatical relations within sentences: (1) verb-object relations in object focus relative clauses were recalled less accurately than verb-object relations in subject focus relative clauses, thus supporting the hypothesis that permuted word order in certain relative clauses interferes with adequate encoding of underlying grammatical relations, and (2) subject-verb relations in nested sentences in which a relative clause intervened between subject and verb (nested sentences) were retained in memory as accurately as uninterrupted subject-verb relations (not nested sentences).     

Subcortical aphasia with deep dyslexia: A case study of a Japanese patient

The reading performance of a Japanese Broca-type aphasic patient on a single-word reading test was investigated. The result indicated that the subject fits the symptom complex of deep dyslexia in more than one aspect. Unique characteristics of this subject included (1) the isolated subcortical site of the lesion, which apparently produced deep dyslexia, and (2) double dissociations between kanji and kana processing and between oral reading and reading comprehension. The performance of this subject was compared with that of another Japanese deep dyslexic subject in S. Sasanuma (1980, In M. Coltheart, K. Patterson, & J. C. Marshall (Eds.), Deep dyslexia, London: Routledge & Kegan Paul). A theoretical implication was attempted based on a dual coding process scheme by S. Sasanuma and O. Fujimura (1978, Cortex, 7, 1-18).     

Multiple-look effects on temporal discrimination within sound sequences

The multiple-look notion holds that the difference limen (DL) decreases with multiple observations. We investigated this notion for temporal discrimination in isochronous sound sequences. In Experiment 1, we established a multiple-look effect when sequences comprised nine standard time intervals (S) followed by an increasing number of comparison time intervals (C), but no multiple-look effect when one trailing C interval was preceded by an increasing number of S intervals. In Experiment 2, we extended the design. There were four sequential conditions: (a) 9 leading S intervals followed by 1, 2, …, or 9 C-intervals; (b) 9 leading C intervals followed by 1, 2, …, or 9 S intervals; (c) 9 trailing C-intervals preceded by 1, 2, …, or 9 S-intervals; and (d) 9 trailing S-intervals preceded by 1, 2, …, or 9 C-intervals. Both the interval accretions before and after the tempo change caused multiple-look effects, irrespective of the time order of S and C. Complete deconfounding of the number of intervals before and after the tempo change was accomplished in Experiment 3. The multiple-look effect of interval accretion before the tempo change was twice as big as that after the tempo change. The diminishing returns relation between the DL and interval accretion could be described well by a reciprocal function.     

Decision-making deficit of a patient with axonal damage after traumatic brain injury

Patients with traumatic brain injury (TBI) were reported to have difficulty making advantageous decisions, but the underlying deficits of the network of brain areas involved in this process were not directly examined. We report a patient with TBI who demonstrated problematic behavior in situations of risk and complexity after cerebral injury from a traffic accident. The Iowa gambling task (IGT) was used to reveal his deficits in the decision-making process. To examine underlying deficits of the network of brain areas, we examined T1-weighted structural MRI, diffusion tensor imaging (DTI) and Tc-ECD SPECT in this patient. The patient showed abnormality in IGT. DTI-MRI results showed a significant decrease in fractional anisotropy (FA) in the fasciculus between the brain stem and cortical regions via the thalamus. He showed significant decrease in gray matter volumes in the bilateral insular cortex, hypothalamus, and posterior cingulate cortex, possibly reflecting Wallerian degeneration secondary to the fasciculus abnormalities. SPECT showed significant blood flow decrease in the broad cortical areas including the ventromedial prefrontal cortex (VM). Our study showed that the patient had dysfunctional decision-making process. Microstructural abnormality in the fasciculus, likely from the traffic accident, caused reduced afferent feedback to the brain, resulting in less efficient decision-making. Our findings support the somatic-marker hypothesis (SMH), where somatic feedback to the brain influences the decision-making process.     

Effects of stimulus preexposure on omission responding and omission-produced dishabituation of the human electrodermal response

As a test of Wagner's (1981) theory of habituation, three experiments examined the effects of stimulus preexposure on electrodermal responding to the absence of a stimulus and on omission-produced dishabituation. The general procedure for all experiments consisted of a preexposure phase in which one stimulus (S1) was presented 20 times, followed by a pairing phase in which S1 was followed by a second event, S2. After a number of S1-S2 pairings, S2 was omitted for one trial and was then represented following S1 on the next trial. Electrodermal activity was measured in all experiments, and in Experiments 2 and 3, a measure of expectancy of S2 in the presence of S1 was also obtained to provide a putative index of S2 priming by S1. Experiments 1 (N=48) and 2 (N=72) employed 15 S1-S2 pairings prior to S2 omission. Significant omission responding and dishabituation to S2 were obtained in both experiments. However, omission effects were not influenced by preexposure presentations of S1. Experiment 3, on the other hand, demonstrated that omission responding and dishabituation were attenuated by 20 preexposures of S1 when only 4 S1-S2 pairings were employed. In addition, Experiments 2 and 3 revealed that although expectation of S2 developed as a function of S1-S2 pairings, it too was reduced by preexposure to S1. Only Experiment 3 provided preexposure effects that are consistent with Wagner's (1981) theory.     

Effects of stimulus omission and stimulus change on dishabituation of the skin conductance response

Three experiments examined the effects of stimulus omission and stimulus change on dishabituation of the skin conductance response. In all experiments, subjects received 17 tone-light or light-tone (S1-S2) pairings, and the primary manipulations were omission of and change in S2 on Trial 16. Responses to S1 and S2 on Trial 17 constituted the data of primary interest. Experiment 1 (N = 72) demonstrated that omission of an expected stimulus was more effective in producing dishabituation than was presentation of an unexpected but not experimentally novel stimulus. Experiment 2 (N = 60) indicated that both omission of an expected stimulus and presentation of an unexpected and experimentally novel stimulus produced dishabituation. Experiment 3 (N = 72) revealed that both the omission and the miscuing of 52 produced reliable dishabituation. The results are interpreted as indicating the importance of a comparison between current input and the stored representation of previous stimulation in the development of habituation.     

Effect of Repeated Evaluation and Repeated Exposure on Acceptability Ratings of Sentences

This study investigated the effect of repeated evaluation and repeated exposure on grammatical acceptability ratings for both acceptable and unacceptable sentence types. In Experiment 1, subjects in the Experimental group rated multiple examples of two ungrammatical sentence types (ungrammatical binding and double object with dative-only verb), and two difficult to process sentence types [center-embedded (2) and garden path ambiguous relative], along with matched grammatical/non-difficult sentences, before rating a final set of experimental sentences. Subjects in the control group rated unrelated sentences during the exposure period before rating the experimental sentences. Subjects in the Experimental group rated both grammatical and ungrammatical sentences as more acceptable after repeated evaluation than subjects in the Control group. In Experiment 2, subjects answered a comprehension question after reading each sentence during the exposure period. Subjects in the experimental group rated garden path and center-embedded (1) sentences as higher in acceptability after comprehension exposure than subjects in the control group. The results are consistent with increased fluency of comprehension being misattributed as a change in acceptability.     

Left occipital lobectomy and the preangular anatomy of reading

Two patients had alexias after left occipital lobectomies. Case 1 was a 55-year-old man with a glioblastoma. At 4 months after surgery he could read slowly, but reading was neither efficient nor pleasant. Case 2 was a 19-year-old male who had a more restricted, medial occipital lobectomy for an encapsulated mesenchymal chondrosarcoma. The tumor did not invade brain initially, and the patient recovered efficient reading after 15 months. It is postulated that Case 2 was able to recover efficient reading because he still had a field of left ventrolateral occipitotemporal cortex connected to homologous cortex on the right.     

Microstructural organization of corpus callosum projections to prefrontal cortex predicts bimanual motor learning

The corpus callosum (CC) is the largest white matter tract in the brain. It enables interhemispheric communication, particularly with respect to bimanual coordination. Here, we use diffusion tensor imaging (DTI) in healthy humans to determine the extent to which structural organization of subregions within the CC would predict how well subjects learn a novel bimanual task. A single DTI scan was taken prior to training. Participants then practiced a bimanual visuomotor task over the course of 2 wk, consisting of multiple coordination patterns. Findings revealed that the predictive power of fractional anisotropy (FA) was a function of CC subregion and practice. That is, FA of the anterior CC, which projects to the prefrontal cortex, predicted bimanual learning rather than the middle CC regions, which connect primary motor cortex. This correlation was specific in that FA correlated significantly with performance of the most difficult frequency ratios tested and not the innately preferred, isochronous frequency ratio. Moreover, the effect was only evident after training and not at initiation of practice. This is the first DTI study in healthy adults which demonstrates that white matter organization of the interhemispheric connections between the prefrontal structures is strongly correlated with motor learning capability.     

Human trace fear conditioning: right-lateralized cortical activity supports trace-interval processes

Pavlovian conditioning requires the convergence and simultaneous activation of neural circuitry that supports conditioned stimulus (CS) and unconditioned stimulus (US) processes. However, in trace conditioning, the CS and US are separated by a period of time called the trace interval, and thus do not overlap. Therefore, determining brain regions that support associative learning by maintaining a CS representation during the trace interval is an important issue for conditioning research. Prior functional magnetic resonance imaging (fMRI) research has identified brain regions that support trace-conditioning processes. However, relatively little is known about whether this activity is specific to the trace CS, the trace interval, or both periods of time. The present study was designed to disentangle the hemodynamic response produced by the trace CS from that associated with the trace interval, in order to identify learning-related activation during these distinct components of a trace-conditioning trial. Trace-conditioned activity was observed within dorsomedial prefrontal cortex (PFC), dorsolateral PFC, insula, inferior parietal lobule (IPL), and posterior cingulate (PCC). Each of these regions showed learning-related activity during the trace CS, while trace-interval activity was only observed within a subset of these areas (i.e., dorsomedial PFC, PCC, right dorsolateral PFC, right IPL, right superior/middle temporal gyrus, and bilateral insula). Trace-interval activity was greater in right than in left dorsolateral PFC, IPL, and superior/middle temporal gyrus. These findings indicate that components of the prefrontal, cingulate, insular, and parietal cortices support trace-interval processes, as well as suggesting that a right-lateralized fronto-parietal circuit may play a unique role in trace conditioning.     

Selective uppercase dysgraphia with loss of visual imagery of letter forms: a window on the organization of graphomotor patterns

We report a patient who, after a left parieto-occipital lesion, showed alexia and selective dysgraphia for uppercase letters. He showed preserved oral spelling, associated with handwriting impairment in all written production; spontaneous writing, writing to dictation, real words, pseudowords, and single letters were affected. The great majority of errors were well-formed letter substitutions: most of them were located on the first position of each word, which the patient always wrote in uppercase (as he used to do before his illness). The patient also showed a complete inability to access the visual representation of letters. As demonstrated by a stroke segmentation analysis, letter substitutions followed a rule of graphomotor similarity. We propose that the patient's impairment was at the stage where selection of the specific graphomotor pattern for each letter is made and that the apparent selective disruption of capital case was due to a greater stroke similarity among letters belonging to the same case. We conclude that a visual format is necessary neither for spelling nor for handwriting.     

Lexical and buffer effects in reading and in writing Noun-Noun compound nouns

Reading and writing Noun-Noun compound nouns was investigated in two Italian aphasic patients: one with phonological dyslexia and the other with phonological dysgraphia. The patients were required to read, write and repeat a list of Noun-Noun compounds and length-matched non-compound nouns. The dyslexic patient RF read compounds better than non-compounds, and his repetition was flawless for both categories. The dysgraphic patient DA wrote non-compounds better than compounds because of a deficit in keeping separate entries at the lemma level. Differential performance when processing compounds and non-compounds is the result of a deficit in different components within the mental lexicon architecture.     

Evidence of syntactic deficits in a fluent aphasic

The syntactic abilities of a mild Wernicke's aphasic were examined in production and comprehension tasks. The patient made few errors involving the omission or substitution of substantives or grammatical markers, especially after the first few weeks of testing. Despite his good ability to produce sentences with acceptable surface form, he continued to make role reversal errors and to produce a restricted range of syntactic forms. In comprehension, he also demonstrated an impairment in his ability to use the syntactic information in a sentence to assign role relations. These syntactic impairments could not be attributed to a short-term memory deficit as the patient showed only a slightly reduced short-term memory span, and showed evidence of having a normal phonological store. Implications for theories of aphasic deficits as well as for theories of normal language processing are discussed.     

Effects of syntactic information on semantic access of ambiguous verbs in spoken language comprehension: Evidence from a cross‐modal priming experiment1

Abstract: The aim of this study was to examine how syntactic information affects the semantic processing of ambiguous verbs in spoken Japanese. The effect of a postpositional particle on semantic access of an ambiguous verb at the end of the sentence was demonstrated in two kinds of sentences, S‐ga‐V sentences (subject, subjective postpositional particle, and ambiguous verb) and O‐wo‐V sentences (object, objective postpositional particle, and ambiguous verb). A cross‐modal priming method was used in which a target noun was presented visually in Kanji (Chinese) characters either one syllable before the end or immediately after the end of the ambiguous verb. Weak multiple priming occurred in the one‐syllable‐before condition, followed by selective access in the immediately after condition, but this multiple access was partially constrained by the preceding postpositional particle. A brief occurrence of multiple access and rapid transition to selective access were detected. Furthermore, objective particles were found to have stronger constraints on multiple access than on subjective particles. A connectionist model using a constraint‐based lexical approach was consistent with the experimental results.     

Religion Benefiting Brain Tumour Patients: A Qualitative Study

As the focus on modern neurosurgery has shifted to the realm of technological advancement, some patients and their loved ones still hold a strong faith in their religion to guide them through the process. This study aimed to determine whether religion as a coping mechanism was beneficial for patients before, during and after craniotomy. Qualitative case study methodology was used. Interviews were conducted with randomly selected 36 adult patients who underwent surgery for a benign or malignant brain tumour. Interviews were audio recorded and transcribed, and the data subjected to thematic analysis. Four overarching themes emerged from the data: (1) religion significantly benefited neurosurgical patients; (2) neurosurgical patients did not require a dedicated religious room in the hospital; (3) neurosurgical patients required religious resources such as leaders and/or groups; and (4) patients were not in favour of their physician engaging in the religious ritual. Most patients found religion to be an effective coping mechanism, offering them strength, comfort, and hope through the surgery. The findings from this study emphasize the need for including a “religious time-out” before and after surgery and the inclusion of religious leaders/groups for those in favour to ensure quality care and patient satisfaction.     

EEG phase synchronization during semantic unification relates to individual differences in children’s vocabulary skill

As we listen to speech, our ability to understand what was said requires us to retrieve and bind together individual word meanings into a coherent discourse representation. This so‐called semantic unification is a fundamental cognitive skill, and its development relies on the integration of neural activity throughout widely distributed functional brain networks. In this proof‐of‐concept study, we examine, for the first time, how these functional brain networks develop in children. Twenty‐six children (ages 4–17) listened to well‐formed sentences and sentences containing a semantic violation, while EEG was recorded. Children with stronger vocabulary showed N400 effects that were more concentrated to centroparietal electrodes and greater EEG phase synchrony (phase lag index; PLI) between right centroparietal and bilateral frontocentral electrodes in the delta frequency band (1–3 Hz) 1.27–1.53 s after listening to well‐formed sentences compared to sentences containing a semantic violation. These effects related specifically to individual differences in receptive vocabulary, perhaps pointing to greater recruitment of functional brain networks important for top‐down semantic unification with development. Less skilled children showed greater delta phase synchrony for violation sentences 3.41–3.64 s after critical word onset. This later effect was partly driven by individual differences in nonverbal reasoning, perhaps pointing to non‐verbal compensatory processing to extract meaning from speech in children with less developed vocabulary. We suggest that functional brain network communication, as measured by momentary changes in the phase synchrony of EEG oscillations, develops throughout the school years to support language comprehension in different ways depending on children's verbal and nonverbal skill levels.     

Reinforcement omission on fixed-interval schedules

Experiments with pigeons and rats showed that: (1) When a brief blackout was presented in lieu of reinforcement at the end of 25% of intervals on a fixed-interval 2-min schedule, response rate was reliably and persistently higher during the following 2-min intervals (omission effect). This effect was largely due to a decrease in time to first response after reinforcement omission. (2) When blackout duration was varied, within sessions, over the range 2 to 32 sec, time to first response was inversely related to the duration of the preceding blackout, for pigeons, and for rats during the first few sessions after the transition from FI 2-min to FI 2-min with reinforcement omission. Post-blackout pause was independent of blackout duration for rats at asymptote. These results were interpreted in terms of differential depressive effects of reinforcement and blackout on subsequent responding.